Many types of cancer originating from intraabdominal organs can involve the intraabdominal membrane called ‘peritoneum’. The peritoneum is a thin tissue that covers both the inner surface of the abdominal wall and the surface of the organs, and it secures the lubrication of the organs by secreting a small amount of fluid. In a cancer originating from the abdominal organs, cancer cells can spread to the peritoneum through neighborhood or spill into the abdomen. This usually indicates that the cancer is in its final stage. Systemic chemotherapies, i.e. intravenous chemotherapies, are insufficient in cancers with peritoneal involvement, because the drugs cannot reach the peritoneum completely in these treatments. The basic principle in this treatment is to destroy the remaining cancer cells by giving a warmed chemotherapeutic agent into the abdomen after removing intraabdominal cancerous organs and tissues (cytoreductive surgery).
Why is the chemotherapeutic agent given by heating? What are the effects of heat?
It is most commonly used in the treatment of ovarian cancer in women. In addition, it is used in large intestine (colon-rectum), stomach, appendix cancers and peritoneal cancers (pseudomyxoma peritonei). It has also been used in pancreatic cancers in recent years.
Fluid (acid) accumulation in the abdomen often occurs in peritoneal involvement. This fluid causes both the patient’s abdomen to swell and the spread of cancer cells to the diaphragm and the entire abdomen. Sometimes enough acid builds up in patients to not allow them to lie down. Even if these liquids are discharged from time to time, there is no solution. Acid persists as long as the underlying cause is present. Many of these patients are told that they are in the last stage of the disease and that there is nothing left to do, and are sent home. Here cytoreductive surgery and heated Chemotherapy are used in the patients and clinical situations we mentioned above.
No. heated Chemotherapy alone is not enough, it is part of the treatment. This treatment is a three-legged treatment.
First of all, a complete or almost complete cytoreduction surgery is required, in which the peritoneum and organs (large intestine, ovary, gall bladder, the affected part of the stomach…) are removed and all tumor tissues are removed. In this surgery, the abdomen is opened across the midline and the whole abdomen is evaluated. The affected peritoneum and organs are removed. In the meantime, it may be necessary to remove some of the large or small intestines and mouth the intestine to the abdominal wall (colostomy or ileostomy). This application is usually a temporary application and the intestine is taken back in after the treatment is over. There is no point in applying HIPEC without this surgery. Or, there is no place to perform this surgery without heated Chemotherapy application. Systemic chemotherapy should follow cytoreductive surgery and heated Chemotherapy.
So “Cytoreductive Surgery + heated Chemotherapy + Systemic Chemotherapy” trio.
It has no place in cases of involvement outside of the abdomen (such as brain, lung, bone metastases). The disease should be limited in the abdomen. In addition, there is no place for heated Chemotherapy treatment in patients with many liver metastases (spread) or liver metastases that cannot be removed. If there are three or fewer liver metastases that can be removed, it is not an obstacle for heated Chemotherapy.
In patients with very common and intense small intestine involvement, removal of most of the small intestines is not suitable for heated Chemotherapy treatment because it is not compatible with life. It may not be possible to detect most of these patients preoperatively, but can be seen when the patient is operated on.
In some patients, heated Chemotherapy can be applied to treat only the acid and help the patient’s comfort. In this case, surgery is not applied, heated Chemotherapy can be applied with catheters placed in the abdomen laparoscopically. However, it is usually a palliative treatment. It does not contribute much to the survival time of the patient.
Heated Chemotherapy application is a part of the operation process. It is performed at the end of a long and difficult surgery, following intraabdominal tumor cleaning, while the patient is still under anesthesia. Before closing the abdomen, two drains are placed in the lower and upper quadrants of the abdomen. A connection is established between these drains and the special device that heats the chemotherapy fluid, and 2 heat probes are placed in the lower and upper parts of the abdomen to monitor the temperature level. These probes allow to see that the temperature remains constant at the desired level as long as chemotherapy is given. The temperature should be between 41-43 degrees. Chemotherapy duration varies between 60-90 minutes. 3.5 liters of chemotherapy fluid is injected into the abdomen. In the meantime, the abdomen is shaken by hand from the outside in order for the chemotherapy to reach everywhere in the abdomen. At the end of this period, the fluid in the abdomen is taken back and the procedure is terminated.
The operation takes about 8-10 hours. It requires experience in both pelvic and hepatobiliary surgery. In addition, experienced radiologists for pre-surgical imaging, medical oncologists for the regulation of chemotherapy programs and treatments of patients, experienced pathologists in terms of accuracy of diagnoses, PET tomography and nucleus medical specialists, expert dieticians to regulate their diet, experienced anesthesiologists who follow patients in intensive care, experienced and equipped intensive care and service personnel and nurses are indispensable parts of this large team. This treatment is a multidisciplinary method.
Most of the patients who are candidates for this treatment are patients with advanced stage disease and life expectancy is limited to months. Therefore, this important detail should not be forgotten when talking about survival time.
heated Chemotherapy application has different long-term results in different cancers. Ovarian cancers are the most beneficial and 5-year survival is around 50%. This rate is around 30% in colon cancers. One-year survival of 43%, 5-year 11% has been reported in gastric cancers. Considering that the normal life span is less than 6 months, especially in advanced stage, metastasized gastric cancer, the success of the given rates can be seen.
The 5-year survival rate for pseudomyxoma peritonei is 66-97%.
This is a complex treatment. Therefore, the risk ratio is higher than standard surgeries. However, despite its complexity, good results are obtained in patients who are well prepared before surgery, observed well during surgery and well managed. Most often, the gastrointestinal system stops for a while (loss of function). Complications such as bleeding, treatment-related kidney failure, clot in the lung or brain, bone marrow failure due to chemotherapy, wound infection, wound dehiscence, anastomotic leakage may occur during the operation. However, most of them can be overcome with the precautions taken in experienced centers and good patient management. Although different rates are given in different studies, the risk of losing patients after this treatment is between 0-7%. Considering the stage and severity of the disease and making a risk-benefit assessment, the risk of complications and death is at an acceptable level.
As a result, cytoreductive surgery and heated Chemotherapy is a long, laborious, highly attentive and adaptable treatment that can be applied by experienced surgeons and teams, but promising, promising and contemporary treatment method in terms of results. Compliance of the patient and his family with the treatment and the medical team is an important detail that will increase the success of the treatment.
The trilogy of “Cytoreductive Surgery + heated Chemotherapy + Systemic Chemotherapy” is the only treatment method that can give a long-term survival (20-50%).
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