Alexander Kerscher

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

BackgroundWe 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.MethodsOne 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.ResultsMedian 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].ConclusionA 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

BackgroundCytoreductive 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.MethodsFrom 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.ResultsThere 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.ConclusionsRecent 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.

Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis: Role of Heat Shock Proteins and Dissecting Effects of Hyperthermia

BackgroundIn 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.MethodsTumor 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.ResultsDifferently 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.ConclusionsTherapeutic 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.

Multimodal therapy in treatment of rectal cancer is associated with improved survival and reduced local recurrence - a retrospective analysis over two decades

BackgroundThe management of rectal cancer (RC) has substantially changed over the last decades with the implementation of neoadjuvant chemoradiotherapy, adjuvant therapy and improved surgery such as total mesorectal excision (TME). It remains unclear in which way these approaches overall influenced the rate of local recurrence and overall survival.MethodsClinical, histological and survival data of 658 out of 662 consecutive patients with RC were analyzed for treatment and prognostic factors from a prospectively expanded single-institutional database. Findings were then stratified according to time of diagnosis in patient groups treated between 1993 and 2001 and 2002 and 2010.ResultsThe study population included 658 consecutive patients with rectal cancer between 1993 and 2010. Follow up data was available for 99.6% of all 662 treated patients. During the time period between 2002 and 2010 significantly more patients underwent neoadjuvant chemoradiotherapy (17.6% vs. 60%) and adjuvant chemotherapy (37.9% vs. 58.4%). Also, the rate of reported TME during surgery increased. The rate of local or distant metastasis decreased over time, and tumor related 5-year survival increased significantly with from 60% to 79%.ConclusionIn our study population, the implementation of treatment changes over the last decade improved the patient’s outcome significantly. Improvements were most evident for UICC stage III rectal cancer.

Single-port laparoscopic cholecystectomy with the x-cone: a feasibility study in 9 pigs.

Objective: Virtually any port system for single-port laparoscopic surgery is for single usage only. The aim of this study was to trial the novel and completely reusable port X-Cone in order to perform a cholecystectomy by one infraumbilical incision. Methods: Single access cholecystectomies were performed in 9 anesthetized domestic pigs in nonsurvival studies. Only one infraumbilical incision was performed for placing the reusable, multichannel steel port system. A newly developed angulated forceps was used besides regularly used instruments in laparoscopic surgery. Results: The gallbladder was successfully removed in 9 pigs. At postmortem examination, the clips placed on the cystic duct and the cystic artery. No bile leakage was found at the operative field. Conclusion: Single-port cholecystectomy with the reusable X-Cone single-port system is safe and feasible. No additional incisions were needed. The system is ergonomically designed, easy to handle, and the learning curve for cholecystectomy is steep.

Early-Elective Single-Incision Laparoscopic Sigmoidectomy for Perforated Diverticulitis Using a Totally Reusable Single-Port Device:

Background: Single-port access (SPA) is an emerging concept in minimally invasive colorectal surgery. The authors report their experience using SPA sigmoidectomy as an early-elective approach to complicated diverticulitis with paracolic abscess. Methods: Between September 2009 und April 2010, 4 patients underwent SPA sigmoidectomy for Hinchey-I diverticulitis using the reusable X-Cone device. Results: After a median time of antibiotic treatment of 8 days, SPA sigmoidectomy was performed successfully in all patients. The median operative time was 200 minutes (range, 187-221 minutes). No intraoperative or postoperative complications were recorded; the median postoperative hospital stay was 7 days (range, 5-7 days). No incisional hernias were observed at midterm follow-up (median, 11.5 months; range, 8-14 months). Conclusions: When performed by an experienced laparoscopic surgeon, early-elective SPA sigmoidectomy is a feasible and safe approach to complicated diverticulitis. The reusability of the X-Cone device ensures that the costs of the procedure are not high.

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

Background and ObjectiveThis study evaluates whether Computer Tomography is an effective procedure for preoperative staging of patients with Peritoneal Carcinomatosis.MethodA 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.ResultsResults 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%).ConclusionComputer 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 tumors accurate extent.

Current status and future directions: management of colon cancer with peritoneal dissemination

Colorectal cancer is one of the most common cancers worldwide, and although it carries a favorable prognosis when detected at early stages, it is associated with limited survival when metastatic disease is present. Modern systemic therapy has improved median survival in those patients with hematogenous dissemination, but the role of these newer combinations of cytotoxic chemotherapy and biological agents remains undefined in patients with peritoneal carcinomatosis. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy have resulted in long-term good outcomes for patients whose carcinomatosis can be completely removed, but offers no advantage over supportive care for those patients with incomplete tumor removal. At the present time, we lack proven therapeutic strategies on how to treat a patient newly diagnosed with peritoneal carcinomatosis of colorectal origin. A large Phase III multi-institutional trial is being developed to address these issues, and will need full collaboration between medical and surgical oncologists.