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REVIEW ARTICLE
Year : 2019  |  Volume : 15  |  Issue : 4  |  Page : 751-754

Interpretation of adverse reactions and complications in Chinese expert consensus of Iodine-125 brachytherapy for pancreatic cancer


1 Department of Gastrointestinal Surgical, Third Hospital of Jilin University, Changchun, China
2 Department of Physical Examination, Third Hospital of Jilin University, Changchun, China

Date of Web Publication14-Aug-2019

Correspondence Address:
Baodong Gai
Department of Gastrointestinal Surgical, Third Hospital of Jilin University, 126 Xiantai St, Changchun 130031
China
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jcrt.JCRT_884_18

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 > Abstract 


Owing to the location of the pancreas and its complex anatomical relationship, it is difficult to perform radioactive Iodine-125 seed implantation in patients with pancreatic cancer as it can cause surgical side effects and further complications. To standardize the procedure of radioactive Iodine-125 seed implantation in the treatment of pancreatic cancer and reduce the occurrence of adverse reactions and complications during and after operation, the Chinese Medical Doctor Association of Radioactive Seed Implantation Technology Expert Committee, Committee of Minimally Invasive Therapy in Oncology, Chinese Anti-Cancer Association, and the Radioactive Seed Therapy Branch organized and helped establish an expert consensus in China regarding radioactive Iodine-125 seed implantation in the treatment of pancreatic cancer. This article aims at interpreting the adverse reactions and complications after the implantation of radioactive seeds.

Keywords: Adverse reactions, complications, consensus, pancreatic cancer, radioactive particles


How to cite this article:
Li Q, Liang Y, Zhao Y, Gai B. Interpretation of adverse reactions and complications in Chinese expert consensus of Iodine-125 brachytherapy for pancreatic cancer. J Can Res Ther 2019;15:751-4

How to cite this URL:
Li Q, Liang Y, Zhao Y, Gai B. Interpretation of adverse reactions and complications in Chinese expert consensus of Iodine-125 brachytherapy for pancreatic cancer. J Can Res Ther [serial online] 2019 [cited 2019 Sep 22];15:751-4. Available from: http://www.cancerjournal.net/text.asp?2019/15/4/751/264309




 > Introduction Top


Pancreatic cancer is a devastating disease with a high malignancy rate. Owing to the occurrence of late symptoms, the majority of patients are not recommended to undergo operations at the time of the diagnosis because of the locally advanced tumors.[1],[2],[3] Patients who are not eligible for a surgical resection tend to present a high risk for local treatment as well as more other complications, leading to a poor clinical efficacy. Thus, it is of importance to search for ways to extend the survival as well as to improve the quality of life in patients with pancreatic cancer. However, brachytherapy through radioactive particle implantation into the carcinoma of the pancreas has an accurate curative effect and the advantages of both safety and minimal invasiveness. Thus, this novel therapy has been used in plenty of domestic medical centers, but the therapeutic procedures are not identical for the application of radioactive particles into the treatment of pancreatic carcinomas. To obtain a homogeneity of the radioactive particle treatment process, the China First Association of Radiological Particle Implantation Technical Experts Committee and the China Anti-Cancer Association Tumor Minimally Invasive Therapeutics Committee of Particle Therapy organized and helped shape the radioactive 125 I particle implantation process for pancreatic cancer in a China expert consensus, contributing to regulate the clinical operation of radioactive particle implantation in the treatment of pancreatic cancer.[4] Since the pancreas is located in a special site where it is endowed with complicated anatomic relationships as well as numerous organs around the abdominal cavity, the operation of particle implantation is difficult to employ, tending to promote surgery injury and postoperative complications. In this article, the section of the adverse reactions and complications after particle implantation in the consensus was interpreted, facilitating the majority of medical workers to correctly understand and handle the related problems.


 > Intraoperative or Postoperative Unavoidable Adverse Reactions and Complications Caused by the Radioactive Particle Implantation in the Treatment of Pancreatic Cancer Top


The intra-operative or postoperative unavoidable adverse reactions and complications by radioactive particle implantation in the treatment of pancreatic cancer indicated in the consensus include those associated with puncture operation and γ-rays released by radioactive particles. Henceforth, adverse reactions and complications can be divided into the following two situations: (1) those that cannot be avoided and (2) those that can be avoided as much as possible via rigorous technical methods. First, we will describe how to deal with the unavoidable side effects and complications.

The treatment mechanism of radioactive particles implantation for pancreatic cancer can be summarized briefly as an anticancer cell action of γ rays emitted by the particles with therapeutic purposes; however, damage to normal tissues and organs occurs while killing the tumor cells using γ rays.

Gastrointestinal symptoms

However, in percutaneous implantation of particles into pancreatic cancer or in open surgery, some target regions are adjacent to the gastrointestinal tract and may passively undergo minor injuries, which is further endangered by γ-rays, causing a transient edema in the gastrointestinal mucosa for 3–7 days. The clinical symptoms of the gastrointestinal tract often include ventosity, nausea, vomiting, loss of appetite, and so on. A more serious concern is gastroparesis, which may occur if patients have severe gastrointestinal injury. There is no necessity to apply a special treatment given the fact that patients presenting slight gastrointestinal symptoms could gradually return to a normal state. Nevertheless, for patients with severe gastrointestinal symptoms, a gastrointestinal mucosal protective agent and gastrointestinal motility drug treatment should be used to ensure short-term symptom attenuation.[5]

So far, an optimal therapeutic dose has not been clearly recommended to be utilized to treat patients suffering from pancreatic cancer with intratumoral particle implantation. The consensus recommended 80–145 Gy of tumor matching peripheral dose and 145 Gy of matched peripheral dose during radical treatment and both are superior to the external radiotherapy dose recommended by the NCCN guidelines. Therefore, combining the shaping of a preoperative implantation plan and accepting a reasonable choice of treatment dose under consideration of both the general status of the patients and the tumor situation are recommended, to minimize the occurrence of gastrointestinal complications.

Ascites

The occurrence of pancreatic fistula should be ruled out first on the condition that in patients with postoperative ascites they appear as pointed out by the consensus. Complications generated by a pancreatic fistula may be more important, requiring active management. After managing the occurrence of pancreatic fistula, the following reasons are supposed to be taken into account: (1) poor nutritional status with low protein ascites, (2) radioactive injury imposed on tumor tissue could produce ascites, (3) small lymphatic vessels are subject to damage due to the separation of tumor surrounding tissue in order to fully show the tumor, and (4) radioactive edema in tumor tissue can compress the blood vessels close to the particle implantation area, such as the portal vein and the superior mesenteric vein, causing a poor reflux, which results in transient portal hypertension and ultimately in ascites.[6] In addition, postoperative ascites may also be associated with a secondary infection triggered by a smaller gastrointestinal perforation by the puncture path passing the gastrointestinal tract.

As ascites emerge, it is important to search for the etiological factors that play a crucial role in the etiological treatment. Patients with hypoproteinemia can receive full enteral and external nutritional support, combined with low-protein therapy correction. Somatostatin, diuretics, and other treatments should be administered to patients with transient portal hypertension. For patients with infections, local drainage, anti-infection, and other treatments should be administered, so that the ascites are gradually absorbed.

It should be noted that cancerous ascites are beyond the scope of this article. The consensus also proposed that pancreatic cancer associated with ascites is a suggestion that the tumor has been extensively metastasized, in which case, particle therapy is not allowed to be performed.

Endocrine and exocrine pancreatic insufficiency

Based on the destruction of the pancreatic tissue produced by tumors, pancreatic endocrine and exocrine insufficiency may appear, which is challenging to recover from, regardless of the treatments applied; the consensus did not elucidate the postoperative adverse reactions resulting from the pancreatic endocrine and exocrine deficits. However, patients with pancreatic cancer frequently present hyperglycemia and indigestion. Although particle implantation is not associated with pancreatic endocrine and exocrine insufficiency, we consider it imperative to emphasize the pancreatic endocrine and exocrine conditions of the patients after particle implantation.

When pancreatic islet cell number is destroyed by pancreatic cancer to the level that it cannot maintain a normal blood sugar level, patients would present elevated blood sugar levels. Thus, the monitoring of patients with blood glucose and exogenous insulin therapy facilities the control of hyperglycemic symptoms.

Pancreatic exocrine insufficiency is mainly caused by the invasion of the tumor into the large scale of the pancreas, leading to little residual normal pancreatic tissue. Perhaps, the obstruction of the main pancreatic duct due to pancreatic head carcinoma can be considered the main reason of pancreatic exocrine insufficiency, presenting a tendency to indigestion, malabsorption, and weight loss, which can be promptly improved via an exogenous administration of pancreatic enzyme replacement.


 > The Process of Particle Implantation Into the Pancreatic Cancer to Avoid Adverse Reactions and Complications Top


Standardized treatment procedures as well as rigorous surgical procedures are able to avoid the vast majority of intraoperative and postoperative complications.

Pancreatic fistula

Pancreatic fistula is attributable to an injury of the pancreatic duct during puncture, which can cause secondary abdominal infection, bleeding, and other serious complications, affecting the postoperative quality of life and even threatening lives. Thus, it is of importance to focus on the pancreatic fistula. As for a small amount of pancreatic fistula with no serious complications, it is well advised to perform gastrointestinal decompression, fasting water, total parenteral nutrition, and inhibition of pancreatic enzyme treatment according to the postoperative treatment section in the consensus. Satisfactorily, patients with these symptoms can recover after the above-mentioned conservative treatment.

It is extremely important to prevent the occurrence of pancreatic fistula and the following measures can be accepted: (1) improve the general state before operation: the systemic conditions affecting the occurrence of pancreatic fistula include advanced age, hyperbilirubinemia, malnutrition, and combination with other systemic diseases;[7] (2) acid-inhibitory drugs and pancreatic enzyme secretion drug inhibitors ought to be given 24 h before surgery and are instrumental to reduce the incidence rate of pancreatic fistula; (3) the preoperative treatment plan should be well planned, and the puncture path should avoid passing the pancreatic duct to avoid damage during the puncture process, serving as the most effective approach to get around pancreatic fistula;[8],[9] (4) during the open surgery of particle implantation, impairment of the main pancreatic duct should be avoided, while ear-brain glue and other biological materials can coat puncture wounds helping pancreatic fistula aggravation; and (5) prophylactic indwelling drainage tube as well as maintaining smooth drainage can play essential roles in monitoring the occurrence of pancreatic fistula,[10] which can be confirmed under the following conditions: the concentration of amylase in the drainage tube or ascites is more than three times higher than that of serum amylase. The drainage volume is >50 ml/day. A confirmation is the presence of a peritoneal irritation sign and/or progressive abdominal pain and/or imaging.[11]

Pancreatic fistula requires to be handled with conservative treatment as soon as it occurs. At the same time, it is necessary to monitor the level of blood, urine amylase, and other biochemical indicators as well as to actively correct the general nutritional status. By these measures, the vast majority of pancreatic fistula can be solved. Moreover, pancreatic fistula triggered by a percutaneous puncture for particle implantation into pancreatic cancer should be treated with ultrasound-guided catheter drainage, which could cure fistula after a sufficient drainage. Patients with a severe infection or bleeding and other major complications are eligible for surgical treatment aiming to replace the drainage tube and maintain smooth drainage, which is also available in the condition of poor drainage.

Hemorrhage

Hemorrhage is a common complication during the process of puncture, mostly on account of the puncture path going through the blood vessels of the abdominal wall or abdominal organs. The consensus pointed out that there was no necessity to apply special treatment if the volume of bleeding was <50 ml, which is endowed with the ability of self-healing and mainly caused by the damage of minor vessels in the abdominal wall or abdominal cavity. Under the conditions of obstructive jaundice and poor liver function, it is crucial to actively adjust the liver function and complement with coagulation factors to improve the coagulation status before surgery, to prevent bleeding. Furthermore, the relative movement of the peritoneal and abdominal organs should be taken into account during the puncture process through the peritoneum. Henceforth, it is recommended to utilize the needle one time to refrain abdominal organs' injury from the needle puncture. However, if damage to a large blood vessel could not be excluded during the puncture process, intraoperative ultrasound or computed tomography imaging should be performed to clarify its existence. In addition, if necessary, hemostasis via pressing as well as hemostatic drugs intraoperatively and other treatment measures should be applied if necessary. As the pancreas is in a deep position, the surgeon should be consulted immediately in the case of a bleeding not alleviating. Too prevent the occurrence of bleeding, a detailed plan of implantation should be made before the operation to be complied to during operation, so that passing through the larger blood vessels throughout the puncture path is avoided, as promoted by the consensus.

Bile duct injury

The biliary duct tends to get injured during the implantation of particles if the tumor is located at the head of the pancreas, leading to postoperative bile fistula because the extrahepatic biliary system pressure is higher than the intra-abdominal pressure. Percutaneous transhepatic biliary drainage can be applied based on the percutaneous peritoneal drainage to reduce the biliary pressure, given that existence of bile fistula could be confirmed by postoperative diagnosis. Ultimately, the majority of bile fistula may recover.

Other rare complications

The consensus pointed out that other rare complications include gastrointestinal perforation, acute pancreatitis, chylous fistula, and infection, which can be cured after symptomatic treatment. Particles may migrate to the liver and lungs without serious complications for most cases. Thus, there is no necessity to perform special treatment.


 > The Approaches to Prevent or Reduce the Incidence of Complications Top


The consensus section regarding reactions and complications mainly focuses on the causes of complication and how to manage them. However, there is no direct indication on how to prevent or reduce the incidence of complications. In fact, the proposal including the choice of indications, preoperative preparation, the operation, postoperative treatment, and other aspects has been proposed in the consensus. In addition, medical centers are required to apply those suggestions in the clinical practice, so that we can obtain a standardization of pancreatic cancer particle implantation in all aspects in order to avoid the occurrence of serious complications.

Acknowledgment

The authors would like to thank Gao Fei (Sun Yat-sen University Affiliated Tumor Hospital), Guo Jinhe (Southeast University Affiliated Zhongda Hospital), Hu Xiaokun (Qingdao University Affiliated Hospital), Huang Xuequan (Third Military Medical University Affiliated Southwest Hospital), Lei Guangyan (Shaanxi Provincial Cancer Hospital), Li Chengli (Shandong University Affiliated Shandong Institute of Medical Imaging), Li Maoquan (Tongji University Interventional Vascular Institute/Tongji University Affiliated Tenth Hospital in vascular surgery), Li Yuliang (Shandong University Second Hospital), Lin Zhengyu (Fujian Medical University First Hospital), Lu Ligong (Zhuhai People's Hospital), Niu Lizhi (Guangzhou Fuda Cancer Hospital), Teng Gaojun (Southeast University Affiliated Zhongda Hospital), Wang Juan (Hebei Provincial People's Hospital), Wang Junjie (Third Hospital Affiliated Peking University), Wang Ruoyu (Dalian University Affiliated Zhongshan Hospital), Wang Zhongmin (Shanghai Jiaotong University School of Medicine Ruijin Hospital), Xiang Hua (Hunan Provincial Peoples' Hospital), Zhang Jianguo (Peking University Dental Hospital), Zhang Jie (Pe king University Dental Hospital) for their kind participation in the discussion of the manuscript.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
 > References Top

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Li Q, Tian Y, Yang D, Liang Y, Cheng X, Gai B. Permanent iodine-125 seed implantation for the treatment of nonresectable retroperitoneal malignant tumors. Technol Cancer Res Treat 2019;18:1-8.  Back to cited text no. 8
    
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Shrikhande SV, Barreto SG, Shetty G, Suradkar K, Bodhankar YD, Shah SB, et al. Post-operative abdominal drainage following major upper gastrointestinal surgery: Single drain versus two drains. J Cancer Res Ther 2013;9:267-71.  Back to cited text no. 10
    
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Hu BY, Wan T, Zhang WZ, Dong JH. Risk factors for postoperative pancreatic fistula: Analysis of 539 successive cases of pancreaticoduodenectomy. World J Gastroenterol 2016;22:7797-805.  Back to cited text no. 11
    




 

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