Faheez Mohamed

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Malignant Peritoneal Mesothelioma: Multi-Institutional Experience

PURPOSEnThis multi-institutional registry study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM).nnnPATIENTS AND METHODSnA multi-institutional data registry that included 405 patients with DMPM treated by a uniform approach that used CRS and HIPEC was established. The primary end point was overall survival. The secondary end point was evaluation of prognostic variables for overall survival.nnnRESULTSnFollow-up was complete in 401 patients (99%). The median follow-up period for the patients who were alive was 33 months (range, 1 to 235 months). The mean age was 50 years (standard deviation [SD], 14 years). Three hundred eighteen patients (79%) had epithelial tumors. Twenty-five patients (6%) had positive lymph nodes. The mean peritoneal cancer index was 20. One hundred eighty-seven patients (46%) had complete or near-complete cytoreduction. Three hundred seventy-two patients (92%) received HIPEC. One hundred twenty-seven patients (31%) had grades 3 to 4 complications. Nine patients (2%) died perioperatively. The mean length of hospital stay was 22 days (SD, 15 days). The overall median survival was 53 months (1 to 235 months), and 3- and 5-year survival rates were 60% and 47%, respectively. Four prognostic factors were independently associated with improved survival in the multivariate analysis: epithelial subtype (P < .001), absence of lymph node metastasis (P < .001), completeness of cytoreduction scores of CC-0 or CC-1 (P < .001), and HIPEC (P = .002).nnnCONCLUSIONnThe data suggest that CRS combined with HIPEC achieved prolonged survival in selected patients with DMPM.

Operative findings, early complications, and long-term survival in 456 patients with pseudomyxoma peritonei syndrome of appendiceal origin.

BACKGROUND: Pseudomyxoma peritonei syndrome is a clinical entity characterized by mucinous ascites usually originating from a perforated mucinous appendiceal tumor. Currently optimal therapy is considered complete macroscopic tumor removal (complete cytoreduction) combined with heated intraperitoneal chemotherapy. When complete cytoreduction is not achievable, major tumor debulking is undertaken. The long-term follow-up of patients undergoing surgery for perforated appendiceal tumors in a national pseudomyxoma center is reported. METHODS: Between March 1994 and July 2009, 456 patients with pseudomyxoma peritonei syndrome from perforated appendiceal tumors underwent surgery. The treatment strategy involved a combination of cytoreductve surgery aiming for macroscopic tumor removal, combined with hyperthermic intraperitoneal chemotherapy with mitomycin C. Where complete tumor removal was not possible, maximal tumor debulking was performed. Perioperative outcomes and predicted 5- and 10-year survival are reported. RESULTS: Overall 15 of 456 (3%) tumors were not resectable at laparotomy. Of the 441 patients who had resection, 289 (66%) had complete cytoreduction and 152 (34%) had major tumor debulking. Postoperative in-hospital mortality was 1.6% and grade 3/4 morbidity was 7%. The Kaplan-Meier method predicted 5- and 10-year overall survival of 69% and 57%, respectively. Five- and 10-year predicted survival was 87% and 74% for the 289 patients who had complete cytoreduction compared with 34% and 23% for the 152 who had major tumor debulking. CONCLUSION: Complete tumor removal was achieved in 289 of 441 (66%) patients with peritoneal dissemination from perforated appendiceal tumors with good long-term survival and probable cure in more than two-thirds.

Morbidity and Mortality With Cytoreductive Surgery and Intraperitoneal Chemotherapy: The Importance of a Learning Curve

Evidence for the efficacy of cytoreductive surgery, combined with hyperthermic intraperitoneal chemotherapy (HIPEC), in the treatment of peritoneal carcinomatosis is accumulating. Many centers around the world now have considerable experience of the complex techniques required to achieve complete cytoreduction with the administration of HIPEC. Procedure-related morbidity ranges from 12% to 67.6% and mortality from 0% to 9% in recent studies of cytoreductive surgery and HIPEC for pseudomyxoma peritonei. A number of specialized centers have studied the factors that influence perioperative complications and mortality and have demonstrated impressive reductions in morbidity and mortality over time. However, for this treatment to be accepted as standard of care, teams undertaking this treatment strategy must aim to minimize morbidity and mortality by learning from the experience of established centers and using the “global learning curve.”

Pathology and prognosis in pseudomyxoma peritonei: a review of 274 cases.

Aims The classification of abdominal mucinous neoplasia is a controversial area. In 2010, WHO published a classification which divides pseudomyxoma peritonei (PMP) into low and high grades. The aim of the authors was to correlate this classification with the prognosis and site of primary neoplasm. Methods The authors reviewed 274 patients with PMP who had undergone surgery at a single institution and classified them according to WHO criteria. The findings were correlated with clinical information and survival data. Results PMP was low grade in 78% of patients and high grade in 22%. The appendix accounted for 94% of lesions, and the most common primary tumour was a low grade appendiceal mucinous neoplasm. Colorectal primaries were more likely to be associated with high grade PMP. There was an excellent correlation between the grade of the PMP and the primary neoplasm; only two cases showed discordant morphology: both were high grade appendiceal adenocarcinomas that were associated with low grade PMP. Nodal metastases were more likely in high grade lesions, but there was no significant difference in the rate of parenchymal organ invasion between low grade and high grade. Low grade morphology was associated with significantly longer survival than high grade (overall 5-year survival of 63% for low grade and 23% for high grade). Conclusions Categorisation as either low grade or high grade by WHO criteria correlates with prognosis. The grade of the PMP is generally consistent with the grade of the primary neoplasm. Colorectal primaries are more likely to be associated with high grade PMP.

Cytoreductive surgery in combination with hyperthermic intraperitoneal chemotherapy improves survival in patients with colorectal peritoneal metastases compared with systemic chemotherapy alone.

Background:Colorectal cancer peritoneal metastasis (CPM) confers an exceptionally poor prognosis, and traditional treatment involving systemic chemotherapy (SC) is largely ineffective. Cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) is increasingly advocated for selected patients with CPM; however, opinions are divided because of the perceived lack of evidence, high morbidity, mortality, and associated costs for this approach. As there is no clear consensus, the aim of this study was to compare outcomes following CRS+HIPEC vs SC alone for CPM using meta-analytical methodology, focusing on survival outcomes. Secondary outcomes assessed included morbidity, mortality, quality of life (QOL), and health economics (HE).Methods:An electronic literature search was conducted to identify studies comparing survival following CRS+HIPEC vs SC for CPM. The odds ratio (OR) was calculated using the Mantel–Haenszel method with corresponding 95% confidence intervals (CI) and P-values. Heterogeneity was examined using the Q-statistic and quantified with I2. The fixed-effect model (FEM) was used in the absence of significant heterogeneity. For included studies, 2- and 5-year survival was compared for CRS+HIPEC vs SC alone.Results:Four studies (three case–control, one RCT) provided comparative survival data for patients undergoing CRS+HIPEC (n=187) vs SC (n=155) for CPM. Pooled analysis demonstrated superior 2-year (OR 2.78; 95% CI 1.72–4.51; P=0.001) and 5-year (OR 4.07; 95% CI 2.17–7.64; P=0.001) survival with CRS+HIPEC compared with SC. Mortality ranged from 0 to 8%. No data were available for the assessment of QOL or HE.Conclusions:Although limited by between-study heterogeneity, the data support the assertion that in carefully selected patients, multimodal treatment of CPM with CRS+HIPEC has a highly positive prognostic impact on medium- and long-term survival compared with SC alone. There is a paucity of comparative data available on morbidity, QOL, and HE.

Complete cytoreduction for pseudomyxoma peritonei is optimal but maximal tumor debulking may be beneficial in patients in whom complete tumor removal cannot be achieved.

BACKGROUND: Pseudomyxoma peritonei is a diffuse peritoneal malignancy that generally originates form a perforated appendiceal tumor. Optimal treatment requires extensive surgical resection to achieve complete cytoreduction combined with hyperthermic intraperitoneal chemotherapy. In a proportion of patients this is impossible, in particular, owing to extensive irresectable small-bowel involvement. There is ongoing debate as to the role of maximal tumor debulking in such cases. OBJECTIVE:u2002 The aim of this study was to assess the outcomes of patients who underwent major tumor debulking for pseudomyxoma peritonei of appendiceal origin and to compare outcomes with patients who had complete cytoreduction during the same period. DESIGN: This is a retrospective study. SETTINGS: This investigation was conducted at a tertiary referral center for peritoneal surface malignancy. PATIENTS: A prospective database of 953 consecutive patients with peritoneal malignancy undergoing surgery at a UK national referral center between 1994 and 2012 was analyzed. Of these patients, 748 (78%) had surgery for pseudomyxoma peritonei of appendiceal origin. MAIN OUTCOME MEASURES: Survival, morbidity, and mortality in both groups were compared. Univariate and multivariate analyses were performed to identify negative prognostic factors in the group that underwent major tumor debulking. RESULTS: Complete cytoreductive surgery was achieved in 543/748 (73%) patients, and 205 (27%) had maximal tumor debulking. Median age was 56 years (172 (31.7%) men) in the complete cytoreductive surgery group and 59 years (108 (52.7%) men) in the maximal tumor debulking group. Overall survival at 3, 5, and 10 years was 90%, 82%, and 64% in the complete cytoreductive group and 47%, 30%, and 22% in the maximal tumor debulking group. The median survival in the maximal tumor debulking group was 32.8 months (95% CI, 24.1–41.5). LIMITATIONS: The retrospective analysis of prospective data was a limitation of this study. CONCLUSIONS: Maximal tumor debulking may help patients with pseudomyxoma peritonei in whom complete cytoreduction cannot be achieved with almost half alive at 3 years with long-term survival in some.

Primary peritoneal serous carcinoma treated by cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy. A multi-institutional study of 36 patients

AIMnPrimary peritoneal serous carcinoma (PPSC) is a rare condition, histologically identical to ovarian serous carcinoma and often diagnosed at late stage. There is not any standardized treatment for PPSC. A retrospective multicentric study was performed in French speaking centers to evaluate cytoreduction surgery and Hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinomatosis from different origins. The manuscripts aim was to study the particular population with PPSC.nnnMETHODSnBetween September 1997 and July 2007, 36 patients with PPSC from 9 institutions underwent 39 procedures.nnnRESULTSnMortality and morbidity rates were 5.6% and 20.6% respectively. The overall survival at 1, 3 and 5 years are respectively 93.6, 71.5 and 57.4%. The median overall survival was not reached. By univariate analysis, the only factor that had prognostic value was PCI (p = 0.03).nnnCONCLUSIONSnThe therapeutic approach combining cytoreductive surgery with HIPEC may achieve long-term survival in patients with PPSC.

Cytoreductive surgery and intraperitoneal chemotherapy for colorectal peritoneal metastases

AIMnTo systematically review the available evidence regarding cytoreductive surgery (CRS) and intraperitoneal chemotherapy (IPC) for colorectal peritoneal metastases (CPM).nnnMETHODSnAn 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.nnnRESULTSnTwenty 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.nnnCONCLUSIONnThe available evidence presented in this review indicates that enhanced survival times can be achieved for CPM after combined treatment with CRS and IPC.

Dukes C colorectal cancer: is the metastatic lymph node ratio important?

PurposeAlthough the regional lymph node status is essential for staging of colorectal cancer, the importance of the total number of collected nodes remains controversial. Our aim was to examine the impact of the metastatic lymph node ratio (LNR) on the survival of patients with Dukes C colorectal cancer.MethodsAll patients with Dukes C histology were selected from a prospectively collected database of all colorectal cancers resected between 1997 and 2007 at our institution. Demographic, histopathological and adjuvant treatment data were collected. The total number of positive lymph nodes was divided by the total number of lymph nodes examined to calculate the LNR. Patients were categorised into LNR groups 1 to 5 according to cut-off points: ≤0.1, 0.21, 0.36, 0.6 and ≥0.61. Survival from the date of operation was calculated using Kaplan–Meier estimates. Multivariate analysis was performed to identify those factors influencing survival.ResultsOf 1,098 patients who underwent colorectal cancer resections, 41% were staged as Dukes C. Sixty-four percent of patients received chemotherapy. The median number of lymph nodes harvested and positive for tumour were 11 (range 1–52) and 4 (range 1–28), respectively. In patients who received chemotherapy, 5-year survival was 69.3% for LNR 1 and 23.6% for LNR 5. When no chemotherapy was given, the 5-year survival was 43.1% for LNR 1 and 8.7% for LNR 5.ConclusionsCurrent evaluation of positive lymph nodes may not accurately stage Dukes C colorectal cancer. The assessment of the LNR is a useful prognostic method in this heterogenous group of patients.

Respect for the Laparoscopic Port Site: Lessons in Diagnosis, Management, and Prevention of Port-Site Hernias Following Laparoscopic Colorectal Surgery

AIMnThe aim of this study was to review the incidence, presentation, diagnosis, and management of early port-site hernias (PSHs) in a single consultant surgeons laparoscopic colorectal practice.nnnMETHODnThis work comprised a review of a prospectively maintained database to identify patients with a early PSH, with a subsequent review of the case notes.nnnRESULTSnOverall, 401 laparoscopic colorectal procedures over a 64-month period were reviewed. The median age was 64 years (range, 18-95), and 54% were female. The incidence of early PSH was 0.75% (3/401) and occurred in port sites greater than 5 mm in size. In each case, a computed tomography scan was required for diagnosis and return to theater was necessary to repair the defect. In all patients, this complication resulted in considerable increase in postoperative stay with associated interventions.nnnCONCLUSIONSnAwareness of the need to close the fascia in all ports over 5 mm, and the techniques available to do so, may reduce the incidence and decrease the morbidity associated with this potentially fatal complication associated with laparoscopic colorectal surgery.