Laparoscopic Extraperitoneal Approach to Bilateral Pelvic Lymph Node Dissection in Low Rectal Cancer: Technique with Video and 3D Modeling.

BACKGROUND: Lateral pelvic lymph node dissection for rectal cancer is a difficult technique due to the complex pelvic anatomy. Recent series have underlined the importance of lateral lymphadenectomy in selective patients to prevent local recurrence of rectal cancer. METHODS: A 65-year-old woman was diagnosed with locally advanced rectal adenocarcinoma of the low rectum with right and left lateral pelvic lymph nodes of respectively 9 and 13 mm. After chemotherapy followed by radiotherapy, the size of the right internal iliac lymph nodes remained enlarged to 5 mm. A laparoscopic extraperitoneal approach was used for total mesorectal excision, complete mesocolic excision, and bilateral lateral lymph node dissection. The extraperitoneal space was divided into the subperitoneal space dissected by a transanal approach and the retroperitoneal space dissected by a transabdominal approach. RESULTS: The operating time was 303 min, and the estimated blood loss was 270 ml. No intraoperative adverse events occurred. Bilateral lymph node dissection was performed with obturator nerve and neurovascular bundle sparing. A postoperative complication classified as Clavien 3a arose with a pelvic infection but no anastomotic leakage. Final pathology disclosed T3N1M0 adenocarcinoma with free surgical margins. The patient never had urinary dysfunction. CONCLUSIONS: The laparoscopic extraperitoneal approach to lateral pelvic lymph node dissection is feasible. For lateral lymph node dissection, the transanal approach may have some advantages over the standard transabdominal approach, with better visibility of and access to the distal internal iliac area. This video may help oncological surgeons to perform this new and complex procedure.

Cytoreductive surgery plus hyperthermic intraperitoneal chemotherapy by laparoscopy via a single-port approach for low-grade peritoneal malignancy.

BACKGROUND: Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) is a long and complex procedure. A minimal invasive approach is rarely performed. The feasibility of laparoscopic CRS and HIPEC via a single port (SP) approach is unknown. The aim of this study was to assess the feasibility of CRS and HIPEC with a SP approach. METHODS: This study is IDEAL stage I-IIa. Patients with low grade and limited peritoneal malignancy were included in a tertiary care cancer center. Intra- and post-operative adverse events were recorded and classified according to medical and surgical dedicated classifications. The main objective measurement to assess feasibility was the conversion to open or multiport surgery. RESULTS: A total of 12 highly selected patients were assessed. The median operating time was 240 min (range, 180-360) and two near miss events were reported. Two conversions to open and multiport surgery occurred. The median comprehensive complication index was 0 (range, 0-42.6) with two severe adverse events (Clavien-Dindo or CTC-AE ≥ 3). The median length of stay was 8.5 days (range, 5-13). CONCLUSION: CRS and HIPEC via a laparoscopic SP approach are feasible and safe in the short term. The next step should be a prospective development study.

Angioedema associated with thrombolysis for ischemic stroke: analysis of a case-control study.

BACKGROUND: Bradykinin-mediated angioedema (AE) is a complication associated with thrombolysis for acute ischemic stroke. Risk factors are unknown and management is discussed. OBJECTIVES: To clarify risk factors associated with bradykinin-mediated AE after thrombolysis for acute ischemic stroke. METHODS: In a case-control study conducted at a French reference centre for bradykinin angiœdema, patients with thrombolysis for acute ischemic stroke and a diagnosis of bradykinin-mediated angiœdema, were compared to controls treated with thrombolysis treatment without angiœdema. RESULTS: Fifty-three thrombolysis-related AE were matched to 106 control subjects. The sites of attacks following thrombolysis for ischemic stroke mainly included tongue (34/53, 64%) and lips (26/53, 49%). The upper airways were involved in 37 (70%) cases. Three patients required mechanical ventilation. Patients with bradykinin-mediated angiœdema were more frequently women [33 (62%) vs. 44 (42%); P = 0.01], had higher frequency of prior ischemic stroke [12 (23%) vs. 9 (8%); P = 0.01], hypertension [46 (87%) vs. 70 (66%); P = 0.005], were more frequently treated with angiotensin-converting enzyme inhibitor [37 (70%) vs. 28 (26%); P < 0.001] and were more frequently hospitalized in intensive care medicine [ICU; 11 (21%) vs. 5 (5%); P = 0.004]. In multivariate analysis, factors associated with thrombolysis-related AE were female sex [odds ratio (OR), 3.04; 95% confident interval (CI), 1.32-7.01; P = 0.009] and treatment with angiotensin-converting enzyme inhibitors [(OR), 6.08; 95% (CI), 2.17-17.07; P < 0.001]. CONCLUSIONS: This case-control study points out angiotensin-converting enzyme inhibitors and female sex as risk factors of bradykinin AE associated with thrombolysis for ischemic stroke.

Morbidity and oncological outcomes of rectal cancer impaired by previous prostate malignancy.

BACKGROUND: Specific surgical and oncological outcomes in patients with rectal cancer surgery after a previous diagnosis of prostate cancer have not been well described. The aim of this study was to compare surgical outcomes in patients with rectal cancer with or without a history of prostate cancer. METHODS: Patients who had surgery for rectal cancer with (PC group) or without (no-PC group) previous curative treatment for prostate cancer were enrolled between January 2001 and December 2015. Comparisons between the two groups were performed by multivariable Cox analysis, and after propensity score matching in a 3 : 1 ratio for demographic and tumour characteristics, and surgical and oncological outcomes. RESULTS: A total of 944 patients with rectal cancer were enrolled, of whom 10·8 per cent had a history of prostate cancer. After matching, 83 patients who had received treatment for prostate cancer were compared with 249 who had not. The PC and no-PC groups were similar regarding patient characteristics. Extended total mesorectal excision, conversion to open surgery, transfusion and tumour perforation were more frequent in the PC group than in the no-PC group. Major surgical morbidity (28 versus 17·2 per cent; P = 0·036), anastomotic leakage (25 versus 13·7 per cent; P = 0·019) and permanent stoma (41 versus 12·4 per cent; P < 0·001) occurred more frequently in the PC group. Local recurrence was increased significantly in the PC group (17 versus 8·0 per cent; P = 0·019), and resulted in a significant decrease in disease-free and overall survival. CONCLUSION: Prostate cancer treatment increases short- and long-term surgical morbidity in patients with rectal cancer, and impairs oncological outcomes.

Multicentre study of laparoscopic or open assessment of the peritoneal cancer index (BIG-RENAPE).

BACKGROUND: The peritoneal cancer index (PCI) is a comparative prognostic factor for colorectal peritoneal metastasis (CRPM). The ability of laparoscopy to determine the PCI in consideration of cytoreductive surgery remains undetermined, and this study was designed to compare it with laparotomy. METHODS: A prospective multicentre study was conducted for patients with no known CRPM, but at risk of peritoneal disease. Surgery began with laparoscopic exploration followed by open exploration to determine the PCI. Concordance between laparoscopic and open assessment was evaluated for the diagnosis of CRPM and for the PCI. RESULTS: Among 50 patients evaluated, CRPM recurrence was found in 29 (58 per cent) and 34 (68 per cent) at laparoscopic and open surgery respectively. Laparoscopy was feasible in 88 per cent (44 of 50) and deemed satisfactory by the surgeon in 52 per cent (26 of 50). Among the 25 evaluable patients with satisfactory laparoscopy, there was concordance of 96 per cent (24 of 25 patients) and 38 per cent (10 of 25) for laparoscopic and open assessment of CRPM and the PCI respectively. Where there were discrepancies, it was laparoscopy that underestimated the PCI. CONCLUSION: Laparoscopy may underestimate the extent of CRPM.

Single-port endoscopic mesocolic and mesorectal excision using an extraperitoneal approach.

BACKGROUND: The extraperitoneal rectal dissection via a transanal approach facilitates the mesorectal dissection. The retroperitoneal approach for mesocolic excision may also offer some similar advantages. To complete the lymphadenectomy of extraperitoneal mesorectal resection, we developed an innovative approach for upper rectal and mesocolic excision via an exclusive retroperitoneal dissection using a single-port access at the site of the future stomy. METHODS: This study was a prospective pilot study and was conducted between 2013 and 2015 at two oncologic centers. Five consecutive patients, with ano-rectal cancer requiring permanent stoma, underwent this procedure. RESULTS: The bowel was never touched or mobilized to perform the lymphadenectomy, and no Trendelenburg was required. The median operative duration was 300 min (range 205-310). The quality of the surgical plane was classified as good (mesorectal) in the five patients. The median circumferential and distal margins were, respectively, 5 mm (range 1-20) and 20 mm (range 5-25). The median number of harvested lymph nodes was 11 (range 5-18). No laparotomy or multiport laparoscopy was required. There was no death. Two patients had perineal wound dehiscence (one minor and one major). CONCLUSIONS: The mesocolic excision via a retroperitoneal approach is feasible, completes naturally the transanal mesorectal excision and may confer several advantages including no morbidity of small bowel manipulation or Trendelenburg position. Further studies are required to analyze this approach.

Aneuploidy: the impact of chromosome imbalance on nuclear organization and overall genome expression.

The organization and dynamics of chromatin within the interphase nucleus as chromosome territories (CTs) and the relationship with transcriptional regulation are not fully understood. We studied a natural example of chromosomal disorganization: aneuploidy due to trisomies 13, 18 and 21. We hypothesized that the presence of an extra copy of one chromosome alters the CT distribution, which perturbs transcriptional activity. We used 3D-FISH to study the position of the chromosomes of interest (18 and 21) in cultured amniocytes and chorionic villus cells from pregnancies with a normal or aneuploid karyotype. We studied the volumes of nuclei and CTs in both conditions and performed a compared transcriptome analysis. We did not observe any differences between euploid and aneuploid cells in terms of the radial and relative CT positions, suggesting that the same rules govern nuclear organization in cases of trisomy. We observed lower volumes for CTs 18 and 21. Overall genome expression profiles highlighted changes in the expression of a subset of genes in trisomic chromosomes, while the majority of transcriptional changes concerned genes located on euploid chromosomes. Our results suggest that a dosage imbalance of the genes on trisomic chromosomes is associated with a disturbance of overall genomic expression.

Screening in asymptomatic SDHx mutation carriers: added value of ¹8F-FDG PET/CT at initial diagnosis and 1-year follow-up.

PURPOSE: Specific recommendations on screening modalities for paraganglioma (PGL) and phaeochromocytoma (PCC) in asymptomatic SDHx mutation carriers (relatives) are still lacking. We evaluated the added value of (18)F-FDG PET/CT in comparison with morphological imaging at initial diagnosis and 1 year of follow-up in this population. METHODS: The study included 30 consecutive relatives with a proven SDHx mutation who were investigated by (18)F-FDG PET/CT, gadolinium-enhanced magnetic resonance angiography of the head and neck, thoracic/abdominal/pelvic (TAP) contrast-enhanced CT and/or TAP MRI. (123)I-MIBG scintigraphy was performed in 20 subjects and somatostatin receptor scintigraphy (SRS) in 20 subjects. The gold standard was based on pathology or a composite endpoint as defined by any other positive imaging method and persistent tumour on follow-up. Images were considered as false-positive when the lesions were not detected by another imaging method or not confirmed at 1 year. RESULTS: At initial work-up, an imaging abnormality was found in eight subjects (27%). The final diagnosis was true-positive in five subjects (two with abdominal PGL, one with PCC and two with neck PGL) and false-positives in the other three subjects (detected with (18)F-FDG PET/CT in two and TAP MRI in one). At 1 year, an imaging abnormality was found in three subjects of which one was an 8-mm carotid body PGL in a patient with SDHD mutaion and two were considered false-positive. The tumour detection rate was 100% for (18)F-FDG PET/CT and conventional imaging, 80% for SRS and 60% for (123)I-MIBG scintigraphy. Overall, disease was detected in 4% of the subjects at the 1-year follow-up. CONCLUSION: (18)F-FDG PET/CT demonstrated excellent sensitivity but intermediate specificity justifying combined modality imaging in these patients. Given the slow progression of the disease, if (18)F-FDG PET/CT and MRI are normal at baseline, the second imaging work-up should be delayed and an examination that does not expose the patient to radiation should be used.

Therapeutic Strategies for Advanced Pancreatic Neuroendocrine Tumors with Segmental Portal Hypertension.

BACKGROUND: Pancreatic neuroendocrine tumors (PNET) locally advanced may lead to significant local symptoms especially segmental portal hypertension (SPH) with risk of bleeding. The aim of our study was to evaluate the role of SPH on the PNET management in an expert center. METHODS: Forty-two patients treated for locally advanced PNET with SPH between January 1984 and December 2012 were retrospectively analyzed. RESULTS: The median age was 55 years (25-75). The median tumor size was 7.5 cm (3-20). Thirty four (80.9%) patients were metastatic mainly in the liver (n=33, 79%) with a frequent (n=16, 38.1%) involvement>20%. The surgery was impossible because of SPH in 7 (16.6%) cases. Pancreatic resection was performed in 28 (66.7%) cases by distal pancreatectomy. Neoadjuvant chemotherapy (n=24, 57%) had no impact on SPH with no modification of collateral circulation. Among operated on patients, complete macroscopic resection was obtained in 19 (67.8%) patients. The mortality and severe morbidity rate was respectively 3.6 and 18%. Five year overall survival (OS) was similar in operated and no operated patients. (61%; p=0.64). The 5-year OS was 77.9 or 55.4% in patients who underwent a complete or incomplete macroscopic resection of primary and metastases, respectively. CONCLUSION: PNET resection associated with SPH is feasible with a low morbimortality. SPH was not improved by chemotherapy. Prolonged survival was observed after complete macroscopic resection.

Comparison of fecal continence and quality of life between intersphincteric resection and abdominoperineal resection plus perineal colostomy for ultra-low rectal cancer.

AIMS: The only two procedures for surgical treatment of ultra-low rectal cancer without a permanent abdominal stoma are the intersphincteric resection (ISR) and the abdominoperineal resection (APR) plus a perineal pseudocontinent colostomy (PCC). This study compared functional results and quality of life following these two techniques. METHODS: Between January 1995 and December 2011, 36 patients had undergone an ISR (n = 14) or a PPC (n = 22) for very low rectal cancer. The Cleveland Clinica Florida (Wexner) fecal incontinence questionnaire and the EORTC Quality of Life questionnaire QLQ-C30 and CR38 had been administered. RESULTS: There were no differences in gender, age, the interval between surgery and questionnaire responses, preoperative TNM staging, perioperative treatment, the laparoscopic approach and circumferential margin involvement rate between the groups. The ISR and PPC led to no difference in quality of life (Qol) and continence with a median Wexner score of respectively 11 and 10 (P = 0.403) and a fecal incontinence rate of 58.2% and 41% (P = 0.221). The incontinent patients had experienced worse social functioning and tended to have worse overall health. The patients who had undergone ISR had more defecation problems and evacuation difficulties. CONCLUSION: Qol and continence are similar between ISR and PPC.

Options and outcome for reconstruction after extended left hemicolectomy.

AIM: A tension-free anastomosis is required to minimize anastomotic leakage after an extended left colectomy when the residual transverse colon is too short to spontaneously reach the pelvis. To resolve this problem, colonic rotation with a right colonic transposition (RCT) or even with a complete intestinal derotation (CID) is mandatory. This study compared these two techniques. METHOD: Between January 2001 and December 2011, 39 patients had undergone right colonic transposition (n = 29) or complete intestinal derotation (n = 10) after an extended left colectomy. All anastomotic complications had been recorded during the follow up. RESULTS: No differences were found between right colonic transposition and complete intestinal derotation in terms of patient characteristics, surgical indications, therapeutic features and risk factors for anastomotic leakage (sex, American Society of Anesthesiology (ASA) score, diabetes, bevacizumab use, colorectal anastomotic level or protective stoma use). Ligature of the middle colic artery was significantly more frequent with right colonic transposition than with complete intestinal derotation (82.7% vs 50%; P = 0.04). An additional colonic resection tended to be required more often in the right colonic transposition group than in the complete intestinal derotation group (55.1% vs 20%; P = 0.054). The anastomotic complication rate was 10.2% and was not significantly different between right colonic transposition and complete intestinal derotation (6.9% vs 20%, P = 0.24). CONCLUSION: Both colonic rotation techniques are feasible and safe. The right colonic transposition and complete intestinal derotation techniques yielded similar results in terms of colorectal anastomotic complications, but right colonic transposition required ligature of the middle colic artery and additional colonic resection tended to be required more frequently.

HIPEC for peritoneal carcinomatosis: does an associated urologic procedure increase morbidity?

PURPOSE: To report the incidence of urinary tract procedures performed during complete cytoreductive surgery (CCRS) plus intraperitoneal chemotherapy, and to report the types of procedure, specific morbidity, risk factors, and treatment. METHODS: Data were extracted from a prospective database of patients with malignant peritoneal disease treated with CCRS plus intraperitoneal chemotherapy who had undergone a resection or suture of the bladder, ureter, or kidney. Patients were eligible whatever the tumor origin. RESULTS: Between 1994 and 2010, among the 598 patients treated with CCRS plus intraperitoneal chemotherapy, 48 (8%) had undergone a resection or suture in the urinary tract. Procedures included 4 nephrectomies, 19 partial cystectomies, 8 surgically repaired bladder injuries, and 18 ureteral resections. Postoperative mortality was 4% and morbidity was 41%. Specific complications included 6 urinary fistulas (12%), two among the 27 bladder sutures (7%) and four among the 18 ureteral sutures (22%) (P = NS). In the multivariate analysis, the risk factors for urinary fistula were severe preoperative malnutrition (P = 0.05, relative risk [RR] = 7.3) and extensive peritoneal disease (peritoneal cancer index ≥20, P = 0.05, RR = 8.3). Urinary fistulas had been treated nonsurgically in most of the cases. CONCLUSIONS: Associated urinary tract procedures had occurred in 8% of the cases but did not greatly increase morbidity. Therefore, urinary tract involvement or injury are not contraindications to performing CCRS plus intraperitoneal chemotherapy. Fistulas had complicated only 12% of urinary sutures, mainly in cases of malnutrition or extensive peritoneal disease.

Results of systematic second-look surgery plus HIPEC in asymptomatic patients presenting a high risk of developing colorectal peritoneal carcinomatosis.

PURPOSE: To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). PATIENTS AND METHODS: From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). RESULTS: PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9-109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). CONCLUSION: Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.

The CD45 tyrosine phosphatase regulates phosphotyrosine homeostasis and its loss reveals a novel pattern of late T cell receptor-induced Ca2+ oscillations.

CD45 is a transmembrane tyrosine phosphatase implicated in T cell antigen receptor (TCR)-mediated activation. In T cell variants expressing progressively lower levels of CD45 (from normal to undetectable), CD45 expression was inversely related to spontaneous tyrosine phosphorylation of multiple proteins, including the TCR zeta chain, and was directly correlated with TCR-driven phosphoinositide hydrolysis. The Ca2+ response in these cells was altered in an unexpected fashion. Unlike wild-type cells, stimulated CD45- cell populations did not manifest an early increase in intracellular Ca2+, but did exhibit a delayed and gradual increase in mean intracellular Ca2+. Computer-aided fluorescence imaging of individual cells revealed that CD45- cells experienced late Ca2+ oscillations that were not blocked by removal of extracellular Ca2+. CD45 revertants had the signaling properties of wild-type cells. Thus, CD45 has a profound influence on both TCR-mediated signaling and phosphotyrosine homeostasis, and its loss reveals a novel role for this tyrosine phosphatase in Ca2+ regulation.

The immunosuppressive and toxic effects of FK-506 are mechanistically related: pharmacology of a novel antagonist of FK-506 and rapamycin.

FK-506 inhibits Ca(2+)-dependent transcription of lymphokine genes in T cells, and thereby acts as a powerful immunosuppressant. However, its potential therapeutic applications may be seriously limited by several side effects, including nephrotoxicity and neurotoxicity. At present, it is unclear whether these immunosuppressive and toxic effects result from interference with related biochemical processes. FK-506 is known to interact with FK-binding protein-12 (FKBP-12), an abundant cytosolic protein with cis-trans peptidyl-prolyl isomerase activity (PPIase) activity. Because rapamycin (RAP) similarly binds to FKBP-12, although it acts in a manner different from FK-506, by inhibiting T cell responses to lymphokines, such an interaction with FKBP-12 is not sufficient to mediate immunosuppression. Recently, it was found that the complex of FKBP-12 with FK-506, but not with RAP, inhibits the phosphatase activity of calcineurin. Here, we used L-685,818, the C18-hydroxy, C21-ethyl derivative of FK-506, to explore further the role of FKBP-12 in the immunosuppressive and toxic actions of FK-506. Although L-685,818 bound with high affinity to FKBP-12 and inhibited its PPIase activity, it did not suppress T cell activation, and, when complexed with FKBP-12, did not affect calcineurin phosphatase activity. However, L-685,818 was a potent antagonist of the immunosuppressive activity of both FK-506 and RAP. Moreover, L-685,818 did not induce any toxicity in dogs and rats or in a mouse model of acute FK-506 nephrotoxicity, but it blocked the effect of FK-506 in this model. Therefore, FK-506 toxicity involves the disruption of biochemical mechanisms related to those implicated in T cell activation. Like immunosuppression, this toxicity is not due to the inhibition of the PPIase activity of FKBP-12, but may be linked to the inhibition of the phosphatase activity of calcineurin by the drug FKBP-12 complex.

Is cyclophilin involved in the immunosuppressive and nephrotoxic mechanism of action of cyclosporin A?

In this report we have approached two questions relating to the mechanism of action of cyclosporin A (CsA). First, we address whether the major cytosolic protein for CsA, cyclophilin, is directly involved in mediating the immunosuppressive activity of this drug, and, in particular, whether inhibition of this protein's peptidyl-prolyl cis-trans isomerase (PPIase) activity results in inhibition of murine T cell activation. Second, we ask whether the nephrotoxicity observed with CsA is related to inhibition of PPIase-dependent pathways in cells other than lymphocytes. Using a series of 61 cyclosporin analogues, we generally found a good correlation between cyclophilin binding and immunosuppressive activity for the majority of analogues analyzed. However, a number of compounds of distinct structural classes were found that could interact with cyclophilin but were much less immunosuppressive than expected. The inability of these analogues to inhibit lymphocyte activation could not be explained by their failure to enter the cell and bind to cyclophilin under the conditions used in the cellular assays. Surprisingly, a nonimmunosuppressive analogue, MeAla-6, which bound well to cyclophilin and was active as a PPIase inhibitor, did not induce renal pathology in vivo. Furthermore, another analogue, MeBm2t, which was immunosuppressive in vitro, possessed little or no activity as a PPIase inhibitor. These findings pose serious questions concerning a direct role of cyclosporin in mediating CsA's immunosuppressive and nephrotoxic activities. In addition, they raise doubts about whether PPIase has a direct function in lymphocyte signal transduction.

Inactivation of Escherichia coli and Lactobacillus plantarum in relation to membrane permeabilization due to rapid chilling followed by cold storage.

The relationship between membrane permeabilization and loss of viability by chilling depending on the chilling rate was investigated in two bacterial models: one Gram-positive bacterium, Lactobacillus plantarum, and one Gram-negative bacterium, Escherichia coli. Cells were cold shocked slowly (2 degrees C/min) or rapidly (2,000 degrees C/min) from physiological temperature to 0 degrees C and maintained at this temperature for up to 1 week. Loss of membrane integrity was assessed by the uptake of the fluorescent dye propidium iodide (PI). Cell death was found to be strongly dependent on the rate of temperature downshift to 0 degrees C. Prolonged incubation of cells after the chilling emphasized the effect of treatment on the cells, as the amount of cell death increased with the length of exposure to low temperature, particularly when cells were rapidly chilled. More than 5 and 3-log reductions in cell population were obtained with L. plantarum and E. coli after the rapid cold shock followed by 7-day storage, respectively. A correlation between cell inactivation and membrane permeabilization was demonstrated with both bacterial strains. Thus, loss of membrane integrity due to the chilling treatments was directly involved in the inactivation of vegetative bacterial cells.

Recurrence of pseudomyxoma peritonei after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy.

Background: Pseudomyxoma peritonei (PMP) is a rare clinical condition characterized by mucinous ascites, typically related to appendiceal or ovarian tumours. Current standard treatment involves cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), but recurrences occur in 20-30 per cent of patients. The aim of this study was to define the timing and patterns of recurrence to provide a basis for modifying follow-up of these patients. Methods: This observational study examined a prospectively developed multicentre national database (RENAPE working group) to identify patients with recurrence after optimal CRS and HIPEC for PMP. Postoperative complications, long-term outcomes and potential prognostic factors were evaluated. Results: Of 1411 patients with proven PMP, 948 were identified who had undergone curative CRS and HIPEC. Among these patients, 229 first recurrences (24·2 per cent) were identified: 196 (20·7 per cent) occurred within the first 5 years (early recurrence) and 30 (3·2 per cent) occurred between 5 and 10 years. Three patients developed a first recurrence more than 10 years after the original treatment. The mean(s.d.) time to first recurrence was 2·36(2·21) years. Preoperative chemotherapy and high-grade pathology were significant factors for early recurrence. Overall survival for the entire group was 77·9 and 63·1 per cent at 5 and 10 years respectively. The principal site of recurrence was the peritoneum. Conclusion: Recurrence of PMP was rare after 5 years and exceptional after 10 years.

Gaseous environments modify physiology in the brewing yeast Saccharomyces cerevisiae during batch alcoholic fermentation.

AIMS: To investigate the impact of different gaseous atmospheres on different physiological parameters in the brewing yeast Saccharomyces cerevisiae BRAS291 during batch fermentation. METHODS AND RESULTS: Yeasts were cultivated on a defined medium with a continuous sparging of hydrogen, helium and oxygen or without gas, permitting to obtain three values of external redox. High differences were observed concerning viable cell number, size and metabolites produced during the cultures. The ethanol yields were diminished whereas glycerol, succinate, acetoin, acetate and acetaldehyde yields were enhanced significantly. Moreover, we observed major changes in the intracellular NADH/NAD(+) and GSH/GSSG ratio. CONCLUSIONS: The use of gas led to drastic changes in the cell size, primary energy metabolism and internal redox balance and E(h). These changes were different depending on the gas applied throughout the culture. SIGNIFICANCE AND IMPACT OF THE STUDY: For the first time, our study describes the influence of various gases on the physiology of the brewing yeast S. cerevisiae. These influences concern mainly yeast growth, cell structure, carbon and redox metabolisms. This work may have important implications in alcohol-related industries, where different strategies are currently developed to control better the production of metabolites with a particular attention to glycerol and ethanol.

Surgical conservative treatment of recurrent bleeding duodenal ulcer.

BACKGROUND/AIMS: Endoscopic hemostasis and proton pump inhibitors (PPI) have decreased the incidence of rebleeding and reduced the need for surgery for bleeding duodenal ulcer (BDU). The gold standard surgical treatment of BDU remains vagotomy-antrectomy. Currently, no recommendation is made on the best procedure when emergency surgery is necessary. The aim of this study was to assess the results of a systematic conservative treatment (CT): under-running bleeding gastroduodenal artery (GDA) and ulcer suture through a duodenotomy with (CT+L group) or without (CT group) GDA double ligation along with continuous intravenous PPI. METHODOLOGY: From 1995 to 2006, 22 consecutive patients (11 per group) underwent emergency surgery for BDU. Mean age was 63 +/- 18 years, ASA score 2.64 +/- 0.7. Ten patients (45%) presented collapse. Mean transfusion number was 11 +/- 9, number of therapeutic endoscopies 1.7 +/- 1, and Rockall score 6 +/- 2. RESULTS: Overall, 2 patients (9%) had rebleeding and 5 patients (22%) died. No death was reported secondary to rebleeding. In the CT+L group, 9 patients (82%) had intravenous PPI, no patient had rebleeding and 2 patients died (22%). CONCLUSIONS: Surgical CT of BDU with continuous PPI is effective, with a low rate of rebleeding. The standard use of vagotomy-antrectomy is questionable.