[ACUTE RESPIRATORY DISTRESS SYNDROME AND OTHER RESPIRATORY DISORDERS IN SEPSIS].

Acute respiratory distress syndrome (ARDS) develops in patients with predisposing conditions that induce systemic inflammatory response such as sepsis, pneumonia, acute pancreatitis, major trauma, or multiple transfusions. Sepsis is the most common cause of ARDS. Sepsis-related ARDS patients have significantly lower PaO2 /FiO2 ratios than patients with non-sepsis-related ARDS. Furthermore, their recovery from lung injury is prolonged, weaning from mechanical ventilation less successful, and extubation rate slower. Clinical outcomes in patients with sepsis-related ARDS are also worse, associated with significantly higher 28-day and 60-day mortality rates (31.1% vs. 16.3% and 38.2% vs. 22.6%, respectively). It is extremely important to optimally adjust ventilator setting to current condition of lungs, while providing all other therapeutic measures in the treatment of sepsis, severe sepsis and septic shock. The pool of data on treatment possibilities for patients with ARDS grows every year, with specifically designed mechanical ventilation strategies. Ventilator modes and adequate positive end-expiratory pressure (PEEP) settings play a major role in these strategies. However, how can we best apply these experimental and clinical data to everyday clinical practice? This article emphasizes protective ventilation as a measure that is proven to reduce mortality in this group of patients, when systematically and consistently applied.

To Pringle or not to pringle: is Pedicle clamping a necessity in liver resection?

A single center prospective study was done to evaluate the role of hepatic portal pedicle clamping (PC) during right hepatectomy (RH) in patients with primary and secondary liver tumors. Cirrhotics were excluded. Two groups were compared for preoperative demographics including diagnosis, tumor size, portal vein embolization and liver enzymes, pre and postoperative hemoglobin levels, percentage of residual liver mass, morbidity and mortality, pedicle clamp time, intensive care unit stay, length of hospital stay and blood loss. We observed no significant difference in the analysis of the post-operative hemoglobin, liver enzymes, residual liver size, size of tumor resected, need for postoperative monitoring in ICU stay, length of hospital stay and blood loss. Mortality and morbidity were the same. None of the patients were transfused during surgery. Our findings show that pedicle clamping was beneficial 15% of the time when uncontrolled intra-operative bleeding was encountered or in a subset of patients with peliosis, steatohepatitis, Jehovah Witness patient, and post-chemotherapy patients. However, its advantage has to be weighed against the disadvantages.

Interactions between immunity and metabolism - contributions from the metabolic profiling of parasite-rodent models.

A combined interdisciplinary research strategy is even more crucial in immunology than in many other biological sciences in order to comprehend the closely linked interactions between cell proliferation, molecular signalling and gene rearrangements. Because of the multi-dimensional nature of the immune system, an abundance of different experimental approaches has developed, with a main focus on cellular and molecular mechanisms. The role of metabolism in immunity has been underexplored so far, and yet researchers have made important contributions in describing associations of immune processes and metabolic pathways, such as the central role of the l-arginine pathway in macrophage activation or the immune regulatory functions of the nucleotides. Furthermore, metabolite supplement studies, including nutritional administration and labelled substrates, have opened up new means of manipulating immune mechanisms. Metabolic profiling has introduced a reproducible platform for systemic assessment of changes at the small-molecule level within a host organism, and specific metabolic fingerprints of several parasitic infections have been characterized by 1H NMR spectroscopy. The application of multivariate statistical methods to spectral data has facilitated recovery of biomarkers, such as increased acute phase protein signals, and enabled direct correlation to the relative cytokine levels, which encourages further application of metabolic profiling to explore immune regulatory systems.

Laparoscopic approach in surgical treatment of rectal cancer.

BACKGROUND: High rates of conversion to open operation and morbidity have been reported after laparoscopic total mesorectal excision (TME) with sphincter preservation for rectal cancer. This study examined risk factors for conversion and morbidity to determine which patients with rectal cancer could benefit from a laparoscopic resection. METHODS: Two hundred patients (117 men) with mid and low rectal cancer treated by laparoscopic TME were studied. The impact of clinical and pathological characteristics on conversion and complications was assessed by multivariable analysis. RESULTS: Reconstruction after TME included 79 low colorectal and 121 coloanal anastomoses. Conversion was necessary in 31 patients (15.5 per cent), and was independently associated with sex, type of anastomosis and intraoperative rectal fixity. Postoperative morbidity in 50 patients (25.0 per cent) was independently associated with sex and type of anastomosis. Men with a stapled anastomosis had a threefold higher rate of conversion (13 (34 per cent) of 38 versus 18 (11.1 per cent) of 162; P < 0.001) and morbidity (22 (58 per cent) versus 28 (17.3 per cent); P < 0.001) than other patients. CONCLUSION: Laparoscopic TME is a good option for women and for men treated by coloanal anastomosis. Technical improvement of laparoscopic stapling is needed before the laparoscopic approach can be offered to all patients.

Cytokeratin 7 and 20 expression in cholangiocarcinomas varies along the biliary tract but still differs from that in colorectal carcinoma metastasis.

In the liver, the immunostaining of cytokeratins (CK) 7 and 20 has been used to distinguish usual peripheral cholangiocarcinomas (CC) and colorectal carcinoma metastasis (CRM). However, other subtypes of CC are not infrequent and may be particularly difficult to distinguish from CRM by histology and even immunohistochemistry. Therefore, 48 CC from different locations, either peripheral (n = 19), or nonperipheral, that is, from the large intrahepatic bile ducts, the hilum, and the extrahepatic bile ducts (n = 29), and with different cytoarchitectural patterns were tested for CK7 and CK20 and compared with 31 CRM. CC were positive for CK7 and CK20 in 96% and 70%, respectively, whatever the architecture and differentiation of the tumor. The labeling index (LI) of CK7 in CC was always high, whereas it was low or moderate for CK20. CK20-positive phenotype was significantly more frequent in nonperipheral than in peripheral CC (82% vs 47%; p = 0.007). CRM were all positive for CK20 with a high LI, and mostly negative (81%) for CK7. In conclusion, (1) the CK immunoprofile of CC varies according to the location of the tumor in the biliary tract, peripheral CC being more often CK7+/CK20-, and nonperipheral ones CK7+/CK20+; and (2) a decision tree based on CK20 LI and CK7 positivity allows the distinction of CRM and CC, even for the nonperipheral type.

Liver adenomatosis with granulomas in two patients on long-term oral contraceptives.

We report two cases of liver cell adenomatosis associated with granulomatous hepatitis, both developed in white women (52 and 39 years of age) on long-term oral contraceptives (for 18 and 12 years, respectively). The first patient underwent surgery for five hepatic tumors 1-7 cm in diameter; the other patient had a partial segmentectomy for a 4-cm hepatic nodule of the right lobe. In both cases, dissection of the liver showed many other diffuse and smaller nodules. Histologically, all tumors were benign liver cell adenomas, with cellular atypia in the largest tumor and associated in both cases with granulomatous hepatitis, with numerous noncaseating epithelioid and giant cell granulomas located either only in the tumors (case 1) or diffusely in the tumoral and nontumoral hepatic parenchyma (case 2). During follow-up, ultrasound showed new nodular lesions in case 2, whereas in case 1 evolution was uneventful. In estroprogestative-associated liver diseases, adenomas are common, but adenomatosis and granulomas are rare. An association of these latter two conditions would seem to be exceptional. The prognosis for adenomatosis remains uncertain.

Adenomatous hyperplasia in cirrhotic livers: histological evaluation, cellular density, and proliferative activity of 35 macronodular lesions in the cirrhotic explants of 10 adult French patients.

We examined 41 consecutive cirrhotic liver explants from French patients for the presence of nodules of adenomatous hyperplasia (AH) and then analyzed these lesions, together with underlying cirrhosis (C) and associated hepatocellular carcinoma (HCC), for various histological parameters, cellular density, and proliferative activity. Thirty-five AHs were identified in 10 livers (prevalence, 24%); seven of 10 were HCV positive. Hepatocellular carcinoma was more frequent in patients with AH than in patients without. The AHs consisted of 17 ordinary (OAH) and 18 atypical (AAH) adenomatous hyperplasia lesions. There was a malignant focus in five of the 18 AAHs. Wide areas of large liver cell dysplasia were frequent in OAH but never found in AAH. Obvious steatosis was frequent in HCC but exceptional in AAH and absent in OAH. There was a significant increase in cellular density in AAH and HCC as compared with C and OAH. Proliferative cell nuclear antigen immunostaining similarly showed an increase in proliferation from OAH or C to AAH and HCC. These data suggest that, in Europe as in Japan, one pathway of hepatocarcinogenesis is a multistep process in which AAH should be considered as a premalignant lesion very close to grade I HCC, while OAH seems to correspond to a regenerative nodule with limited proliferative ability.

Early patchy hepatic necrosis. Its appearance after bile-duct ligation in rats with a portacaval shunt.

We incidentally observed that rats with portacaval shunts (PCS) had patchy hepatic necrosis after bile-duct ligation (BDL). Rats with two weeks of PCS underwent BDL, then were killed after 0,5 or 20 hours, or two or four days; rats undergoing sham PCS were used as controls. Patchy hepatic necrosis distributed at random within the acinus was mainly lytic after five and 20 hours, then displayed inflammatory features after two days. The inflammation tends to disappear by four days, with a differentiation of new hepatocytes into neo-bile ducts. These necrotic areas were 60 times more severe after five hours, and 20 times more severe after 20 hours in rats undergoing PCS than in those undergoing sham PCS. In the former group, necrosis after five hours represented 1.92% of the total area examined. Histological characteristics and the high incidence with PCA suggest that necroses have vascular origin.

Chance discovery of hepatic fibrosis in patient with asymptomatic hypervitaminosis A.

A liver biopsy specimen was obtained from a 50-year-old patient whose clinical and functional liver tests showed no abnormalities but who had for some time a high vitamin A intake (109 X 10(6) IU over four years). Liver architecture was normal. Sinusoids were slightly dilated in zone 2. Perisinusoidal cells were numerous and enlarged. On Sirius red staining, there was mild fibrosis of the central veins, portal tracts, and terminal portal venules and perisinusoidal fibrosis in zone 1 of the acinus. Liver vitamin A level was increased. By electron microscopy, perisinusoidal cells filled with numerous lipid droplets had slightly dilated rough endoplasmic reticulum, numerous minute filament condensations below the plasma membrane, and stellate-shaped processes giving them the appearance of fibroblast-myofibroblast-like cells. Numerous collagen bundles, fibrils, amorphous material, and fragments of basement membrane-like material were identified in Disse's space. Immunocytochemistry showed increased amounts of collagen types I, III, IV, laminin, and fibronectin. This observation suggests that vitamin A per se, and not the cellular damage often seen in hypervitaminosis A, is responsible for fibrosis.

[Conformal therapy of locally advanced cholangiocarcinoma of the main bile ducts]. / Radiothérapie conformationnelle des cholangiocarcinomes de la voie biliaire principale localement évolués.

PURPOSE: Retrospective study of 23 patients treated with conformal radiotherapy for a locally advanced bile duct carcinoma. PATIENTS AND METHODS: Eight cases were irradiated after a radical resection (R0), because they were N+; seven after microscopically incomplete resection (R1); seven were not resected (R2). A dose of 45 of 50 Gy was delivered, followed by a boost up to 60 Gy in R1 and R2 groups. Concomitant chemotherapy was given in 15 cases. RESULTS: Late toxicity included a stenosis of the duodenum, and one of the biliary anastomosis. Two patients died from cholangitis, the mechanism of which remains unclear. Five patients are in complete remission, six had a local relapse, four developed a peritoneal carcinosis, and six distant metastases. Actuarial survival rate is 75%, 28% and 7% at 1, 3 and 5 years, respectively (median: 16.5 months). Seven patients are still alive with a 4 to 70 months follow-up. Survival is similar in the 3 small subgroups. The poor local control among R0N+ cases might be related to the absence of a boost to the "tumor bed". In R1 patients, relapses were mainly distant metastases, whereas local and peritoneal recurrences predominated in R2. CONCLUSION: Conformal radiochemotherapy delivering 60 Gy represents a valuable palliative approach in locally advanced biliary carcinoma.

[Perfusion-fixation of liver needle biopsy: technic]. / Perfusion-fixation des biopsies hépatiques à l'aiguille: technique.

Technical details concerning the perfusion-fixation of liver needle biopsies are described. The biopsy (less than or equal to 0,5 cm length) migrated in a Pasteur pipette filled with heparinized Ringer solution and stopped when its diameter corresponded to the internal diameter of the pipette. The pipette was cut above the upper part of the biopsy. The biopsy was perfused with a thin needle (external diameter 0.2 mm) struck in the upper part of the biopsy under binocular microscopy control. Fixation medium, 2.5 p. 100 glutaraldehyde, was aspirated at the inferior extremity of the pipette. The aspiration speed was equal to the perfusion speed (0.15 ml/min). The biopsy was perfused for 5-8 min. This simple technique allows for detailed electron microscopic examination of sinusoids, sinusoidal and perisinusoidal cells as well as of the spaces of Disse.

[Gastric duplication or pancreatic pseudocyst. Diagnostic difficulties apropos of a case]. / Duplication gastrique ou pseudo-kyste pancréatique. Difficultés diagnostiques à propos d'un cas.

Gastric duplication was diagnosed in a 50 year-old patient who was initially thought to have a pancreatic pseudo-cyst until laparotomy was performed. There are many clinical and radiological similarities between gastric duplication and pancreatic pseudo-cyst. However, the following elements can suggest the diagnosis of gastric duplication in the case of the discovery of a cystic mass in the gastric or pancreatic area: normal pancreatic enzyme levels, ultrasonic identification of a hyperechoic inner rim and a hypoechoic outer rim with peristaltic movements into the cyst, visualization of a communication between the cyst and the gastro-intestinal tract, and detection of associated vertebral abnormalities. Surgical treatment of gastric duplication is only necessary in symptomatic cases.

[Hiatal hernia with intrathoracic gastric volvulus as a rare cause of biliary obstruction]. / Hernie hiatale avec volvulus intrathoracique: une cause rare d'ictère obstructif.

Gastric volvulus can complicate paraesophageal hiatal hernia. Acquired gastric torsion results in acute or chronic gastrointestinal symptoms. Biliary complications are possible but exceptional. A case of asymptomatic diaphragmatic hiatal hernia with intrathoracic gastric volvulus presenting as a cholestatic syndrome secondary to stretching and tension of the common bile duct in the diaphragmatic hiatus is reported. This observation emphasizes the possibility of direct relationship between two otherwise frequent diagnostics: hiatal hernia and biliary obstruction. Only one similar case has been reported to date.

[Premalignant lesions and hepatocellular carcinoma on non cirrhotic liver overloaded with iron]. / Lésions précancéreuses et carcinome hépatocellulaire développés sur foie non cirrhotique surchargé en fer.

A 68-year old mildly obese Caucasian man underwent hepatic resection for multinodular hepatocellular carcinoma which had developed in the left lobe of a non-cirrhotic liver. The only risk factors found were heavy drinking, smoking, and serum markers of hepatitis B virus without virus genome in hepatocytes. The non tumoral liver was mildly fibrotic and iron overloaded (hepatic iron index: 1.6) with three types of iron-free lesions: (i) periportal clear hepatocyte foci, (ii) hyperplastic nodules and (iii) dysplastic or neoplastic nodules with well to moderately-differentiated hepatocellular carcinoma. The genetic investigation was negative for the C282Y and the H63D mutations of the HFE gene. This observation illustrates the multistep process of carcinogenesis in the non-cirrhotic liver and raises the question of i) the origin of this iron overload possibly linked to insulin resistance syndrome and ii) the role of iron as a co-carcinogen.

[Liver transplantation and constrictive pericarditis]. / Transplantation hépatique et péricardite constrictive.

We report the case of a patient with refractory ascitis due to a constrictive pericarditis who underwent a liver transplantation with the initial diagnosis of cryptogenic cirrhosis. The cardiac origin was suspected 5 months post surgery when a liver biopsy showed lesions in favor of a post sinusoidal shunt. The diagnosis was confirmed by the increased values of the right intra-ventricular pressures. We discuss the causes of the delay of the diagnosis and, in particular, the difficulty to interpret vascular liver lesions. Such vascular lesions were present on the needle biopsy performed prior to transplantation but wrongly interpreted as cirrhosis.

[Vascular pathology of the portal vein distal branches: a rare cause of liver transplantation and a protean clinical presentation]. / Pathologie vasculaire des branches distales de la veine porte.

We report 5 cases of liver transplantation which showed phlebosclerotic lesions of the distal portal vein on the explant confirming a diagnosis of hepatoportal sclerosis. This lesion was associated with nodular regenerative hyperplasia (2 cases), incomplete septal cirrhosis (4 cases) and tumors (2 cases, 1 adenoma and 1 hepatocellular carcinoma). Indications for transplant were chronic liver failure (1 case), encephalopathy without liver insufficiency (2 cases), an adenoma (1 case), a liver mass (1 case). Three patients out of 5 had a past history of surgical portacaval shunts to treat variceal bleeding non related to cirrhosis, one had a spontaneous portacaval shunt, and 2 had undergone a splenectomy for pancytopenia. The review of liver biopsies (4 cases out of 5) performed during surgery showed distal portal vein phlebosclerotic lesions. The diagnosis of hepatoportal sclerosis associated with complications, which is obvious retrospectively, is seldom made prior to transplantation. Portacaval shunts could play at least a partial role in the progressive deterioration of the liver.

[Upper extremity deep venous thrombosis. 40 hospitalized patients]. / Thromboses veineuses profondes des membres supérieurs: à propos de 40 patients hospitalisés.

Deep venous thrombosis is 50 times less frequent in upper than in lower limbs. Data remain poor in the literature. Forty consecutive patients (24 males, 16 females, mean age: 54.5 years) were retrospectively analysed from 161 subjects who underwent venous explorations of the upper extremity for a 3.5 year period in the same center. Diagnosis of thrombosis was made by duplex ultrasonography (n =37) or phlebography (n =3). Main clinical manifestations were edema (n =36) and pain (n =29). Location of thrombosis was humeral (n =1), axillary (n =2), or sub-clavian (n =37, 2 bilateral). The majority of thrombosis (n =29) were secondary to cancer and venous catheter (n =19, 15 implanted ports), to central catheter alone (n =3) or cancer alone (n =7). The 11 others were associated with thoracic outlet syndrome (n =6) or apparent primary thrombosis (n =5). Thrombophilia was identified in 6 out of these 11. During follow up [mean of 9 months (0,5-36)], two patients developed pulmonary embolism, 14 a post-thrombotic syndrome and 16 patients died. Initial therapy included heparin (n =36) or fibrinolysis (n =4). Upper extremity deep venous thrombosis are mostly associated with cancers and venous catheters. Thrombophilia is frequent in the other cases. Heparin followed by oral anticoagulation is the optimal therapy whose duration depends upon underlying condition. Fibrinolysis has not been useful for preventing post-thrombotic syndrome in our study.

[Three deceptive cases of intrahepatic metastases of colorectal origin with endobiliary growth, simulating cholangiocarcinoma. Importance of immunostaining of cytokeratin 7 and 20]. / Trois cas trompeurs de métastases intrahépatiques d'origine colorectale à développement endobiliaire, simulant un cholangiocarcinome. Intérêt de l'immunomarquage des cytokératines 7 et 20.

Malignant tumors of the liver with intrabiliary growth are rare, except for some cholangiocarcinomas. Metastases with intrabiliary growth, whatever their origin, are rare. Moreover, colorectal metastasis can be particularly difficult to distinguish morphologically from some cholangiocarcinomas. We report 3 cases of late colorectal metastasis with intrabiliary growth, presenting as cholangiocarcinomas of the large ducts. Immunostaining with cytokeratins 7 and 20 attested the diagnostic and pointed out the spreading pattern of colorectal metastasis within biliary ducts. This study illustrates the capacity, probably underestimated, for colorectal metastasis to develop in the lumen of bile ducts and emphasizes the relevance of cytokeratin 7 and 20 immunostainings in such cases.

[Hepatobiliary cystadenoma with mesenchymal stroma: a hormone dependent tumor. Report of five cases with immunohistochemical study of hormone receptors]. / Cystadénome hépatobiliaire à stroma mésenchymateux: une tumeur hormonodépendante?

Hepatobiliary cystadenomas with mesenchymal stroma are rare neoplasms, which occur only in females; they have a strong tendency to recur and a potential for malignant transformation. Microscopic features are characteristic but clinical findings are highly variable and laboratory data non specific. We report 5 cases with immunohistochemical study, showing the characteristics of mesenchymal stromal cells: myofibroblastic phenotype and expression of progesterone receptors in all cases and estrogen receptors in 3 out of 5 cases. These results point out the possible hormonal dependance of this tumor.

[Anorectal reconstruction by coloperineal anastomosis and dynamic double graciloplasty after abdomino-perineal resection]. / Reconstruction anorectale par anastomose colo-périnéale et double graciloplastie dynamique après amputation abdomino-périnéale.

UNLABELLED: The aim of this study was to assess the technical and functional results of total anorectal reconstruction with double dynamic graciloplasty after abdominoperineal resection (APR). PATIENTS AND METHODS: From May 1995 to December 1996. 10 patients (6 males and 4 females), with a mean age of 54 years (range 39-74), underwent anorectal reconstruction for low rectal adenocarcinoma. All patients had preoperative radiotherapy and six had postoperative chemotherapy. The surgical procedure was performed in three stages: 1) APR, coloperineal anastomosis, double graciloplasty and ileostomy; 2) three months later, implantation of stimulator and leads; 3) after a two-months training period, the stoma was closed. RESULTS: There was no postoperative mortality. Early and late morbidity occurred in 5 patients: 2 colonic fistulas, 1 necrosis of colon, 1 ileostomy prolapse, 1 neosphincter stenosis, 1 sepsis of stimulator. No patient had recurrence of the disease (mean follow-up 16 months), but two patients died at 3 and 8 months, respectively from anorexia and pulmonary embolism. Seven patients were available for evaluation (2 fistula, 1 death). Before training, the resting pressure and the squeeze pressure were 30 and 175 cm H2O respectively. At the time of evaluation, the electrical stimulated pressure was 95 cm H2O. Six of these 7 patients were continent (5 with spontaneous defecation, 1 with enemas) and 1 was incontinent. CONCLUSIONS: Anorectal reconstruction with dynamic graciloplasty can be an alternative to permanent colostomy for selected patients after APR. However, there is a high morbidity and the quality of life of the patients must be evaluated.