Incidence, time course and independent risk factors for metachronous peritoneal carcinomatosis of gastric origin--a longitudinal experience from a prospectively collected database of 1108 patients.

BACKGROUND: Comprehensive evidence on the incidence, time course and independent risk factors of metachronous peritoneal carcinomatosis (metaPC) in gastric cancer patients treated with curative intent in the context of available systemic combination chemotherapies is lacking. METHODS: Data from a prospectively collected single-institutional Center Cancer Registry with 1108 consecutive patients with gastric adenocarcinoma (GC), clinical, histological and survival data were analyzed for independent risk factors and prognosis with focus on the development of metaPC. Findings were then stratified to the time periods of treatment with surgery alone, 5-Fluorouracil-only and contemporary combined systemic perioperative chemotherapy strategies, respectively. RESULTS: Despite R0 D2 gastrectomy (n = 560), 49.6% (±5.4%) of the patients were diagnosed with tumour recurrence and 15.5% (±1.8%) developed metaPC after a median time of 17.7 (15.1-20.3) months after surgery resulting in a tumour related mortality of 100% with a median survival of 3.0 months (2.1 - 4.0). Independent risk factors for the development of metaPC were serosa positive T-category, nodal positive-status, signet cell and undifferentiated gradings (G3/G4). Contemporary systemic combination chemotherapy did not improve the incidence and prognosis of metaPC (p = 0.54). CONCLUSIONS: Despite significant improvements in the overall survival for the complete cohort with gastric cancer over time, those patients with metaPC did not experience the same benefits. The lack of change in the incidence, and persistent poor prognosis of metaPC after curative surgery expose the need for further prevention and/or improved treatment options for this devastating condition.

Hyperthermic intraperitoneal chemotherapy in patients with peritoneal carcinomatosis: role of heat shock proteins and dissecting effects of hyperthermia.

BACKGROUND: In patients with isolated peritoneal carcinomatosis (PC) of gastrointestinal cancer, hyperthermic intraperitoneal chemotherapy (HIPEC) represents a promising treatment option integrated into multimodal concepts. Heat shock proteins (HSP) seem to play a major role in cellular stress during HIPEC therapy. We analyzed differentially hyperthermic conditions and HSPs responsible for cell stress-mediated repair mechanisms in tumor tissues from patients who underwent HIPEC therapy and in an in vitro hyperthermic model. METHODS: Tumor tissues from our patient cohort with isolated PC were selected for further analysis when representative material was available before and after HIPEC therapy. To further dissect the role of HSPs under conditions of hyperthermia, gene and protein expression was additionally determined, together with cellular apoptosis and proliferation in human HT-29 colon cancer cells. RESULTS: Differently up-regulated HSP70/72 and HSP90 gene and protein expression was found in all investigated patient tumors. In vitro studies confirmed observations from clinical tumor analysis as underlying HSP-mediated cell stress mechanisms. Moreover, results from proliferation and apoptosis assays combined with differentiated HSP expression analysis demonstrated the relevance of preselecting specific target temperatures to achieve optimal toxic effects on remaining tumor cells in vivo. CONCLUSIONS: Therapeutic approaches like HIPEC to achieve antiproliferative and apoptosis-inducing cellular effects in patients with PC are negatively influenced by highly conserved HSP mechanisms in tumor cells. This study shows for the first time that specific hyperthermic conditions are necessary to be established to achieve optimal toxic effects on tumor cells during HIPEC therapy, a finding that opens potentially new therapeutic strategies.

Influence of modern systemic therapies as adjunct to cytoreduction and perioperative intraperitoneal chemotherapy for patients with colorectal peritoneal carcinomatosis: a multicenter study.

BACKGROUND: To evaluate the role of modern systemic therapies and its role as palliative or curative therapy for patients with colorectal peritoneal carcinomatosis with an emphasis on patient selection with the colorectal Peritoneal Surface Disease Severity Score (PSDSS). METHODS: From three specialized treatment centers, patients with colorectal peritoneal carcinomatosis were identified between December 1988 to December 2009 to receive best supportive care, standard, or modern systemic therapies. Intent was classified as palliative or curative (if treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy). Patients were stratified according to the PSDSS. Survival was estimated by the Kaplan-Meier method. RESULTS: Palliative and curative treatment achieved a median survival of 9 (95% confidence interval [95% CI] 5.9-12.8) and 38 (95% CI 30.2-45.2) months, respectively (P < 0.001). The type of chemotherapy in the palliative and curative group influenced outcome (P < 0.001, P = 0.011, respectively). In the palliative group, PSDSS I/II had a median survival of 24 (95% CI 15.6-32.6) and PSDSS III/IV had a median survival of 6 (95% CI 4.9-8.0) months (P < 0.001). In the curative group, PSDSS I/II had a median survival of 49 (95% CI 40.0-58.3) and PSDSS III/IV had a median survival of 31 (95% CI 20.4-40.9) months (P = 0.002). CONCLUSIONS: Modern systemic therapies were associated with improved outcome in patients with colorectal peritoneal carcinomatosis treated systemically alone or with cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Preoperative evaluation with the PSDSS may improve patient selection and optimize outcomes.

Optimizing of preoperative computed tomography for diagnosis in patients with peritoneal carcinomatosis.

BACKGROUND AND OBJECTIVE: This study evaluates whether Computer Tomography is an effective procedure for preoperative staging of patients with Peritoneal Carcinomatosis. METHOD: A sample of 37 patients was analyzed with contrast enhanced abdominal Computer Tomography, followed by surgical staging. All Computer Tomography scans were evaluated 3 times by 2 radiologists with one radiologist reviewing 2 times. The efficacy of Computer Tomography was evaluated using the Spearman correlation coefficient. Correlations were analyzed by abdominopelvic region to assess results of the Peritoneal Carcinomatosis Index (PCI) aggregating the 13 regions. Surgical findings were compared to radiological findings. RESULTS: Results indicate high correlations between the surgical and radiological Peritoneal Carcinomatosis Indices. Analyses of the intra-class correlation between the first and second reading of one radiologist suggest high intra-observer reliability. Correlations by abdominopelvic region show higher values in the upper and middle regions and relatively lower values in the lower regions and the small bowel (correlation coefficients range between 0.418 and 0.726, p < 0.010; sensitivities range between 50% and 96%; and specificities range between 62% and 100%). CONCLUSION: Computer Tomography represents an effective procedure in the preoperative staging of patients with PC. However, results by abdominopelvic region show lower correlation, therefore suggest lower efficacy. These results are supported by analyses of sensitivity and accuracy by lesion size. This suggests that Computer Tomography is an effective procedure for pre-operative staging but less for determining a tumor's accurate extent.

Evaluation of best supportive care and systemic chemotherapy as treatment stratified according to the retrospective peritoneal surface disease severity score (PSDSS) for peritoneal carcinomatosis of colorectal origin.

BACKGROUND: We evaluate the long-term survival of patients with peritoneal carcinomatosis (PC) treated with systemic chemotherapy regimens, and the impact of the of the retrospective peritoneal disease severity score (PSDSS) on outcomes. METHODS: One hundred sixty-seven consecutive patients treated with PC from colorectal cancer between years 1987-2006 were identified from a prospective institutional database. These patients either received no chemotherapy, 5-FU/Leucovorin or Oxaliplatin/Irinotecan-based chemotherapy. Stratification was made according to the retrospective PSDSS that classifies PC patients based on clinically relevant factors. Survival analysis was performed using the Kaplan-Meier method and comparison with the log-rank test. RESULTS: Median survival was 5 months (95% CI, 3-7 months) for patients who had no chemotherapy, 11 months (95% CI, 6-9 months) for patients treated with 5 FU/LV, and 12 months (95% CI, 4-20 months) for patients treated with Oxaliplatin/Irinotecan-based chemotherapy. Survival differed between patients treated with chemotherapy compared to those patients who did not receive chemotherapy (p = 0.026). PSDSS staging was identified as an independent predictor for survival on multivariate analysis [RR 2.8 (95%CI 1.5-5.4); p < 0.001]. CONCLUSION: A trend towards improved outcomes is demonstrated from treatment of patients with PC from colorectal cancer using modern systemic chemotherapy. The PSDSS appears to be a useful tool in patient selection and prognostication in PC of colorectal origin.

Morbidity and mortality of 109 consecutive cytoreductive procedures with hyperthermic intraperitoneal chemotherapy (HIPEC) performed at a community hospital.

BACKGROUND: Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (HIPEC) is playing an increasing role in the management of isolated peritoneal dissemination of gastrointestinal malignancies. Historically this surgery is associated with a high morbidity and mortality. Recognizing this, our study was developed to prospectively evaluate morbidity and mortality after cytoreductive surgery with HIPEC performed at a community hospital. METHODS: From January 19, 2005 to January 9, 2008, 109 consecutive patients successfully underwent cytoreductive surgery with HIPEC for peritoneal surface malignancies. All cases were performed by a single surgeon at a 323-bed community hospital. Using an institutional review board approved study we prospectively evaluated postoperative complications using the standard National Institutes of Health morbidity and mortality grading system. RESULTS: There was no 30-day or inpatient mortality. Overall grade III and IV morbidity was 30.2% (33 of 109 patients); 29.3% of the patients had at least one grade III complication, with the most common being postoperative anemia requiring a blood transfusion in 20 of the 109 patients (18.3%). Eight patients (7.3%) had wound infections, and three patients (2.7%) developed pneumonia. One patient required computerized tomography guided drainage of a pelvic abscess. There were 3 (2.7%) grade IV complications, with only one patient requiring reoperation. CONCLUSIONS: Recent studies at tertiary medical centers have shown acceptable morbidity and mortality with this procedure. Our study demonstrates that this procedure can be safely performed in the community setting as well if surgeons, other medical professionals, and ancillary caregivers have great experience in this procedure.

The importance of radiological controls of anastomoses after upper gastrointestinal tract surgery - a retrospective cohort study.

INTRODUCTION: This study was designed to analyze whether routine radiological controls of anastomoses in the upper gastrointestinal tract an early detection of anastomotic leaks. PATIENTS AND METHODS: 135 patients who underwent upper gastrointestinal tract surgery were retrospectively analyzed. Patients in the first group (n = 55) underwent routine radiological control of the anastomoses. In the second group (n = 80) the radiological control was only performed in case of clinical symptoms or signs of anastomotic leaks. RESULTS: The incidence of anastomotic leaks in the patients seen by us was 5.2%, equivalent to 7 of 135 patients In Group 1 leaks were seen in 4 of 55 patients (7,2%) in group 2 leaks were seen in 3 of 80 (3,8%). The radiological control of the anastomoses with contrast swallow showed the leakage in two cases. Twice the results were false negative. The sensitivity of computed tomography was 100%. DISCUSSION: Routine radiological control of anastomoses with contrast swallow only has low sensitivity. This procedure should not be performed routinely any more.The radiological control should be used in cases with signs of anastomotic leakage or with postoperatively impaired gastrointestinal passage.