Cytoreductive surgery and intraperitoneal chemotherapy for pseudomyxoma peritonei

Background and aims Surgical improvement can be achieved in selected patients with pseudomyxoma peritonei (PMP) by major cytoreductive surgery and intraperitoneal chemotherapy (IPEC). The purpose of this retrospective study was to analyze morbidity, mortality, and survival following therapy.Patients and methods Between July 1995 and September 2003, 28 patients (mean age 56 years, range 28–79) with PMP were operated on with the aim of complete macroscopical cytoreduction. Surgery was followed by IPEC.Results A macroscopically complete cytoreduction was achieved in 11 patients (40%). The mean operating time was 6 h with a mean of three peritonectomy procedures per patient. Cisplatin (15 out of 28), mitomycin C (6 out of 28) and 5-FU (7 out of 28) were used for the intraoperative chemotherapy. Overall morbidity was 36%. Most frequent surgical complications were digestive fistulae (3 out of 28), abscesses (5 out of 28) and bleeding (2 out of 28). Two patients died postoperatively. Patients with low tumor volume (mean survival time 78±11 vs. 37±9 months, p=0.05) and complete cytoreduction (73±10 vs. 24±8 months, p<0.05) had an improved prognosis.Conclusions Cytoreductive surgery combined with IPEC is associated with acceptable morbidity and mortality. Complete cytoreduction may improve survival, particularly in selected patients with PMP who have a low tumor volume, complete cytoreduction, and no organ metastases.Z. Güner and U. Schmidt contributed equally to this paper     

Management of pseudomyxoma peritonei

INTRODUCTION Pseudomyxoma peritonei (PMP) is a rare disease[1]. It refers to a progressive disease process within the peritoneum which originates from the appendix or ovaries and is characterised by the production of copious amounts of mucinous fluid resu…     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

Gastric cancer associated peritoneal carcinomatosis(GCPC) has a poor prognosis with a median survival of less than one year. Systemic chemotherapy including targeted agents has not been found to significantly increase the survival in GCPC. Since recurrent gastric cancer remains confined to the abdominal cavity in many patients, regional therapies like aggressive cytoreductive surgery( CRS) and hyperthermic intraperitoneal chemotherapy(HIPEC) have been investigated for GCPC. HIPEC has been used for three indications in GC- as an adjuvant therapy after a curative surgery, HIPEC has been shown to improve survival and reduce peritoneal recurrences in many randomised trials in Asian countries; as a definitive treatment in established PC, HIPEC along with CRS is the only therapeutic modality that has resulted in longterm survival in select groups of patients; as a palliative treatment in advanced PC with intractable ascites, HIPEC has been shown to control ascites and reduce the need for frequent paracentesis. While the results of randomised trials of adjuvant HIPEC from western centres are awaited, the role of HIPEC in the treatment of GCPC is still evolving and needs larger studies before it is accepted as a standard of care.     

Incidence of leukopenia after intraperitoneal vs combined intravenous/intraperitoneal chemotherapy in pseudomyxoma peritonei

AIM: To investigate the clinical impact of post-hyperthermic intraperitoneal chemotherapy(HIPEC) leukopenia, intraperitoneal and combined intravenous/intraperitoneal drug administrations were compared.METHODS: Two patient cohorts were retrospectively analyzed regarding the incidence of postoperative leukopenia. The first cohort(n = 32) received Mitomycin C(MMC)-based HIPEC intraperitoneally(35 mg/m2 for 90 min) and the second cohort(n = 10) received a bidirectional therapy consisting of oxaliplatin(OX)(300 mg/m2 for 30 min) intraperitoneally and 5-fluorouracil(5-FU) 400 mg/m2 plus folinic acid 20 mg/m2 intravenously. The following data were collected retrospectively: Age, sex, length of operation, length of hospital stay, amount of resection including extent of peritonectomy, peritoneal cancer index, CC(completeness of cytoreduction)-status and leukocyte-count before cytoreductive surgery(CRS) and HIPEC, on days 3, 7 and 14 after CRS and HIPEC. HIPEC leukopenia was defined as 4000 cells/m3. RESULTS: Leukopenia occurred statistically more often in the MMC than in the OX/5-FU-group(10/32 vs 0/10; P = 0.042). Leukopenia set-on was on day 7 after CRS and MMC-HIPEC and lasted for two to three days. Three patients(33%) required medical treatment. Patients affected by leukopenia were predominantly female(7/10 patients) and older than 50 years(8/10 patients). Thelength of hospital stay tended to be higher in the MMCgroup without reaching statistical significance(22.5± 11 vs 16.5 ± 3.5 d). Length of operation(08:54 ± 01:44 vs 09:48 ± 02:28 h) were comparable between patients with and without postoperative leukopenia. Prior history of systemic chemotherapy did not trigger postHIPEC leukopenia. Occurrence of leucopenia did not trigger surgical site infections, intraabdominal abscess formations, hospital-acquired pneumonia or anastomotic insufficiencies. CONCLUSION: Surgeons must be aware that there is a higher incidence of postoperative leukopenia in MMCbased HIPEC protocols primarily affecting females and older patients.     

肿瘤细胞减灭术加腹腔热灌注化疗治疗结直肠癌腹膜转移癌的临床研究

目的：探讨肿瘤细胞减灭术（CRS）加腹腔热灌注化疗（HIPEC）治疗结直肠癌腹膜转移癌（ CRC PC）的疗效及安全性。方法选取结直肠癌腹膜转移癌（ CRC PC）患者67例,随机分为治疗组（ CRS＋HIPEC）38例,对照组（CRS＋静脉辅助化疗）29例,比较两组的生存期、生存率、术后并发症及化疗毒副作用。结果治疗组中位生存期23.0个月,显著长于对照组的11.0个月（ P＜0.01）,治疗组1、2、3年生存率分别为70.9％、45.7％、8.2％,分别优于对照组的68.8％、21.2％、0％。术后并发症发生率两组相似（ P＞0.05）。化疗毒副作用：对照组恶心呕吐、白细胞减少、血小板减少发生率较治疗组高（P＜0.01）,而治疗组腹胀、腹泻发生率较对照组高（ P＜0.01或P＜0.05）;两组其他毒副作用相似（ P＞0.05）。结论 CRS＋HIPEC治疗CRC PC能明显延长患者生存期,并发症和化疗毒副作用并没有明显增加。     

Selection criteria for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in gastric cancer

Peritoneal carcinomatosis in gastric cancer is associated with a dismal prognosis.Systemic chemotherapy is not effective because of the existence of a blood-peritoneal barrier.Cytoreductive surgery and intraperitoneal chemotherapy can improve survival and quality of life in selected patients.Patient selection for this multimodal approach is one of the most critical issues,and calls for interdisciplinary evaluation by radiologists,medical and surgical oncologists,and anaesthetists.This article sets forth cri...     

Current role of hyperthermic intraperitoneal chemotherapy in the treatment of peritoneal carcinomatosis from colorectal cancer

Peritoneal carcinomatosis is one of the most common routes of dissemination of colorectal cancer (CRC). It is encountered in 7% of patients at primary surgery, while it develops in about 4% to 19% of patients after curative surgery and in up to 44% of patients with recurrent CRC. Peritoneal involvement from colorectal malignancies has been considered traditionally as a manifestation of terminal disease, due to limited response to conventional surgical and chemotherapeutic treatments. In the past few years t...     

Current status and future strategies of cytoreductive surgery plus intraperitoneal hyperthermic chemotherapy for peritoneal carcinomatosis

This article is to offer a concise review on the use of cytoreductive surgery （CRS） plus intraperitoneal hyperthermic chemotherapy （IPHC） for the treatment of peritoneal carcinomatosis （PC）. Traditionally, PC was treated with systemic chemotherapy alone with very poor response and a median survival of less than 6 too. With the establishment of several phase Ⅱ studies, a new trend has been developed toward the use of CRS plus IPHC as a standard method for treating selected patients with PC, in whom sufficient cytoreduction could be achieved. In spite of the need for more high quality phase Ⅲ studies, there is now a consensus among many surgical oncology experts throughout the world about the use of this new treatment strategy as standard care for colorectal cancer patients with PC. This review summarizes the current status and possible progress in future.     

Peritoneal carcinomatosis of colorectal origin: Incidence, prognosis and treatment options

Peritoneal carcinomatosis (PC) is one manifestation of metastatic colorectal cancer (CRC). Tumor growth on intestinal surfaces and associated fluid accumulation eventually result in bowel obstruction and incapacitating levels of ascites, which profoundly affect the quality of life for affected patients. PC appears resistant to traditional 5-fluorouracil-based chemotherapy, and surgery was formerly reserved for palliative purposes only. In the absence of effective treatment, the historical prognosis for these patients was extremely poor, with an invariably fatal outcome. These poor outcomes likely explain why PC secondary to CRC has received little attention from oncologic researchers. Thus, data are lacking regarding incidence, clinical disease course, and accurate treatment evaluation for patients with PC. Recently, population-based studies have revealed that PC occurs relatively frequently among patients with CRC. Risk factors for developing PC have been identified: right-sided tumor, advanced T-stage, advanced N-stage, poor differentiation grade, and younger age at diagnosis. During the past decade, both chemotherapeutical and surgical treatments have achieved promising results in these patients. A chance for long-term survival or even cure may now be offered to selected patients by combining radical surgical resection with intraperitoneal instillation of heated chemotherapy. This combined procedure has become known as hyperthermic intraperitoneal chemotherapy. This editorial outlines recent advancements in the medical and surgical treatment of PC and reviews the most recent information on incidence and prognosis of this disease. Given recent progress, treatment should now be considered in every patient presenting with PC.     

Chinese expert consensus on cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal malignancies

Locoregional spread of abdominopelvic malignant tumors frequently results in peritoneal carcinomatosis(PC). The prognosis of PC patients treated by conventional systemic chemotherapy is poor, with a median survival of 6 mo. However, over the past three decades, an integrated treatment strategy of cytoreductive surgery(CRS) + hyperthermic intraperitoneal chemotherapy(HIPEC) has been developed by the pioneering oncologists, with proved efficacy and safety in selected patients. Supported by several lines of clinical evidence from phases Ⅰ, Ⅱ and Ⅲ clinical trials, CRS + HIPEC has been regarded as the standard treatment for selected patients with PC in many established cancer centers worldwide. In China, an expert consensus on CRS + HIPEC has been reached by the leading surgical and medical oncologists, under the framework of the China Anti-Cancer Association. This expert consensus has summarized the progress in PC clinical studies and systematically evaluated the CRS + HIPEC procedures in China as well as across the world, so as to lay the foundation for formulating PC treatment guidelines specific to the national conditions of China.     

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases

AIM: To systematically review the available evidence regarding cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for colorectal peritoneal metastases (CPM).METHODS: An electronic literature search was carried out to identify publications reporting oncological outcome data (overall survival and/or disease free survival and/or recurrence rates) following CRS and IPC for treatment of CPM. Studies reporting outcomes following CRS and IPC for cancer subtypes other than colorectal were only included if data were reported independently for colorectal cancer-associated cases; in addition studies reporting outcomes for peritoneal carcinomatosis of appendiceal origin were excluded.RESULTS: Twenty seven studies, published between 1999 and 2013 with a combined population of 2838 patients met the predefined inclusion criteria. Included studies comprised 21 case series, 5 case-control studies and 1 randomised controlled trial. Four studies provided comparative oncological outcome data for patients undergoing CRS in combination with IPC vs systemic chemotherapy alone. The primary indication for treatment was CPM in 96% of cases (2714/2838) and recurrent CPM (rCPM) in the remaining 4% (124/2838). In the majority of included studies (20/27) CRS was combined with hyperthermic intraperitoneal chemotherapy (HIPEC). In 3 studies HIPEC was used in combination with early post-operative intraperitoneal chemotherapy (EPIC), and 2 studies used EPIC only, following CRS. Two studies evaluated comparative outcomes with CRS + HIPEC vs CRS + EPIC for treatment of CPM. The delivery of IPC was performed using an “open” or “closed” abdomen approach in the included studies.CONCLUSION: The available evidence presented in this review indicates that enhanced survival times can be achieved for CPM after combined treatment with CRS and IPC.     

Experience after 100 patients treated with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

AIM: To investigate perioperative patient morbidity/mortality and outcome after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).METHODS: Of 150 patients 100 were treated with cytoreductive surgery and HIPEC and retrospectively analyzed. Clinical and postoperative follow-up data were evaluated. Body mass index (BMI), age and peritoneal carcinomatosis index (PCI) were chosen as selection criteria with regard to tumor-free survival and perioperative morbidity for this multimodal therapy.RESULTS: CRS with HIPEC was successfully performed in 100 out of 150 patients. Fifty patients were excluded because of intraoperative contraindication. Median PCI was 17 (1-39). In 89% a radical resection (CC0/CC1) was achieved. One patient died postoperatively due to multiorgan failure. Neither PCI, age nor BMI was a risk factor for postoperative complications/outcome according to the DINDO classification. In 9% Re-CRS with HIPEC was performed during the follow-up period.CONCLUSION: Patient selection remains the most important issue. Neither PCI, age nor BMI alone should be an exclusion criterion for this multimodal therapy.     

Current treatment options for colon cancer peritoneal carcinomatosis

Peritoneal carcinomatosis (PC), the dissemination of cancer cells throughout the lining of the abdominal cavity, is the second most common presentation of colon cancer distant metastasis. Despite remarkable advances in cytotoxic chemotherapy and targeted therapy for colon cancer over the last 15 years, it has been repeatedly shown that these therapies remain ineffective for colon cancer PC. Recently, there has been a rapid accumulation of reports that cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy (CRS-HIPEC) prolongs the life of colon cancer PC patients. Here, we will review the clinical presentation, the mechanisms of disease progression, and current treatment options for colon cancer PC, with a focus on the benefits and limitations of CRS-HIPEC.     

短期腹膜复发性结肠癌经减瘤术联合腹腔热灌注化疗一例

结肠癌术后腹膜复发是导致治疗失败的原因之一。规范手术操作、提高手术质量是降低结肠癌术后复发的有效手段。结肠癌腹膜种植转移行减瘤术联合腹腔热灌注化疗安全有效。     

Peritoneal carcinomatosis of colorectal cancer: incidence,prognosis, and treatment modalities

Background and aims Intraperitoneal carcinomatosis accounts for 25–35% of recurrences of colorectal cancer. Studies demonstrate that peritoneal carcinomatosis is not necessarily a terminal condition with no options for treatment or cure.Results The combination of aggressive cytoreductive surgery and intra-abdominal hyperthermia chemotherapy improves long-term overall survival in selected patients but is a time-consuming procedure (approx. 12 h) and entails high mortality (5%) and morbidity (35%)). Most commonly used drugs are mitomycin C and platinum compounds, which have synergistic toxic effects on tumor cells when hyperthermia is applied.Conclusion Since combined treatment seems promising only in peritoneal carcinomatosis stages I and II, the precondition for a reasonable combined treatment is careful staging. The mode of chemotherapy, the kind of drugs used for chemoperfusion, the timing of surgery, and the role of additional systemic chemotherapy must be evaluated in randomized studies.     

Malignant peritoneal mesothelioma: treatment with maximal cytoreductive surgery plus intraperitoneal chemotherapy

OBJECTIVE: To report survival results in patients with diffuse malignant peritoneal mesothelioma (MPM) treated with maximal cytoreductive surgery followed by immediate intraperitoneal chemotherapy, and to compare them with the median survival of 12-24 months obtained with the standard treatment based on systemic chemotherapy. PATIENTS AND METHODS: Twenty-six patients underwent this new regional approach and a median follow-up of 55 months was achieved after this treatment. Complete cytoreductive surgery (residual disease < 2 mm) was performed in all but one patient. Intraperitoneal chemotherapy was performed with hyperthermia (4245 degrees C) and oxaliplatin in 22 patients. The last 12 patients additionally received irinotecan. Data were prospectively verified and retrospectively analyzed. RESULTS: One patient died postoperatively (4%), and morbidity attained 54%. The median survival exceeded 100 months and the overall 5-year survival rate was 63%. This small series lacks the statistical power required to conduct a well-grounded study on prognostic factors, particularly as the completeness of the surgery is not analyzable here. However, the low-grade histological types had a better disease-free survival rate that was of borderline significance compared to their high-grade counterparts. CONCLUSION: This new approach combining complete cytoreductive surgery considerably increases the survival of patients with MPM compared with the standard treatment based on systemic chemotherapy.     

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.     

结直肠癌腹膜转移预防和治疗腹腔用药中国专家共识（V 2019）

我国结直肠癌发病率和死亡率均位于恶性肿瘤的前列，腹膜转移作为常见转移部位，是治疗失败的常见原因之一。目前结直肠癌腹膜转移的腹腔预防和治疗性药物种类繁多，但作用剂量和时间尚未形成规范化的治疗模式。因此为了规范术中预防和治疗性腹腔干预方法，中国医师协会结直肠肿瘤专业委员会组织国内相关领域权威专家，制定《结直肠癌腹膜转移预防和治疗腹腔用药中国专家共识》（以下简称《共识》），旨在提高我国结直肠肿瘤的整体诊治水平，延长结直肠癌患者生存时间并改善生活质量。     

Complete peritonectomy and intraperitoneal chemotherapy for recurrent rectal cancer with peritoneal metastasis

A 68-year-old man underwent laparoscopic low anterior resection for rectal carcinoma in December 2006. Nearly 19 mo after the operation, he developed recurrent rectal cancer with peritoneal metastasis. In September 2008, he subsequently underwent a laparotomy with a peritonectomy, omentectomy, splenectomy, and a Hartmann procedure. Hyperthermic intraperitoneal oxaliplatin 750 mg was administered. The patient was discharged with no postoperative complications and has been well with postoperative FOLFOX chemotherapy.     

The utility of hyperthermic intra-abdominal chemotherapy with gemcitabine for the inhibition of tumor progression in an experimental model of pancreatic peritoneal carcinomatosis,in relation to their behavior with pancreatic cancer stem cells CD133+ CXCR4+

ObjectiveThe origin of pancreatic cancer has been identified as a population of malignant pancreatic stem cells CD133+ CXCR4+ immunophenotype. These cells have high capacity for early locoregional invasion, being responsible for early recurrence and high mortality rates of pancreatic cancer. We propose a study for decreasing tumor progression of pancreatic cancer by reducing the volume and neoplastic subpopulation of pancreatic cancer stem cells CD133+ CXCR4+. Therefore, we develop a new therapeutic model, characterized by the application of HIPEC (Hyperthermic Intraperitoneal Chemotherapy) with gemcitabine.DesignPancreatic tumor cell line: human cell line BxPC-3. The animal model involved 18 immunosuppressed rats 5 weeks weighing 150–200 gr. The implantation of 13 × 10⁶ cells/mL was performed with homogeneous distribution in the 13 abdominopelvic quadrants according to the peritoneal carcinomatosis index (PCI) and were randomized into three treatment groups. Group I (4 rats) received intravenous saline. Group II (6 rats) received intravenous gemcitabine. Group III (8 rats) received HIPEC at 41 °C for 30 min with gemcitabine + gemcitabine IV. A histological study confirmed pancreatic cancer and immunohistochemical quantification of pancreatic cancer stem cells CD133+ CXCR4+ tumor cells.ResultsThere was a population decline of pancreatic cancer stem cells CD133+ CXCR4+ in the HIPEC group with respect to the other two groups (p < 0.001). There was a decrease in PCI between treatment groups (p < 0.05).ConclusionThe initial results are encouraging since there is a declining population of cancer stem cells CD133+ CXCR4+ in the HIPEC group and decreased tumor volume compared to the other two treatment groups. All the conclusions are only valid for BxPC3 cell line, and the effects HIPEC on Kras-driven pancreatic tumors remain to be determined.