Prognostic Factors of Survival in Repeat Liver Resection for Recurrent Colorectal Metastases: Review of Sixty-Two Cases Treated at a Single Institution

PURPOSE: Liver metastases develop in 50 percent of patients with colorectal carcinoma. Recurrent liver disease is usual. Repeat liver resection remains the only curative treatment. The aim of this study was to review our data on repeat hepatectomy and to analyze potential prognostic factors of survival.METHOD: Patients who underwent repeat liver resection for metastases of colorectal carcinoma between January 1992 and August 2007 were identified from a prospective database and their medical records were analyzed. RESULTS: Of 62 patients who underwent a second hepatectomy, 15 underwent a third hepatectomy, and two underwent a fourth hepatectomy. There was no perioperative mortality. Morbidity was less than 20 percent for the first and second hepatectomies. Overall 5-year survival rate after first hepatectomy was 40 percent. Univariate analysis identified three risk factors confirmed by log-rank test and multivariate Cox regression analysis: serum carcinoembryonic antigen concentrations >5 ng/ml at first hepatectomy (HR = 2.265; CI = 1.140-4.497; P = 0.020), anatomic resection (HR = 2.124; CI = 1.069-4.218; P = 0.031), and tumors ≥3 cm at the second resection (HR = 2.039; CI = 1.013-4.103; P = 0.046). CONCLUSION: Our study shows that repeat hepatectomy for liver metastases of colorectal carcinoma may be performed with low mortality and morbidity. Preoperative concentration of carcinoembryonic antigen at first hepatectomy, tumor size, and type of anatomic resection are independent prognostic factors

Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy

BACKGROUND: Peritoneal carcinomatosis (PC) from gastric cancer has long been regarded a terminal disease with a short median survival. New locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved and suggest improved survival. MATERIALS AND METHODS: A retrospective multicentric study was performed in French-speaking centers to evaluate the toxicity and the principal prognostic factors in order to identify the best indications. All patients had cytoreductive surgery and PIC: hyperthermic intraperitoneal chemotherapy (HIPEC) and/or early postoperative intraperitoneal chemotherapy (EPIC). RESULTS: The study included 159 patients from 15 institutions between February 1989 and August 2007. The median follow-up was 20.4 months. HIPEC was the PIC used for 150 procedures. Postoperative mortality and grade 3-4 morbidity rates were 6.5 and 27.8%, respectively. By multivariate analysis, the institution had a significant influence on toxicity. The overall median survival was 9.2 months and 1-, 3-, and 5-year survival rates were 43, 18, and 13%, respectively. The only independent prognostic indicator by multivariate analysis was the completeness of cytoreductive surgery. For patients treated by complete cytoreductive surgery, the median survival was 15 months with a 1-, 3-, and 5-year survival rate of 61, 30, and 23%, respectively. CONCLUSIONS: The therapeutic approach combining cytoreductive surgery with PIC for patients with gastric carcinomatosis may achieve long-term survival in a selected group of patients (limited and resectable PC). The high mortality rate underlines this necessarily strict selection that should be reserved to experienced institutions involved in the management of PC and gastric surgery

Cancer cachexia: Measured and predicted resting energy expenditures for nutritional needs evaluation

ObjectiveCancer cachexia is associated with weight loss, poor nutritional status, and systemic inflammation. Accurate nutritional support for patients is calculated on resting energy expenditure (REE) measurement or prediction. The present study evaluated the agreement between measured and predicted REE (mREE and pREE, respectively) and the influence of acute phase response (APR) on REE. Methods Thirty-six patients with cancer were divided into weight-stable (WS; weight loss <2%) and weight-losing (WL; weight loss >5%) patients. Measured REE was measured by indirect calorimetry and adjusted for fat-free mass (FFM). The Bland-Altman approach was used to assess the agreement between mREE and pREE from the Harris-Benedict equations (HBE). Blood levels of C-reactive protein were assessed. Results There was no difference in mREE between groups (WS 1677 ± 273, WL 1521 ± 305) even when mREE was adjusted for FFM (WS 1609 ± 53, WL 1589 ± 53). In WL patients, FFM-adjusted REE correlated with blood C-reactive protein levels (r = 0.471, P = 0.048). HBEs tend to underestimate REE in both groups. Conclusion WL and WS patients with cancer had similar REEs but were different in terms of APR. APR could contribute to weight loss through enhancing REE. In a clinical context, HBE was in poor agreement with mREE in both groups

Use of FDG-PET/CT for peritoneal carcinomatosis before hyperthermic intraperitoneal chemotherapy

BACKGROUND: Peritoneal carcinomatosis (PC) is associated with a very poor prognosis. Complete cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy has been shown to improve survival rates of PC. However, this treatment is beneficial for patients if the complete cytoreductive surgery is macroscopically completed before implementing hyperthermic intraperitoneal chemotherapy. Even so, a strict selection of patients is of fundamental importance because of the invasive nature of the intervention. The aim of this study was to assess the performance of FDG-PET/CT examinations for the diagnosis and evaluation of the extent of PC. METHODS: A retrospective analysis was conducted on 28 consecutive patients with suspected PC, scheduled for a complete cytoreductive surgery and hyperthermic intraperitoneal chemotherapy, and who underwent an FDG-PET/CT examination. We compared the results of PET examinations with histological and intraoperative findings. The extent of PC was assessed precisely using a simplified \u27peritoneal cancer index\u27, within the three modalities (PET, surgery and histology). RESULTS: Of 28 patients, 23 had histological PC. The sensitivity and specificity of the PET examination for the diagnosis of PC were, respectively, 82 and 100%. Even if the extent of PC was underestimated by PET, there was a good correlation when compared with histology and intraoperative results. CONCLUSION: PET presented a good performance level in the diagnosis and evaluation of the extent of PC. PET/CT examinations could be useful to avoid unnecessary surgery

Impact of 18F-fluoro-deoxy-glucose positron emission tomography (FDG-PET) in recurrent colorectal cancer

Purpose: The aim of the study was to evaluate the diagnostic performance, the prognosis factors and the therapeutic impact of 18F-FDG positron emission tomography (FDG-PET) in the detection of recurrent colorectal cancers. Methods: Sixty PET/CT with 18F-FDG and CT were performed in 52 patients, at the Paul Papin cancer center between 2003 and 2005, following suspicion of colorectal cancer relapse. The FDG-PET impact on the clinical management was studied by examination of multidisciplinary concertations results. Survival analysis were realized with a mean follow up of 2.2 years. Results: Recurrence was confirmed for 50 explorations by histologic (n = 32), radiologic (n = 14) or clinical (n = 4) findings. Twenty patients died during the time of the study. On a patient based analysis, FDG-PET sensitivity, specificity and overall accuracy were 90, 90, 90% respectively compared with 74, 50 and 70% for CT. FDG-PET changed the clinical management in 18 cases (30%). A positive FDG-PET signal, more than one hepatic lesion, more than two lymph node lesions detected on FDG-PET and more than two hepatic lesions on CT were characterized as bad prognostic factors for survival. Multivariate analysis showed that the only independent bad prognostic factor was the FDG-PET detection of more than two liver lesions. Conclusion: These results confirmed the important impact of FDG-PET in the clinical management of patients with a suspected recurrence of colorectal cancer

Synthetic biology approaches in drug discovery and pharmaceutical biotechnology

Synthetic biology is the attempt to apply the concepts of engineering to biological systems with the aim to create organisms with new emergent properties. These organisms might have desirable novel biosynthetic capabilities, act as biosensors or help us to understand the intricacies of living systems. This approach has the potential to assist the discovery and production of pharmaceutical compounds at various stages. New sources of bioactive compounds can be created in the form of genetically encoded small molecule libraries. The recombination of individual parts has been employed to design proteins that act as biosensors, which could be used to identify and quantify molecules of interest. New biosynthetic pathways may be designed by stitching together enzymes with desired activities, and genetic code expansion can be used to introduce new functionalities into peptides and proteins to increase their chemical scope and biological stability. This review aims to give an insight into recently developed individual components and modules that might serve as parts in a synthetic biology approach to pharmaceutical biotechnology