Intra-operative fluorescence angiography is reproducible and reduces the rate of anastomotic leak after colorectal resection for cancer: a prospective case-matched study.

AIM: Intra-operative fluorescence angiography (IOFA) with indocyanine green provides information on tissue perfusion that may help prevent an anastomotic leak (AL). The aim of this study was to assess the impact of IOFA on outcomes after left-sided colonic or low anterior resection with anastomosis for colorectal cancer. METHODS: All patients with left-sided colonic or rectal cancer, operated between June 2017 and December 2018, were prospectively included. IOFA has been routinely implemented since May 2018. Reproducibility of IOFA, after a 1:1 matching for relevant clinical risk factors of AL, was studied in patients with IOFA (IOFA+) and without IOFA (IOFA-). Outcomes were compared in terms of postoperative events such as clinically relevant AL as the primary end-point. RESULTS: In the IOFA+ group, changing of the initially planned colon transection due to inadequate perfusion occurred in five out of 46 patients (10.9%). Agreement between intra-operative assessment and postoperative blind review of IOFA was deemed strong (Cohen's kappa index 0.893, 95% CI 0.788-0.998, P < 0.001). Among 111 patients, 42 matched patients were included in each group. There was significantly more clinically relevant AL in the IOFA- group compared to the IOFA+ group (16.7% vs 2.4%, P = 0.026) involving significantly more anastomotic dehiscence which required re-intervention (19% vs 2.4%, P = 0.014). Additionally, more descending colon ischaemia/necrosis was observed in the IOFA- group compared with the IOFA+ group (9.5% vs 0%, P = 0.040). CONCLUSION: In this prospective case-matched study, IOFA decreased the occurrence of clinically relevant AL due to necrosis of the descending colon or anastomosis. Upon blind review, perfusion assessment using IOFA was reproducible.

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.

An unusual case of Y-shaped right renal vein.

Vascular renal anomalies are frequent, multiple and well described and result from errors in vessel embryogenesis between the 6th and 10th week of gestation. Historically, variations are described in anatomic dissection and currently mostly in image interpretation. We report an anatomic variation concerning the right renal vein which, to our knowledge, has never been described in the literature either by dissection or by radiological examination. This variation was discovered during the routine dissection of an embalmed male body. It consists of a Y-shaped right renal vein and is associated with multiple retroperitoneal variations: a bilateral accessory renal artery, a trident ending of the right renal artery and a left testicular vein variation. Venous and arterial renal anatomy and its variations are fundamentally important in renal surgery, especially concerning living donor renal grafts. These variations may be diagnosed thanks to injected tomodensitometry which has a good sensitivity and specificity for anomalies. Preoperative diagnosis of an anatomic vascular renal variation may reduce morbidity during surgery, which is why precise examination of injected tomography should be mandatory.

Intraperitoneal clearance as a potential biomarker of cisplatin after intraperitoneal perioperative chemotherapy: a population pharmacokinetic study.

BACKGROUND: Intraperitoneal (IP) perioperative chemotherapy with cisplatin is an interesting option in ovarian cancer treatment. A combination of cisplatin with IP epinephrine (already shown to improve IP and decrease systemic platinum (Pt) exposure) was evaluated using a population pharmacokinetic analysis. METHODS: Data from 55 patients treated with cisplatin-based IP perioperative chemotherapy with (n=26) or without (n=29) epinephrine were analysed using NONMEM. RESULTS: Epinephrine halves clearance between peritoneum and serum (IPCL) and increases the Pt central volume of distribution, IP exposure and penetration in tissue. IPCL has a better predictive value than any other parameter with respect to renal toxicity. CONCLUSION: This confirms that IPCL could be useful in assessing renal toxicity. As IPCL is also linked to tissue penetration and IP exposure, it may be proposed as biomarker. In addition to a Bayesian estimation, we propose a single-sample calculation-way to assess it. Prospective studies are needed to validate IPCL as a biomarker in this context.

Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients.

Neuronal growth factors hold promise for providing therapeutic benefits in various neurological disorders. As a means of ensuring adequate central nervous system delivery of growth factors and minimizing significant adverse side effects associated with systemic delivery methods, we have developed an ex vivo gene therapy approach for protein delivery using encapsulated genetically modified xenogeneic cells. Ciliary neurotrophic factor (CNTF) has been shown in various rodent models to reduce the motor neuron cell death similar to that seen in amyotrophic lateral sclerosis (ALS). The initial trials focusing on the systemic administration of CNTF for ALS have been discontinued as a result of major side effects, thus preventing determination of the potential efficacy of the molecule. In order to deliver CNTF directly to the nervous system, we conducted a phase I study in which six ALS patients were implanted with polymer capsules containing genetically engineered baby hamster kidney cells releasing approximately 0.5 microgram of human CNTF per day in vitro. The CNTF-releasing implants were surgically placed within the lumbar intrathecal space. Nanogram levels of CNTF were measured within the patients' cerebrospinal fluid (CSF) for at least 17 weeks post-transplantation, whereas it was undetectable before implantation. Intrathecal delivery of CNTF was not associated with the limiting side effects observed with systemic delivery. These results demonstrate that neurotrophic factors can be continuously delivered within the CSF of humans by an ex vivo gene therapy approach, opening new avenues for the treatment of neurological diseases.

[Hepatopulmonary syndrome]. / Le syndrome hépatopulmonaire.

Hepatopulmonary syndrome is characterized by the presence of portal hypertension with or without cirrhosis, an increased alveolar-arterial oxygen partial pressure difference greater than or equal to 15 mm Hg, and dilated pulmonary capillaries. Hepatopulmonary syndrome is found in up to 20% of patients with cirrhosis and should be considered in any patient who develops dyspnea or hypoxemia. Contrast echocardiography is enough to make the diagnosis of hepatopulmonary syndrome. The exact pathophysiology of hepatopulmonary syndrome remains unknown but nitric oxide is an important factor underlying hepatopulmonary syndrome. Hypoxemia progressively deteriorates and worsens the prognosis of cirrhotic patients. Hypoxemic patients must be controlled regularly to optimise the timing of liver transplantation. Indeed, a preoperative PaO(2) of less than or equal to 50 mm Hg alone or in combination with an isotopic shunt fraction greater than or equal to 20% are the strongest predictors of postoperative mortality. There are currently no effective medical therapies for hepatopulmonary syndrome but garlic powder and iloprost inhalation demonstrate clinical improvements in the pre- and in the post-transplant period.

Differential inhibition of rat and human hepatic cytochrome P450 by Andrographis paniculata extract and andrographolide.

The inhibitory effect of Andrographis paniculata extract (APE) and andrographolide (AND), the most medicinally active phytochemical in the extract, on hepatic cytochrome P450s (CYPs) activities was examined using rat and human liver microsomes. For this purpose, CYP1A2-dependent ethoxyresorufin-O-deethylation, CYP2B1-dependent benzyloxyresorufin-O-dealkylation, CYP2B6-dependent bupropion hydroxylation, CYP2C-dependent tolbutamide hydroxylation, CYP2E1-dependent p-nitrophenol hydroxylation and CYP3A-dependent testosterone 6 beta-hydroxylation activities, were determined in the presence and absence of APE or AND (0-200 microM). APE inhibited ethoxyresorufin-O-deethylation activity in rat and human liver microsomes, with apparent Ki values of 8.85 and 24.46 microM, respectively. In each case, the mode of inhibition was noncompetitive. APE also inhibited tolbutamide hydroxylation both in rat and human microsomes with apparent Ki values of 8.21 and 7.51 microM, respectively and the mode of inhibition was mixed type. In addition, APE showed a competitive inhibition only on CYP3A4 in human microsomes with Ki of 25.43 microM. AND was found to be a weak inhibitor of rat CYP2E1 with a Ki of 61.1 microM but did not affect human CYP2E1. In conclusion, it cannot be excluded from the present study that APE could cause drug-drug interactions in humans through CYP3A and 2C9 inhibition.

Emergency surgery for obstructing colonic cancer: a comparison between right-sided and left-sided lesions.

PURPOSE: Few studies compare management and outcomes of obstructive colonic cancer, depending on the tumor site. We aim to evaluate the differences in patient characteristics, tumor characteristics, and outcomes of emergency surgery for obstructive right-sided versus left-sided colonic cancers. METHODS: Between 2000 and 2009, 71 consecutive patients had an emergency colectomy following strict and clear definition of obstruction in a single institution. We retrospectively analyzed pre, per, and postoperative data that were prospectively collected. RESULTS: There were 31 and 40 patients in the right and left group, respectively. Patients aged over 80 were more frequent in the right group (p = 0.03). At operation, ileocecal valve was less often competent in the right group (p = 0.03). The one-stage strategy was more frequent in the right group (p = 0.008). Patients in the right group had a higher rate of nodes invasion (p = 0.04). One- and two-year mortality rate in the right group had a tendency to be higher. CONCLUSIONS: Patients presenting with a right obstructive colonic cancer are older, have a more advanced locoregional disease, and are more often treated in a one-stage strategy than patients with a left obstructive tumor.

Combined Treatment of a Gallbladder Volvulus with a Common Bile Duct Obstruction.

Gallbladder volvulus is a rare disease and can lead to an acute cholecystitis. We report the case of an elderly woman with a gallbladder volvulus, diagnosed at CT scan and treated by surgery and endoscopic sphincterotomy.

[Ganglioneuroma revealed by complicated nephritic colic]. / Ganglioneurome rétropéritonéal révélé par une colique néphrétique compliquée.

INTRODUCTION: Ganglioneuroma is a rare benign nervous tumour frequently located in the retroperitoneal area. We report the case of a 22-year-old female patient where this tumour was revealed by nephritic colic complicated by pyelitis and kidney abscess. EXEGESIS: The patient presented with brutal feverish lumbar pains and urinary signs. Abundant iconography, in particular contrasted enhanced sonography, allowed to show a massive retroperitoneal lump and a puncture-biopsy indicated a ganglioneuroma which was surgically removed by laparotomy. Signs may be varied and misleading. Biological and radiological exams are useful for the diagnosis which can only be confirmed by the thorough histological examination of the removed sample. CONCLUSION: A large retroperitoneal lump without alteration of the patient's health should point to this diagnosis, since the complete surgical removal leads to recovery without recurrence, but all the other differential diagnoses must first be dismissed.

[Retrospective and comparative study of the medicoeconomical impact of a new mesh in the treatment of anterior abdominal wall incisinal hernia]. / Etude comparative rétrospective de l'impact médicoéconomique d'un renfort innovant dans la cure des éventrations de la paroi abdominale antérieure.

STUDY AIM: Determine the gain of hospitalization cost using a new intraperitoneal mesh compared to the retro-muscular pre-fascial implantation of a polyester mesh. PATIENTS AND METHODS: From January 1998 to June 2000, 52 patients with incisional hernia of the anterior abdominal wall were operated using intraperitoneal Parietex composite Mesh. The cost of surgery, anesthesia and hospitalization in this group were compared to similar data from a group of 21 patient where a Mesrsuture mesh in a prefascial retromuscular position was used. RESULTS: Parietex Composite Mesh in intraperitoneal position allows a significative reduction in surgery time, anesthesia time and hospitalization. The clinical results were confirmed by cost savings. CONCLUSION: Using new innovative medical device changing surgery technique insures significant cost saving despite its initial additional cost and increases patient's comfort during hospitalization.

Professional risks when carrying out cytoreductive surgery for peritoneal malignancy with hyperthermic intraperitoneal chemotherapy (HIPEC): A French multicentric survey.

BACKGROUND: Over the last two decades, many surgical teams have developed programs to treat peritoneal carcinomatosis with extensive cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC). Currently, there are no specific recommendations for HIPEC procedures concerning environmental contamination risk management, personal protective equipment (PPE), or occupational health supervision. METHODS: A survey of the institutional practices among all French teams currently performing HIPEC procedures was carried out via the French network for the treatment of rare peritoneal malignancies (RENAPE). RESULTS: Thirty three surgical teams responded, 14 (42.4%) which reported more than 10 years of HIPEC experience. Some practices were widespread, such as using HIPEC machine approved by the European Community (100%), individualized or centralized smoke evacuation (81.8%), "open" abdominal coverage during perfusion (75.8%), and maintaining the same surgeon throughout the procedure (69.7%). Others were more heterogeneous, including laminar flow air circulation (54.5%) and the provision of safety protocols in the event of perfusate spills (51.5%). The use of specialized personal protective equipment is ubiquitous (93.9%) but widely variable between programs. CONCLUSION: Protocols regarding cytoreductive surgery/HIPEC and the associated professional risks in France lack standardization and should be established.

Central nervous system delivery of recombinant ciliary neurotrophic factor by polymer encapsulated differentiated C2C12 myoblasts.

Neurotrophic factors hold promise for the treatment of neurodegenerative diseases. Intrathecal transplantation of polymer encapsulated cell lines genetically engineered to release neurotrophic factors provides a means to deliver them continuously behind the blood-brain barrier. Long-term delivery, however, may benefit from the use of conditionally mitotic cells to avoid the overgrowth observed with continuously dividing cell lines. Myoblast lines have all the advantages of dividing cell lines, i.e., unlimited availability, possibility for in vitro screening for the presence of pathogens, suitability for stable gene transfer and clonal selection. Furthermore they can be differentiated into a nonmitotic stage upon exposure to low-serum-containing medium. In this study, mouse C2C12 myoblasts were transfected with a pNUT expression vector containing the human ciliary neurotrophic factor (CNTF) gene. hCNTF expression and bioactivity were demonstrated by Northern blot, ELISA assay, and measurement of choline acetyltransferase (ChAT) activity in embryonic spinal cord motor neuron cultures. One C2C12 clone was found to secrete 200 ng of CNTF/10(6) cells per day. The rate of secretion of hCNTF was not altered upon differentiation of C2C12 myoblasts. A bromodeoxyuridine (BrdU) proliferation assay indicated that approximately 12% of the myoblasts continue to divide after 4 days in low-serum-containing medium. The presence of the herpes simplex thymidine kinase gene (HSV-tk) in the expression vector, however, provides a way to eliminate these dividing myoblasts upon exposure to ganciclovir, therefore increasing the safety of the encapsulation technology using established cell lines. Encapsulated hCNTF-C2C12 cells can partially rescue motor neurons from axotomy-induced cell death. In adult rats, intrathecal implantation of encapsulated hCNTF-C2C12 cells or control C2C12 confirmed the long-term survival of these cells and their potential use as a source of neurotophic factors for the treatment of neurodegenerative diseases.

Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF.

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containing around 10(6) genetically modified cells surrounded by a semipermeable membrane, is implanted intrathecally; it provides for slow continuous release of hCNTF at a rate of 0.25 to 1.0 micrograms/24 hours. The semipermeable membrane prevents immunologic rejection of the cells and interposes a physical, virally impermeable barrier between cells and host. Moreover, the device and the cells it contains may be retrieved in the event of side effects. A vector containing the human CNTF gene was transfected into a line of baby hamster kidney cells (BHK) with calcium phosphate using a dihydrofolate reductase-based selection vector with a SV40 promoter and contains a HSV-tk killer gene. hCNTF is a potent neurotrophic factor which may have utility for the treatment of ALS. Systemic delivery of hCNTF in humans has been frustrated by peripheral side effects, the molecule's short half life, and its inability to cross the blood-brain barrier. The gene therapy approach described in this protocol is expected to mitigate such difficulties by local intrathecal delivery of a known quantity of continuously-synthesized hCNTF from a retrievable implant.

Pattern of chromosomal imbalances in non-B virus related hepatocellular carcinoma detected by comparative genomic hybridization.

Only limited data are available on comparative genomic hybridization (CGH) in hepatocellular carcinoma (HCC). They concern mainly B virus related HCC. Therefore, we used CGH to detect chromosomal imbalances in 16 non-B virus related HCC in alcoholic cirrhosis in 7 cases (HA1 to HA7), in C virus cirrhosis in 7 cases (HC1 to HC7), in non-cirrhotic liver in 2 cases (NC1, NC2), and in 9 non-malignant cirrhotic tissues. The most frequent imbalances in HCC were gains of whole chromosomes or chromosomal regions 7 or 7q (10/16, 62%), 1q (9/16, 56%), 5 or 5q (9/16, 56%), 8q (8/16, 50%), 6p (6/16, 37%), 15q (5/16, 31%), 20 or 20q (5/16, 31%), and losses of 17p (6/16, 37%), and 8p (5/16, 31%). High-level gains were identified in HCC on 1q (2/16), 3q (1/16), 7q (1/16), and 8q (3/16). No chromosomal imbalances were detected in any of the cirrhotic tissues. Most of the gains, losses, and amplifications detected in this CGH study corresponded well to those identified in previous studies, except for gains of whole chromosome 5 or 7 and/or of chromosome arms 5q or 7q and losses on 4q. Our results suggest that other chromosomal regions are involved in hepatocarcinogenesis.

Cellular localisations of interleukin-1 beta, interleukin-6 and tumor necrosis factor-alpha mRNA in a parasitic granulomatous disease of the liver, alveolar echinococcosis.

Alveolar echinococcosis (AE), an uncommon and very severe parasitic liver disease, can be considered as an "infectious model" of granulomatous disease, where cellular immunity plays a key role in the defence against Echinococcus multilocularis, the larval cestode responsible for the disease. We analysed the localisation of the expression of the pro-inflammatory cytokines IL-1 beta, IL-6 and TNF-alpha mRNA in human AE liver lesions, in the periparasitic granulomas and in the hepatic parenchyma, as well as the phenotypic characteristics of the cells on serial sections. In situ hybridizations, using anti-sense 35S dUTP-labeled IL-1 beta, IL-6 and TNF-alpha riboprobes, were performed on cryostat liver sections; the sense probes were used as negative controls. IL-1 beta, IL-6 and TNF-alpha mRNA were observed in macrophages located at the extreme periphery of the granuloma, between the lymphocytic ring and the liver parenchyma, in patients with active AE. No cytokine mRNA expression was observed in a patient with an abortive case. Only TNF-alpha mRNA was located in the periparasitic area, in cells morphologically identified as macrophages but exhibiting an unusual phenotype (CD 11b-, CD 25+); this particular expression was observed only in those patients with very fertile lesions, associated with centro-granulomatous necrosis. These results show that pro-inflammatory cytokines are consistently produced by macrophages at the periphery of the periparasitic granuloma and can serve as mediators of acute-phase protein secretion and of fibrogenesis in that location.(ABSTRACT TRUNCATED AT 250 WORDS)

A twenty-year history of alveolar echinococcosis: analysis of a series of 117 patients from eastern France.

OBJECTIVES: Alveolar echinococcosis of the liver is a very rare and severe parasitic disease due to the growth of the larva of Echinococcus multilocularis. The aim of this paper was to describe a 20-year study of the epidemiological, clinical and therapeutic aspects of alveolar echinococcosis in eastern France. DESIGN: One hundred and seventeen consecutive cases, diagnosed and followed in our liver unit, were studied from 1972 to 1993. METHODS: Data from 85 patients followed since 1983 (period B) were compared to data from a first series of 32 patients (period A) collected from 1972 to 1982; 1983 was chosen as the cut-off year because of the numerous changes that occurred in the diagnosis, follow-up and treatment of the disease at this time, in particular the introduction of parasitostatic benzimidazoles. RESULTS: The results of patient follow-up were evaluated in December 1997. The cumulative prevalence was 2.5 per 100,000 persons in period A whereas it reached 6.6 per 100,000 in period B. The annual incidence in period B was 7.3 on average, compared with 2.7 in period A. Twenty-nine per cent of patients from period B were asymptomatic at the time of diagnosis compared with 10% in period A. This change was correlated with less advanced liver lesions, and was related to the extensive use of abdominal ultrasound, and from 1987, serological screening. Curative resections were performed in 24% of the cases in period B versus only 3% in period A. From 1986, liver transplantations were performed in eight patients from period A and 13 patients from period B. In period B, palliative surgery was frequently replaced by radiological non-operative procedures to treat abscesses and jaundice. From 1982, 73 patients received benzimidazoles for a period of time ranging from 4 to 138 months. Stabilization of the lesions was observed in two-thirds of the patients. Episodes of jaundice or digestive haemorrhage due to portal hypertension were 31.5 and 11 times less frequent respectively in patients from period B compared with period A. Actuarial survival at 5 years improved from 67% in period A to 88% in period B in patients of similar age. CONCLUSIONS: Radical changes in the diagnosis and the management of alveolar echinococcosis have occurred during the last decade. Together they have contributed to an improvement in the status of the patients affected by this very severe parasitic disease.

Quaternary ammonium compound stresses induce specific variations in fatty acid composition of Pseudomonas aeruginosa.

The involvement of cell membrane fatty acids in resistance of Pseudomonas aeruginosa to Quaternary Ammonium Compounds (QACs) stresses was investigated. The strain was grown in a medium with increasing concentrations of different biocides: two QACs, and two non-QACs. In the presence of two QACs only, the strain was able to grow with increasing concentrations. During cellular adaptation to QACs, the resistance to the same biocide increased. A principal component analysis was performed with whole of fatty acid compositions which highlighted a specific variation for the cultures in presence of QACs. These modifications gave evidence of the outer membrane involvement in cellular response to the presence of QACs.

Effect of temperature and physiological state on the fatty acid composition of Pseudomonas aeruginosa.

The influence of temperature and physiological state on fatty acid profiles of cell membranes of a gram-negative bacteria was studied in this work. It has been shown that fatty acid composition is largely modified by these two parameters. Lipids play an important role in the composition and the function of cell membranes. These modifications of membrane structures are very important to understand because of their consequences on cell viability.