Phase II studies: International registry of colorectal carcinomatosis.

Peritoneal carcinomatosis (PC) is a common manifestation of colorectal cancer and has traditionally been regarded as a terminal disease with a short median survival. Over the last decade, a new local-regional therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy has evolved and promising survival results were reported in large phase II studies. A retrospective multicentric study of 506 patients from 28 institutions 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) within the 7 days following surgery. The morbidity and mortality rates were 22.9% and 4%, respectively. Patients in whom cytoreductive surgery was complete had a median survival of 32.4 months compared to 8.4 months for patients in whom complete cytoreductive surgery was not possible (p < 0.001). 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 histological differentiation were negative independent prognostic indicators. The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in carefully selected group of patients with PC from colorectal origin and offer a chance for cure or palliation in this condition. Further collaboration between peritoneal surface malignancy treatment centres are needed in order to standardize indications, intraperitoneal chemotherapy and peritonectomy techniques.     

Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND:

Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival.

METHODS:

A retrospective, multicenter cohort study was performed in French‐speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies.

RESULTS:

The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement.

CONCLUSIONS:

A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long‐term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC. Cancer 2010. © 2010 American Cancer Society.     

Management of peritoneal surface malignancy with cytoreductive surgery and perioperative intraperitoneal chemotherapy.

AIMS: A new treatment strategy combining maximal cytoreductive surgery for treatment of macroscopic disease and maximal perioperative intraperitoneal chemotherapy for residual microscopic disease, suggests that in a selected group of patients benefit is possible. The purpose of this study was to report our experience with this combined treatment and to identify the principal prognostic factors. METHODS: The study included 266 patients from 9 institutions operated on between July 1990 and July 2004. The median age was 55 years. RESULTS: The mortality rate was 7.8% and the morbidity rate 37.5%. The overall median survival was 13.7 months. Positive independent prognostic factors by multivariate analysis were gender, perioperative intraperitoneal chemotherapy and treatment by the second-look procedure. CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with perioperative intraperitoneal chemotherapy achieved long-term survival in a selected group of patients with an acceptable morbidity and mortality.     

Treatment of peritoneal carcinomatosis from colorectal cancer by cytoreductive surgery and hyperthermic perioperative intraperitoneal chemotherapy.

PURPOSE: Peritoneal carcinomatosis from colorectal cancer is resistant to standard treatments and median survival time for patients ranges between 6 and 8 months. Aggressive cytoreductive surgery with hyperthermic intraperitoneal perioperative chemotherapy may increase median survival. METHOD: Patients undergoing cytoreductive surgery and perioperative hyperthermic chemotherapy (mitomycin C, intraoperatively; 5-fluorouracil early post-operatively) for peritoneal carcinomatosis from colorectal cancer from 1996 to 2003 were evaluated retrospectively. RESULTS: From 1996 to 2003, 18 cytoreductive procedures were performed. The post-operative morbidity rate was 44.4% with no treatment related mortality. The median total operation time was 5 h 28 min (range: 3 h 20 min to 7 h 10 min). The median follow-up was 21 months. The median survival was 15 months. CONCLUSION: Surgical debulking and perioperative intraperitoneal chemotherapy improved survival with acceptable morbidity and mortality. Completeness of the resection was the most important prognostic indicator.     

Cytoreductive surgery and perioperative intraperitoneal chemotherapy for peritoneal carcinomatosis from colorectal carcinoma: non-mucinous tumour associated with an improved survival

AIMS: Cytoreductive surgery combined with perioperative intraperitoneal chemotherapy has been reported as a treatment option for patients with peritoneal carcinomatosis from colorectal carcinoma. METHODS: Thirty patients with colorectal peritoneal carcinomatosis underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy. All appendiceal cancers were excluded. All patients were followed until January 2006 or death. Univariate analysis was performed to evaluate significant prognostic factors for overall survival, defined from the time of surgery. RESULTS: There were 13 male patients. The mean age at the time of surgery was 54years. There was no hospital mortality. The mean duration of hospital stay was 27days. The overall median survival was 29months, with 1- and 2-year survival of 72% and 64%, respectively. Twenty-one patients had complete cytoreduction and their 1- and 2-year survival rates were 85% and 71%, respectively. Univariate analysis demonstrated that patients with non-mucinous colorectal adenocarcinoma, Peritoneal Cancer Index (PCI) < or =13, and complete cytoreduction were associated with an improved survival. CONCLUSIONS: This study reported on 30 patients who underwent cytoreductive surgery and perioperative intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis. Patients with mucinous tumour had relatively more extensive intraperitoneal disease. Non-mucinous colorectal adenocarcinoma, PCI < or =13, and complete cytoreduction were associated with an improved survival.     

The management of synchronous peritoneal carcinomatosis and hematogenous metastasis from colorectal cancer.

AIMS: Combined local and distant dissemination for colorectal cancer occurs especially in younger patients. New strategies combining maximal cytoreductive surgery with intraperitoneal and systemic chemotherapy have been used in an attempt to prolong survival with an acceptable morbidity and mortality. METHODS: Twenty-seven patients with histologically proven peritoneal carcinomatosis from colorectal cancer had distant metastases in addition to peritoneal carcinomatosis. The goal for treatment in all patients was complete local and distant cytoreduction. Aggressive intraperitoneal and systemic chemotherapy was used. The endpoint for all the analysis was survival from the time of definitive treatment at our Institution. RESULTs: In addition to peritoneal carcinomatosis, 16 patients had liver metastases, six patients had lung metastases, four had liver and lung metastases and one had supraclavicular lymph-node metastases. Median survival time (MST) for the entire group was 15.2 months. Patients that received a complete cytoreductive surgery had a MST of 20.6 months and patients with incomplete cytoreduction had a MST of 9.0 months (p= 0.0471). Post-operative morbidity and mortality was 14.8 and 0%, respectively. CONCLUSION: A group of carefully selected patients with peritoneal carcinomatosis and distant metastases from colorectal cancer may benefit from cytoreductive surgery and intraperitoneal chemotherapy.     

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.     

Current status of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis from colorectal cancer

Peritoneal carcinomatosis (PC) arising from colorectal cancer (CRC) is generally considered a terminal condition with no treatment options. However novel treatment strategies have emerged combining cytoreductive surgery (CRS), including peritonectomy procedures, with intraperitoneal chemotherapy. The intraoperative application of cytotoxic drugs combined with hyperthermia (hyperthermic intraperitoneal chemotherapy [HIPEC]) has been considered to deliver cytotoxicity most effectively to peritoneal tumor implants. In selected groups of patients with no remaining macroscopic tumor manifestations on peritoneal surfaces after CRS and HIPEC, median survival times may reach 5 years, with a 5 year overall survival rate of 50%. HIPEC has been performed with different cytotoxic drugs, in combination with early postoperative intraperitoneal chemotherapy (EPIC), and embedded into various systemic perioperative and/or postoperative chemotherapeutic regimens. Prognosis largely depends on the intraabdominal tumor burden, which can be assessed by the peritoneal cancer index (PCI), and the completeness of cytoreduction. In this review we discuss the most relevant prognostic parameters, the outcome of patients with PC from CRC treated with CRS and HIPEC, and the impact of different chemotherapeutic variations used during HIPEC. From this analysis it can be concluded that CRS and HIPEC offers a chance for long-term survival in selected patients with PC of colorectal origin.     

Cytoreductive surgery and intraoperative intraperitoneal hyperthermic chemotherapy in patients with peritoneal carcinomatosis of colorectal origin

The median survival in patients with peritoneal carcinomatosis from colorectal adenocarcinoma is, with conventional approaches, only about six months. Combined treatment consisting of maximum cytoreductive surgery plus intraoperative intraperitoneal hyperthermic chemotherapy has been shown, albeit in small non-comparative series, to increase disease-free survival and overall survival, compared with previous series. Further, a randomized trial has demonstrated better results (a median survival of 22.4 months) with cytoreduction plus intraperitoneal chemotherapy compared with conventional chemotherapy. Technical considerations, infrastructure requirements and possible complications imply specialized centres and staff. Surgery consists of peritonectomy of affected areas and fulguration of all macroscopic lesions. Intraperitoneal chemotherapy must reach all parts of the peritoneal cavity and the temperature of the hyperthermic procedure must be maintained between 42–44°C. Three prognostic factors associated with this procedure are: pathologic tumour grade, peritoneal carcinomatosis index, and cytoreductive surgery grade.     

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal carcinomatosis: Prognosis and treatment of recurrences in a cohort study

Background

Cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) treatment of colorectal peritoneal carcinomatosis (PC) is gaining acceptance, but controversy remains. The primary aims were to analyse the outcome and prognostic variables of colorectal PC patients treated with CRS and IPC, and to report on the outcome of additional surgical treatments of subsequent recurrences.

Methods

Patients referred for treatment of colorectal PC between 1996 and 2010 were included in a cohort. The following data was collected: clinicopathological parameters, survival, recurrences, perioperative chemotherapy and type of IPC (hyperthermic intraperitoneal chemotherapy, HIPEC; or sequential postoperative intraperitoneal chemotherapy, SPIC). Multivariable analyses were conducted on potential prognostic factors for overall survival (OS).

Results

In the 151-patient cohort, the median OS was 34 months (range: 2–77) for CRS and HIPEC with five-year survival predicted at 40% (five-year disease-free survival 32%). For CRS and SPIC, the OS was 25 months (range: 2–188) with five-year survival at 18%. Open-and-close patients survived 6 months (range: 0–14) with no five-year survival (HIPEC vs. SPIC p = 0.047, SPIC vs. open-and-close p < 0.001). Adjuvant systemic chemotherapy was a noteworthy independent prognostic factor in the multivariable analysis. OS for patients undergoing additional surgical treatment of recurrences was 25 months vs. 10 months with best supportive care or palliative chemotherapy (p = 0.01).

Conclusion

Substantial long-term survival is possible in patients with colorectal PC. HIPEC was associated with better OS than SPIC and adjuvant systemic chemotherapy may improve the outcome in patients. Good OS is achievable in selected patients undergoing additional surgical treatment of isolated liver or peritoneal recurrences after prior complete CRS.     

Synchronous extraperitoneal and intraperitoneal dissemination of appendix cancer.

BACKGROUND: The aim of this study was to report the role of combined treatments, including cytoreductive surgery and perioperative regional chemotherapy, in patients with synchronous systemic and intraperitoneal dissemination of appendix cancer. METHODS: Patients with synchronous systemic and intraperitoneal dissemination of appendix cancer were treated with cytoreductive surgery and perioperative regional chemotherapy. Variables statistically analyzed with survival as an end point included demographic characteristics, prior surgical score (PSS), tumour marker levels, peritoneal cancer index (PCI), and completeness of cytoreduction (CC). RESULTS: Mean follow up was 42.6 months, median survival time (MST) for 15 patients was 28 months and 5-year survival rate was 29.4%. Female patients had a longer MST than male patients (p=0.0199). Survival was better in patients with PSS 0 and 1 (p=0.0277). Patients with elevated CEA and CA 19-9 levels had a shorter MST (p=0.0083 and p=0.0193, respectively). PCI and CC comparisons did not show significant differences. Morbidity (n=2) and mortality (n=2) rates were 13.3% respectively. CONCLUSION: Acceptable morbidity and mortality and a 29.4% 5-year survival rate allows cytoreductive surgery and regional chemotherapy to be considered as a treatment option for selected patients with synchronous systemic and intraperitoneal dissemination of appendix cancer.     

Incidence and prognosis of synchronous colorectal carcinomatosis: evolution since 1985?

Evaluation of: Lemmens VE, Klaver YL, Verwaal VJ, Rutten HJ, Coebergh JW, de Hingh IH. Predictors and survival of synchronous peritoneal carcinomatosis of colorectal origin: a population-based study. Int. J. Cancer 128, 2717-2725 (2011). Until recently, colorectal peritoneal carcinomatosis was considered inaccessible to curative therapy, hence the paucity of epidemiological and clinical features available to date regarding the disease. In this retrospective study, spanning 1995-2008, approximately 5% of the patients with colorectal cancer, recorded in the cancer registry of southern Netherlands, had synchronous carcinomatosis, confined to the peritoneum in nearly half of them. Despite progress in chemotherapy, surgery and anesthesiology, the survival of patients with synchronous carcinomatosis has not increased (median survival of 8 months), unlike that of patients with liver metastases. Although, only 11% of the patients had undergone complete cytoreductive surgery followed by hyperthermic intraperitoneal chemotherapy during the latest period (2006-2008). In the future, all patients with isolated colorectal carcinomatosis should be evaluated for curative therapy with complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.     

Curative treatment of peritoneal carcinomatosis arising from colorectal cancer by complete resection and intraperitoneal chemotherapy.

BACKGROUND: Peritoneal carcinomatosis (PC) is fatal, despite standard systemic chemotherapy. A new approach that combines maximal surgery with maximal regional chemotherapy has potential to cure selected patients who have colorectal PC. The authors have reported the oncologic results of this combined treatment. METHODS: The authors performed a retrospective study of 64 patients who had PC arising from colorectal adenocarcinomas, 19 (29.6%) of whom also had other metastases. These patients were treated by complete resection of all detectable tumors and by a 5-day course of early intraperitoneal chemotherapy (EPIC) with mitomycin C, then by 5-fluorouracil (n = 37), or by intraoperative intraperitoneal chemohyperthermia (IPCH) with mitomycin C, alone or combined with cisplatin (n = 27), in 2 separate trials. In the trial of IPCH, aimed at selecting the most reliable procedure in terms of spatial diffusion and thermal homogeneity, the 27 patients were treated with 7 different procedures. The extent of PC was assessed precisely by using a peritoneal index. The median follow-up period for the entire patient population was 51.7 months. RESULTS: The postoperative mortality and morbidity rates were 9.3% and 54.6%, respectively. Most severe complications occurred in patients who required extensive cytoreductive surgery. Global and disease-free survival rates were respectively 60.1% and 54.7% at 2 years and were 27.4% and 18.4% at 5 years. Results were significantly better (P = 0.04) when patients were metastasis-free (apart from PC) and when the peritoneal index was lower than 16 (P = 0.005). IPCH seemed to be more effective than EPIC for treatment of PC. CONCLUSION: This treatment plan, which combined maximal surgery with maximal regional chemotherapy, cured approximately 25% of patients. This strategy was mainly applicable to patients with limited intraperitoneal cancer volume and no extraperitoneal involvement. IPCH proved to be more effective than EPIC but more difficult to use correctly. Future results should improve through routine use of the optimal hyperthermia procedure, with improvements in the composition of instillate, better patient selection, and the reduction in the rate of complications that occurs with physician experience.     

洛铂联合多西他赛行肿瘤细胞减灭术加腹腔热灌注化疗治疗同时性胃癌腹膜癌*

目的:分析洛铂联合多西他赛行肿瘤细胞减灭术（cytoreductive surgery,CRS ）加腹腔热灌注化疗（hyperthermic intraperitoneal chemotherapy ,HIPEC）治疗同时性胃癌腹膜癌（peritoneal carcinoma,PC）的疗效及安全性。方法:50例胃癌PC患者接受52次CRS+HIPEC治疗,药物为洛铂100 mg、多西他赛120 mg,加入12000 mL生理盐水加热至（43± 0.5）℃ 持续灌注60min。主要终点指标为总生存期,次要终点评价指标为围手术期安全性。结果:患者中位随访期22.5 个月,中位生存期14.3 个月（95%CI:7.6～21.0）,1、2、3 年生存率分别为58% 、40% 、32% 。无围手术期死亡,12例（23.1%）出现严重不良事件。多因素分析显示,完全细胞减灭、术前肿瘤标记物水平正常、术后化疗≥ 6 个周期为影响预后的独立因素。结论:对于同时性胃癌PC患者,洛铂联合多西他赛行CRS+HIPEC可延长患者的总生存期,安全可行。      

结直肠癌腹膜转移的多学科综合治疗

腹膜转移是结直肠癌常见转移部位之一,传统观念认为其预后差,没有手术治疗的价值。近年来,随着外科技术、精确控温的腹腔热灌注化疗以及多学科综合治疗的进步,对结直肠癌腹膜转移的认识和治疗策略发生很大的变化,拟就这一问题进行综述。在预后方面,如果仅行姑息性化疗,结直肠癌腹膜转移的预后差于肝、肺等非腹膜部位的转移;但对于一部分合适的患者施行完全性腹膜减瘤术联合腹腔热灌注化疗,则可能使部分患者获得长期生存;腹膜转移癌的预后因素包括腹膜播散癌指数、减瘤术完全性程度、是否合并腹膜外转移(肝脏等)、腹膜表面疾病严重程度评分和日本腹膜分期等。在治疗方面,完全性腹膜减瘤术联合腹腔热灌注化疗以及全身治疗(化疗+靶向治疗),可能是最佳的多学科综合治疗策略。     

Cytoreductive surgery and hyperthermic intraperitoneal chemoperfusion versus systemic chemotherapy alone for colorectal peritoneal carcinomatosis

BACKGROUND:

Survival benefit of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion was demonstrated by a prospective randomized trial for colorectal peritoneal carcinomatosis. Because of a recent substantial improvement in chemotherapy, the authors analyzed treatment options of colorectal carcinomatosis in the current era.

METHODS:

Consecutive patients with colorectal carcinomatosis treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion from 2001 to 2007 were included. The control group patients with carcinomatosis received contemporary chemotherapy alone. Overall survival was the primary endpoint.

RESULTS:

All patients underwent systemic chemotherapy. The cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion group (n = 67) was similar to the control group (n = 38) in sex, tumor grade, site of tumor origin, T status, and N status. The control group was, however, older (59 vs 51 years; P<.001). Median survival measured from the diagnosis of peritoneal disease was longer with cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion (34.7 months vs 16.8 months; P<.001). Presence of liver metastasis was a significant negative predictor of survival (hazard ratio, 2.13).

CONCLUSIONS:

The authors concluded that 1) contemporary chemotherapy is associated with prolonged survival among patients with carcinomatosis as compared with historical controls, and 2) addition of cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion to modern chemotherapy regimens may significantly prolong survival. Cytoreductive surgery combined with hyperthermic intraperitoneal chemoperfusion and systemic chemotherapy are not competitive therapies, and they both have a role in a multidisciplinary approach to patients with carcinomatosis. Cancer 2010. © 2010 American Cancer Society.     

细胞减灭术联合腹腔热灌注化疗治疗胃癌腹膜转移的系统评价

目的:系统评价细胞减灭术(cytoreductive surgery,CRS)联合腹腔热灌注化疗(hyperthermic intraperitoneal chemotherapy,HIPEC)治疗胃癌伴腹膜转移患者的临床有效性和安全性,为临床应用与深入研究提供参考.方法:计算机检索PubMed、Cochrane图书馆、EMbase、MEDLINE(Ovid)、CNKI、维普中刊数据库、中国生物医学文献数据库,收集利用CRS联合HIPEC治疗胃癌伴腹膜转移患者的所有研究,包括随机对照试验(randomized controlled trail,RCT)和非随机对照试验(non-randomized controlled trail,非RCT),对纳入研究主要从生存期和安全性两方面进行统计分析.结果:纳入1项RCT和8项非RCT,共504例患者.生存期方面,RCT中,CRS联合HIPEC组的中位生存期为11个月,明显高于单纯CRS组的7个月(P=0.003).8项非RCT中,CRS联合HIPEC治疗的1、2、3年合计总体生存率分别为52.9%、27.1%、16.8%.手术切除程度达到CC 0~1分是预后较好的预测指标.安全性方面,非RCT显示联合治疗方案围手术期总体死亡率为4.8%,严重并发症的合计发生率为24.9%,在RCT中这两项数据分别为0和13.1%.结论:对于胃癌伴腹膜转移,尤其是达到CC 0~1切除的患者,CRS联合HIPEC能延长患者的生存期,但同时存在较高的严重并发症发生率.     

Outcomes following synchronous liver resection,cytoreductive surgery and hyperthermic intraperitoneal chemotherapy for colorectal liver and peritoneal metastases: A bi-institutional study

PurposeSynchronous liver resection, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal liver (CRLM) and peritoneal metastases (CRPM) has traditionally been contraindicated. However, latest practice promotes specialist, multidisciplinary-led consideration for select patients. This study aimed to evaluate the perioperative and oncological outcomes of synchronous resection in the management of CRLM and CRPM from two tertiary referral centres.MethodThis bi-institutional, retrospective, cohort study included patients undergoing simultaneous liver resection, CRS and HIPEC for metastatic colorectal cancer from 2013 to 2020. Patients treated with ablative liver techniques, staged operative approaches and extra abdominal disease were excluded. Overall survival (OS) and disease-free survival (DFS) rates were assessed. Univariate and multivariate analyses identified variables associated with survival and major morbidity (Clavien-Dindo grade III/IV).ResultsTwenty-three patients were included. The median peritoneal carcinomatosis index (PCI) was 9 (range 0–22). There were two major liver resections and 21 minor resections. CC-0 resections were achieved in all patients. Major morbidity occurred in 7 patients. There were no deaths at 90 days. PCI was independently associated with morbidity (p = 0.04). PCI >10 (p = 0.069), major morbidity (p = 0.083) and presence of KRAS mutation (p = 0.052) approached significance for poor OS. Median follow up was 21 months (4–54 months). Median OS was 37 months, 3-year survival 54%, and median DFS 18 months.ConclusionSynchronous liver resection, cytoreductive surgery and HIPEC is feasible in selected patients with low-volume CRPM and CRLM. Increasing PCI is associated with postoperative major morbidity, and should be considered during operative planning.     

Extensive cytoreductive surgery followed by intra-operative hyperthermic intraperitoneal chemotherapy with mitomycin-C in patients with peritoneal carcinomatosis of colorectal origin

Peritoneal seeding from colorectal cancer has a very poor prognosis and is relatively resistant to systemic chemotherapy. We performed a phase I/II trial to investigate the feasibility and effectiveness of extensive cytoreductive surgery in combination with intra-operative hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. 29 patients with peritoneal carcinomatosis of colorectal origin without evidence of distant metastases underwent cytoreductive surgery and intra-operative HIPEC with mitomycin-C (MMC), followed by systemic chemotherapy with 5-fluorouracil (5-FU)/leucovorin. Surgical complications occurred in 11 patients (38%). One patient died directly related to the treatment, resulting in a mortality rate of 3%. MMC toxicity existed mainly of leucocytopenia (in 15 patients; 52%). After a median follow-up of 38 months (range 26-52 months) we found a 2- and 3-year survival rate (Kaplan-Meier) of 45 and 23%, respectively. Extensive cytoreductive surgery and HIPEC is feasible in patients with peritoneal seeding of colorectal cancer. First results suggest that a higher median survival could be achieved compared with conventional palliative surgery and systemic chemotherapy, therefore a randomised phase III study is now being conducted.