Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy versus cytoreductive surgery alone for colorectal peritoneal metastases (PRODIGE 7): a multicentre, randomised, open-label, phase 3 trial.

BACKGROUND: The addition of hyperthermic intraperitoneal chemotherapy (HIPEC) to cytoreductive surgery has been associated with encouraging survival results in some patients with colorectal peritoneal metastases who were eligible for complete macroscopic resection. We aimed to assess the specific benefit of adding HIPEC to cytoreductive surgery compared with receiving cytoreductive surgery alone. METHODS: We did a randomised, open-label, phase 3 trial at 17 cancer centres in France. Eligible patients were aged 18-70 years and had histologically proven colorectal cancer with peritoneal metastases, WHO performance status of 0 or 1, a Peritoneal Cancer Index of 25 or less, and were eligible to receive systemic chemotherapy for 6 months (ie, they had adequate organ function and life expectancy of at least 12 weeks). Patients in whom complete macroscopic resection or surgical resection with less than 1 mm residual tumour tissue was completed were randomly assigned (1:1) to cytoreductive surgery with or without oxaliplatin-based HIPEC. Randomisation was done centrally using minimisation, and stratified by centre, completeness of cytoreduction, number of previous systemic chemotherapy lines, and timing of protocol-mandated systemic chemotherapy. Oxaliplatin HIPEC was administered by the closed (360 mg/m2) or open (460 mg/m2) abdomen techniques, and systemic chemotherapy (400 mg/m2 fluorouracil and 20 mg/m2 folinic acid) was delivered intravenously 20 min before HIPEC. All individuals received systemic chemotherapy (of investigators' choosing) with or without targeted therapy before or after surgery, or both. The primary endpoint was overall survival, which was analysed in the intention-to-treat population. Safety was assessed in all patients who received surgery. This trial is registed with ClinicalTrials.gov, NCT00769405, and is now completed. FINDINGS: Between Feb 11, 2008, and Jan 6, 2014, 265 patients were included and randomly assigned, 133 to the cytoreductive surgery plus HIPEC group and 132 to the cytoreductive surgery alone group. After median follow-up of 63·8 months (IQR 53·0-77·1), median overall survival was 41·7 months (95% CI 36·2-53·8) in the cytoreductive surgery plus HIPEC group and 41·2 months (35·1-49·7) in the cytoreductive surgery group (hazard ratio 1·00 [95·37% CI 0·63-1·58]; stratified log-rank p=0·99). At 30 days, two (2%) treatment-related deaths had occurred in each group.. Grade 3 or worse adverse events at 30 days were similar in frequency between groups (56 [42%] of 133 patients in the cytoreductive surgery plus HIPEC group vs 42 [32%] of 132 patients in the cytoreductive surgery group; p=0·083); however, at 60 days, grade 3 or worse adverse events were more common in the cytoreductive surgery plus HIPEC group (34 [26%] of 131 vs 20 [15%] of 130; p=0·035). INTERPRETATION: Considering the absence of an overall survival benefit after adding HIPEC to cytoreductive surgery and more frequent postoperative late complications with this combination, our data suggest that cytoreductive surgery alone should be the cornerstone of therapeutic strategies with curative intent for colorectal peritoneal metastases. FUNDING: Institut National du Cancer, Programme Hospitalier de Recherche Clinique du Cancer, Ligue Contre le Cancer.

Second-look surgery plus hyperthermic intraperitoneal chemotherapy versus surveillance in patients at high risk of developing colorectal peritoneal metastases (PROPHYLOCHIP-PRODIGE 15): a randomised, phase 3 study.

BACKGROUND: Diagnosis and treatment of colorectal peritoneal metastases at an early stage, before the onset of signs, could improve patient survival. We aimed to compare the survival benefit of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC), with surveillance, in patients at high risk of developing colorectal peritoneal metastases. METHODS: We did an open-label, randomised, phase 3 study in 23 hospitals in France. Eligible patients were aged 18-70 years and had a primary colorectal cancer with synchronous and localised colorectal peritoneal metastases removed during tumour resection, resected ovarian metastases, or a perforated tumour. Patients were randomly assigned (1:1) to surveillance or second-look surgery plus oxaliplatin-HIPEC (oxaliplatin 460 mg/m2, or oxaliplatin 300 mg/m2 plus irinotecan 200 mg/m2, plus intravenous fluorouracil 400 mg/m2), or mitomycin-HIPEC (mitomycin 35 mg/m2) alone in case of neuropathy, after 6 months of adjuvant systemic chemotherapy with no signs of disease recurrence. Randomisation was done via a web-based system, with stratification by treatment centre, nodal status, and risk factors for colorectal peritoneal metastases. Second-look surgery consisted of a complete exploration of the abdominal cavity via xyphopubic incision, and resection of all peritoneal implants if resectable. Surveillance after resection of colorectal cancer was done according to the French Guidelines. The primary outcome was 3-year disease-free survival, defined as the time from randomisation to peritoneal or distant disease recurrence, or death from any cause, whichever occurred first, analysed by intention to treat. Surgical complications were assessed in the second-look surgery group only. This study was registered at ClinicalTrials.gov, NCT01226394. FINDINGS: Between June 11, 2010, and March 31, 2015, 150 patients were recruited and randomly assigned to a treatment group (75 per group). After a median follow-up of 50·8 months (IQR 47·0-54·8), 3-year disease-free survival was 53% (95% CI 41-64) in the surveillance group versus 44% (33-56) in the second-look surgery group (hazard ratio 0·97, 95% CI 0·61-1·56). No treatment-related deaths were reported. 29 (41%) of 71 patients in the second-look surgery group had grade 3-4 complications. The most common grade 3-4 complications were intra-abdominal adverse events (haemorrhage, digestive leakage) in 12 (23%) of 71 patients and haematological adverse events in 13 (18%) of 71 patients. INTERPRETATION: Systematic second-look surgery plus oxaliplatin-HIPEC did not improve disease-free survival compared with standard surveillance. Currently, essential surveillance of patients at high risk of developing colorectal peritoneal metastases appears to be adequate and effective in terms of survival outcomes. FUNDING: French National Cancer Institute.

Intra-abdominal recurrence from colorectal carcinoma: Differences and similarities between local and peritoneal recurrence.

BACKGROUND: Peritoneal recurrences from colo-rectal cancer can be isolated (PR) or associated with local recurrences (LR). The purpose of this study was to analyze patterns and outcomes of LR and PR. METHODS: Analyze from a prospective database of 108 patients treated with CCS plus HIPEC at two cancer centers between 2008 and 2015. RESULTS: The population was divided into an LPR group (presence of LR with or without PR, n = 56) and a PR group (isolated PR, n = 52). The patients characteristics (age, sex, Charlson score, PCI) or perioperative treatments were comparable between the groups. The median number of resected organs for tumor involvement (respectively, 2 vs 1; p < 0.001), the percentage of patients with metastatic lymph nodes (LN+) from the resected specimen (respectively, 25% vs 7%; p = 0.016) and the mortality rate (respectively, 9% vs 0%; p = 0.023) were significantly higher in the LPR group. After a median follow-up of 32 (1-108) months, median overall survival was comparable between the two groups (respectively, 46 vs 42 months; p = 0.262). CONCLUSIONS: LR is associated with a higher incidence of organ invasion, LN involvement (25%) and postoperative mortality. Optimal surgical resection of LR with systematic lymphadenectomy of invaded organs seems mandatory.

Prolonged perioperative thoracic epidural analgesia may improve survival after cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for colorectal peritoneal metastases: A comparative study.

OBJECTIVE: To assess the effectiveness of prolonged perioperative thoracic epidural analgesia (PEA) on long term survival of patients who underwent a complete cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM). BACKGROUND: Grade III-IV morbidity affects long term outcomes after CRS and HIPEC. As compared with opioid administered via patient-controlled analgesia (PCA), PEA reduces morbidity. METHOD: From 2005 to 2016, 150 patients underwent CRS plus HIPEC with or without prolonged PEA. Clinical data and outcomes collected from prospective database were analyzed. Survival was assessed in terms of analgesic method using Kaplan-Meier plots and a propensity score. RESULTS: Patients 'characteristics of 59 patients in PCA group were comparable to those of 91 patients in PEA group, except for age, ASA score and fluid requirements, significantly more important in PEA group. Grade III-IV morbidity was 62.7% in PCA group compared with 36.3% in PEA group (p = 0.0015). Median overall survival (OS) of PEA group was 54.7 months compared to 39.5 months in PCA group (p = 0.0078). When adjusted on the covariates, using the propensity score, the PEA significantly improves OS [HR 0.40 (95% CI: 0.28-0.56)] (p < 0.0001) and disease free survival (DFS) [HR 0.61 (95% CI: 0.45-0.81] (p < 0.0007) CONCLUSIONS: In this retrospective study of patients who underwent a complete CRS and HIPEC for colorectal peritoneal metastases, the perioperative thoracic epidural analgesia prolonged for over 72 h reduced significantly the grade III-IV morbidity and may improve OS and DFS.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Peritoneal Carcinomatosis in the Elderly: A Case-Controlled, Multicenter Study.

OBJECTIVE: This study was designed to identify factors associated with morbidity and mortality in patients older than 70 years who underwent cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for peritoneal carcinomatosis (PC). BACKGROUND: Major surgery is associated with higher morbidity and mortality in elderly patients. For PC, CRS and HIPEC is the only current potential curative therapy, but the risks inherent to this patient population have called its benefits into question. METHODS: We retrospectively analyzed a multi-center database from 1989 to 2015. All patients who underwent CRS and HIPEC for PC were selected and patients older than 70 years were matched 1:4 with a younger cohort according to cancer origin, peritoneal cancer index (PCI), and completeness of cytoreduction. Major morbidity and mortality were analyzed. RESULTS: Of 2328 patients, 188 patients older than aged 70 years were matched with 704 younger patients. Patients older than aged 70 years demonstrated a higher American Society of Anesthesiologist score (≥ASA III 10.8 vs. 6.6 %, p = 0.008). There was no difference in overall 90-day morbidity (≥70: 45.7 % vs. <70: 44.5 %; p = 0.171); however, patients older than 70 years had significantly more cardiovascular complications (13.8 vs. 9.2 %, p = 0.044). Differences between the older and younger cohorts failed to reach significance for 90-day mortality (5.4 and 2.7 %, respectively; p = 0.052), and failure-to-rescue (11.6 and 6.1 %, respectively; p = 0.078). In multivariate analysis, PCI > 7 (95 % CI 1.051-5.798, p = 0.038) and HIPEC duration (95 % CI 1.106-6.235, p = 0.028) were independent factors associated with morbidity in elderly patients. CONCLUSIONS: CRS and HIPEC appear feasible for selected patients older than aged 70 years, albeit with a higher risk of medical complications associated with increased mortality.

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for First Relapse of Ovarian Cancer.

BACKGROUND: To assess impact of surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) in patients treated for a first relapse of ovarian cancer (FROC). PATIENTS AND METHODS: Patients with a FROC treated with second-line chemotherapy, surgery and HIPEC were retrospectively included from 13 Institutions. Studied parameters were interval free between the end of initial treatment and the first relapse, second-line chemotherapy, peritoneal cancer index and completeness of surgery, HIPEC, mortality and morbidity, pathological results and survival. RESULTS: From 2001 to 2010, 314 patients were included. The main strategy was secondary chemotherapy followed by surgery and HIPEC (269/314-85.6%). Mortality and morbidity rates were respectively 1% and 30.9%. Median follow-up was 50 months, 5-year overall survival was 38.0%, with no difference between platinum-sensitive or -resistant patients and 5-year disease-free survival was 14%. CONCLUSION: HIPEC allows encouraging survival in the treatment of FROC, better in case of complete surgery, with acceptable mortality and morbidity rates.

Survival benefit of hyperthermic intraperitoneal chemotherapy for recurrent ovarian cancer: a multi-institutional case control study.

BACKGROUND: Hyperthermic intraperitoneal chemotherapy (HIPEC) and complete surgical removal of the tumor, in relapsing patients may provide a clinical benefit. There is no consensus considering the place of HIPEC for patients who had first ovarian cancer relapse. To assess for possible efficacy of HIPEC on overall survival (OS) rates in this situation, we performed a multi-institutional study. METHODS: The current study was a retrospective case control multi-institutional study comparing a group of patients treated with HIPEC to a group of patients treated without HIPEC. Inclusion criteria were first relapse of a serous ovarian carcinoma and >6 months after the end of initial treatment. Exclusion criteria were another pathological subtype of ovarian cancer, a relapse at <6 months after initial treatment, and a second relapse or more. We aimed to assess OS, morbidity, and mortality rates and prognostic factors. RESULTS: From June 1997-July 2011, 42 patients were included, 23 in the HIPEC group and 19 in the control group. Each patient from the two groups had a complete secondary surgery at the time of the first relapse. At 4 years OS was 75.6 % in the HIPEC group and 19.4 % in the control group (p = 0.013). In a multivariate analysis, HIPEC and interval-free before the end of initial treatment were both independent prognostic factors. CONCLUSION: When compared to the control group, complete secondary surgery and HIPEC appear to afford a better OS rate than complete secondary surgery alone, in case of first ovarian cancer relapse. Further randomized trials are warranted to confirm these results.

Prevalence of and risk factors for morbidity after elective left colectomy: cancer vs noncomplicated diverticular disease.

HYPOTHESIS: Independent risk factors for postoperative morbidity after colectomy are most likely linked to disease characteristics. DESIGN: Retrospective analysis. SETTING: Twenty-eight centers of the French Federation for Surgical Research. PATIENTS: In total, 1721 patients (1230 with colon cancer [CC] and 491 with diverticular disease [DD]) from a databank of 7 prospective, multisite, randomized trials on colorectal resection. INTERVENTION: Elective left colectomy via laparotomy. MAIN OUTCOME MEASURES: Preoperative and intraoperative risk factors for postoperative morbidity. RESULTS: Overall postoperative morbidity was higher in CC than in DD (32.4% vs 30.3%) but the difference was not statistically significant (P = .40). Two independent risk factors for morbidity in CC were antecedent heart failure (odds ratio [OR], 3.00; 95% confidence interval [CI], 1.42-6.32) (P = .003) and bothersome intraluminal fecal matter (2.08; 1.42-3.06) (P = .001). Three independent risk factors for morbidity in DD were at least 10% weight loss (OR, 2.06; 95% CI, 1.25-3.40) (P = .004), body mass index (calculated as weight in kilograms divided by height in meters squared) exceeding 30 (2.05; 1.15-3.66) (P = .02), and left hemicolectomy (vs left segmental colectomy) (2.01; 1.19-3.40) (P = .009). CONCLUSIONS: Patients undergoing elective left colectomy for CC or for DD constitute 2 distinct populations with completely different risk factors for morbidity, which should be addressed differently. Improving colonic cleanliness (by antiseptic enema) may reduce morbidity in CC. In DD, morbidity may be reduced by appropriate preoperative nutritive support (by immunonutrition), even in patients with obesity, and by preference of left segmental colectomy over left hemicolectomy. By decreasing morbidity, mortality should be lowered as well, especially when reoperation becomes necessary.

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 'peritoneal cancer index', 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.

Toward curative treatment of peritoneal carcinomatosis from nonovarian origin by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy: a multi-institutional study of 1,290 patients.

BACKGROUND: Peritoneal carcinomatosis (PC) from nonovarian malignancies long has been regarded as a terminal disease. Over the past decade, new locoregional therapeutic approaches combining cytoreductive surgery with perioperative intraperitoneal chemotherapy (PIC) have evolved that have demonstrated improved survival. METHODS: A retrospective, multicenter cohort study was performed in French-speaking institutions to evaluate toxicity and principal prognostic factors after cytoreductive surgery and PIC (hyperthermic intraperitoneal chemotherapy [HIPEC] and/or early postoperative intraperitoneal chemotherapy [EPIC]) for PC from nongynecologic malignancies. RESULTS: The study included 1290 patients from 25 institutions who underwent 1344 procedures between February 1989 and December 2007. HIPEC was performed in 1154 procedures. The principal origins of PC were colorectal adenocarcinoma (N = 523), pseudomyxoma peritonei (N = 301), gastric adenocarcinoma (N = 159), peritoneal mesothelioma (N = 88), and appendiceal adenocarcinoma (N = 50). The overall morbidity and mortality rates were 33.6% and 4.1%, respectively. In multivariate analysis, patient age, the extent of PC, and institutional experience had a significant influence on toxicity. The overall median survival was 34 months; and the median survival was 30 months for patients with colorectal PC, not reached for patients with pseudomyxoma peritonei, 9 months for patients with gastric PC, 41 months for patients with peritoneal mesothelioma, and 77 months for patients with PC from appendiceal adenocarcinoma. Independent prognostic indicators in multivariate analysis were institution, origin of PC, completeness of cytoreductive surgery, extent of carcinomatosis, and lymph node involvement. CONCLUSIONS: A therapeutic approach that combined cytoreductive surgery with PIC was able to achieve long-term survival in a selected group of patients who had PC of nonovarian origin and had acceptable morbidity and mortality. The current results indicated that this treatment should be centralized to institutions with expertise in the management of PC.

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.

Peritoneal colorectal carcinomatosis treated with surgery and perioperative intraperitoneal chemotherapy: retrospective analysis of 523 patients from a multicentric French study.

PURPOSE Peritoneal carcinomatosis (PC) from colorectal cancer traditionally is considered a terminal condition. Approaches that combine cytoreductive surgery (CRS) and perioperative intraperitoneal chemotherapy (PIC) have been developed recently. The purpose of this study was to assess early and long-term survival in patients treated with that strategy. PATIENTS AND METHODS A retrospective-cohort, multicentric study from French-speaking countries was performed. All consecutive patients with PC from colorectal cancer who were treated with CRS and PIC (with or without hyperthermia) were included. Patients with PC of appendiceal origin were excluded. Results The study included 523 patients from 23 centers in four French-speaking countries who underwent operation between 1990 and 2007. The median follow-up was 45 months. Mortality and grades 3 to 4 morbidity at 30 days were 3% and 31%, respectively. Overall median survival was 30.1 months. Five-year overall survival was 27%, and five-year disease-free survival was 10%. Complete CRS was performed in 84% of the patients, and median survival was 33 months. Positive independent prognostic factors identified in the multivariate analysis were complete CRS, PC that was limited in extent, no invaded lymph nodes, and the use of adjuvant chemotherapy. Neither the grade of disease nor the presence of liver metastases had a significant prognostic impact. CONCLUSION This combined treatment approach against PC achieved low postoperative morbidity and mortality, and it provided good long-term survival in patients with peritoneal scores lower than 20. These results should improve in the future, because the different teams involved will gain experience. This approach, when feasible, is now considered the gold standard in the French guidelines.

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 > or =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.

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

OBJECTIVE: Cancer 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.

Surgeon-dependent predictive factors for mortality after elective colorectal resection and immediate anastomosis for cancer or nonacute diverticular disease: multivariable analysis of 2,605 patients.

BACKGROUND: Multivariable analysis best identifies independent risk factors. STUDY DESIGN: We conducted a prospective evaluation of 2,605 patients through univariate analysis followed by nonconditional multiple logistic regression analysis on 39 pre-, intra-, and postoperative factors, analyzed according to preoperative factors alone, preoperative and intraoperative factors together, and all 3 combined. The purpose was to identify surgeon-dependent independent risk factors for mortality after elective colorectal surgery, with immediate anastomosis for cancer and nonacute diverticular disease. RESULTS: Overall mortality was 3.5%. Through multivariable analysis, five risk factors were found when preoperative data were analyzed alone. Four remained (age between 60 and 75 years, age greater than 75 years, male gender, and heart failure) and 4 new factors (palliative resection, total colectomy, respiratory failure, and surgeon-dependent fecal soiling [the only surgeon-dependent factor]) appeared when pre- and intraoperative factors were analyzed together. Of the latter, two remained stable when all three categories of risk factors were combined and analyzed (palliative resection and total colectomy), and the two others disappeared. Of the eight pre-, intra-, and postoperative factors combined, two new factors appeared: extrasurgical site (ESS) and surgeon-dependent, organ space surgical site (O/SSS) morbidity. CONCLUSIONS: Every effort must be made to collect specific, surgeon-dependent (technical and clinical) data, along with administrative data, for multivariable analysis of risk factors. Classification into three periods (pre-, pre- and intraoperative together, and pre-, intra-, and postoperative combined) enables determination of relevant, surgeon-dependent risk factors (fecal soiling and postoperative morbidity) for which there are direct preventive actions.

Prospective multicentric randomized study comparing periareolar and peritumoral injection of radiotracer and blue dye for the detection of sentinel lymph node in breast sparing procedures: FRANSENODE trial.

PURPOSE: To determine the optimal injection path for blue dye and radiocolloid for sentinel lymph node (SLN) biopsy in early breast cancer. PATIENTS AND METHODS: A prospective randomized multicentric study was initiated to compare the peritumoral (PT) injection site to the periareolar (PA) site in 449 patients. RESULTS: The detection rate of axillary SLN by lymphoscintigraphy was significantly higher (P = .03) in the PA group (85.2%) than in the PT group (73.2%). Intraoperative detection rate by blue dye and/or gamma probe was similar (99.11%) in both groups. The rate of SLN detection was somewhat higher in the PA group than in the PT group: 95.6% versus 93.8% with blue dye (P = .24) and 98.2% versus 96.0% by probe (P = .16), respectively. The number of SLNs detected by lymphoscintigraphy and by probe was significantly higher in the PA group than in the PT group, 1.5 versus 1.2 (P = .001) and 1.9 versus 1.7 (P = .02). The blue and hot concordance was 95.6% in the PA group and 91.5% in the PT group (P = .08). The mean ex vivo count of the SLN was significantly higher in the PA group than in the PT group (P < .0001). CONCLUSION: This study strongly validates the PA injection technique given the high detection rate (99.1%) of SLN and the high concordance (95.6%) between blue dye and the radiotracer, as well as higher significant ex and in vivo counts, improving SLN probe detection.

Tumor quantification of several fluoropyrimidines resistance gene expression with a unique quantitative RT-PCR method. Implications for pretherapeutic determination of tumor resistance phenotype.

Pretherapeutic determination of tumor resistance to chemotherapy is a main challenge, hindered by the low number of mechanisms characterized at the same time, the small size of the clinical specimens and the heterogeneity of the techniques or the lack of true quantification. The aim of the present study was to determine in real time quantitative RT-PCR, tumor cell expression of several transcripts involved in cancer cell resistance with a unique cDNA sample from a tumor biopsy. The technique had to be suitable in clinical practice for determination of several factors involved in resistance to a given drug family, for example, fluoropyrimidines resistance factors: thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), thymidine kinase (TK), dihydrofolate reductase (DHFR), folylpolyglutamate synthetase (FPGS). A frame-shifted artificial construct was designed specifically to work within the same conditions. We validated our technique by quantifying expressions of these 5 genes starting from tissue samples of colorectal carcinoma and the surrounding normal mucosa of 33 different patients. That real time quantitative RT-PCR technique using the frame-shifted artificial construct as a standard provided a real comparison and quantification of different resistance factors. Tumor resistance phenotype determination based on that approach will be investigated in a control study.

Repeat hepatectomy for recurrent colorectal liver metastases.

PURPOSE: Liver resection represents the best and potentially curative treatment for metastatic colorectal cancer (MCC) to the liver. After resection, however, most patients develop recurrent disease, often isolated to the liver. The aim of this study was to determine the value of repeat liver resection for recurrent MCC and to analyze the factors that can predict survival. PATIENTS AND METHODS: From January 1992 to October 2002, 42 patients from a group of 168 patients resected for MCC were submitted to 55 repeat hepatectomies (42 second, 11 third, and 2 fourth hepatectomies). Records were retrospectively reviewed. The primary tumor was carcinoma of the colon in 26 patients and carcinoma of the rectum in 16 patients. Liver metastases were synchronous in 24 patients (57.1%). RESULTS: There were 25 men and 17 women with the mean age of 63.5 years (range: 34-80). There was no intraoperative or postoperative mortality. The morbidity rates were 9.5%, 14.3%, and 18.2% (P = 0.6) respectively after a first, second, or third hepatectomies. No patients needed reoperation. Operative duration was longer after a second or third hepatectomie than after a first hepatectomie without difference for operative bleeding. Overall 5-year survivals were 33%, 21%, and 36% respectively after a first, second, or third hepatectomies. Factors of prognostic value on univariate analysis included serum carcinoembryonic antigen levels (P = 0.01) during the first hepatectomy, the presence of extrahepatic disease (P = 0.05) and tumor size larger than 5 cm (P = 0.04) during the second hepatectomie. CONCLUSIONS: Repeat hepatectomies can provide long-term survival rates similar to those of first hepatectomies.

[Thyroid metastases of an adrenocortical carcinoma 41 years after the diagnosis of the primary tumor]. / Métastases thyroïdiennes d'un corticosurrénalome 41 ans après le diagnostic de la tumeur initiale.

Thyroid metastasis are rare and represent less than 4% of malignant thyroid tumors in clinical series. They can develop many years after diagnosis of the primary tumor. We report a case of thyroid metastasis of adrenocortical carcinoma, 41 years after the diagnosis of the primary tumor. Such a long latent interval is exceptional. To our knowledge, this is the first case published. Based on current literature, we offer a brief review on thyroid metastasis and differential diagnosis of thyroid gland clear cell neoplasm.