Joerg Pelz

Early- and Long-Term Outcome Data of Patients With Pseudomyxoma Peritonei From Appendiceal Origin Treated by a Strategy of Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy

PURPOSE Pseudomyxoma peritonei (PMP) originating from an appendiceal mucinous neoplasm remains a biologically heterogeneous disease. The purpose of our study was to evaluate outcome and long-term survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) consolidated through an international registry study. PATIENTS AND METHODS A retrospective multi-institutional registry was established through collaborative efforts of participating units affiliated with the Peritoneal Surface Oncology Group International. RESULTS Two thousand two hundred ninety-eight patients from 16 specialized units underwent CRS for PMP. Treatment-related mortality was 2% and major operative complications occurred in 24% of patients. The median survival rate was 196 months (16.3 years) and the median progression-free survival rate was 98 months (8.2 years), with 10- and 15-year survival rates of 63% and 59%, respectively. Multivariate analysis identified prior chemotherapy treatment (P < .001), peritoneal mucinous carcinomatosis (PMCA) histopathologic subtype (P < .001), major postoperative complications (P = .008), high peritoneal cancer index (P = .013), debulking surgery (completeness of cytoreduction [CCR], 2 or 3; P < .001), and not using HIPEC (P = .030) as independent predictors for a poorer progression-free survival. Older age (P = .006), major postoperative complications (P < .001), debulking surgery (CCR 2 or 3; P < .001), prior chemotherapy treatment (P = .001), and PMCA histopathologic subtype (P < .001) were independent predictors of a poorer overall survival. CONCLUSION The combined modality strategy for PMP may be performed safely with acceptable morbidity and mortality in a specialized unit setting with 63% of patients surviving beyond 10 years. Minimizing nondefinitive operative and systemic chemotherapy treatments before definitive cytoreduction may facilitate the feasibility and improve the outcome of this therapy to achieve long-term survival. Optimal cytoreduction achieves the best outcomes.

Evaluation of a peritoneal surface disease severity score in patients with colon cancer with peritoneal carcinomatosis.

Systemic therapy and cytoreduction (CRS) with hyperthermic intra‐peritoneal chemotherapy (HIPEC) may benefit selected patients with carcinomatosis from colon cancer (PC). This study presents the results of a consecutive series of patients evaluated under a single strategy.

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.

Summary of current therapeutic options for peritoneal metastases from colorectal cancer

Peritoneal metastases remain an under addressed problem for which this review serves to investigate the efficacy of systemic chemotherapy and radical surgical treatments in this disease entity.

The American Society of Peritoneal Surface Malignancies evaluation of HIPEC with Mitomycin C versus Oxaliplatin in 539 patients with colon cancer undergoing a complete cytoreductive surgery

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are gaining acceptance as treatment for selected patients with colorectal cancer with peritoneal carcinomatosis (CRCPC). Tremendous variations exist in the HIPEC delivery.

American Society of peritoneal surface malignancies opinion statement on defining expectations from cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer

JESUS ESQUIVEL, MD,* POMPILIU PISO, MD, VIC VERWAAL, MD, THOMAS BACHLEITNER-HOFMANN, MD, OLIVIER GLEHEN, MD, SANTIAGO GONZÁLEZ-MORENO, MD, MARCELLO DERACO, MD, JOERG PELZ, MD, RICHARD ALEXANDER, MD, AND GABRIEL GLOCKZIN, MD Department of Surgical Oncology, Cancer Treatment Centers of America, Philadelphia, Pennsylvania Division of Surgical Oncology, Hospital Barmherzige, Regensburg, Germany National Cancer Institute, Amsterdam, The Netherlands Vienna University Hospital, Vienna, Australia Department of Surgical Oncology, Centre Hospitalier Lyon-Sud, Pierre-Benite, France Department of Surgical Oncology, MD Anderson Cancer Center, Madrid, Spain Department of Surgery, National Cancer Institute, Milan, Italy Department of Surgery, University of Wuerzburg, Wuerzburg, Germany Department of Surgical Oncology, University of Maryland, Baltimore, Maryland Department of Surgical Oncology, Regensburg University Hospital, Regensburg, Germany

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.

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.

Surgery for colorectal peritoneal carcinomatosis

Abstract Peritoneal carcinomatosis occurs in patients with advanced gastrointestinal and gynecological malignancies and also in patients who experience recurrence after treatment failure of the primary tumor. Malignant disease in the peritoneal cavity is a morbid and significant predictor of a diminished survival in a cancer patient. Systemic chemotherapy alone will not be adequate to palliate or treat patients with peritoneal carcinomatosis. Cytoreductive surgery is a new surgical technique that is performed using peritonectomy procedures to allow total eradication of peritoneal tumors. Intraperitoneal chemotherapy regimens such as intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC) and early postoperative intraperitoneal chemotherapy (EPIC) are effective adjuvant treatment to treat the minimal residual disease after cytoreductive surgery to reduce the risk of locoregional recurrence. A substantial body of evidence available in the current literature has documented the survival benefits of combining cytoreductive surgery and intraperitoneal chemotherapy to treat a previously fatal phase of malignancy. This review provides a summary of the developments in the understanding and treatment of peritoneal surface malignancy from colorectal cancer.

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.