[Surgical treatment for recurrent intra-abdominal mucinous neoplasms]. / Chirurgische Therapie im Rezidivfall bei intraabdominellen muzinösen Neoplasien.

BACKGROUND: The gold standard in the treatment of mucinous intra-abdominal neoplasms is cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC). Despite complete cytoreduction up to 45% of patients develop recurrences. METHOD: A search and analysis of the current literature were carried out. RESULTS: There is still controversy regarding the best treatment strategy for patients with recurrent pseudomyxoma peritonei (PMP) after CRS and HIPEC. The clinical management of these patients depends on many factors, such as the site and volume of recurrence, histological subtype and symptoms. Treatment options range from repeated surgery with curative intent with or without HIPEC to watch and wait strategies. In selected patients redo surgery is feasible and safe with low morbidity and mortality. Iterative complete CRS can result in a median 5­year overall survival of more than 80%. Debulking surgery leads to a prolonged survival and to symptom control fora period with of nearly 2 years. CONCLUSION: Repeated complete cytoreduction of recurrent PMP can result in long-term survival. Tumor debulking surgery may be particularly beneficial for symptomatic patients.

[Peritoneal carcinomatosis secondary to CUP syndrome : Diagnosis and indications for multimodal treatment]. / Peritonealkarzinose beim CUP­Syndrom : Diagnostik und Indikationsstellung für die multimodale Therapie.

CLINICAL PROBLEM: Peritoneal carcinomatosis secondary to cancer of unknown primary (CUP) syndrome is a rare entity for which there are no uniform treatment recommendations or guidelines. The median survival time is 3 months. DIAGNOSIS: Computed tomography (CT), magnetic resonance imaging (MRI), and 18F­FDG positron emission tomography (PET)/CT are valid imaging modalities for the detection of peritoneal carcinomatosis. The sensitivity of all techniques is highest for large, macronodular peritoneal carcinomatosis manifestations. A limitation of all imaging techniques is limited and small-nodular peritoneal carcinomatosis. Also, peritoneal metastasis in the small bowel mesentery or diaphragmatic domes can only be visualized with low sensitivity. Therefore, exploratory laparoscopy should be considered as the next diagnostic step. In half of these cases an unnecessary laparotomy can be avoided, because the laparoscopy revealed diffuse, small-nodule involvement of the small bowel wall and thus an irresectable situation. TREATMENT: In selected patients, performing complete cytoreduction followed by hyperthermic intra-abdominal chemotherapy (HIPEC) is a good therapeutic option. Therefore, the identification of the extent of peritoneal tumor manifestation as accurately as possible is important for the definition of the increasingly complex oncological therapy strategies.

[Current treatment recommendations for pseudomyxoma peritonei]. / Aktuelle Behandlungsempfehlungen beim Pseudomyxoma peritonei.

BACKGROUND: The term pseudomyxoma peritonei (PMP) describes a clinical syndrome characterized by the presence of gelatinous intraperitoneal accumulation of mucus. It mostly originates from a mucocele of the vermiform appendix. Affected patients are often asymptomatic for a long time. Because of its indolent nature it is usually diagnosed at an advanced stage. Clinical presentation is determined by the dissemination of the tumor. METHOD: A search and analysis of the current literature were carried out. RESULTS: Based on the morphological characteristics PMP subtypes with various malignant potential can be differentiated. The prognosis depends on the histopathological differentiation and the clinical stage. The treatment spectrum varies from laparoscopic appendectomy to complete cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). CONCLUSION: Due to the rarity of PMP there are no prospective randomized studies. Therefore, there is still controversy regarding the best stage-dependent treatment strategy. This review article attempts to clarify the optimal management of mucinous neoplasms of the appendix and PMP taking the clinical presentation and the histological differentiation into consideration.

[Hyperthermic intraperitoneal chemotherapy]. / Hypertherme intraperitoneale Chemotherapie.

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are recognized as the standard of care for selected patients with peritoneal malignancies. A complete macroscopic cytoreduction is the basis for a successful multimodal treatment. The significance of intraperitoneal chemotherapy is still under discussion. This review explains the principles and the value of HIPEC within the multimodal treatment context.

The current practice of cytoreductive surgery and HIPEC for colorectal peritoneal metastases: Results of a worldwide web-based survey of the Peritoneal Surface Oncology Group International (PSOGI).

BACKGROUND: At present, selected patients with resectable colorectal peritoneal metastases (CRC-PM) are increasingly treated with a combination therapy of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). The aim of this study was to investigate the current worldwide practice. METHODS: HIPEC experts from 19 countries were invited through the Peritoneal Surface Oncology Group International (PSOGI) to complete an online survey concerning their personal expertise and current hospital and countrywide practice. RESULTS: It is estimated that currently more than 3800 patients with CRC-PM (synchronous and metachronous) are annually treated with CRS and HIPEC in 430 centers. Integration of CRS and HIPEC in national guidelines varies, resulting in large treatment disparities between countries. Amongst the experts, there was general agreement on issues related to indication, surgical technique and follow up but less on systemic chemotherapy or proactive strategies. CONCLUSION: This international survey demonstrates that CRS and HIPEC is now performed on a large scale for CRC-PM patients. Variation in treatment may result in heterogeneity in surgical and oncological outcomes, emphasising the necessity to reach consensus on several issues of this comprehensive procedure. Future initiatives directed at achieving an international consensus statement are needed.

Cytoreductive surgery and HIPEC improve survival compared to palliative chemotherapy for biliary carcinoma with peritoneal metastasis: A multi-institutional cohort from PSOGI and BIG RENAPE groups.

BACKGROUND: Peritoneal metastasis from biliary carcinoma (PMC) is associated with poor prognosis when treated with chemotherapy. OBJECTIVE: To evaluate the impact on survival of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), and compare with conventional palliative chemotherapy for patients with PMC. MATERIAL AND METHODS: A prospective multicenter international database was retrospectively searched to identify all patients with PMC treated with a potentially curative CRS/HIPEC (CRS/HIPEC group). The overall survival (OS) was compared to patients with PMC treated with palliative chemotherapy (systemic chemotherapy group). Survival was analyzed using Kaplan-Meier method and compared with Log-Rank test. RESULTS: Between 1995 and 2015, 34 patients were included in the surgical group, and compared to 21 in the systemic chemotherapy group. In the surgical group, median peritoneal cancer index was 9 (range 3-26), macroscopically complete resection was obtained for 25 patients (73%). There was more gallbladder localization in the surgical group compared to the chemotherapy group (35% vs. 18%, p = 0.001). Median OS was 21.4 and 9.3 months for surgical and chemotherapy group, respectively (p=0.007). Three-year overall survival was 30% and 10% for surgical and chemotherapy group, respectively. CONCLUSION: Treatment with CRS and HIPEC for biliary carcinoma with peritoneal metastasis is feasible and may provide survival benefit when compared to palliative chemotherapy.

[PIPAC and HIPEC-competing or supplementary therapeutic procedures for peritoneal metastases]. / PIPAC und HIPEC ­ konkurrierende oder ergänzende Therapieverfahren bei peritonealen Metastasen.

Peritoneal carcinomatosis remains a therapeutic challenge. The combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is currently the only potentially curative option with good results. For good oncological results a complete macroscopic cytoreduction is essential. This mostly requires a complex operative procedure with significant morbidity and mortality. Therefore, multimodal treatment is limited to a few highly selected patients. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new minimally invasive approach, the value and spectrum of applications of which are still under investigation; however, the articles on PIPAC published so far are encouraging and PIPAC is therefore a possible palliative therapy option for patients who are not eligible for CRS and HIPEC. The aim of this review is to present a summary of the recent data regarding CRS-HIPEC and PIPAC.

Best practice for perioperative management of patients with cytoreductive surgery and HIPEC.

Due to the significantly improved outcome and quality of life of patients with different tumor entities after cytoreductive surgery (CRS) and HIPEC, there is an increasing number of centers performing CRS and HIPEC procedures. As this procedure is technically challenging with potential high morbidity and mortality, respectively, institutional experience also in the anesthetic and intensive care departments is essential for optimal treatment and prevention of adverse events. Clinical pathways have to be developed to achieve also good results in more comorbid patients with border line indications and extensive surgical procedures. The anesthesiologist has deal with relevant fluid, blood and protein losses, increased intraabdominal pressure, systemic hypo-/hyperthermia, and increased metabolic rate in patients undergoing cytoreductive surgery with HIPEC. It is of utmost importance to maintain or restore an adequate volume by aggressive substitution of intravenous fluids, which counteracts the increased fluid loss and venous capacitance during this procedure. Supplementary thoracic epidural analgesia, non-invasive ventilation, and physiotherapy are recommended to guarantee adequate pain therapy and postoperative extubation as well as fast-track concepts. Advanced hemodynamic monitoring is essential to help the anesthesiologist picking up information about the real-time fluid status of the patient. Preoperative preconditioning is mandatory in patients scheduled for HIPEC surgery and will result in improved outcome. Postoperatively, volume status optimization, early nutritional support, sufficient anticoagulation, and point of care coagulation management are essential. This is an extensive update on all relevant topics for anesthetists and intensivists dealing with CRS and HIPEC.

CRS-HIPEC Prolongs Survival but is Not Curative for Patients with Peritoneal Carcinomatosis of Gastric Cancer.

PURPOSE: Peritoneal carcinomatosis (PC) is a dismal feature of gastric cancer that most often is treated by systemic palliative chemotherapy. In this retrospective matched pairs-analysis, we sought to establish whether specific patient subgroups alternatively should be offered a multimodal therapy concept, including cytoreductive surgery (CRS) and intraoperative hyperthermic chemotherapy (HIPEC). METHODS: Clinical outcomes of 38 consecutive patients treated with gastrectomy, CRS and HIPEC for advanced gastric cancer with PC were compared to patients treated by palliative management (with and without gastrectomy) and to patients with advanced gastric cancer with no evidence of PC. Kaplan-Meier survival curves and multivariate Cox regression models were applied. RESULTS: Median survival time after gastrectomy was similar between patients receiving CRS-HIPEC and matched control patients operated for advanced gastric cancer without PC [18.1 months, confidence interval (CI) 10.1-26.0 vs. 21.8 months, CI 8.0-35.5 months], resulting in comparable 5-year survival (11.9 vs. 12.1 %). The median survival time after first diagnosis of PC for gastric cancer was 17.2 months (CI 10.1-24.2 months) in the CRS-HIPEC group compared with 11.0 months (CI 7.4-14.6 months) for those treated by gastrectomy and chemotherapy alone, resulting in a twofold increase of 2-year survival (35.8 vs. 16.9 %). CONCLUSIONS: We provide retrospective evidence that multimodal treatment with gastrectomy, CRS, and HIPEC is associated with improved survival for patients with PC of advanced gastric cancer compared with gastrectomy and palliative chemotherapy alone. We also show that patients treated with CRS-HIPEC have comparable survival to matched control patients without PC. However, regardless of treatment scheme, all patients subsequently recur and die of disease.

A comprehensive treatment for peritoneal metastases from gastric cancer with curative intent.

Recently, Peritoneal Surface Oncology Group International (PSOGI) developed a novel comprehensive treatment consisting of cytoreductive surgery (CRS) and perioperative chemotherapy (POC) for the treatment of peritoneal metastases (PM) from gastric cancer with curative intent. This article reviews the results of this treatment and verifies its indication. In this strategy, peritoneal cancer index (PCI) is determined by laparoscopy, and a peritoneal port is placed. Neoadjuvant bidirectional intraperitoneal/systemic chemotherapy (NIPS) is performed for 3 cycles, and then laparotomy is performed. Cytoreductive surgery with peritonectomy procedures and hyperthermic intraperitoneal chemoperfusion (HIPEC) are performed. Multivariate analyses showed that completeness of cytoreduction, pathologic response to NIPS and PCI level and cytologic status after NIPS, as independent prognostic factors. PCI less than cut-off level after NIPS, negative cytology after NIPS, and positive response to NIPS were identified as the indications for comprehensive treatment. Patients who hold these criteria should be considered as the candidates for CRS and HIPEC.

Low surface contamination by cis/oxaliplatin during hyperthermic intraperitoneal chemotherapy (HIPEC).

AIM: The aim of this study was to evaluate contamination by platinum drugs in the operating room during hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: Environmental sampling of 151 wipe samples from surfaces on the HIPEC devices and operating room floors was performed for platinum in six German hospitals during 19 HIPEC procedures. Additionally, 45 wipe samples from surgeons' and perfusionists' protective gloves were analyzed. RESULTS: Platinum concentrations from the HIPEC devices and operating room floors ranged from 0.07 to 110,000 pg/cm(2) (Median: 1.5 pg/cm(2)) with high contamination on the regulation knob and reservoir after HIPEC procedure, particularly when injecting the cytostatic drug into the reservoir via syringe. Samples from perfusionists' and surgeons' protective gloves ranged between 0.01 and 729 ng/pair. CONCLUSIONS: Although sporadically high platinum concentrations on surfaces on the HIPEC device and operating room floor were detected, our study revealed that low surface loads are definitely possible and can be documented by wipe samples. Important factors for achieving low surface contamination are the use of infusion bags instead of syringes for injection of the cytostatic solution, careful cleaning of the device after HIPEC and wearing of two pairs of gloves.

[The techniques of peritonectomy and hyperthermic intraperitoneal chemotherapy]. / Technik der Peritonektomie sowie der hyperthermen intraperitonealen Chemotherapie.

The treatment of peritoneal carcinomatosis represents a challenge in the therapy for gastrointestinal cancer. A multimodal approach with complete surgical cytoreduction and hyperthermic intraperitoneal chemotherapy can improve the prognosis in selected patients. Complete surgical cytoreduction, consisting of parietal and visceral peritonectomy, is a sophisticated procedure, frequently requiring multivisceral resections and should only be performed by experienced visceral surgeons. In addition, hyperthermic intraperitoneal chemotherapy is of some complexity. Furthermore, regarding the learning curve for this procedure, combined treatment should only be performed in specialised centres. Under optimal conditions, the therapy can be carried out with reasonable morbidity and mortality rates. Patients with peritoneal carcinomatosis should be evaluated by an interdisciplinary team concerning this multimodal therapy option and, if applicable, they should be referred to therapy within the framework of clinical studies.

Peri-operative anaesthetic management of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy.

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is a long and complex procedure with significant blood and fluid loss during debulking and important pathophysiological alterations during the HIPEC phase. We performed a retrospective analysis of 78 consecutive patients undergoing cytoreductive surgery with HIPEC at a university hospital. Our data demonstrate large intra-operative fluid turnover, with 51% of patients requiring a blood transfusion. During HIPEC, airway pressure and central venous pressure increased with a lower oxygenation ratio as a result of increased intra-abdominal pressure with the closed abdomen technique. As a consequence of the raised body temperature, heart rate, end tidal carbon dioxide and arterial lactate levels increased with a slight metabolic acidosis. Peri-operative analysis of routine clotting parameters revealed disturbances of the coagulation status. For pain management, 72% of patients received supplementary thoracic epidural analgesia with consequential peri-operative opioid sparing and a reduced duration of postoperative ventilation.

[Peritoneal carcinomatosis. Surgical treatment, including hyperthermal intraperitoneal chemotherapy]. / Peritonealkarzinose. Chirurgische Behandlungsmöglichkeiten einschliesslich hyperthermer intraperitonealer Chemotherapie.

Colorectal cancer is a common malignant disease with increasing incidence and a significant cause of death in cancer patients. More than 10% of patients with colorectal cancer show peritoneal carcinomatosis at initial diagnosis. Moreover, peritoneal metastasis is a common sign of recurrence. Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) are a new treatment strategy for highly selected patients with peritoneal carcinomatosis. Numerous studies show prolonged survival after CRS and HIPEC with acceptable morbidity and mortality rates. Accurate preoperative diagnostics and patient selection play a pivotal role in postoperative patient outcome. This promising treatment strategy is discussed regarding surgical technique, intraperitoneal chemotherapy, and patient outcome.

Multimodality treatment of peritoneal carcinomatosis from colorectal cancer: first results of a new German centre for peritoneal surface malignancies.

BACKGROUND: The presence of peritoneal carcinomatosis arising from colorectal cancer is associated with a poor prognosis. It was the purpose of this study to analyze morbidity, mortality, and survival after major cytoreductive surgery and intraperitoneal chemotherapy. MATERIALS AND METHODS: Thirty-two patients with peritoneal carcinomatosis were operated between April 2004 and June 2006 with the aim of complete macroscopical cytoreduction. All had a primary colorectal carcinoma. Surgery in these patients was followed by hyperthermic intraperitoneal chemotherapy (HIPEC) consisting of mitomycin C and doxorubicin. Data were analyzed retrospectively. RESULTS: Of all patients, 16 had appendix and 16 non-appendiceal colorectal carcinoma. A macroscopically complete cytoreduction was achieved in 24 patients by parietal and visceral peritonectomy procedures. All resections were combined with HIPEC. Overall morbidity was 34%. Most frequent surgical complications were intestinal obstruction (4/32), enteric fistula (2/32), pancreatitis (2/32), and bile leakage (2/32). One patient presented grade 4 renal toxicity. There was no hospital mortality. The median follow-up was 12 months. The 1-year overall survival rate is 96%. All patients after complete cytoreduction are still alive. CONCLUSIONS: Cytoreductive surgery combined with HIPEC is associated with an acceptable morbidity and low mortality. Complete cytoreduction may improve survival, particularly in well-selected patients having a low tumor volume and no extra-abdominal metastases.

[Surgical management of patients with peritoneal carcinomatosis of gastrointestinal origin]. / Chirurgische behandlung von peritoneal disseminierten gastrointestinalen tumoren.

Peritoneal carcinomatosis is found in approximately 15 % of patients with colorectal cancer during the course of their disease, and is associated with a poor prognosis. Even more patients with gastric cancer develop peritoneal seeding. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) have been introduced in the past decade and have led to 5-year survival rates of 30 to 40 % for selected patients with colorectal cancer and peritoneal carcinomatosis. These numbers have been demonstrated by many retrospective analyses and by prospective Phase II studies. The clinical assessment to select patients who will benefit from the combined therapy and achievement of complete macroscopic cytoreduction both play a crucial role. Less favourabale results have been achieved for patients suffering from stage IV gastric cancer with peritoneal seeding. Promising results were demonstrated for postoperative intraperitoneal chemotherapy following curative gastrectomy. Patients with hepatic, biliary and pancreatic cancers and peritoneal carcinomatosis do not benefit from cytoreductive surgery. There is a need for further multicentre, prospective trials analysing the use of hyperthermic intraperitoneal chemotherapy. They should be conducted in the specialised centres by interdisciplinary teams.

Improved prognosis following peritonectomy procedures and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from appendiceal carcinoma.

AIMS: The prognosis of patients with peritoneal carcinomatosis from gastrointestinal malignancies is poor. The aim of this study was to analyse the results of multimodality treatment for peritoneal carcinomatosis of appendiceal carcinoma. PATIENTS AND METHODS: From 07/95 to 01/00, 17 patients (13 males, 4 female, median age 58 years) underwent peritonectomy procedures in combination with intraperitoneal hyperthermic chemotherapy. Surgical, pathological and survival data were analysed retrospectively. RESULTS: All patients had undergone previous surgical treatment and one patient had received chemotherapy. In all patients peritonectomy procedures, as described by Sugarbaker, were performed with the aim of achieving a macroscopically complete cytoreduction (range 2-6, median 4 procedures per patient). Following resection, open hyperthermic intraperitoneal chemotherapy with cisplatin was performed. Eleven patients had postoperative complications (predominantly "non-surgical") and two patients died postoperatively. The 4-year survival rate was 75%. Complete cytoreducion had a statistically significant positive influence on long-term survival. CONCLUSIONS: In selected patients (WHO status 0/1, minimal residual disease, no distant metastases, complete cytoreduction), the prognosis for patients with peritoneal carcinomatosis of appendiceal origin can be improved by peritonectomy procedures and hyperthermic intraperitoneal chemotherapy. Postoperative morbidity may be increased due to "non-surgical" complications.

[Intraoperative (hyperthermic) intraperitoneal chemotherapy--considerations and aspects of safe intra- and postoperative treatment with cytostatic drugs]. / Intraoperative (hypertherme) intraperitoneale Chemotherapie-Uberlegungen und Aspekte zum sicheren intra- und postoperativen Umgang mit Zytostatika.

The application of open intraoperative intraperitoneal chemotherapy following cytoreductive surgery for the treatment of pseudomyxoma peritonei or peritoneal carcinomatosis requires safety precautions for the medical and non-medical personnel. In agreement with already existing rules, precautions were established which result in an optimum of safety. These concern the preparation of the cytostatic drugs, the application in the operating room as well as personal precautions intra- and postoperatively. After the establishment of theses recommendations, 22 patients were treated with open intraperitoneal chemotherapy in 1.5 years without any severe accidents. Therefore, a safe intraoperative use of cytotoxic drugs is possible. At the moment, the indication for such an approach may be given in peritoneal carcinomatosis from appendix, colon or ovarian cancer. In the future, an adjuvant application in other gastrointestinal malignancies (e.g. T3/T4 gastric carcinoma) may be considered.

[Scintigraphic method to test the function of intraperitoneal draining catheters for regional intraabdominal chemotherapy]. / Szintigraphische Uberprüfung der Funktion intraperitoneal liegender Katheter zur regionalen intraabdominellen Chemotherapie Scintigraphic Method to Test the Function of Intraperitoneal Draining Catheters for Regional Intraabdominal Chemotherapy.

AIM: Intraoperative peritoneal chemohyperthermia (IPCH) followed by one or more courses of closed intraperitoneal chemotherapy via peritonealdialysis-catheter (Zellermann) is a promising concept for treatment of peritoneal carcinomatosis. METHODS: To prove the functionality of the catheter a scintigraphic method is introduced using a liquid solution of sodium chloride-- Tc-99m-Diethylenetriaminepentaacetic acid (Tc-99m-DTPA) (500 ml). This study was aimed to look for problems over the period of application and to measure the intraperitoneal distribution and resorption of the fluid. RESULTS: One leakage and 3 revisible obstructions occured in 26 applications done in 20 patients. The upper right and the central abdomen was not reached as extensive as the other regions. The abdomen was divided into 9 regions of equal size. In 4 out of 19 patients (20%) the fluid tracer was missed in more than 3 regions (up to 40% of the total area). CONCLUSIONS: It is to early to decide whether methological modifications are necessary in these cases, but closed chemotherapies in patients with maldistribution may not be indicated. This will be in particular necessary if there is a relation between the maldistribution and the location of recurrencies. The demonstrated simple scintigraphic method, however, is able to recognize patients at risk.