Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

201 consecutive cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) procedures in a single Asian tertiary centre

Introduction: Peritoneal carcinomatosis (PC) is increasingly being treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We provide a review of a high-volume Asian institute's experience and survival outcomes with this procedure.

Methods: Data were prospectively collected from 201 consecutive CRS and HIPEC procedures performed in a single institution between April 2001 and November 2015. Our primary endpoints were overall survival (OS) and disease-free survival (DFS), and secondary endpoints were morbidity and mortality.

Results: 77% of patients were Chinese, 9% were Malay, 6% were Indian and 8% were other ethnicities. Primary tumours were colorectal (30%), ovarian (32%), appendiceal (20%), primary peritoneal (6.5%), mesothelioma (4.5%) and others (5%). The median peritoneal cancer index (PCI) was 12, and 92% of patients achieved a completeness of cytoreduction score (CC) of 0. High-grade morbidity occurred in 25.8% of cases, and there were no 30-day mortalities. At 5-years, the OS was 55.1% and DFS was 20.3%. Factors associated with improved OS on multivariate analysis were PCI <15 (p?p?=?0.016).

Conclusions: The combined treatment of CRS and HIPEC is beneficial and is associated with reasonable morbidity and mortality in Asian patients with PC from colorectal, ovarian, appendiceal, primary peritoneal and mesothelioma primaries. Complete cytoreduction and extent of disease are the most important prognostic factors for survival.     

Clinical efficacy of cytoreductive surgery and hyperthermic chemotherapy in peritoneal carcinomatosis from gastric cancer

Evaluation of: Yang XJ, Huang CQ, Suo T et al. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a Phase III randomized clinical trial. Ann. Surg. Oncol. 18(6), 1575–15781 (2011).

Peritoneal carcinomatosis (PC) is the most common pattern of metastasis and recurrence in patients with gastric cancer and is associated with poor clinical outcome and survival. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) was recently established as a new treatment option for PC of gastrointestinal cancer. However, the role of cytoreductive surgery in gastric cancer and the intrinsic role of HIPEC remains unclear. The evaluated article presented a single center Phase III study, randomizing 68 patients with PC from gastric cancer to surgical cytoreduction only (CRS; n = 34) versus cytoreduction plus HIPEC with cisplatin and mitomycin (CRS+HIPEC; n = 34). Median overall was 6.5 months in the CRS group and 11.0 months in the CRS+HIPEC group (p = 0.046). Serious adverse events were acceptable in both groups. Multivariate analysis found CRS+HIPEC, synchronous PC, complete cytoreduction, systemic chemotherapy >6 cycles and no incidence of severe adverse events independent predictive factors for survival. This was the first study to show the positive effects of HIPEC in addition to CRS in PC independently of the tumor entity. In patients with gastric cancer, multimodal treatment concepts combining surgical cytoreduction and HIPEC may provide a new option in carefully selected patients.     

Diffuse malignant peritoneal mesothelioma: Long-term survival with complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC)

BackgroundPrognosis of diffuse malignant peritoneal mesothelioma (DMPM) has been recently improved by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). As with other peritoneal surface malignancies, the survival benefit is maximal when a complete surgical cytoreduction is achieved, but additional factors predicting long-term outcome are still poorly understood. We sought to investigate outcome and prognostic factors in patients with DMPM treated by complete cytoreduction and HIPEC.MethodsFrom a prospective database, we selected 108 patients with DMPM undergoing complete cytoreduction (residual tumour nodules ?2.5 mm) and closed-abdomen HIPEC with cisplatin and doxorubicin or mitomycin-C. Twenty-seven patient-, tumour- and treatment-related variables were assessed by multivariate analysis with respect to overall (OS) and progression-free (PFS) survival. A panel of immunohistochemical markers was tested.ResultsOperative mortality was 1.9% and major morbidity 38.9%. Median follow-up was 48.8 months (95% confidence interval (CI) 37.1–60.6). Median OS and PFS were 63.2 months (95%CI 29.6–96.7) and 25.1 months (95%CI 5.1–45.1). The survival curve reached a plateau after 7 years, representing 19 actual survivors of 39 patients (43.6%) with potential follow-up ?7 years. Cytokeratin 5/6, calretinin, Wilms tumour-1 (WT-1), podoplanin and epithelial growth factor receptor (EGFR) were mostly positive. At multivariate analysis, epithelial histological subtype, negative lymph-nodes, ?10% Ki67-positive cells correlated with both increased OS and PFS. Positive podoplanin correlated to increased PFS.ConclusionsAfter complete cytoreduction and HIPEC, prognosis of DMPM is primarily dependent on pathologic and biologic features. Patients with DMPM surviving ?7 years appeared to be cured. Cure rate was 43.6%. Proliferative index and podoplanin may be used for prognostic stratification.     

Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival

Background: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) benefits selected patients with peritoneal mesothelioma. We present the outcomes of this treatment strategy in a UK peritoneal malignancy national referral centre.

Methods: Observational retrospective analysis of data prospectively collected in a dedicated peritoneal malignancy database between March 1998 and January 2016.

Results: Of 1586 patients treated for peritoneal malignancy, 76 (4.8%) underwent surgery for peritoneal mesothelioma. Median age was 49?years (range 21–73?years). 34 patients (45%) were female. Of the 76 patients, 39 (51%) had low grade histological subtypes (mostly multicystic mesothelioma), and 37 (49%) had diffuse malignant peritoneal mesothelioma (DMPM; mostly epithelioid mesothelioma). Complete cytoreduction was achieved in 52 patients (68%) and maximal tumour debulking (MTD) was performed in 20 patients (26%); the remaining 4 patients (5%) underwent a laparotomy with biopsy only. HIPEC was administered in 67 patients (88%). Median overall (OS) and disease-free survival (DFS) after CRS was 97.8 (80.2–115.4) and 58.8 (47.4–70.3) months, respectively. After complete cytoreduction, 100% overall survival was observed amongst patients with low-grade disease. Ki-67 proliferation index was significantly associated with survival outcomes after complete cytoreduction for DMPM and was an independent predictor of decreased survival.

Conclusion: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.     

Long-term survival with peritoneal mucinous carcinomatosis from intraductal mucinous papillary pancreatic carcinoma treated with complete cytoreduction and hyperthermic intraperitoneal chemotherapy

Traditionally, peritoneal carcinomatosis (PC) was regarded as an untreatable condition; however, the introduction of locoregional therapies combining cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) approximately two decades ago has changed this view. There is controversy, however, when a PC arises from pancreatic cancer. We have reported on an extraordinary case of an aggressive pseudomixoma peritonei arising from an invasive intraductal papillary mucinous neoplasm (IPMN) treated with complete cytoreduction and HIPEC. This combination of treatments has not been previously described. Moreover, a very long-term disease-free survival of up to 70 months has been achieved by this combined approach. This approach may provide some optimism for considerable life extension in selected patients who present with an aggressive peritoneal mucinous carcinomatosis of pancreatic origin considered suitable only for palliative care.     

Randomized trial of cytoreduction and hyperthermic intraperitoneal chemotherapy versus systemic chemotherapy and palliative surgery in patients with peritoneal carcinomatosis of colorectal cancer.

PURPOSE: To confirm the findings from uncontrolled studies that aggressive cytoreduction in combination with hyperthermic intraperitoneal chemotherapy (HIPEC) is superior to standard treatment in patients with peritoneal carcinomatosis of colorectal cancer origin. PATIENTS AND METHODS: Between February 1998 and August 2001, 105 patients were randomly assigned to receive either standard treatment consisting of systemic chemotherapy (fluorouracil-leucovorin) with or without palliative surgery, or experimental therapy consisting of aggressive cytoreduction with HIPEC, followed by the same systemic chemotherapy regime. The primary end point was survival. RESULTS: After a median follow-up period of 21.6 months, the median survival was 12.6 months in the standard therapy arm and 22.3 months in the experimental therapy arm (log-rank test, P =.032). The treatment-related mortality in the aggressive therapy group was 8%. Most complications from HIPEC were related to bowel leakage. Subgroup analysis of the HIPEC group showed that patients with 0 to 5 of the 7 regions of the abdominal cavity involved by tumor at the time of the cytoreduction had a significantly better survival than patients with 6 or 7 affected regions (log-rank test, P <.0001). If the cytoreduction was macroscopically complete (R-1), the median survival was also significantly better than in patients with limited (R-2a), or extensive residual disease (R-2b; log-rank test, P <.0001). CONCLUSION: Cytoreduction followed by HIPEC improves survival in patients with peritoneal carcinomatosis of colorectal origin. However, patients with involvement of six or more regions of the abdominal cavity, or grossly incomplete cytoreduction, had still a grave prognosis.     

Surgery for Peritoneal Mesothelioma

Malignant peritoneal mesothelioma (MPM) is a rare, progressive, and ultimately fatal disease in almost all afflicted individuals. MPM is a cancer that arises diffusely from the serosa of the abdominal cavity and progresses almost exclusively in this region; understanding its characteristic tumor biology has been the reasoning behind the development of treatment strategies designed to control disease progression in the peritoneum. This principally includes operative cytoreduction and hyperthermic intra-operative perfusion of intraperitoneal chemotherapy (HIPEC). This approach has been administered either alone or in combination with early postoperative intraperitoneal chemotherapy (EPIC), or as a component of a more protracted multimodal approach employing initial debulking surgery, intraperitoneal chemotherapy, and whole abdominal radiotherapy. Median overall survivals of up to 7 years have been observed in series of patients selected for operative cytoreduction and HIPEC. Factors associated with good outcome are female gender, age less or equal to 60 years, and the ability to achieve a complete extirpation of all gross peritoneal disease. In patients with symptomatic ascites, complete palliation is achieved in almost all cases. However, this treatment strategy is not without complications and carries a morbidity of 25% and mortality up to 7%. Despite these risks, the best overall survival data have been associated with this surgical approach. At our institution, we advocate cytoreduction and HIPEC as the standard management for patients with MPM for whom operative cytoreduction appears possible and safe. We believe this treatment approach should be considered as the standard of care for patients with MPM.     

Referral pathways and outcome of patients with colorectal peritoneal metastasis (CRPM)

IntroductionTraditionally patients with colorectal peritoneal metastases (CRPM) were offered palliative chemotherapy and best supportive care. With the introduction of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), patients in the UK have been referred to nationally approved centres. This study describes the pattern of referral and outcomes of patients managed through one UK centre.Methodsand Methods: A prospective register recorded referrals, demographics, prior treatment pathways, and specialist multidisciplinary team (MDT) decisions (2002-2015). Peritoneal cancer index (PCI) was recorded intra-operatively; complete cytoreduction was deemed when a CC0/1 was achieved. Complications were classified using NCI CTCAE. v.4. Median overall survivals (OS) were described for those treated by CRS/HIPEC and in derived estimates for patients with isolated peritoneal metastases treated by chemotherapy alone in the ARCAD trials consortium.ResultsTwo-hundred-eighty-six patients with CRPM were referred. Despite increasing numbers of referrals annually, the proportion of patients selected for CRS/HIPEC decreased from 64.5%, to 40%, and to 37.1% for 2002–09, 2010–12, and 2013–15, respectively (p < 0.017). CRS/HIPEC was undertaken in 117 patients with a median PCI of 7 and CC0/1 achieved in 86.3%. NCI CTCAE grade 3/4 complication rates were 9.4%; 30-day mortality was 0.85%. Median OS following CRS/HIPEC was 46.0 months: that for patients not receiving CRS/HIPEC was 13.2 months.ConclusionThe evolution of the national peritoneal treatment centre over 14 years has been associated with increased referral numbers, refinement of selection for major surgery, matched with achievements of low complication rates and survival advantages in selected patients compared with traditional non-surgical treatments.     

Selection of patients and staging of peritoneal surface malignancies

Peritoneal carcinomatosis (PC) is a common evolution of cancer of the gastrointestinal tract, and has been traditionally regarded as a terminal disease with short median survival. During the last 20 years, thanks to its favourable oncologic results, a new loco-regional therapeutic approach, combining cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC), has an important development. Due to its significant, but acceptable, morbidity and mortality, and high cost, this comprehensive management plan requires knowledgeable patient selection. Quantitative prognostic indicators are required to assess a patient's eligibility. Large multicenter studies have identified several prognostic factors, which can be used for a better selection of patients who would benefit from the combination of cytoreductive surgery with HIPEC. Indications for treatment of PC with cytoreduction and HIPEC are now validated for several diseases: peritoneal mesothelioma, pseudomyxoma peritonei, PC from the appendix, and colorectal cancer. Indications are still under discussion for gastric and ovarian carcinomatosis. Computed tomography is the best radiological for staging the disease. The extent of peritoneal carcinomatosis is, however, difficult to evaluate preoperatively, and precise evaluation is most often performed during surgical exploration. Cytoreductive surgery associated with HIPEC for the treatment of peritoneal carcinomatosis should be performed for young patients with limited and resectable carcinomatosis, in specialized institutions involved in the management of peritoneal surface malignancies.     

细胞减灭术加腹腔热灌注化疗治疗胃癌腹膜转移癌的临床研究

  目的   分析细胞减灭术（Cytoreductive surgery,CRS）加腹腔热灌注化疗（Hyperthermic intraperitoneal chemotherapy,HIPEC）治疗胃癌腹膜癌（Peritoneal carcinomatosis,PC）的疗效和安全性。   方法  对106例胃癌PC患者随机分为CRS组或CRS+ HIPEC组,前者行常规手术治疗,后者行CRS+HIPEC,药物为羟基喜素碱（HTPC）20 mg加丝裂霉素（MMC）30 mg,或多西他赛120 mg加顺铂120 mg,溶于生理盐水12 L,温度（43±0.5）℃,时间60~90 min。主要终点指标为总体生存期,次要终点指标为安全性。   结果  入组患者106例,CRS组45例,CRS+HIPEC组61例,两组的主要临床病理指标平衡。至患者的中位随访期30个月时,胃癌PC相关死亡率在CRS组为93.3%（42/45）,CRS+HIPEC组为77.0%（47/61,P < 0.05）。两组患者的中位生存期在CRS组是7.0个月（95%CI:5.8~8.2个月）,CRS+HIPEC组是11.1个月（95% CI:8.3~13.9个月,P=0.003）。治疗相关的严重不良事件在CRS组为6例,CRS+HIPEC组为8例（P>0.05）。多因素分析显示CRS+HIPEC治疗、胃癌同时性PC患者、肉眼可见完全肿瘤细胞减灭、不发生严重不良事件、系统性化疗6个周期以上为影响预后的独立参数。   结论  对于胃癌同时性PC患者,CRS+HIPEC可延长生存期,并不明显增加严重不良事件。      

Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal malignancy: preliminary results of a multi-disciplinary teamwork model in Asia

Background: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is an emerging surgical procedure for peritoneal carcinomatosis (PC). CRS/HIPEC is a complicated treatment that requires multi-disciplinary teamwork (MDT), which may be lacking when establishing a CRS/HIPEC programme. Herein, we report our preliminary treatment outcomes with the early implementation of an MDT model for CRS/HIPEC.

Methods: From April 2015 to December 2016, 45 patients with a diagnosis of PC who received CRS/HIPEC were reviewed retrospectively in a single institution in Taiwan.

Results: Among the 45 patients, CRS was mainly performed by laparotomy (n?=?42), and only three patients with limited PC underwent laparoscopic CRS. The first 13 patients received treatment before the MDT had been established (group 1), and the other 32 patients were treated after the MDT had been established (group 2). The highest peri-HIPEC body temperature in group 2 was significantly lower than that in group 1 (36.8?°C vs. 37.5?°C, p?p?=?0.202). Pre-CRS/HIPEC abdominal pain significantly increased the risk of post-operative major complications (p?=?0.017).

Conclusions: Our experience suggests that the early implementation of an MDT model when establishing a CRS/HIPEC programme at a single institution may result in a higher complete cytoreduction rate and lower major complication rate, and also shorten the learning curve of this complicated procedure.     

A novel treatment protocol with 6 cycles of neoadjuvant chemotherapy followed by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in stage III primary ovarian cancer

BackgroundFew prospective studies investigated neoadjuvant chemotherapy (NAC), interval cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in advanced ovarian cancer. We report the results of a phase II study where 6 rather than 3 cycles of NAC, followed by CRS and HIPEC, were adopted (HIPEC_ovaio, EudraCT number 2007-005674-31).Materials and methodsBetween 2007 and 2014, 56 patients with stage III primary ovarian cancer and peritoneal carcinomatosis were assigned to 6 cycles of platinum and taxane-based NAC. Of these, two had progression, 8 underwent palliative surgery, and 46 had CRS and HIPEC.ResultsA complete pathological response was observed in 9 patients. Of 46 patients who completed the treatment protocol, 29 had no macroscopic residual tumor. Postoperative grade III morbidity rate was 28.2%; no grade IV complications or mortality events were observed. Five-year overall survival (OS) of the entire series was 36 ± 7% (median: 36, 95% CI: 26–45 months). In 46 patients treated by CRS and HIPEC, 5-year OS was 42 ± 8% (median: 53, 95% CI: 29–76 months), and 5-year progression-free survival was 26 ± 7% (median: 23, 95% CI: 19–27 months). Completeness of cytoreduction, peritoneal cancer index and FIGO stage resulted as significant prognostic factors.ConclusionsA novel protocol consisting of 6 cycles of NAC, followed by CRS and HIPEC, is associated with notable improvement in peritoneal carcinomatosis, limited postoperative morbidity risk and high survival rates in responders, and could deserve further investigations in randomized clinical trials.     

Toxicity and mortality of cytoreduction and intraoperative hyperthermic intraperitoneal chemotherapy in pseudomyxoma peritonei--a report of 103 procedures.

AIMS: To report on treatment related toxicity and mortality in patients with pseudomyxoma peritonei (PMP) treated by cytoreduction in combination with intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and to identify prognostic factors. METHODS: A review was performed of 103 procedures of cytoreduction and intraoperative HIPEC for PMP between 1996 and 2004. Toxicity was graded according to the National Cancer Institute Common Toxicity Criteria (NCI CTC) classification. A surgical complication was defined as any post-operative event that needed re-intervention. Pre and peroperative factors were studied on their relationship to toxicity and mortality. RESULTS: The median hospital stay was 21 days (4-149) with a treatment related toxicity of 54% and a 30 days mortality of 3%. In univariate analysis, toxicity was associated with abdominal tumour load (p<0.01), completeness of cytoreduction (p<0.01), and age (p=0.05). Surgical complications, mainly small bowel perforations/suture leaks, were the main cause of toxicity. A favourable pathology decreased mortality. CONCLUSIONS: Cytoreduction in combination with intraoperative HIPEC in PMP patients is a treatment with a relatively high toxicity, but a considerable long-term survival in selected patients. Toxicity is mainly surgery related. Concentration of cases to acquire sufficient experience and better selection on age, pathology, and extent of disease is essential to reduce treatment related toxicity and mortality.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal and gastrointestinal origin shows acceptable morbidity and high survival

Background

Peritoneal carcinomatosis from colorectal origin carries a poor prognosis. Recent clinical studies show that cytoreductive surgery (CS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) improves survival of selected patients with a colorectal carcinoma and isolated peritoneal carcinomatosis in the absence of extra-abdominal metastases. Here, we report the clinical outcomes and survival after cytoreductive surgery and HIPEC of the first cohort of patients treated in our institution.

Methods

Sixty-seven patients underwent a laparotomy. Complete cytoreduction could be performed in 49 patients, who underwent a total of 53 CS–HIPEC procedures. All had peritoneal carcinomatosis originating from primary colorectal, cecal, appendiceal, and gastric tumors.

Results

In patients who underwent CS–HIPEC, an R0 resection could be achieved in 4%, R1 in 88%, and R2 in 8%. The 30-day mortality was 0; one patient died in-hospital after 10 weeks. The median hospital stay was 12 days (range 4–56). The overall morbidity was 43%, including extended gastroparesis (11%), anastomotic failure (11%) and intra-abdominal abscess (9%). Mean time to clinical recurrence was 12 months (range 4–22). The actuarial 1-year survival was 88% and 2-year survival was 75%.

Conclusion

In well-selected patients referred to a specialized institution, CS–HIPEC has an accep table morbidity and high survival rate.     

Outcomes for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in the elderly

BackgroundCytoreductive surgery (CRS) with heated intraperitoneal chemotherapy (HIPEC) has gained acceptance in the treatment of peritoneal carcinomatosis (PC) with reported morbidity and mortality rates of 27–56% and 0–11% respectively. The safety and outcome of such major operation in the elderly remains unclear. We report our experience at a high volume tertiary center.MethodA total of 170 consecutive patients underwent CRS-HIPEC for peritoneal carcinomatosis between March 2007 and July 2012. Mitomycin C (88.8%) was administered intraperitoneally at 42 °C for 90 min. Patients were categorized into two groups according to the age at the time of surgery: Group 1 (≤65 years-old) and Group 2 (>65 years-old). Differences between the groups were analyzed. Univariate and multivariate analyses were performed to identify variables associated with major morbidity.ResultsOf the 170 patients, 35 were older than 65 years. The two most common tumor sites were colorectal and appendiceal cancer. The perioperative morbidity and mortality rates in the elderly were 18.8% and 8.6% respectively. Gender, tumor type, estimated blood loss >400 mL, intraoperative blood transfusion, operative time >6 h, bowel anastomosis, intraoperative PCI >16, and extent of cytoreduction (Δ PCI) were not associated with major morbidity in the older group (p > 0.05). At a median follow-up of 15.7 months (0.2–53.5 months), recurrence rate for colorectal/appendiceal PC at 1 year was 48.0% in Group 1 and 44.3% in Group 2 (p = NS). Median survival for the colorectal/appendiceal carcinomatosis patients in Group 1 (n = 81) was 29.79 (SE 4.7) months and in Group 2 (n = 20) was 21.2 (SE 3.0) months, (p = 0.06, NS).ConclusionCRS-HIPEC procedures for peritoneal carcinomatosis in the elderly demonstrate comparable perioperative outcome in well-selected patients. Optimal cytoreduction was achieved in the majority of cases and survival was not significantly different from that of the younger group.     

Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy for the management of peritoneal carcinomatosis from colorectal cancer: a multi-institutional study.

PURPOSE: The three principal studies dedicated to the natural history of peritoneal carcinomatosis (PC) from colorectal cancer consistently showed median survival ranging between 6 and 8 months. New approaches combining cytoreductive surgery and perioperative intraperitoneal chemotherapy suggest improved survival. PATIENTS AND METHODS: A retrospective multicenter study was performed to evaluate the international experience with this combined treatment and to identify the principal prognostic indicators. All patients had cytoreductive surgery and perioperative intraperitoneal chemotherapy (intraperitoneal chemohyperthermia and/or immediate postoperative intraperitoneal chemotherapy). PC from appendiceal origin was excluded. RESULTS: The study included 506 patients from 28 institutions operated between May 1987 and December 2002. Their median age was 51 years. The median follow-up was 53 months. The morbidity and mortality rates were 22.9% and 4%, respectively. The overall median survival was 19.2 months. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months, compared with 8.4 months for patients in whom complete cytoreductive surgery was not possible (P <.001). Positive independent prognostic indicators by multivariate analysis were complete cytoreduction, treatment by a second procedure, limited extent of PC, age less than 65 years, and use of adjuvant chemotherapy. The use of neoadjuvant chemotherapy, lymph node involvement, presence of liver metastasis, and poor histologic differentiation were negative independent prognostic indicators. CONCLUSION: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with PC from colorectal origin with acceptable morbidity and mortality. The complete cytoreductive surgery was the most important prognostic indicator.     

Hyperthermic intraperitoneal chemotherapy with cisplatin and paclitaxel in advanced ovarian cancer: a multicenter prospective observational study

Objective

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been recently reported with favorable oncological outcomes as treatment of advanced epithelial ovarian cancer (EOC). The aim of this study was to demonstrate the feasibility of CRS+HIPEC with cisplatin and paclitaxel for the treatment of advanced EOC.

Methods

This is a prospective observational study of 54 patients, from April 2007 to October 2013, with primary or recurrent peritoneal carcinomatosis due to EOC. The mean age was 54.51±9.34. Thirty patients (59%) had primary EOC, and 24 patients (41%) had recurrent disease.

Results

Mean peritoneal cancer index was 10.11 (range, 0 to 28), complete cytoreduction (CC0) was achieved for 47 patients (87%), CC1 for seven patients (13%). Patients with suboptimal cytoreduction (CC2 and CC3) were not included in the study. The mean stay in intensive care unit was 4.73±5.51 days and the mean hospitalization time was 24.0±10.03 days. We did not observe any intraoperative death. Seven patients (13%) required additional operations. Three patients (5.6%) died within 30 days from the procedure. Severe complications were seen in 19 patients (35.2%). During the follow-up period, disease recurred in 33 patients (61.1%); the median disease-free survival time was 12.46 months and the median overall survival time was 32.91 months.

Conclusion

CRS+HIPEC with cisplatin and paclitaxel for advanced EOC is feasible with acceptable morbidity and mortality. Additional follow-up and further studies are needed to determine the effects of HIPEC on long term survival.     

Place de la chimiothérapie hyperthermique intrapéritonéale (CHIP) dans la prise en charge du cancer de l’ovaire : expérience monocentrique institutionnelle

The peritoneal carcinomatosis of ovarian cancer led to the development of optimal cytoreduction surgery completed by hyperthermic intraperitoneal chemotherapy (HIPEC). The main goal of this study is to evaluate the feasibility, tolerance and efficacy of this technique in patients with ovarian cancer. A retrospective monocentric study has evaluated 43 patients with HIPEC procedures from 1995 to 2009. After a complete cytoreduction surgery, a HIPEC procedure with cisplatin is performed. Data on complications and survival parameters were collected. Prognostic factors were also analyzed. Post-surgery complications included one death due to a septic shock (2.3%) and six patients have presented major complications (13.9%). The median of overall survival and progression free survival were 53.6 and 39 months, respectively. Patients with a primary complete surgical cytoreduction of the peritoneal carcinomatosis presented overall survival length of 131 months versus 84 months without initial complete resection (P < 0.0001). Surgical cytoreduction combined with HIPEC is a feasible procedure with acceptable morbid-mortality rates. The initial complete resection of the peritoneal carcinomatosis significantly increases survival and represents a strong prognostic factor.     

Étude prospective de la qualité de vie après une CHIP par oxaliplatine pour carcinose péritonéale

BackgroundCytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy (HIPEC) is now the reference technique for limited peritoneal carcinomatosis (PC). Operative mortality is actually at 3 or 4%, and decrease as morbidity. Together, they did not limit acceptation of HIPEC. However, one of the major limitation of this aggressive treatment is that patient can be afraid to impair overall quality of life (QoL). The aim of this article was to assess QoL in patients at least 12 months after HIPEC using Oxaliplatin.MethodPatients completed a questionnaire before and after surgery at 1, 3, 6 and 12 months. QoL was assessed with the EORTC QLQ-C30 questionnaire.ResultatsBetween September 2006 and October 2008, 32 of 35 patients who had undergone HIPEC were interviewed. PC originated in primary lesions of the colon/rectum (N = 17), ovary (N = 3), stomach (N = 3), appendix (N = 2), mesothelium (N = 2), pseudomyxoma peritonei (N = 3) and primary carcinoma of peritoneum (N = 2). The percentage of patients completing the questionnaire at each time point was: baseline = 87% (N = 28); 1 and 3 months = 46% (N = 15); 6 months = 62% (N = 20); and 12 months = 59% (N = 19). Morbidity and mortality were respectively 35 and 5%. Median hospital stay was 19 days. QoL score had decreased considerably in 60% of patients in the early postoperative assessment period after HIPEC (1 month), as compared with baseline score. Forty five per cent had reported significant pain and limitations on physical functioning. QoL score had returned to baseline at 3 months in 53,3% of patients: 20% reported lack of energy and fatigue. Fifty-five and 73% of patients had recovered their overall QoL at 6 and 12 months, respectively. Also, psychosocial problems, diarrhea and constipation, and peripheral neuropathy of oxaliplatin were reported in 20% of survivors over the course of the first year after HIPEC.ConclusionShort-term QoL with physical and functional well-being are impaired in the first few months after surgery plus HIPEC using oxaliplatin. Long-term QoL returns to baseline at 3 months; however 20% of patients still report psychosocial problems, gastrointestinal symptoms and oxaliplatin-induced neuropathy. It is useful and important for patients to see this HIPEC QoL data at the time of consultation before treatment.