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   Table of Contents - Current issue
January-March 2019
Volume 15 | Issue 1
Page Nos. 1-264

Online since Wednesday, March 13, 2019

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Sequential simulation computed tomography allows assessment of internal rectal movements during preoperative chemoradiotherapy in rectal cancer p. 1
Dae Sik Yang, Jung Ae Lee, Won Sup Yoon, Nam Kwon Lee, Young Je Park, Suk Lee, Chul Yong Kim
DOI:10.4103/jcrt.JCRT_227_17  PMID:30880746
Purposes: The purpose of this study was to assess the internal rectal movement and to determine the factors related to extensive internal rectal movement using sequential simulation computed tomography (CT) images. Materials and Methods: From 2010 to 2015, 96 patients receiving long-course preoperative chemoradiotherapy were included in our retrospective study. The initial simulation CT (Isim-CT) and follow-up simulation CT (Fsim-CT) for a boost were registered according to the isocenters and bony structure. The rectums on Isim-CT and Fsim-CT were compared on four different axial planes as follows: (1) lower pubis symphysis (AXVERYLOW), (2) upper pubis symphysis (AXLOW), (3) superior rectum (AXHIGH), and (4) middle of AXLOW and AXHIGH (AXMID). The involved rectum in the planning target volume was evaluated. The maximal radial distances (MRD), the necessary radius from the end of Isim-CT rectum to cover entire Fsim-CT rectum, and the common area rate (CAR) of the rectum (CAR, (Isim-CT∩Fsim-CT)/(Isim-CT)) were measured. Linear regression tests for the MRDs and logistic regression tests for the CARs were conducted. Results: The mean ± standard deviation (mm) of MRDs and CAR <80% for AXVERYLOW, AXLOW, AXMID, and AXHIGH were 2.3 ± 2.5 and 8.9%, 3.0 ± 3.7 and 17.4%, 4.0 ± 5.2 and 27.1%, and 4.1 ± 5.2 and 25%, respectively. For MRDs and CARs, a higher axial level (AXVERYLOW/AXMID-HIGH, P = 0.018 and P = 0.034, respectively), larger bladder volume (P = 0.054 and P = 0.017, respectively), smaller bowel gas extent (small/marked, P = 0.014 and P = 0.001, respectively), and increased bowel gas change (decrease/increase, both P < 0.001) in rectum were associated with extensive internal rectal movement in multivariate analyses. Conclusions: As a result of following internal rectal movement through sequential simulation CT, the rectum above the pubis symphysis needs a larger margin, and bladder volume and bowel gas should be closely observed.
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To determine the utility of fluorodeoxyglucose-positron emission tomography-computed tomography scan in predicting pathological response in operated carcinoma rectum patients after initial neoadjuvant chemoradiation p. 9
Neelam Sharma, Puneet Takkar, Abhishek Purkayastha, Braj Kishore Singh
DOI:10.4103/jcrt.JCRT_873_17  PMID:30880747
Background: The objective of this study was to determine whether [18F]-fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET CT) scan could predict the pathological response in carcinoma rectum patients after surgery in patients receiving neoadjuvant concurrent chemoradiotherapy (NACCRT). Setting and Design: A prospective study was carried out from March 2015 to March 2017; 39 patients of histopathologically proven, locally advanced, potentially operable, of adenocarcinoma rectum were included in the study. Methods: Patients had a pretreatment FDG-PET-CT scan and repeat scan after 6–8 weeks of NACCRT. The change in mean maximum standardized uptake value ([%Δ SUVmax]) was compared with the tumor regression grade (TRG) in the postoperative histology. TRG of 1 and 2 was deemed responders and 3–5 was nonresponders. Statistical Analysis: Chi-square test, one-way ANOVA, and receiver operating characteristics curve analysis were used. All analyses were done using SPSS 17.0 version. Results: In 61.5% responders receiving NACCRT, the SUV fell from 10.91 ± 3.70 to 4.14 ± 1.73, respectively, while in 38.5% nonresponders, SUV fell from 11.65 ± 2.66 to 4.23 ± 1.3. SUV Δ% was 63.03 ± 10.17 in nonresponders and 61.32 ± 11.81 in responders with a nonsignificant P = 0.646. The P value did not reach a statistical significance as far as reduction in SUV values pre- and post-NACCRT is concerned in both responders as well as nonresponders. Conclusion: Hence, we concluded that assessment with FDG PET CT scan in carcinoma rectum patients' postneoadjuvant treatment cannot be the only imaging modality or assessing the response and postoperative histopathology remains the gold standard.
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rs12904 polymorphism in the 3'-untranslated region of ephrin A1 ligand and the risk of sporadic colorectal cancer in the Iranian population p. 15
Miganoosh Simonian, Meysam Mosallaei, Sharifeh Khosravi, Rasoul Salehi
DOI:10.4103/jcrt.JCRT_766_17  PMID:30880748
Background: Colorectal cancer (CRC) is rated as the second cause of cancer death. Genetic determinants are considered as driving forces in the development of sporadic CRC. Single-nucleotide polymorphisms (SNPs), due to their abundance in the human genome with collectively huge effect on cellular signaling pathways, are attributed as the main genetic factor in disease susceptibility including cancers. MicroRNAs are contributing to posttranslational gene regulation. They exert their regulatory function by binding to their specific recognition sequences located at 3'-untranslated region (UTR) of mRNAs. In the present study, we have elucidated the role of rs12904, a naturally occurring SNP, in the recognition site of miR200c in the 3'UTR of ephrin A1 ligand gene, in the development of sporadic CRC in the Iranian population. Materials and Methods: A case–control study using 152 CRC patients and 160 noncancerous counterparts was conducted to determine the rs12904 genotypes using polymerase chain reaction–restriction fragment length polymorphism method. Results: The results revealed no significant association between the rs12904 and sporadic CRC (odds ratio = 0.97, 95% confidence interval = 0.70–1.34). The frequency of genotypes and also alleles of the mentioned polymorphism were not significantly different between case and control groups (P = 0.765 and P = 0.847, respectively). Conclusion: The results suggest that this polymorphism probably has not a crucial role in the Iranian CRC risk and is not an important potential risk factor in molecular diagnostics of mentioned disease among the Iranian population.
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Exercise prehabilitation program for patients under neoadjuvant treatment for rectal cancer: A pilot study p. 20
Lidia B Alejo, Itziar Pagola-Aldazabal, Carmen Fiuza-Luces, Daniel Huerga, María Victoria de Torres, Ana Soria Verdugo, María Jesus Ortega Solano, José Luis Felipe, Alejandro Lucia, Ana Ruiz-Casado
DOI:10.4103/jcrt.JCRT_30_17  PMID:30880749
Context: Prehabilitation is emerging as a method of preparing patients physically and mentally for the often disabling effects of cancer treatment. Aims: This study aims to assess the feasibility and to explore the potential effects of a prehabilitation program consisting of educational physical exercise sessions in patients with rectal cancer undergoing neoadjuvant chemoradiotherapy treatment (NCRT). Settings and Design: This was a pilot study with 12 patients (3 males and 9 females, age 61 ± 7 years). Subjects and Methods: The program included six educational sessions of exercise during NCRT. Adherence to the intervention; quality of life (QoL); anxiety and depression; body mass index; physical fitness (peak oxygen uptake (VO2peak), handgrip and dynamic leg strength); and physical activity (PA) levels were measured. Statistical Analysis Used: Data are reported as the mean ± standard deviation or medians and interquartile ranges for questionnaire-derived data. Secondary outcome measures were compared using the nonparametric Wilcoxon test. The threshold P value for significance was calculated after correction for multiple comparisons using the Bonferroni method. Results: Adherence to the program was 64 of 72 possible exercise education sessions completed, i.e., 89%. We detected a trend toward a significant improvement in VO2peak after the intervention (P = 0.015), together with reduced scores for both depression (P = 0.017) and the QoL domain “emotional function” (P = 0.027). Mean levels of moderate to vigorous PA tended to increase after the exercise program (P = 0.091). Conclusions: Exercise might be an effective prehabilitation strategy for surgery during the period of NCRT.
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Association of clinicopathological features with E-cadherin (CDH1) gene-160 C>A promoter polymorphism in Turkish colorectal cancer patients p. 26
Anzel Bahadir, Gokalp Eral, Metin Budak, Fumio Shimamoto, Mehmet Ali Korpinar, Sibel Erdamar, Handan Tuncel
DOI:10.4103/jcrt.JCRT_1277_16  PMID:30880750
Background and Aim of Study: The role of E-cadherin (CDH1) gene-160 C>A (rs16260) promoter polymorphism in colorectal cancer (CRC) still remains inconclusive. The aim of this study is to investigate the associations between the CDH1-160 C>A polymorphism with the susceptibility and clinicopathological development of CRC in the Turkish patients. To our knowledge, this is the first report examining the role of CDH1 polymorphism in Turkish CRC patients. Materials and Methods: A total of 92 colorectal carcinoma cases (including 62 colon and 30 rectal cancer patients) and the corresponding adjacent normal tissues as controls were studied. The polymorphism was genotyped using polymerase chain reaction-restriction fragment length polymorphism analysis. Clinicopathological features including patient's age, gender, tumor stage, and tumor location (colon/rectum) were compared statistically with the polymorphism status. Results: There was no significant difference in both genotype and allele frequencies of the CDH1 polymorphism between colorectal tumor cases and normal samples (P = 0.472 and 0.508, respectively). Furthermore, no significant associations were observed between the CDH1 polymorphism status and age, gender, tumor stage, and tumor location of the colorectal tumor cases (all P > 0.05). Conclusions: These results indicate that CDH1-160 C>A polymorphism does not contribute to the genetic susceptibility of CRC and the polymorphism may not be a direct effect on the progression of the disease in Turkish CRC patients.
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Potential using of microRNA-34A in combination with paclitaxel in colorectal cancer cells p. 32
Hadis Soltani-Sedeh, Shiva Irani, Reza Mirfakhraie, Masoud Soleimani
DOI:10.4103/jcrt.JCRT_267_17  PMID:30880751
Background: MicroRNAs are small noncoding RNAs which modulate gene expression at different levels. It has been shown that downregulation of miR-34a occurs in varieties of cancers including colorectal cancer (CRC). In this study, we investigated the potential tumor inhibitory effects of miR-34a alone or in combination with paclitaxel in CRC cells. Materials and Methods: SW480 cells were transduced with lentiviral overexpressed miR-34a. First, using 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide assay, the effect of miR-34a induction alone or in combination with paclitaxel on the cell viability and cell proliferation were estimated. Then, the expression level of target genes was measured using quantitative reverse transcription-polymerase chain reaction analysis. Eventually, the role of miR-34a and paclitaxel on cell cycle were determined with flow cytometry. Results: Gene expression analysis showed that miR-34a downregulates the expression of BCL2 and SIRT1 genes at mRNA level. Furthermore, miR-34a has a potential to reduce cell viability and cell cycle arrest at G1 phase. Combination of paclitaxel with overexpression of miR-34a significantly decreased cell viability compared to cell treated with miR-34a or paclitaxel alone. Interestingly, a combination of miR-34a and paclitaxel arrested cell cycle at two phases. Conclusion: Our results suggested that combination therapy of miR-34a and paclitaxel could be considered as the potential treatment of CRC.
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Downregulation of DBN1 is related to vincristine resistance in colon cancer cells Highly accessed article p. 38
Zhongmin Han, Hemei Huang, Tao Zhang
DOI:10.4103/0973-1482.192766  PMID:30880752
Objective: This study was aimed to investigate the relationship between the expression of drebrin (DBN1) gene and resistance in colon cancer to reveal the mechanism of tumor drug resistance and provide a basis for the reversal of this drug resistance in tumor cells. Materials and Methods: The human colon carcinoma cell line HCT-8 was used, and vincristine (VCR)-resistant colon cancer cell line HCT-8/V was established by gradually increasing the concentration of VCR. Polymerase chain reaction (PCR) primers were designed for DBN1 gene. The DBN1 differential expression in colon cancer sensitive and resistant cell lines was detected by fluorescence quantitative PCR. Western blot analysis was used to study DBN1 expression in the resistant cells further. Results: VCR resistance of HCT-8/V cell line was established. Quantitative PCR and Western blot results showed that DBN1 expression in the resistant cell line was significantly lower, the difference being statistically significant (P < 0.05). Conclusion: Low DBN1 gene expression may be associated with colon cancer cell resistance to VCR.
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Noncirrhotic portal hypertension: An under-reported late adverse event of SIRT in metastatic colorectal cancer patients p. 42
Lourdes Gutierrez, Santiago Méndez, Mercedes Mitjavila, Elba Llop, Clara Salas, Ana Ruiz-Casado
DOI:10.4103/jcrt.JCRT_1398_16  PMID:30880753
Introduction: Selective internal radiation therapy (SIRT) is increasingly used in different scenarios. Although portal hypertension (PHT) has been described as a nonclinically relevant finding after SIRT, its real incidence could have been neglected due to the nature of the diseases for which SIRT is indicated. Case Reports: Here we report three cases with clinically relevant late PHT after treatments including SIRT and oxaliplatin among others. Discussion: The sequential use of oxaliplatin and SIRT in patients with colorectal cancer metastases could have additive effects on the liver.
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The prognostic and predictive significance of plasma type 1 plasminogen activator inhibitor and endoglin in metastatic colorectal cancer patients treated with bevacizumab-containing chemotherapy p. 48
Oznur Bal, Ahmet Siyar Ekinci, Mutlu Dogan, Cigdem Atay, Ayse Demirci, Berna Oksuzoglu, Selim Kilic
DOI:10.4103/jcrt.JCRT_1253_16  PMID:30880754
Aim: This study aims to evaluate the prognostic and predictive value of plasma plasminogen activator inhibitor-1 (PAI-1) and endoglin in metastatic colorectal cancer (mCRC) patients receiving chemotherapy with bevacizumab. Materials and Methods: Between April 2012 and September 2013, 47 mCRC patients with a mean age of 58.5 ± 9.6 years were included in the study. Male-to-female ratio was 29/18. The baseline and posttreatment plasma PAI-1 and serum endoglin levels after 3 cycles of bevacizumab-containing chemotherapy were evaluated. The percent change between baseline and posttreatment levels after treatment was also recorded. Results: The median follow-up duration was 26.6 months (range 1.8–70.2 months). The clinical benefit rate was 70% (partial response [32%], stable disease [38%]). Overall survival was 20.8 ± 1.5 months. The patients with progressive disease had statistically significantly higher baseline PAI-1 level (57.9 pg/mL vs. 29.9 pg/mL, P = 0.036). The percent change of the plasma PAI-1 level after the third cycle of treatment was also statistically significantly lower in those with clinical benefit (P = 0.035). However, there was no statistically significant difference in endoglin level and its change after therapy with respect to the response to treatment (P = 0.771 and P = 0.776, respectively). Plasma PAI-1 level had no statistically significant effect on survival (P = 0.709). Conclusion: Baseline plasma PAI-1 level and its percent change with bevacizumab were shown to have statistically significant predictive value for the response to therapy whereas serum endoglin had no statistically significant predictive value for the response to therapy. However, neither PAI-1 nor endoglin had prognostic significance in mCRC.
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Prognostic effect of red cell distribution width-to-platelet ratio in colorectal cancer according to tumor stage and localization p. 54
Burak Bilgin, Mehmet Ali Nahit Sendur, Mutlu Hizal, Didem Sener Dede, Muhammed Bülent Akinci, Sümeyye Ulutas Kandil, Samet Yaman, Abdussamet Yalçin, Mehmet Kiliç, Bülent Yalçin
DOI:10.4103/jcrt.JCRT_624_17  PMID:30880755
Introduction: Colorectal cancer (CRC) is one of the most common cancers worldwide and survival is still approximately 24 months. Recently, importance of the molecular features, tumor localization, and also inflammatory status is increased, and most of these entities can be used as a predictive marker for colon tumor. However, since most of these tests are expensive and unachievable, there is a need for new prognostic and predictive markers that can be used easily and are inexpensive. Aim: We aimed to investigate the prognostic effect of red cell distribution width (RDW)-to-platelet ratio (RPR) which reflects inflammatory status and can be calculated basically by using center blood count (CBC) parameters on CRC according to tumor stage and localization. Methods: Newly diagnosed 312 CRC patients between 2010 and 2016 were retrospectively analyzed. Patients' demographics, including survival data and tumor characteristics, were obtained from medical charts. RPR was calculated using CBC parameters at the time of diagnosis. Cutoff value for RPR was set at 0.05 and the patient population was divided into two arms (arm A: RPR ≥0.05 and arm B: RPR <0.05). The patients were stratified according to the tumor stage (early and advanced disease) and tumor localization (right sided and left sided). Results: Totally, 312 patients were enrolled to the study. Nearly 81.9% of the patients were at early stage and 18.1% were at advanced stage at the time of diagnosis. In patients with early-stage disease, no significant disease-free survival and overall survival (OS) was found in both arms (P = 0.88 and P = 0.085, respectively). In arm A, OS was nonsignificantly better in the entire and left-sided advanced tumor compared to arm B. In patients with right-sided advanced cancer, OS was statistically significantly better for arm A compared to arm B (median OS; RPR ≥0.05: 24.8 months vs. <0.05: 13.9 months; P = 0.035). Discussion: RPR can be a useful prognostic marker in CRC, especially in right-sided advanced tumors. Conclusion: RPR can be used as a prognostic marker in CRC but should be validated with further investigation.
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Analysis of poliovirus receptor, CD155 expression in different human colorectal cancer cell lines: Implications for poliovirus virotherapy Highly accessed article p. 61
Sareh Zhand, Seyed Masoud Hosseini, Alijan Tabarraei, Abdolvahab Moradi, Mohsen Saeidi
DOI:10.4103/jcrt.JCRT_13_17  PMID:30880756
Context: Poliovirus (PV) receptor (CD155) is expressed on several kinds of cells and exerts diverse functions. Various investigations have confirmed that changes in CD155 expression in cancer cell lines affect metastasis, proliferation, and migration. Aims: The purpose of the present study was to investigate the CD155 transcript and protein expression in human colon adenocarcinoma cell lines in comparison to normal fetal human colon (FHC) cells. Materials and Methods: The CD155 expression level in four human adenocarcinoma cell lines and normal colon cell line were assessed using the SYBR green quantitative real-time polymerase chain reaction (PCR) and flowcytometry. Results: The results of real-time PCR indicated that CD155 was significantly overexpressed in all human adenocarcinoma cell lines (P = 0.000). The highest and the lowest expression level of CD155 messenger RNA was observed in SW480 and HT29 cell lines by 491.14, and 12.04 fold changes, respectively, in comparison with the human normal cell line (FHC). Results of flowcytometry indicate that protein was strongly expressed in cancer cell lines. SW480 cells showed the highest CD155 protein expression level of 98.1%, whereas this protein expression was 1.3% in human normal colon cell line (FHC). Totally, these data indicate that CD155 expression is significantly elevated in cancer cell lines. Conclusions: The preferential expression of CD155 on cancer cell lines rather than on normal cell line suggests that CD155 could be targeted for future PV virotherapy.
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Investigation of apoptotic effect of juglone on CCL-228-SW 480 colon cancer cell line p. 68
Dilek Bayram, Meltem Özgöçmen, Ilkay Armagan, Murat Sevimli, Gülçin Yavuz Türel, Nurgül Şenol
DOI:10.4103/jcrt.JCRT_880_17  PMID:30880757
Background: Colon cancer is a major cause of morbidity and mortality in the world. Juglone is a natural compound which has been isolated from Juglans mandshurica Maxim, and it has various pharmacological effects such as antiviral, antibacterial, and anticancer. In our study, we aimed to investigate the effect of juglone on CCL-228-SW 480 colon carcinoma cell line in monolayer and spheroid culture medium. Materials and Methods: The CCL-228-SW 480 cell lines were cultured in both monolayer and spheroid cultures. Cells were treated with juglone at 24, 48, and 72 h of incubation. ID50 inhibition was determined on the dose for juglone and after it was found 20 μM was applied to the cells to examine the effect of juglone on CCL-228-SW 480 colon carcinoma cell line. After Juglone was applied the BrdU marking index, Transferase dUTP Nick ends Labeling (TUNEL) assay, active caspase-3 assay, apoptosis-inducing factor (AIF) assay were determined by immunohistochemistry in both the monolayer and spheroid cultures. Results: The control group had a healthy pattern of S-phase fraction, and many of the CCL-228-SW 480 cells nuclei were observed to be positive for BrdU. Terminal Deoxynucleotidyl TUNEL-positive cells, active Caspase-3, and AIF were detected after treatment with juglone in both the monolayer and spheroid cultures. Conclusions: The dead cell count was higher in the CCL-228-SW 480 cell lines with juglone applied than in the controls. Juglone significantly inhibits the proliferation and induces the apoptosis of CCL-228-SW 480 cells in vitro.
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Detection of cancer stem cell-related markers in different stages of colorectal carcinoma patients of Indian origin by immunohistochemistry p. 75
LP Chaitra, Akila Prashant, CS Gowthami, B Hajira, MN Suma, SS Mahesh, GV Manjunath, CS Sheeladevi
DOI:10.4103/jcrt.JCRT_991_16  PMID:30880758
Context: Although the incidence rate of colorectal cancer (CRC) in all Indian cancer registries is very close to the lowest rate in the world, westernization has shown an increasing trend in the recent years. Recurrence is reported in CRC because the slowly proliferating stem cells escape the chemotherapeutic regimen. Aim: To detect the presence of CD133 and CD44 in human CRC specimens and to correlate the level of marker expression with tumor staging. Materials and Methods: We included 26 colorectal carcinoma patients between 20 and 70 years of age. Histological and immunohistochemical analysis of CD133 and CD44 was done in sections of 5 μm prepared from paraffin-embedded blocks with most representative areas. Statistical Analysis: All analyses were performed using Microsoft Excel 2010 and SPSS version 22. Results: CD133 expression was seen exclusively on the cell membrane at the glandular luminal surface with dot-like cytoplasmic staining. In the normal mucosa, CD44 expression was seen in the superficial region of the cell, whereas in most of the carcinomas, the staining was localized in the basolateral region of the cell. Both CD133 and CD44 showed significant correlation with tumor stage. Conclusions: In the present study, CD133 and CD44 show significant correlation with tumor staging. Cancer stem cell markers have shown similar pattern of expression in the patients of Indian origin. Using combination of markers for staging is preferred as it increases the sensitivity and specificity.
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The association between survivin −31G>C polymorphism and susceptibility to sporadic colorectal cancer in a Southern Chinese population p. 82
Jun Huang, Yisheng Wei, Xiaodong Zhou, Lei Wang, Meijin Huang, Jianping Wang
DOI:10.4103/0973-1482.202894  PMID:30880759
Background: The case–control study aimed to investigate the association between the −31G>C polymorphism in the promoter of survivin gene and the susceptibility to sporadic colorectal cancer (CRC) in a Southern Chinese population. Materials and Methods: The study was carried out on 711 healthy controls and 702 CRC cases of a Southern Chinese population. Survivin gene −31G>C genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism. The association between CRC risk and −31G>C genetic polymorphism was estimated using an unconditional logistic regression model. Results: The number of CC genotype carried in CRC patients was much higher than those of controls (P < 0.001). Compared with CC genotypes, GC, GG genotypes and −31G wild-type genotypes (i.e., GC + GG) had a significantly decreased risk of CRC (P < 0.001). In addition, survivin −31G wild-type genotypes were not associated with decreased risk of sporadic CRC patients with body mass index (BMI) ≥28.0 kg/m2, family cancer history, and premenopausal. Conclusion: Survivin −31G>C polymorphism is associated with sporadic CRC risk in the Southern Chinese population. The −31G wild-type genotypes and GC, GG genotypes are the independent protective factors against sporadic CRC excluding those with a BMI ≥28.0 kg/m2, family cancer history, and premenopausal.
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Survival of familial adenomatous polyposis coexistence colorectal cancer in Iran p. 87
Seyed Kazem Mirinezhad, Seyed Yaqoob Moaddab, Mortaza J Bonyadi, Masoud Shirmohammadi, Amir Taher Eftekharsadat, Mohammad Hossein Somi
DOI:10.4103/jcrt.JCRT_421_17  PMID:30880760
Context: Familial adenomatous polyposis (FAP) is an autosomal dominant disorder. Colorectal cancer (CRC) has been implicated as the most common cause of death in FAP patients, especially in those with coexisting CRC at initial diagnosis (FAP-CRC). Aim: We aimed to determine the survival rate of FAP-CRC and the factors affecting FAP-CRC survival. Setting and Design: This was a retrospective cohort FAP study conducted in northwest Iran. Subjects and Methods: From 2006 to 2016, 51 FAP-CRC individuals were selected from among 4588 CRC patients. Statistical Analysis: A Student's t-test, life table method, log-rank tests, a Kaplan–Maier survival curve, and Cox regression analysis were performed and a value of P < 0.05 was set as statistically significant. Results: A total of 51 FAP-CRC patients were selected, (30 males and 21 females), with a mean age of 42.2 years at diagnosis. The most common presenting symptom was abdominal pain and the most common primary tumor site was the rectum. The 1-, 5- and 10-year overall survival rates were 76%, 59%, and 52%, respectively. Factors affecting the FAP-CRC survival rate, namely, sex, age at CRC diagnosis, and extracolonic manifestations showed no significant differences. The difference in 5-year survival rates between patients with colon and rectal cancers was significant (75% vs. 33%, P = 0.02). The survival rate was significantly higher among patients with disease Stages I and II than those in disease Stages III and IV (P = 0.001). 5-year survival rates in patients with ileal pouch-anal anastomosis and ileorectal anastomosis were 71% and 78%, respectively (P = 0.001). There was an interesting difference in survival between FAP and attenuated FAP (P = 0.01). In cox regression analysis, distant metastasis was a significant predictor of survival (P = 0.001). Conclusions: Long-term survival from FAP-CRC remains poor; therefore, early-stage detection and the choice of an appropriate surgical method can improve survival in such patients.
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Four percent formalin application for the management of radiation proctitis in carcinoma cervix patients: An effective, safe, and economical practice p. 92
Brij Sharma, Manish Gupta, Rajesh Sharma, Ankur Gupta, Neetu Sharma, Mukesh Sharma, Vineeta Sharma, Siddharth Vats, Manoj Gupta, Rajeev Kumar Seam
DOI:10.4103/jcrt.JCRT_393_17  PMID:30880761
Context: Radiotherapy is a very effective treatment modality for pelvic malignancies such as carcinoma of the cervix. However, it is quite common for chronic radiation proctitis (CRP) to manifest after radical radiotherapy. CRP is a source of significant morbidity, and there is a lack of effective treatment modalities. There also exists a general lack of guidelines on management of CRP. Aims: To assess the benefit from 4% formalin application for the treatment of Grade >2 CRP among patients previously treated with radical radiotherapy for cervical carcinoma. Settings and Design: This retrospective descriptive study involved 29 eligible patients who were treated from November 2010 - November 2015 for CRP with 4% formalin application. Materials and Methods: Of the 1864 patients of carcinoma cervix treated during the said patients, 29 patients fulfilled the eligibility criteria. Eligible patients were invited telephonically for follow-up and were assessed for response and complications of the procedure. Results: The treatment of hemorrhagic radiation proctitis with local formalin instillation is effective, well tolerated and safe procedure. The procedure is inexpensive, technically simple and can be done on an outpatient basis. 62% patients had complete freedom from rectal bleed, while 34.5% patients had partial benefit. Only one patient required diversion colostomy for persistent bleeding.
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Isobaric tags for relative and absolute quantitation-based proteome analysis of Vietnamese colorectal carcinoma tissues Highly accessed article p. 96
Thi Thu Hien Pham, Kim Phuong Uyen Le, Phuong Uyen Vo, Kieu Minh Le, Teck Kwang Lim, Qinsong Lin, Thi Thu Hoai Nguyen
DOI:10.4103/0973-1482.202889  PMID:30880762
Context: Colorectal cancer (CRC) is one of the most common malignancies and one of the leading causes of cancer death worldwide. Establishing early detection methods or markers of CRC is central to improve the survival rate of CRC patients. Nowadays, new molecular tools have been developed to acquire further knowledge on tumor progression. Aims: Comparative proteomics analysis of Vietnamese colorectal carcinoma in different stages was performed to gain an insight into the molecular events taking place in CRC and metastasis. Subjects and Methods: In this study, the comparative protein expression analysis of ten paired CRC and its corresponding noncancerous tissue samples was performed using the combination of isobaric tags for relative and absolute quantitation labeling and mass spectrometry (MS). The data obtained were further analyzed with Ingenuity Pathways Analysis (IPA) system. Results: Based on the MS/MS spectra analyzed by ProteinPilot software, 684 proteins were identified, out of which 215 were observed to be differentially expressed in at least 1 sample pair. Individual protein expression and variation have been identified for each patient. IPA system demonstrated cytoskeletal signaling as the top-ranked functional pathway network associated with the oncogenic function. Conclusions: Our study supplemented the understanding about proteome of Vietnamese CRC patients and identified statistically protein expression differences among samples assisting in finding effective biomarkers for CRC diagnostics.
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Various addiction patterns, dietary habits, associated medical problems, and socioeconomic status in gastrointestinal malignancies: A prospective study in rural area of Maharashtra, India p. 104
Vandana Shailendra Jain, Darshana Kawale, Shailendra M Jain, Chaitali Waghmare, Gopal Pemmaraju
DOI:10.4103/jcrt.JCRT_925_17  PMID:30880763
Background: Gastrointestinal (GI) malignancies are increasing with advancing age. Various addictions and poor dietary habits are among the major risk factors. Early detection is difficult until patient notices symptoms. Primary prevention by knowing various risk factors and early symptom awareness will help in early diagnosis and better treatment outcome. Objectives: This study is carried out to see various addiction patterns, dietary habits, associated medical problems, and socioeconomic status with various sites involved in GI malignancies, at a tertiary care teaching hospital of Western Maharashtra, India. Materials and Methods: Prospective questionnaire-based study was carried out for 11 months. A total of 100 diagnosed carcinoma cases of GI tract malignancy were taken for study. Results and Conclusions: Out of total 100 cases, 61 were male and 39 were female. The most common site involved was esophagus (41) followed by rectosigmoid, colon and cecum, stomach, and anal canal (29, 14, 13, and 3, respectively). There were 45% of cases above 60 years of age. The most common addiction was smokeless tobacco. Most of the patients belonged to lower and upper lower class (64%). Majority of cases (81%) were nonvegetarian, only 16% were pure vegetarian. Most of the cases (85%) were in advanced stage of disease (III and IV). Awareness program for harmful effects of various addictions and importance of high-fiber diet (vegetarian diet) will help in health promotion and prevention of various malignancies. Awareness about the early symptoms of GI malignancy will help in early detection of disease and better treatment outcome.
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miR-146a is deregulated in gastric cancer p. 108
Bahareh Adami, Hossein Tabatabaeian, Kamran Ghaedi, Ardeshir Talebi, Mansoureh Azadeh, Elnaz Dehdashtian
DOI:10.4103/jcrt.JCRT_855_17  PMID:30880764
Background: Gastric cancer is one of the most significant reasons for cancer-related death. miR-146a is one of the dysregulated factors associated with gastric tumorigenesis. However, deregulation of this microRNA (miRNA) has become controversial. Moreover, the inflammation-mediating role of this miRNA implies that miR-146a might be dysregulated by gastric cancer-related pathogens, such as Helicobacter pylori. However, the dysregulation of miR-146a in H. pylori-infected gastric tumors has not been widely studied. Objectives: We aimed to analyze the expression level of miR-146a in gastric cancer tissues and then to assess any potential association between miR-146a and H. pylori infection and other clinical characteristics. Materials and Methods: miR-146a expression level was quantitatively studied by reverse transcription quantitative polymerase chain reaction, in 144 fresh tissues including 44 normal and 100 gastric cancer samples. Results: A dramatic overexpression of miR-146a was observed in primary gastric tumors. miR-146a showed lower expression in progressed tumors with greater stages and lymph node metastasis. Conclusion: miR-146a is highly expressed in primary gastric tumor independent of H. pylori infection. It is highly expressed in the lower stages and lymph node-negative tumors. It might suggest the importance of upregulation and downregulation of this miRNA in the initiating/promoting and progressive steps of gastric tumorigenesis, respectively.
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Evaluation of circulating miR-21 and miR-222 as diagnostic biomarkers for gastric cancer p. 115
Sahar Sarmasti Emami, Reza Nekouian, Abolfazl Akbari, Amirhossein Faraji, Vida Abbasi, Shahram Agah
DOI:10.4103/jcrt.JCRT_592_17  PMID:30880765
Introduction: Gastric cancer is responsible for a large number of death worldwide and its high death rate is associated with a lack of noninvasive tools in GC diagnosis. MicroRNAs (miRNAs), as gene regulators, were shown to dysregulate in different types of cancer. Moreover, it is proven that miRNAs are stable in serum/plasma, so they can be used as a potential noninvasive marker in GC diagnosis. The objective of this study is to investigate the plasma miRNA expression in GC samples compared to controls as a potential biomarker in cancer diagnosis. Materials and Methods: Expression levels of miR-21 and miR-222 were assessed using quantitative real-time polymerase chain reaction in plasma of 30 GC patients and 30 healthy controls. Diagnostic value of selected miRNAs was evaluated using receiver operating characteristic curve. Target prediction was done using bioinformatics tools to investigate the signaling pathways and function of the selected miRNAs. Results: Our results demonstrated that the expression levels of miR-21 and miR-222 were significantly higher in GC plasma than in the controls (P < 0.0001, P = 0.043). The sensitivity and specificity for miR-21 and in plasma were 86.7% and 72.2% and for miR-222 were 62.5% and 56.2%, respectively. Bioinformatics analysis revealed that most target genes of miR-21 and miR-222 are involved in cancer-related signaling pathway such as tumor initiation and progression. Conclusion: Our results indicated that miR-21 and miR-222 in plasma samples can be served as a potential noninvasive tool in GC detection. Furthermore, the miRNA target prediction manifested that miR-21 and miR-222 involve in key processes associated with GC initiation and development.
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The administration of peroxisome proliferator-activated receptors α/γ agonist TZD18 inhibits cell growth and induces apoptosis in human gastric cancer cell lines p. 120
Yuhong Ma, Bin Wang, Ling Li, Fang Wang, Xichao Xia
DOI:10.4103/0973-1482.208753  PMID:30880766
Aim of Study: This study is to investigate the effects of a novel peroxisome proliferator-activated receptor (PPAR) α/γ dual agonist TZD18 on cell growth, apoptosis, caspase activity, mitochondrial membrane potential, cytochrome c release, and apoptotic-related protein expression in MKN-45 cells. Materials and Methods: 3-(4, 5-dimethylthiazolyl)-2,5-diphenyltetrazolium bromide assay against various human cancer cell lines was performed to investigate the whether TZD18 could in reduce the proliferation rates of cancer cells. The percentages of apoptotic cells and mitochondrial membrane potential level were determined by flow cytometry. The subcellular localization of cytochrome c was examined by immunofluorescence microscopy. Western blotting assay was performed to reveal the expression of apoptosis-related proteins. Results: The results showed that the administration of TZD18 could inhibit the growth of MKN-45 cells in a dose- and time-dependent manner. In addition, the apoptotic ratio increased sharply along with a significant increase of caspase activities, mitochondrial membrane potential, and cytochrome c release following TZD18 exposure. The expression of Bax and p27kip1 increased significantly, whereas the expression level of Bcl-2 protein was downregulated. Conclusion: These results indicated that the administration of PPAR α/γ agonist TZD18 may inhibit cell growth by inducing the apoptotic process in MKN-45 cells.
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Long noncoding RNA microvascular invasion in hepatocellular carcinoma is an indicator of poor prognosis and a potential therapeutic target in gastric cancer Highly accessed article p. 126
Aihua Wang, Lei Du, Kaitong Jiang, Qingyin Kong, Xiutian Zhang, Luning Li
DOI:10.4103/0973-1482.204882  PMID:30880767
Background: Long noncoding RNAs (lncRNAs) have been shown to have a fundamental role in cancer initiation and development. LncRNA microvascular invasion in hepatocellular carcinoma (MVIH) has been identified as a potential prognostic marker in several cancers; however, its role in gastric cancer (GC) has not been elucidated. Materials and Methods: A total of 152 tissue samples from patients underwent GC surgical resection in Linyi People's Hospital between 2007 and 2010 were collected. Quantitative real-time polymerase chain reaction was conducted to examine the expression level of lncRNA MVIH. The selection of clinically important cut-off scores for MVIH expression was based on receiver operating characteristic curve analysis. Then, the association between MVIH and GC clinicopathological parameters was analyzed. Moreover, univariate and multivariate Cox regression analysis were performed to reveal the relationship between MVIH and GC prognosis. Results: GC tissues exhibited a higher lncRNA MVIH expression level than paired nontumoros tissues. High MVIH level was revealed to be associated with the T stage, tumor-node-metastasis (TNM) stage and lymphatic metastasis of GC. Specially, patients with high MVIH expression level showed significantly shorter overall survival rate and progression-free survival rate. Moreover, invasion depth, distant metastasis, TNM stage, and MVIH expression were identified as risk factors of GC poor prognosis on univariate Cox regression analyses. By further analyzing these factors with multivariate logistic regression, high MVIH, and distant metastasis were discovered to be independent risk factors of GC prognosis. Conclusions: High MVIH is an independent risk factor of GC prognosis. LncRNA MVIH may serve as a potential therapeutic target and a prognostic marker of GC patients.
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A clinical and surgical challenge: Retrorectal tumors p. 132
Ali Kilic, Fatih Basak, Meliha Seyma Su Dur, Abdullah Sisik, Ali Ediz Kivanc
DOI:10.4103/0973-1482.183192  PMID:30880768
Aims: Retrorectal tumors are rare, mostly benign tumors and named due to their localization. Diagnoses of these tumors are usually delayed because of nonspecific complaints and symptoms. Magnetic resonance imaging has beneficial uses both for diagnosis and treatment. In this study, we reviewed a case series of retrorectal tumors. Subjects and Methods: The patients who were diagnosed with retrorectal tumors between 2008 and 2015 were analyzed. This investigation was conducted at a Tertiary Education and Research Hospital. Sixteen patients were included in this study. Patients' demographic data, imaging workups, surgical operation reports, pathologic examination results, postoperative complications, and follow-up results were examined. Descriptive statistics, median, and standard deviation for continuous variables were used. The primary outcomes measured were diagnostic conflict, knowledge, and preference for surgery. Statistical Analysis Used: Definitive statistical methods (mean, standard deviation, median, frequency, and percentage) were used to evaluate the study data. Results: One patient refused operation and one was in preoperative preparation period. Fourteen of sixteen patients were operated. Two (14.3%) of operated patients have malignant histopathological result (one gastrointestinal stromal tumor, one ganglioneuroblastoma). Rest of the operated patients' histopathological reports was as follows: Four schwannomas, three epidermoid cysts, two tailgut cyst, one dermoid cyst, one teratoma, and one angiomyolipoma. Eight patients were operated by posterior incision, five patients with transabdominal approach, and one patient with combined approach. Conclusions: Retrorectal tumors are rare cases, and treatment of retrorectal tumors is surgery and should be operated in referenced hospitals to avoid diagnostic and therapeutic problems.
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Discovered on gastrointestinal stromal tumor 1, a keystone in the diagnosis of extraintestinal gastrointestinal stromal tumors p. 138
Kausalya Kumari Sahu, Rohit Tapadia, Jyoti Ramanath Kini, Radha R Pai, Hema Kini, M Nirupama, KS Pooja
DOI:10.4103/jcrt.JCRT_28_17  PMID:30880769
Introduction: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract (GIT) but have a low incidence. Arising from the interstitial cells of Cajal, GISTs occur at different sites in the GIT with stomach being the most common. They can rarely be seen at sites outside the GIT such as omentum, retroperitoneum and are called as extraintestinal GISTs (EGIST). They have a spindle or epithelioid cell morphology and show positivity by immunohistochemistry (IHC) for CD117. Our aim was to study the clinicopathological and immunohistochemical profile of our cases of EGISTs. Materials and Methods: A cross-sectional study of EGISTs received from 2010 to 2015 was done. IHC with CD117 and discovered on GIST1 (DOG1) was performed and tumors were scored based on the percentage of cells that stained positive. Thirteen abdominal non-GIST spindle cell tumors were included in the study as controls. Results: Seven cases of EGIST were included (four-omental, three-retroperitoneal). All cases stained positive for CD117 and DOG1. One case of epithelioid EGIST scored 4 + with DOG1 and 2 + with CD117. Another case with mixed morphology scored 2 + with DOG1 and 4 + with CD117. All controls were negative for both markers. Conclusion: EGISTs are one of the rare differentials for spindle cell lesions outside the GIT. Although both markers stain positive, DOG1 showed higher score with epithelioid GISTs.
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Preoperative assessment of malignant potential of gastrointestinal stromal tumor by dual-time-point 18F-fluorodeoxyglucose positron emission tomography imaging: Usefulness of standardized uptake value and retention index p. 142
Yeongkeun Kwon, Eunkyung Park, Kisoo Pahk, Sungeun Kim, Min Ju Kim, Daniel Graf, Sungsoo Park
DOI:10.4103/jcrt.JCRT_1093_16  PMID:30880770
Background: To evaluate the usefulness of preoperative imaging with F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) for noninvasive risk assessment of gastrointestinal stromal tumor (GIST). Materials and Methods: A retrospective review including 32 patients with pathologically proven GIST. Preoperative FDG-PET scan results including maximum standardized uptake values (SUVs) of the GISTs at 1 h postinjection (SUV1) were available for all tumors and SUVs at 2 h postinjection (SUV2) were available for 22 tumors. When both SUV1 and SUV2 were available, a retention index (RI, %) was calculated, and the correlation of these PET parameters with the histopathologic results was analyzed. Results: SUV1 was significantly higher in tumors in the high-risk group (6.0 ± 2.7) compared to those in the low risk (3.0 ± 1.6) or very low-risk (2.7 ± 1.2) groups (P = 0.009 and 0.011, respectively). At a cutoff of 5.2, the SUV1 demonstrated sensitivity of 80% and a specificity of 89% for predicting high-risk GISTs. Tumor size was significantly correlated with SUV1 (r = 0.68, P < 0.001) and SUV2 (r = 0.66, P = 0.001), and SUV1, SUV2, and RI were significantly higher in tumors with mitotic index > 5/50 high-power field than in those with lower mitotic index. RI was significantly higher in tumors with C-kit mutation than in those with no C-kit mutation. Conclusion: SUV1 measured during preoperative FDG-PET imaging correlated well with malignant potential of GISTs, especially for high-risk versus Low-/very-low-risk tumors. RI values correlated well with mitotic counts and C-kit mutation, suggesting that this mutation may have some influence on tumor metabolism.
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Blocking of methionine aminopeptidase-2 by TNP-470 induces apoptosis and increases chemosensitivity of cholangiocarcinoma p. 148
Sonexai Kidoikhammouan, Wunchana Seubwai, Atit Silsirivanit, Sopit Wongkham, Kanlayanee Sawanyawisuth, Chaisiri Wongkham
DOI:10.4103/jcrt.JCRT_250_17  PMID:30880771
Context: Resistance of cancer cells to chemotherapeutic drugs is a major pitfall of the failure of chemotherapy treatment for cholangiocarcinoma (CCA). A new therapeutic strategy that can improve treatment efficacy is mandatory for CCA patients. Our previous findings demonstrated the overexpression of methionine aminopeptidase-2 (MetAP2) in CCA patients. In addition, supplementation of TNP-470, a MetAP2 inhibitor, significantly inhibited the growth and metastatic activities of CCA cell lines. However, the molecular mechanism of antitumor activity of TNP-470 and the synergistic antitumor activity of TNP-470 combined with chemotherapeutic drugs are still unknown. Aims: The aim of this study is to evaluate the molecular mechanism of anticancer activity and the potential use of TNP-470 as a chemosensitizing agent in CCA cell lines. Materials and Methods: Cell cycle and apoptosis of CCA cell lines were evaluated using flow cytometry with propidium iodide staining. Expression of apoptosis regulatory proteins was measured by Western blotting. The chemosensitizing effect of TNP-470 was determined using combination index. Results: TNP-470 inhibited the growth of CCA cells via induction of apoptosis through activation of the p38-phosphorylation and up- and down-regulation of Bax and Bcl-xL, respectively. Furthermore, TNP-470 significantly enhanced the antitumor activity of 5-fluorouracil, cisplatin, doxorubicin, and gemcitabine. Conclusions: The present results show that TNP-470 could be a potential therapeutic or adjuvant agent for CCA.
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Prospective observational study on cholelithiasis in patients with carcinoma gall bladder in a tertiary referral hospital of Eastern India p. 153
Prosanta Kumar Bhattacharjee, Durgaprasad Nanda
DOI:10.4103/jcrt.JCRT_939_17  PMID:30880772
Context: Gallbladder carcinoma (GBCA) is the fifth most common types of gastrointestinal malignancy and is the most common malignancy of the biliary tract. Cholelithiasis, gallbladder polyps, porcelain gall, and choledochal cysts are common known associations with GBCA. Because of the better understanding of the etiopathogenesis, the traditional nihilistic attitude toward the prognosis has, over the years, given way to greater interest and hope for treating the disease. Long-term survival has been reported in patients with resectable lesions in the hands of expert hepatobiliary surgeons. Objective: This prospective observational study was conducted at a tertiary referral hospital of Eastern India on patients with the diagnosis of GBCA. The main objective was to assess the incidence of gallstones in patients with GBCA, and the relationship, if any, between the size and number of stones and GBCA in our patient cohort. Materials and Methods: This prospective observational study was conducted, over a period of 2 years, at a tertiary referral hospital of Eastern India which caters to patients from all the neighboring districts. A total of 54 patients with the diagnosis of GBCA were included in the study. Data on their demographic and clinical profile, the incidence of associated gallstones, their size (<3 or ≥3cm), and number (solitary or multiple) were collected. Known predisposing factors of GBCA, if any, in those presenting without stones were noted. Results: GBCA was found to afflict females 2.4 times as frequently as males. Patients, irrespective of their sex, were mostly in their sixth decade. Approximately three-fourth of the cases had associated cholelithiasis. The number of stones had no correlation with the disease. However, contrary to available published data, stones <3 cm were significantly more common in our study cohort. Conclusion: The results of this study reaffirm that cholelithiasis is a strong predisposing factor for GBCA and females with gallstones in their sixth decade, are more at risk. Although number of stones was not found to be an independent risk factor, patients with stones <3 cm (mostly multiple) were found to be more at risk in our study.
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Myricetin ameliorates cytokine-induced migration and invasion of cholangiocarcinoma cells via suppression of STAT3 pathway p. 157
Pattarapon Tuponchai, Veerapol Kukongviriyapan, Auemduan Prawan, Sarinya Kongpetch, Laddawan Senggunprai
DOI:10.4103/jcrt.JCRT_287_17  PMID:30880773
Aim of Study: Cholangiocarcinoma (CCA) is an aggressive cancer with considerable metastatic potential. Various cytokines secreted by tumor cells or cells in the tumor environment can promote the metastasis of CCA. The aim of the present study was to investigate the effect of myricetin on the inhibition of cytokine-induced migration and invasion and the associated cellular mechanisms in human CCA cells. Materials and Methods: CCA KKU-100 cells were treated with a pro-inflammatory cytokine mixture consisting of interleukin-6, interferon-γ, and tumor necrosis factor-α. The migratory and invasive ability of KKU-100 cells were determined using a wound-healing assay and transwell invasion assay. The effect of myricetin on cytokine-induced STAT3 activation in CCA cells was determined using Western blot analysis. The real-time polymerase chain reaction was performed to determine messenger RNA expression. Results: Myricetin significantly inhibited cytokine-induced migration and invasion of KKU-100 cells. Detailed molecular analyses revealed that myricetin suppressed the activation of the STAT3 pathway, evidently by a decrease of the active phospho-STAT3 protein expression after myricetin treatment. The cytokine-mediated upregulation of metastasis- and inflammatory-associated genes, which are downstream genes of STAT3 including the intercellular adhesion molecule-1, matrix metalloproteinase-9, inducible nitric oxide synthase, and cyclo-oxygenase 2 (COX-2), were also significantly abolished by myricetin treatment. Moreover, the anti-migratory and anti-invasive activities of a widely prescribed COX inhibitor, indomethacin, were also revealed. Conclusion: This finding reveals the anti-metastatic effect of myricetin against CCA cells which is mediated partly through suppression of the STAT3 pathway. This compound could be potentially useful as a therapeutic agent against CCA.
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An experimental protocol for in situ colorectal liver metastases ablation by radiofrequency toward a standard procedure p. 164
Daniel Gonganau-Nitu, Radu Razvan Scurtu, Calin Gheorghe Precup, Constantin Ciuce
DOI:10.4103/jcrt.JCRT_344_17  PMID:30880774
Background: Radiofrequency ablation (RF) is already a viable alternative to surgical resection for focal liver tumors treatment. The use of RF ablation in combination with surgery or chemotherapy and the large panel of RF tools need new experimental models to develop new opportunities for this kind of therapy. Purpose: The purpose of this study was to identify the optimal RF parameters that will allow in situ colic cancer liver metastases destruction with minimal secondary effects. Materials and Methods: The CC531s colic cancer tumor cells were used to induce liver metastases in 30 synergic Wag/Rij rats. When metastases reached at least 1 cm in diameter, RF generator RITA 1500X, and expandable tip RF probe Starburst SDE (Angiodynamics, USA) was used for the RF ablation. The animal survival rate and the RF-induced lesions have been studied, while only the generator delivered power has been modified (90W, 20W, and 10W, respectively). Results: Survival was significantly low in the group with 90W-delivered power RF. Moreover, statistically significant differences were revealed between groups with high and low RF power, regarding the morphological changes of the liver parenchyma and the adjacent organs, without significant difference on the RF therapeutically effect. Conclusions: In an experimental setting, an increased RF generator power induces important lesions of the abdominal organs with subsequently important mortality rate, without improving the RF therapeutic efficiency.
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Role of stereotactic body radiation therapy in liver metastasis: A pilot study from tertiary cancer institute in India p. 169
Shikhar Kumar, Rakesh Kapoor, Arun S Oinam, Naveen Kalra, Ajay Duseja
DOI:10.4103/jcrt.JCRT_647_16  PMID:30880775
Purpose: This trial studies the feasibility and potential utility of stereotactic body radiation therapy in patients with unresectable liver metastasis. Aims: (1) The aim of this study is to assess the local response of the liver lesions poststereotactic body radiation therapy regarding number and size of lesions and (2) to evaluate the toxicity to organ (s) at risk. Materials and Methods: A total of 15 patients were enrolled in this study from November 2014 to October 2015. The inclusion criteria for this study were patients having 1–3 liver metastasis from any solid tumor except germ cell tumor or lymphoma with no evidence of progressive disease (PD) outside the liver. A planning four dimensional-computed tomography (CT) scan was taken. Planning target volume was generated by giving margin of 5 mm. Dose prescribed was 36 Gy in 3#. Response was defined by CT abdomen done at 3 and 6 months poststereotactic body radiation therapy as per RECIST guideline (v1.1). Results: At 3 months poststereotactic body radiation therapy, five patients had partial response, five patients had stable disease, and five patients had PD as per RECIST criteria. Out of 20 assessable lesions, 16 were controlled at 3 months poststereotactic body radiation therapy. The actuarial local control rate was 86% at 3 months and 77% at 6 months poststereotactic body radiation therapy. The median progression free survival was 7 months. Two patients experienced Grade 2 gastric toxicity and one patient experienced Grade 2 small bowel toxicity. No cases of radiation-induced liver disease were observed. Conclusions: This trial examines the feasibility of stereotactic body radiotherapy to liver metastasis in the Indian scenario. It shows excellent tolerability and is a safe therapeutic option for inoperable patients, showing good local control.
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The effects of coadministration of tilorone dihydrochloride and culture supernatants from Lactobacillus reuteri on the mouse hepatoma cell line p. 176
Mahsa Alem, Amir Ali Shahbazfar, Payman Zare, Hossein Tayefi-Nasrabadi
DOI:10.4103/jcrt.JCRT_41_17  PMID:30880776
Context: Tilorone dihydrochloride is a therapeutic agent with a different mechanism in cancer. The species of Lactobacillus have an important role in cytotoxic effect. Aims: Because of unknown effects of tilorone and culture supernatants from Lactobacillus reuteri on hepatoma, the aim of this study is to evaluate apoptotic, cytotoxic, and therapeutic effects of tilorone on mouse hepatoma cell line with and without culture supernatants from L. reuteri. Materials and Methods: To do so, after cell line culture, cells were divided into different groups such as negative control, treatment with four doses of tilorone, positive control of supernatant (single dose), and combination therapy groups of different doses of tilorone with supernatant (constant doses), for 48 h. All groups were studied with pathologic tests, biochemical study, tetrazolium dye (3-(4, 5- dimethylthiazol -2-yl)-2, 5-diphenyltetrazolium bromide [MTT]) assay, and absolute real-time-polymerase chain reaction (RT-PCR) were done to assess Bax and Bcl-2 genes expression, as molecular studies. Results: MTT assay results revealed that the tilorone tissue culture IC50 (TCIC50) on the Hepa1-6 cell line was 50 μg/ml. RT-PCR analysis showed that tilorone dihydrochloride induced upregulation and downregulation in expression of Bax and Bcl-2, respectively. Simultaneous, antioxidant effect has also seen in a way that prevented necrosis, in biochemical analysis. These results were dose dependent and statistically significant compared to the control group. Conclusions: Based on these results, it appeared that this agent could be a good candidate for further evaluation as effective chemotherapy acting through the induction of apoptosis in hepatoma. The cell death caused through bacterial supernatant was rather necrosis than apoptosis.
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A pilot study of the impact of Vitamin C supplementation with neoadjuvant chemoradiation on regulators of inflammation and carcinogenesis in esophageal cancer patients p. 185
Mohamed M.M Abdel-Latif, Mawash Babar, Dermot Kelleher, John V Reynolds
DOI:10.4103/jcrt.JCRT_763_16  PMID:30880777
Aims: Vitamin C plays a role in chemoprevention in cancer treatment, and Vitamin C modulates many regulators of inflammation in in vitro studies. The aim of this study is to assess the effect of Vitamin C supplementation with neoadjuvant chemoradiation in esophageal adenocarcinoma on the nuclear factor-kappa B (NF-κB) and associated cytokines. Materials and Methods: A total of 20 patients undergoing multimodal treatment for esophageal adenocarcinoma were randomized to receive Vitamin C (1000 mg/day) orally for 4 weeks or no supplementation. Pre- and post-Vitamin C endoscopic biopsies were used for the study of NF-κB activity and cytokine analysis. Results: NF-κB activity along with cytokines was activated in the cancer tissue pretreatment. Down-regulation in NF-κB activity was observed in 25% of cases, two from the Vitamin C arm posttreatment. There was a significant reduction in cytokines levels in the cancer group, and this effect was more pronounced in the Vitamin C group (P < 0.05). Conclusions: Vitamin C supplementation had a mild protective effect in modulating of regulators of inflammation and carcinogenesis. Further studies with larger numbers of endpoints are needed to evaluate its effect on modulation of chemoradiation responses.
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Epigenetic deregulations of Wnt/β-catenin and transforming growth factor beta-Smad pathways in esophageal cancer: Outcome of DNA methylation p. 192
Virendra Singh, Avninder Pal Singh, Ira Sharma, Laishram Chandreshwor Singh, Jagannath Sharma, Bibhuti Bhusan Borthakar, Avdhesh Kumar Rai, Amal Chandra Kataki, Sujala Kapur, Sunita Saxena
DOI:10.4103/jcrt.JCRT_634_17  PMID:30880778
Background: Promoter methylation of tumor suppressor genes (TSGs) is a well-reported portent in carcinogenesis; hence, it is worthy to investigate this in high-risk Northeast population of India. The study was designed to investigate methylation status of 94 TSGs in esophageal squamous cell carcinoma (ESCC). Further, the effect of OPCML promoter methylation on gene expression was analyzed by immunohistochemistry. Moreover, in silico protein–protein interactions were examined among 8 TSGs identified in the present study and 23 epigenetically regulated genes reported previously by our group in ESCC. Materials and Methods: Methylation profiling was carried out by polymerase chain reaction array and OPCML protein expression was examined by tissue microarray-based immunohistochemistry. Results: OPCML, NEUROG1, TERT, and WT1 genes were found hypermethylated and SCGB3A1, CDH1, THBS1, and VEGFA were hypomethylated in Grade 2 tumor. No significant change in OPCML expression was observed among control, Grade 1, and Grade 2 tumor. Conclusively, hypermethylation of the studied OPCML promoter in Grade 2 tumor produced no effect on expression. Unexpectedly, OPCML expression was downregulated in Grade 3 tumor in comparison to other groups signifying that downregulation of OPCML expression may lead to higher grade of tumor formation at the time of diagnosis of ESCC in patients. Significant interactions at protein level were found as VEGFA:PTK2, CTNNB1:CDH1, CTNNB1:VEGFA, CTNNB1:NEUROG1, CTNND2:CDH1, and CTNNB1:TERT. These interactions are pertinent to Wnt/β-catenin and TGF-β-Smad pathways. Conclusions: Deranged OPCML expression may lead to high-grade ESCC as well as epigenetically regulated genes, that is, CDH1, CTNNB1, CTNND2, THBS1, PTK2, WT1, OPCML, TGFB1, and SMAD4 may alter the Wnt/β-catenin and TGF-β-Smad pathways in ESCC. Further study of these genes could be useful to understand the molecular pathology of ESCC with respect to epithelial-mesenchymal transition (EMT) mediated by Wnt/β-catenin and TGF-β signaling pathways.
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Evaluation of positional accuracy of the Varian's exact-arm and retractable-arm support electronic portal imaging device using intensity-modulated radiotherapy graticule phantom p. 204
Ranjit Singh, HS Kainth, Sachin Dev, Gurjot Singh, D Mehta, JS Shahi, Baljinder Singh, Teerth Raj Verma
DOI:10.4103/jcrt.JCRT_707_17  PMID:30880779
Purpose: The aim of the present study was to compare the positional accuracy of varian's exact-arm (E-arm) and retractable-arm (R-arm) supporting electronic portal imaging device (EPID) systems (amorphous silicon flat-panel detector) using the intensity-modulated radiotherapy (IMRT) graticule phantom. Materials and Methods: The known shifts of 0.5, 1.0, and 1.5 cm were introduced to the given phantom in longitudinal, lateral, and vertical directions, respectively, with respect to treatment couch of medical linear accelerator. The experiment was repeated for different gantry angle and varying source to imager distances (SIDs). The images were acquired for each shift at varying SIDs and beam orientations for both EPID supporting systems. The corresponding shifts obtained from treatment planning system (TPS) were recorded and compared. Results: The known (expected) and observed (recorded from TPS) shifts obtained for different beam angles (namely, 0°, 90°, 180°, and 270° for anterior, left lateral, posterior, and right-lateral portal images, respectively) in the longitudinal, lateral, and vertical direction at varying SID were compared. The maximum shift in the observed value from the expected one was 3 and 2 mm, respectively, out of the all beam configuration for R-arm and E-arm. These shifts were randomly observed for all imager position and beam orientation. Conclusion: The IMRT graticule phantom is an effective tool to check the mechanical characteristic and consistency of different EPID supporting arms. The effect of EPID sag due to gravity (gantry and treatment couch) was not significant for detection of shift in patient's position. The E-arm support EPID has better mechanical stability and accuracy in detection of patient's position than that of R-arm.
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Search of an ideal location of isocenter in intensity-modulated radiotherapy treatment plans: A dosimetrical approach p. 211
Abhijit Mandal, Anupam Kumar Asthana, Satyajit Pradhan, Uday Pratap Shahi, Sunil Choudhary
DOI:10.4103/jcrt.JCRT_985_16  PMID:30880780
Aim: The aim of this study is to identify an ideal location of isocenter in intensity-modulated radiotherapy (IMRT) treatment plans. Materials and Methods: A total of 28 clinical target volumes and 4 English capital letters (C, L, T, and H) target volumes were considered in this study. Two IMRT treatment plans were generated for each target volume in the ECLIPSETM treatment planning system (TPS), first one with isocenter automatically placed (ISOAUTO) by TPS and the second one with geometric center-based isocenter (ISOGEOM). The geometric center of a cuboid volume, which was formed encompassing around the target volume in sagittal, transverse, and frontal planes, is considered as the geometric center of the target volume as well as the isocenter (ISOGEOM) of the IMRT plans. While performing the IMRT treatment plans using the beam angle optimization and dose volume optimization, the normal tissue objectives and target volume objectives were kept similar in both the plans. The dosimetrical parameters between the two groups of plans were compared. Results: The distance between ISOGEOM and ISOAUTO ranged from 0.16 cm to 3.04 cm with a mean and median of 0.85 cm and 0.69 cm, respectively. The ISOGEOM-based IMRT plans exhibited statistically significant advantages in total monitor units reduction (100% of cases, P ≤ 0.001), total number of field reduction (66% of cases, P ≤ 0.001), and reduction of patient mean dose (69% of cases, P ≤ 0.001) over ISOAUTO-based IMRT plans. The conformity index, homogeneity index and target mean dose were comparable between both group of plans. Conclusion: Significant dosimetrical advantages may be observed, when the geometric centroid of target volume is considered as isocenter of IMRT treatment plan.
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Assessment of radiation leakage from treatment applicator of Siemens Primus Plus and Siemens Artiste linear accelerators p. 216
Motahareh Karbaf, Mohammad Hadi Hadizadeh Yazdi, Mahdi Ghorbani, Sara Abdollahi
DOI:10.4103/jcrt.JCRT_1096_16  PMID:30880781
Aim: The purpose of this study is to measure radiation leakage of Siemens Primus Plus and Siemens Artiste linear accelerators in electron mode and to compare the leakage level with that recommended by the International Electrotechnical Commission (IEC) standard. Materials and Methods: In this assessment, Siemens Primus Plus linear accelerator with 10 cm × 10 cm, 15 cm × 15 cm, and 25 cm × 25 cm applicators was used. The radiation leakage in lateral and vertical directions was measured for Siemens Primus Plus and Siemens Artiste linear accelerators. Results: Data derived from radiation leakage measurement for Siemens Primus Plus and Siemens Artiste linear accelerators in lateral direction from the field edge and in vertical direction from the applicator were reported. The radiation leakage data were then compared with the IEC standard to evaluate in-air field leakage. Conclusion: Comparing the radiation leakage level from fields with the IEC standard for two applicators, the maximum that was occurred for 12 MeV electron beam and applicator size of 10 cm × 10 cm in Siemens Artiste linear accelerator was 2.3%, which is less than the IEC's recommended limit of 10%. It is concluded that the leakage amount is much less than the specified limit and that both of the linear accelerators have high level of safety. Considering the measurement stage, it also needs to be noted that the beam angle affected the radiation leakage level from field edge, and in 25° angle, it is higher than in 0° angle. Comparing radiation leakage from the right side of the field for the two linear accelerators, the amount of leakage for Siemens Primus Plus linear accelerator is more than Siemens Artiste linear accelerator.
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Commissioning of portal dosimetry using a novel method for flattening filter-free photon beam in a nontrue beam linear accelerator p. 223
Arun Gandhi, Subramani Vellaiyan, VS Subramanian, Thirumalaiswamy Shanmugam, Kathirvel Murugesan, Kala Subramanian
DOI:10.4103/jcrt.JCRT_1181_16  PMID:30880782
Aim: The aim of this study is to commission and validate the portal dosimetry (PD) system using an indirect method for flattening filter free (FFF) photon beam of the upgraded c-series linear accelerator. Background: Varian Medical System clinacs with amorphous-silicon portal imager panel (aSi-1000) do not have PD for FFF beams. Recently, our c-series linear accelerator was upgraded to deliver 6MV FFF (6MVFFF) photon beam with the highest dose rate of 1400 monitor unit (MU)/min. The study, therefore, focuses on the commissioning and validation of PD for the 6MVFFF beam. Materials and Methods: An indirect method was implemented to predict the portal dose for FFF beam in Eclipse as the treatment planning system does not have direct prediction algorithm for FFF beam (version. 11). Dosimetrical characteristics of aSi-electronic portal imaging device (EPID) were evaluated for 6MVFFF beam and validation of PD for 6MVFFF beam was performed for open fields along with pretreatment quality assurance of intensity-modulated radiation therapy (IMRT), volumetric-modulated arc therapy (VMAT), and stereotactic radiosurgery (SRS) techniques for 30 patients planned with 6MVFFF beam. Results: ASi-EPID saturates between 100 and 130 cm source to detector distance (SDD) for 6MVFFF beam and resolved at more than 140 cm SDD. The squared correlation coefficient (R2) for MU linearity was found to be 1 (R2 = 1), and instantaneous dose response linearity at different SDD's was found to be 0.999 (R2 = 0.999) for the 6MVFFF beam. Maximum gamma area index (GAI) for 3% dose difference and 3 mm distance-to-agreement criteria for IMRT, VMAT, and SRS/stereotactic radiotherapy plans was 97.9% ± 0.3%, 96.3% ± 0.5%, and 98.2% ± 0.2%, respectively. Conclusion: The results reveal that this novel method can be used to commission portal dosimetry for 6MVFFF beam as it is a convenient, faster, and accurate method.
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Effects of acetylsalicylic acid on rats: An in vivo experimental study in azaserine-rat model p. 231
Hasan Yildiz, Erkan Kalipci, Haydar Oztas, Deniz Yildiz
DOI:10.4103/jcrt.JCRT_1319_16  PMID:30880783
Aim: The effect of acetylsalicylic acid (ASA) on thiol levels was studied in a rat model of azaserine carcinogenesis. Materials and Methods: ASA and azaserine were applied to the animals to research changes in cellular sulfhydryl (–SH) content and variations in free and protein-bound molecules containing the –SH group. Such effects in rats injected with azaserine were investigated at low (200 ppm) and high (400 ppm) concentrations of ASA over a relatively short (6 months) and a relatively long (12 months) period. Results: Changes in the hepatic, pancreatic, and renal –SH contents were also determined. Conclusion: Compared to the other tissues studied, the liver contained the highest levels of both free and protein-bound –SH.
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Tissue composition effect on dose distribution in radiotherapy with a 6 MV photon beam of a medical linac p. 237
Mahdi Ghorbani, Atefeh Vejdani Noghreiyan, Zahra Sadat Tabatabaei, Delaram Pakravan, David Davenport
DOI:10.4103/jcrt.JCRT_706_16  PMID:30880784
Aim: The aim of this study is to evaluate soft-tissue composition effect on dose distribution for various soft tissues in radiotherapy with a 6 MV photon beam of a medical linac. Background: The compositions of various soft tissues are different which could affect dose calculations. Materials and Methods: A phantom and Siemens Primus linear accelerator were simulated using MCNPX Monte Carlo code. In a homogeneous cubic phantom, six types of soft tissue and three types of tissue-equivalent materials were defined separately. The soft tissues were muscle (skeletal), adipose tissue, blood (whole), breast tissue, soft tissue (9-component), and soft tissue (4-component). The tissue-equivalent materials included water, A-150 tissue equivalent plastic and perspex. Photon dose relative to dose in 9-component soft tissue at various depths on the beam's central axis was determined for the 6 MV photon beam. The relative dose was also calculated and compared for various MCNPX tallies including *F8, F6, and *F4. Results: The results of the relative photon dose in various materials relative to dose in 9-component soft tissue using different tallies are reported in the form of tabulated data. Minor differences between dose distributions in various soft tissues and tissue-equivalent materials were observed. The results from F6 and F4 were practically the same but differ with the *F8 tally. Conclusions: Based on the calculations performed, the differences in dose distributions in various soft tissues and tissue-equivalent materials are minor but they could be corrected in radiotherapy calculations to upgrade the accuracy of the dosimetric calculations.
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Cytotoxic activity of extracts and fractions from Paramignya trimera root and Phyllanthus amarus against pancreatic cancer cell lines p. 245
Van Tang Nguyen, Christopher J Scarlett
DOI:10.4103/jcrt.JCRT_85_18  PMID:30880785
Objective: The aim of this study was to assess cytotoxic activity of extracts and fractions from the Paramignya trimera root (PTR) and Phyllanthus amarus (PA) against two pancreatic cancer cell lines (primary: BxPc3 and secondary: CFPAC1). Materials and Methods: The root of PT and whole plant of PA were used in this study. The extracts and fractions from the PTR and PA were prepared using microwave-assisted extraction and high-performance liquid chromatography, respectively. The cytotoxic activity was assessed using the Dojindo Cell Counting Kit-8 assay. Results: The findings showed impressive cytotoxic capacity of the PTR extract against both pancreatic cancer cells of BxPc3 and CFPAC1 in a range of concentrations from 50 to 200 μg/mL, which was higher than those of ostruthin (67 μM), gemcitabine (50 nM), and four its fractions (50 μg/mL), and to be comparable to a saponin-enriched extract from Quillaja bark at 200 μg/mL. In contrast, the cytotoxic capacity of the PA extract and nine its fractions against these pancreatic cancer cell lines was significantly lower (P < 0.05) than those of gemcitabine (50 nM) and Quillaja bark extract (200 μg/mL) and being comparable to phyllanthin (4.8 μM). The IC50 values of the PTR extract against BxPc3 and CFPAC1 cancer cells were 32.12 and 36.65 μg/mL, respectively, which was much lower than that of the PA extract against CFPAC1 cancer cells (128.81 μg/mL). Conclusion: The outcomes obtained from this study reveal that the PTR extract is a lead source for the potential development of novel antipancreatic cancer drugs and/or functional foods.
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Synchronous primary cancers: Renal cell carcinoma and rectal cancer p. 250
M C.Suresh Babu, Vikas Asati, K Govind Babu, MN Suma, LK Rajeev, KN Lokesh
DOI:10.4103/jcrt.JCRT_45_17  PMID:30880786
Although cancers of rectum and kidney are common malignancies, the occurrence of primary synchronous neoplasms of these organs has been reported rarely. Very few case reports are available in literature till date. The relationship between these two events remains unclear, probably because of the rarity of the association. In this report, we describe incidentally detected renal cell carcinoma in an elderly man, during staging workup of rectal adenocarcinoma and both malignancies were surgically managed simultaneously with curative intent.
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Recurrent intestinal obstruction in a patient of Peutz–Jeghers syndrome p. 252
Sundeep Kumar, Preeti Arora, Pabitra Goswami
DOI:10.4103/jcrt.JCRT_866_17  PMID:30880787
Peutz–Jeghers syndrome is a rare hamartomatous polyposis syndrome characterized by the presence of intestinal polyps and mucocutaneous melanotic pigmentations. It is associated with various gastrointestinal and extraintestinal malignancies. This case report deals with the clinical presentation, investigations, operative findings, and outcome of a patient harboring this disease. A 45-year-old female presented to us with intermittent colicky abdominal pain for the last 6 months and a single episode of melena 1 month back. She had a previous history of resection of a jejunal growth 22 years back. The histopathology report was suggestive of papillary adenocarcinoma. On examination, hyperpigmented macules were seen on her lips and buccal mucosa. Laparotomy revealed multiple polyps mainly in the proximal small intestine and a focus of ileoileal intussusception. A limited resection was done.
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Successful definitive concurrent chemoradiotherapy in a patient with esophageal cancer and Child–Pugh B cirrhosis of the liver p. 255
Atsuto Katano, Hideomi Yamashita, Keiichi Nakagawa
DOI:10.4103/jcrt.JCRT_338_17  PMID:30880788
This case report demonstrates successful concurrent chemoradiotherapy for esophageal cancer without severe adverse events in a patient with cirrhotic disease. A 63-year-old Japanese male with alcoholic liver cirrhosis was referred to our hospital for treatment of superficial esophageal cancer. Endoscopic submucosal dissection was performed and the patient was diagnosed as having squamous cell carcinoma of the esophagus that was pathologically staged as pT1bN0M0. When a superficial tumor involves the submucosa, esophagectomy is usually recommended. However, the patient was at high risk of perioperative morbidity and mortality because of impaired liver function. As an alternative to esophagectomy, the patient received concurrent chemoradiotherapy, comprising nedaplatin 64 mg/m2 on days 1 and 34 and S-1 80 mg/body orally on days 1–14 and 34–47 with concurrent radiotherapy of 50 Gy in daily fractions of 2 Gy. He has shown no signs of recurrence in the 30 months since his treatment.
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A well-differentiated neuroendocrine tumor (Grade I) arising in a tailgut cyst Highly accessed article p. 258
Angad Singh, Swapnil Karnik, Bhushan Khedkar, Sanjay Deshmukh, Kedar Deodhar
DOI:10.4103/0973-1482.189236  PMID:30880789
Tailgut cysts are rare congenital lesions presenting as retrorectal space masses. They can occur in all age groups. Patients often present with ill-defined nonspecific symptoms and the diagnosis if often delayed. Malignancy arising in a tailgut cyst is an even rarer and unique occurrence. A precise diagnosis can be made only after complete excision and histopathological examination of the retrorectal space mass. We describe here a case of a 63-year-old male presenting with chronic constipation, who was diagnosed with a well-differentiated neuroendocrine tumor (Grade I) arising in a tailgut cyst after surgical excision.
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Adenocarcinoma in a tailgut cyst: A rare case report p. 261
Jyoti Valecha, Sandeep S Ojha, Abhishek Sharma, Ramrao Nilkanthe
DOI:10.4103/jcrt.JCRT_212_17  PMID:30880790
Tailgut cysts (TGCs) are rare congenital lesions derived from the remnants of primitive hindgut and are usually lined by squamous, transitional, or glandular epithelium. Malignant transformation in TGC may occur which is still rarer. Most common malignancies that arise from these cysts are adenocarcinomas. Preoperative diagnosis is difficult as high degree of suspicion is required for the diagnosis. We report here a case of adenocarcinoma arising in a tale gut cyst diagnosed preoperatively and till date very few cases have been reported in literature.
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Retraction: Modulation of the Sirt-1/P53 axis by butyrate inhibits the Hepatitis B virus replication p. 264

DOI:10.4103/0973-1482.240666  PMID:30197374
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Retraction: Quality-of-life and self-esteem outcomes after oncoplastic breast-conserving surgery p. 264
DOI:10.4103/0973-1482.253971  PMID:30880791
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