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Despite the rapid discovery of genes for rare genetic disorders, we continue to encounter individuals presenting with hitherto unknown syndromic manifestations. Here, we have studied four affected people in three families presenting with cholestasis, congenital diarrhea, impaired hearing and bone fragility, a clinical entity we have termed O2HE (Osteo-Oto-Hepato-enteric) syndrome. Whole exome sequencing of all affected individuals and their parents identified biallelic mutations in Unc-45 Myosin Chaperone A (UNC45A), as a likely driver for this disorder. Subsequent in vitro and in vivo functional studies of the candidate gene indicated a loss of function paradigm, wherein mutations attenuated or abolished protein activity with concomitant defects in gut development and function.

The liver represents the third most frequent site of metastasis in patients with breast cancer. We performed in vivo selection using 4T1 breast cancer cells to identify genes associated with the liver metastatic phenotype. Coincident with the loss of numerous tight-junctional proteins, we observe claudin-2 overexpression, specifically in liver-aggressive breast cancer cells. We further demonstrate that claudin-2 is both necessary and sufficient for the ability of 4T1 breast cancer cells to colonize and grow in the liver. The liver-aggressive breast cancer cells display a claudin-2-mediated increase in their ability to adhere to extracellular matrix (ECM) components, such as fibronectin and type IV collagen. Claudin-2 facilitates these cell/matrix interactions by increasing the cell surface expression of α(2)β(1)- and α(5)β(1)-integrin complexes in breast cancer cells. Indeed, claudin-2-mediated adhesion to fibronectin and type IV collagen can be blocked with neutralizing antibodies that target α(5)β(1) and α(2)β(1) complexes, respectively. Immunohistochemical analyses reveal that claudin-2, although weakly expressed in primary human breast cancers, is readily detected in all liver metastasis samples examined to date. Together, these results uncover novel roles for claudin-2 in promoting breast cancer adhesion to the ECM and define its importance during breast cancer metastasis to the liver.

We reviewed the indications for and the results of bone marrow examination (BME) from HIV-infected patients as an attempt to improve its diagnostic yield. One-hundred-and-eight bone marrow specimens from 90 patients during a 3-year period were examined. A cytological, histological and microbiological study was carried out on the specimens. Forty-three evaluable examinations (40% of total) performed for cytopenia showed normo- or hypercellularity in 33 (77%). Fifty bone marrow specimens were cultured for mycobacteria with a yield of 42% when the indication was persistent fever. Positive cultures yielded Mycobacterium avium complex in 8 out of 12 patients. Twenty-seven patients had both culture and biopsy; granulomas were associated with all the positive (10/10) and with 1 out of 17 negative cultures (chi-square test: p < 0.001). A bone marrow involvement with lymphoma was found in 2 out of 6 patients with previously diagnosed lymphoma, and biopsy revealed a lymphoma in 2 patients. Morphological bone marrow examination should be associated with other techniques in order to appreciate bone marrow production. Bone marrow biopsy is useful for the investigation of persistent fever since granulomas suggestive of disseminated mycobacteria are frequent and allow a treatment to be initiated before microbiological confirmation and antibiotic susceptibility test.

Introduction/objectifs/but La prise en charge du cancer necessite une coordination des professionnels de sante, dont l’amelioration est un objectif du plan cancer 2014–2019, notamment par le developpement de la telemedecine. L’objectif est de decrire les usages existants de telemedecine pour la prise en charge du cancer en France en 2016. Materiel et methode Une revue de la litterature a ete conduite pour identifier les usages de la telemedecine appliquee a la prise en charge du cancer en France en septembre 2016. Resultats/observations La telemedecine est utilisee pour le depistage des cancers cutanes par tele-expertise notamment en Rhone-Alpes, en Corse, et en Picardie. La telepathologie est utilisee pour le diagnostic des cancers avec tele-expertise synchrone en Ile-de-France (IDF), et asynchrone de relecture systematique par le CNR des mesotheliomes ou pour les lesions mammaires par le groupe SENOPATH. En phase therapeutique, un projet concerne la telesurveillance a domicile de patients beneficiant d’une chimiotherapie et/ou d’une therapie ciblee administree par voie orale en IDF. La telesurveillance du cancer du poumon a ete aussi experimentee en Pays de la Loire pour le depistage des rechutes. La teleconsultation est aussi utilisee pour les soins palliatifs en EHPAD dans les Hauts-de-France avec TelePallia ® et en Aquitaine. L’utilisation de la telemedecine pour la prise en charge du cancer se developpe en France en accord avec le Plan Cancer 3. La poursuite du developpement de la telemedecine appliquee au cancer est a encourager avec son evaluation rigoureuse pour l’amelioration de la prise en charge des patients.

Breast cancer is the most frequent feminine cancer in France and its incidence increases steadily. The time of access to medical care is an indicator of the quality of the treatments recommended by the Plan Cancer 2009-2013, as it influences the diagnosis and reduces psychological morbidity during the pre-diagnosis phase. The one-day diagnosis is a recently initiated concept, which offers to get the results of the biopsy on the day it is performed and facilitates the setting-up of therapeutic care with the surgeon met during the one-day medical consultations. The aim of this study is to evaluate the satisfaction of patients who benefited from a one-day breast lesion diagnosis, as well as confirm the decrease of time of access to medical treatment.This is an observational, non-interventional and single-centre study based on 27 patients who benefited from one-day breast lesions diagnosis over two years. The patients were only included who had a classified lesion ACR 4 or 5 and visible in the ultrasound. We analyzed the histological concordance between the biopsy and the definitive histology, the time of access to medical care, and the therapeutic treatments We analyzed the psychological impact of such an organization by sending to the patients a questionnaire including the Psychological Consequence Questionnaire (PCQ) and the Breast Cancer Anxiety Indicator (BCA) allowing to estimate the anxiety generated by the pre-diagnostic phase, the DC-Sat allowing to estimate the satisfaction of the consultation of announcement, as well as the same day diagnosis benefit.The patients were 59.8 years old in average [33-87]. The average time between the date of the mammography and the one-day diagnosis consultation (including the biopsy) was 15.0 days [0-60]. Fifty-seven percent of the patients considered this time as short. The average time between the biopsy date and the start of the treatment was 15.9 days [4-30]. The one-day diagnosis took an average of 1.6 days [1-5]. The results of the PCQ showed an important emotional impact during the diagnosis phase, and the average BCA score reached an average of 3.9 on a scale of 5. However, the patients were very satisfied with the diagnosis consultation with an average of 8.7 on a scale of 10, and 95% think the one-day diagnosis is beneficial to the patients.This study shows that the one-day breast-damage diagnosis enables to improve the time of access to care, and meets the current recommendations. Even though faster access to treatment does not reduce the psychological morbidity of awaiting diagnosis, the patients express their satisfaction and find the rapidity of the pre-diagnosis phase beneficial.In view of this study, the one-day breast-damage diagnosis appears to be a quality feature in the process of access to care and treatment of the patients.

Background We explored the addition of rituximab to high-dose cytarabine (ara-C), oxaliplatin (L-OHP), and dexamethasone [R-DHAOx], in resistant and relapsed patients with CD20-positive follicular non-Hodgkin's lymphoma. Methods Twenty-two patients were included; they were treated previously with one to five chemotherapy regimens, including 13 patients who had also received rituximab. R-DHAOx consisted of rituximab, 375 mg/m 2 , day 1; dexamethasone, 40 mg/d, days one to four; L-OHP, 130 mg/m 2 , day 1; and ara-C, 2000 mg/m 2 every 12 h, day 2. Courses were repeated every 21 days for eight courses. Results Twenty-one patients (95%) achieved a complete response and one had a partial response. Responses were obtained in patients with and without resistance to prior treatment, either alone or combined with rituximab. The median follow-up time was 58.3 months (range, 8.7–92.6 months). Progression-free survival reached a plateau at 84% at 38.2 months. Only two of the 21 complete responders have relapsed. Tumor molecular markers disappeared in all 10 complete responders whose markers were found before treatment. Peripheral neuropathy related to the cumulative dose of L-OHP, and myelosuppression were the most prominent toxic effects. Conclusions R-DHAOx is highly active for salvage treatment of patients with follicular non-Hodgkin's lymphoma, and it produces long-term antitumor efficacy.

Hydroxyethyl starch (HES) is a macromolecular preparation that has been used as a volume expander since 1991. Renal toxicity of high-dose HES is now well recognized but potential renal toxicity of low-dose HES is poorly documented. Acute renal toxicity of cyclosporin A (CyA) may be responsible for osmotic nephrosis-like lesions. We report here the case of a 30-year-old male who developed cirrhosis due to hepatitis B and delta viruses and polymyositis. Polymyositis was treated with CyA, prednisone and plasma exchanges using low-dose HES as the replacement fluid. Renal insufficiency occurred with biopsy-proven osmotic nephrosis-like lesions, considered to be secondary to HES infusions and/or CyA.

The presence of Epstein-Barr virus (EBV) was studied in 56 gastric carcinomas from Western patients by in-situ hybridization for EBV-encoded RNAs (EBER). EBV-positive and negative carcinomas were compared for various pathological parameters including p53 overexpression.EBERs transcripts were detected in seven cases overall: four cases of 52 conventional carcinomas (7. 7%) and three cases of four gastric carcinomas with lymphoid stroma (75%). EBER positivity was diffuse in five cases and restricted to a localized area of the tumour in two cases of conventional carcinoma. A monoclonal EBV genomic pattern was demonstrated in the case tested by Southern blot analysis. By immunohistochemical analysis, neither EBV latent or lytic cycle proteins nor C3d/EBV receptor were expressed by neoplastic cells. EBER positivity was significantly correlated with prominent lymphoid reaction (P = 0.0002) which was associated with numerous PS100-positive dendritic cells and with HLA-DR expression by tumour cells (P = 0.03). p53 immunoreactivity in more than 30% of tumour cells was detected in 25 out 49 EBV-negative cases and was absent in EBV-positive cases except in one case with focal EBER-positivity.Focal staining for EBER is an unusual finding in the setting of gastric carcinoma and these results suggest that there might be two types of EBV-associated gastric carcinoma in which the viral infection will play a different role. The presence of a stromal lymphoid reaction which is strongly correlated with EBV positivity, is associated with antigen-presenting ability by HLA-DR-positive tumour cells or abundant dendritic cells. The function of p53 appears preserved in all EBV-associated carcinomas except in one case with focal EBER expression whereas the immunohistochemical pattern of p53 is suggestive of a mutational phenomenon in 51% of EBV-negative cases.

A case of laparoscopic autopsy for unexplained inpatient death is reported. The procedure is minimally invasive, easy to perform, accurate, and not disfiguring, rendering it easy to accept among mourning families.

In the West, hepatocellular carcinoma rarely occurs in patients without cirrhosis. In these patients, epidemiological factors and the histopathology of the non-neoplastic liver are not well known. The aim of this study was to clarify these points.We studied 30 patients (26 men, 28-87 years) with hepatocellular carcinoma and histologically-proven non-cirrhotic livers. Serological markers of HBV and HCV infection, as well as alcohol and tobacco consumption were evaluated. Pathological changes in the non-tumorous liver (fibrosis, inflammation, steatosis, alcoholic hepatitis lesions, iron overload, and large cell dysplasia) were systematically assessed using semi-quantitative scores.Twenty patients had alcohol intakeor =30 g/d and 16 were smokers. Serological HBV or HCV markers were positive in 10 patients. Only four patients had no exposure to alcohol or tobacco and no serological markers of HBV or HCV Histological examination showed that all livers had pathological changes. Seventeen patients (57%) had clearly-identified chronic liver disease: chronic hepatitis (n = 10) or alcoholic liver disease (n = 7). Non-specific and moderate pathological changes were observed in the 13 other patients (43%), with different degrees of fibrosis, activity, steatosis, and iron overload. Large cell dysplasia was present in 12 patients (40%).In our study, all patients with hepatocellular carcinoma and non-cirrhotic livers had non-tumorous pathological liver changes, especially iron overload and large cell dysplasia. These results suggest that hepatocellular carcinoma originates from an abnormal histological background, even in non-cirrhotic liver.

When renal insufficiency occurs in classical antineutrophil cytoplasm antibody- (ANCA) associated vasculitides, histological examination usually finds pauci-immune focal segmental glomerulonephritis. We report on 2 cases of histologically proven necrotizing vasculitis associated with IgA nephropathy. Concomitant vasculitis and IgA nephropathy has only rarely been reported but this joint occurrence may not be coincidental as its pathophysiology is not known. Among vasculitides, IgA nephropathy has more frequently been associated with Henoch-Schoenlein purpura: one microscopic polyangiitis unusual because the patient simultaneously presented ANCA and microaneurysms, and the other Churg-Strauss syndrome associated with mild renal insufficiency. This uncommon association might represent a possible overlap syndrome between these ANCA-associated vasculitides and IgA nephropathy or simply a new type of glomerulonephritis that must be taken into account in these vasculitides.

The authors report a case of laparoscopy post mortem for unexplained inpatient death. It is minimally invasive, easy to perform, accurate, and not disfiguring. As well, it is easy to accept among mourning families. It should be considered when consent for conventional autopsy is lacking.

The aim of this retrospective study is to evaluate the impact of laparoscopic appendicectomy on the incidence of histologically normal appendices. Between 1987 and 1997, 1220 consecutives patients--with an average age of 23.5 years (17-73) and including 841 women (69%)--underwent appendicectomy due to the presence of at least one of the following 3 criteria: right iliac fossa guarding, fever greater than 38 degrees C and hyperleucocytosis greater than 10,000. Patients were divided into two group.: First group with 930 patients were operated by laparotomy and the other group of 355 patients underwent laparoscopic exploration with appendicectomy when macroscopic abnormalities were observed (290 cases). In all cases, the appendices were examined under blind conditions and classified as normal or pathological, and were subsequently classified according to the nature and the severity of the lesions. In group I (laparotomy), the incidence of histologically normal appendices was 25.1%. In group II (laparoscopic), this incidence was only 8.2%. The difference was significant (p = 0.015). In 65 cases (18.3%), a macroscopically normal appendix was left in place: in 55 cases the symptoms were due to another identified cause, however, in 10 cases no cause was found. This study suggests that laparoscopy significantly reduces the number of histologically normal appendices because an other cause is identified more easily provided macroscopically normal appendices are not removed with a small proportion (5-10%) cases of early appendicitis with only mucosal involvement. In the absence of other causes for the symptoms, a three-day course of antibiotics can be tried in order to treat possible mucosal lesions. This approach reduces costs without having any adverse consequences on outcome.

Infiltrating leukocyte population appears at the time of implantation in the endometrium of human and other mammals with hemochorial placentation. This leukocyte population is mainly composed of macrophages and typical granular lymphocytes CD56+ CD16-. 63 endometrial samples were studied using immunocytochemistry, before IVF and embryo transfer. We evaluated the sensibility for the assessment of immunological relevant infiltrating cells, of classical histopathologic examination compared with quantitation of leukocyte-common-antigen antibody immunostaining. 21 samples were thoroughly studied during proliferative phase.The sensibility of classical histologic analysis for the semi-quantitative assessment of leukocyte population, even when performed by an experienced histopathologist, is only 62%. When leukocyte population during proliferative phase is dense, it is mainly composed of macrophages and CD56+ CD16- lymphocytes.Immunological reaction already reported around the time of implantation may occur at other period of the menstrual cycle. Close mechanisms of the control and functions of this characteristic reaction remain to clarify.

Giant-cell hepatitis is rare in adults and its significance has not been clarified. We report the clinical and histological characteristics and outcome in a group of adult patients with giant-cell hepatitis.Seventeen patients with giant-cell hepatitis, hospitalized in our unit between 1976 and 1992, were studied retrospectively. Giant-cell hepatitis was defined as at least two hepatocytes with four or more nuclei per cell on liver biopsy. Clinical and biochemical parameters, liver histology, and the serological profile of HAV, HBV, HCV, HIV, HSV, EBV, CMV, and paramyxovirus were evaluated. Paramyxovirus immunochemistry was performed in 6 liver biopsies.There were 11 females and 6 males, an average of 48 years old (range: 29-80). Four patients had a well-defined etiology: acute hepatitis B infection with a favorable outcome in 2 cases, clometacine induced-hepatitis resulting in death from liver failure in one case, and chronic hepatitis B and C in one patient with AIDS. Among the 13 patients in which the etiology could not be determined, histologically defined acute hepatitis was observed in 8 and chronic hepatitis in 5. Nine patients were treated with immunosuppressive drugs. One patient was lost to follow-up. Eight patients responded to treatment, but 5 patients progressed to cirrhosis between 5 months and 7 years. Two of the 4 patients with unexplained liver disease who did not receive any treatment died of liver failure.In patient with acute or chronic hepatitis without an identified cause (with or without autoimmune abnormalities), the presence of giant-cell hepatitis seems to have a similar evolution as active autoimmune hepatitis. The poor prognosis of these patients suggests that early immunosuppressive treatment is justified.

Long term treatment by fibrates could induce chronic hepatitis associated with auto-antibodies. The aim of this study was to assess the features of this hepatitis.Baseline clinical and biological features, and liver biopsy in 5 patients with fibrate-induced chronic hepatitis were studied, as well as their outcome.At enrollment, patients (4 men, mean age 65 years) had highly (n = 3) or mildly (n = 2) increased serum aminotransferase activity, hypergammaglobulinemia and high titers of anti-nuclear antibodies (with homogenous fluorescence in 3 cases). Liver biopsies demonstrated a lympho-plasmocytic infiltrate in all cases. Hepatocellular necrosis was multilobular in 2 cases, and mild to moderate, located in lobular and periportal areas in 3 cases. Cirrhosis was found at presentation in 3 cases and developed within a few months in the 2 other patients. After discontinuation of fibrates, aminotransferase activity normalized within 6 weeks either spontaneously (n = 3) or under immunosuppressive treatment (n = 2). Immunosuppression was rapidly withdrawn in 2 patients (18 months) without relapse, while one patient was treated for 4 years because of relapse after early withdrawal. A second liver biopsy performed 6 months after discontinuation of fibrates in an untreated-patient showed no inflammation or necrosis.These observations suggest that fibrates could trigger chronic liver disease resembling type I auto-immune chronic hepatitis, which resolves after drug withdrawal.

Patients with acquired immunodeficiency syndrome are often susceptible to atypical dissemination of visceral leishmaniasis. Digestive localizations seem to be relatively frequent. Colonic localizations reported in the literature are endoscopically normal or show superficial mucosal lesions. We describe an original case of leishmaniasis associated with a colonic pseudotumoral stenosis with perforated ulcer penetrating in the mesocolon. Striking inflammation of mesenteric blood vessels, even far from the ulcer, suggested an ischemic mechanism for the colonic stenosis. These findings raise the hypothesis that vasculitis is secondary to mucosal parasitic infection.

Although many studies concerning the prognostic factors of resected hepatocellular carcinoma have been performed, the prognostic information provided by needle biopsy of these tumors has not yet been extensively studied.One hundred twenty-four white patients with histologically-confirmed hepatocellular carcinoma were entered into a prospective study from 1990 to 1992 with followed-up through October 1994. Most of the patients had cirrhosis (79%). Patients were classified according to Okuda's staging: Stage I (50%), Stage II (47%), and Stage III (3%). The one-year survival rate was estimated at 58% in Okuda's Stage I, and 15% in Stages II and III. Edmondson's grading, mitotic index, and proliferating cell nuclear antigen labeling index were studied on each biopsy. Univariate and multivariate analyses were performed to determine the prognostic significance of the different parameters.According to Edmondson's critera, 13 of the hepatocellular carcinomas were Grade I, 63 Grade II, 42 Grade III, and 6 Grade IV. There was a significant correlation between Edmondson's grade, mitotic index, and proliferating cell nuclear antigen labeling index (P0.01). Univariate analysis showed both the histologic grade (P0.001) and mitotic index (P0.05) correlated with survival. Cox's model indicated that Edmondson's grading yields additional prognostic information for Okuda's staging (P0.001). The one-year survival rate for Okuda's Stage I was 76% for Edmondson's Grades I + II versus 23% for Grades III + IV.Edmondson's grading appears to be an important prognostic parameter for patients with hepatocellular carcinoma, and could help stratify patients for clinical trials.

Adenoid cystic (cylindromatous) carcinoma is a rare tumor. It accounts for approximately1-3% of primary adenocarcinomas of the cervix uteri. Its origin is debatable. It has a higher incidence in postmenopausal women but can develop in patients under 40. An association of adenoid cystic carcinoma with squamous cell carcinoma has been reported.A case of invasive adenoid cystic (cylindromatous) carcinoma associated with an in situ squamous cell carcinoma of the cervix detected on Papanicolaou smears is reported. Ultrastructural studies provided findings that confirmed that the hyaline material corresponded to the remnants of the lamina densa of the basement membrane of malignant cells.The concurrence of these two tumors supports the hypothesis that adenoid cystic carcinoma of the cervix may develop from multipotent reserve cells.

Nodular regenerative hyperplasia of the liver is characterized by diffuse nodularity of the hepatic parenchyma without fibrotic septa. It may be related to venous or arterial obstruction in the portal tract. We report a case of primary antiphospholipid syndrome associated with nodular regenerative hyperplasia in a 45-year old woman. The patient had an ischemic stroke, associated with an acute arterial ischemia of the left leg. She had high titers of serum anticardiolipin antibodies. Nodular regenerative hyperplasia of the liver was histologically confirmed and was associated with anicteric cholestasis. This case provides additional evidence that a thrombotic mechanism may play a role in the pathogenesis of nodular regenerative hyperplasia of the liver.

We report an Hepatitis B Virus reactivation, in a patient with an end-stage Human Immunodeficiency Virus infection who developed a rapidly progressive liver failure in four months. The main histological features include ballooning of hepatocytes and ground glass transformation, without significant inflammation. Immunohistochemical staining showed a high expression of viral antigens. This case can be related to "Fibrosing Cholestatic Hepatitis", first described after liver transplantation for cirrhosis B. The mechanism of hepatocellular damage is likely to be a direct cytotoxicity of hepatitis B virus.

The search of small-caliber vascular prosthesis for myocardial revascularization and arterial reconstruction has led to an investigation of cryopreserved arterial allografts in a sheep model. Carotid arteries with an internal diameter of 4 mm and length of 10 cm were harvested from donor sheep and soaked immediately in a cold saline solution. Nine arteries were cryopreserved in a nutrient media containing 10% DMSO as cryoprotectant and then were stored in a liquid nitrogen vapor at -150 degrees C to -170 degrees C. In recipient sheep from different species, arterial substitution of a 10 cm segment of carotid artery was realised by implantation of fresh (n = 9) or cryopreserved (n = 9) carotid artery allografts. After 3 months, the allografts were harvested. In both groups: 7/9 were patent at the time of explantation. Components of arterial allograft rejection were observed in most fresh and cryopreserved arteries: intimal thickening with cell proliferation was seen in fresh (3/7) and cryopreserved (4/8) arteries; Loss of smooth muscle medial cells was constant; Adventitia was involved by a marked inflammatory reaction. A non cellular fibrous intimal thickening and presence of large medial calcifications were essentially observed in cryopreserved arteries. In conclusion, these results show that at three months post implantation, there is little difference in the outcome of fresh and cryopreserved arterial allografts. Cryopreservation does not reduce the apparent antigenicity of small diameter arterial allografts.

Background TH-302 is a hypoxia targeted prodrug with a hypoxia-triggered 2-nitroimidazole component designed to release the DNA alkylator, bromo-isophosphoramide mustard (Br-IPM), when reduced in severe hypoxia. A randomized Phase 2B study (NCT01144455) was conducted to assess the benefit of G + T to standard dose G as first-line therapy of PAC. Materials and methods An open-label multi-center study of two dose levels of TH-302 (240 mg/m2 or 340 mg/m2) in combination with G versus G alone (randomized 1:1:1). G (1000 mg/m2) and T were administered IV over 30-60 minutes on Days 1, 8 and 15 of a 28-day cycle. Patients on the G could crossover after progression and be randomized to a G + T arm. The primary efficacy endpoint was a comparison of progression-free survival (PFS) between the combination arms and G alone (80% power to detect 50% improvement in PFS with one-sided alpha of 10%). Summary PFS outcome has previously been reported; more detailed PFS as well as the initial overall survival (OS) data are presented. Results 214 pts were treated; 164 (77%) Stage IV and 50 (23%) Stage IIIB. Median age 65 (range 29-86); 126 M/88 F; 40% ECOG 0/60% ECOG 1. Receiving 6 or more cycles: 32% G; 45% G + T240; 55% G + T340. Median PFS was 3.6 mo in G vs 5.5 mo in G + T240 (p = 0.031) and 6.0 mo in G + T340 (p = 0.008). Poorer prognostic factors (older age, poorer performance status, reduced albumin) were associated with larger treatment effect. Median OS was 7.0 mo in G vs 9.0 in G + T240 and 9.5 mo in G + T340. RECIST best response was 12% in G vs 17% in G + T240 and 27% in G + T340. CA19-9 decreases were significantly greater G + T340. A >50% CA19-9 decrease was 52% with G vs 50% with G + T240 and 70% with G + T340. AEs leading to discontinuation were: 16% G, 15% G + T240 and 11% G + T340. Rash (45% in G + T340) and stomatitis (36% in G + T340) were greater in combination, 4 pts Grade 3 rash. Grd 3/4 thrombocytopenia were 11% G, 39% G + T240 and 59% G + T340 and Grd 3/4 neutropenia were 28% G, 56% G + T240 and 59% G + T340. Conclusions The combination of G plus TH-302 improved the efficacy of G. A TH-302 dose of 340 mg2 was identified for future studies. Skin and mucosal toxicity and myelosuppression were the most common TH-302 related AEs with no increase in treatment discontinuation. Disclosure All authors have declared no conflicts of interest.

Use of cryopreserved small-caliber arterial allografts for arterial bypass procedures has been suggested. In addition to immunological tolerance, long term in vivo success of these grafts may be dependent on the viability of arterial cells after cryopreservation. Metabolic and functional capabilities of arterial smooth muscle cells were evaluated by studying the enzyme histochemical expressions of sheep carotid arteries after various time of cryopreservation (7 days, 90 to 150 days) and their contractile responses after freezing. The results indicated that cryopreserved arteries exhibited 4 features: (a) the enzyme activities were globally maintained, (b) the spontaneous endogenous oxido-reduction (NitroBT test) was reduced, (c) contractile responses against KCl and norepinephrine were abolished, (d) metabolic status of frozen arteries was independent of the duration of cryopreservation. These data suggest that cryopreserved arterial muscle cells may be depleted in electron donors and/or energy-rich nucleotides substrates. This defect is present after short or long time of cryopreservation.

The simultaneous disclosure of a lymphoblastic B cell lymphoma and sarcoidosis is reported herein. The initially undiagnosed sarcoidosis leads to discuss the differential diagnosis of a sarcoid-like reaction associated to the lymphoma. The association of sarcoidosis and malignant lymphoproliferative disease is not fortuitous; nevertheless the simultaneity of the two diagnoses, the lymphoblastic type of the lymphoma and the colocalization of granulomatous and lymphomatous lesions in lung and liver are unusual features.

The authors report a case of adenoid cystic (cylindromatous) carcinoma of the endocervical canal associated with an intraepithelial squamous cell carcinoma of the cervical os in a 60-year-old woman suffering from metrorrhagia. Immunohistochemical study demonstrated labeling of cylindromatous cells with anti-actin, anti-vimentin and anti-keratin antibodies. Ultrastructural study provided significant findings to confirm that the hyaline material surrounded by tumor cells was derived from the remnants of the lamina densa of the basement membrane of tumor lobules. These morphological data are similar to those observed in adenoid cystic carcinomas (cylindromas) of salivary glands. They support the hypothesis that adenoid cystic carcinoma of the cervix may develop from the multipotent reserve cells.

Introduction Apres transplantation hepatique (TH), la cinetique de l’infection par le virus de l’hepatite C (VHC) sur le greffon est plus rapide avec un risque de cirrhose estime a environ 30 % a 5 ans. L’indication d’une retransplantation hepatique (reTH) en cas de maladie severe sur le greffon reste pour l’instant peu etudiee. Le but de cette etude etait d’etudier l’evolution des patients infectes par le VHC retransplantes pour les complications de la reinfection du greffon par le VHC. Patients et Methodes L’etude a porte sur une population monocentrique de 504 patients infectes par le VHC, suivis entre 1986 et 2008, et transplantes pour les complications d’une cirrhose virale C. Une indication de reTH a ete posee chez 28 patients, d’âge moyen de 45 ( ± 8) ans. L’indication de reTH a ete posee en raison de complications techniques (non fonction du greffon, thrombose artere hepatique) (n = 11), d’une infection severe du VHC sur le greffon (n = 11), de rejet chronique (n = 5) et d’hepatite alloimmune (n = 1). La survie des patients apres reTH a ete comparee a celle d’un groupe de 114 patients transplantes pour les complications d’une cirrhose C, apparie sur l’âge du donneur. Resultats Parmi les 11 patients retransplantes pour recidive virale C severe sur le greffon, l’intervalle moyen entre les 2 TH etait de 92 mois (± 62). Le score moyen de MELD avant reTH etait de 22,5 (± 6,2). Trois patients avaient une insuffisance renale chronique necessitant une double greffe foie-rein. Cinq des 11 patients sont decedes en raison de complications infectieuses (n = 3), et de reinfection precoce severe par le VHC (n = 2). La survie actuarielle apres reTH etait de 60 % a 1 an et de 48 % a 5 ans. La survie actuarielle des patients apres reTH et a partir de la premiere TH etait de 65 % alors qu’elle etait de 76 % dans le groupe des patients apparies transplantes pour cirrhose C, sans difference significative (p = 0,64). La vitesse de progression moyenne de la fibrose avant reTH etait de 1,27 (± 1,0) points de fibrose par an alors qu’elle etait de 1,2 (± 1,4) points de fibrose par an chez les patients ayant survecu plus d’un an apres reTH (NS). Conclusion Dans cette etude, les patients retransplantes pour recidive virale C severe sur le greffon ont une survie a un an de 60 % et a 5 ans de 48 %. La reTH ne semble pas aggraver le pronostic par rapport au groupe de patients transplantes pour cirrhose C, apparie sur l’âge du donneur. La progression de la fibrose n’est pas plus severe apres retransplantation hepatique.

Introduction La survie apres TH chez les patients co-infectes VIH/VHC est moins bonne que celle des patients mono-infectes du fait d’une recidive virale C severe sur le greffon. Le but de ce travail etait de caracteriser ce type d’evolution apres TH chez les patients co-infectes VIH/VHC. Patients et Methodes Entre decembre 1999 et janvier 2008, 68 patients VIH+ ont ete transplantes du fait d’une cirrhose virale C (infection VHC seule n = 43, co-infection VHB/VHC ou VHB/VHD/VHC n = 5, associee a un ethylisme chronique n = 5, carcinome hepatocellulaire (CHC) n = 15). Resultats Il s’agit de 12 femmes et 56 hommes, l’âge moyen lors de la TH etait de 44,7 ans (29-62). Chez 42 patients la greffe a ete realisee a partir d’un donneur cadaverique, chez 19 patients dans le cadre d’un programme domino et chez 7 patients a partir d’un donneur vivant. Le genotype VHC etait 1 pour 35 patients, 2 pour 1 patient, 3 pour 17 patients et 4 pour 9 patients. Un traitement anti-VHC a ete instaure chez 31 patients ; 3 patients ont eu une reponse prolongee, 2 patients etaient repondeurs-rechuteurs et tous les autres etaient non repondeurs ou intolerants au traitement. Parmi ces patients 23 sont decedes (34 %), 9 patients d’une cause non liee au VHC, 4 patients d’une recidive de CHC, et 10 patients de la recidive du VHC. Parmi les deces dus a une recidive virale C, 7 patients (70 %) ont developpe une hepatite fibrosante cholestatique (HFC), et chez 2 patients une toxicite au traitement anti-retroviral est survenue. Le delai moyen d’apparition de l’HFC etait de 6 mois (1-14). Lors du diagnostic histologique d’HFC, le taux moyen de bilirubine totale etait de 166 umol/L (22-342), le taux moyen de GGT de 545 UI/L (158-995) et le taux moyen des ASAT et des ALAT etait de 294 UI/L (84-664) et de 267 UI/L (80-749) respectivement. Le delai moyen d’apparition de la cirrhose a ete de 20 (12-36) mois. La charge virale VHC au moment du diagnostic de HFC etait de 6,9 cp/mL log 10 (5,6-9). Tous ces patients ont recu un traitement anti VHC (PegIFN + Ribavirine) dans un delai moyen de 4,5 mois post TH (1-11). Une reponse virologique a ete observee chez 2 patients (repondeurs-rechuteurs), les 7 patients non repondeurs sont decedes dans un delai moyen de 20,7 (4-43) mois. Conclusion Dans notre serie de patients greffes co-infectes (VHC/VIH) 19,1 % ont developpe une cirrhose et 13 % une hepatite fibrosante cholestatique dans un delai moyen de 20,1 mois (3-38) et de 6 mois (1-14) respectivement. Un traitement anti-VHC instaure plus precocement devrait permettre de ralentir la progression et la severite de l’infection virale C sur le greffon chez ces patients.

We report a 25-year-old patient with a progressive asymmetric peripheral neuropathy of the distal lower limbs. Imaging studies showed enlargement of lumbosacral roots, plexus, and proximal sciatic nerve. Sacral plexus biopsy revealed amyloidosis associated with endoneurial edema. Immunohistochemistry with anti-prealbumin, serum amyloid A, and immunoglobulin light chain antisera failed to label the amyloid.

Whipple's disease and pulmonary and lymph node tuberculosis have been diagnosed in a 70 year-old man hospitalized for weight loss and fever. The tuberculous or Whipple's disease-related nature of associated non-necrotizing epithelioid hepatic granulomas could not be determined. The existence of cellular immune defects in Whipple's disease could explain the association with tuberculosis, which has not been previously reported in the literature.

Hyalinizing trabecular adenoma of the thyroid gland is an uncommon neoplasm that was recently described by Carney et al. (1987). It is important to recognize this tumor, considered benign, as it may mimic papillary carcinoma, medullary carcinoma or paraganglioma. We present two cases with histological and immunohistochemical criteria and discuss the diagnostic problems. Grossly, this small tumor is yellow tan and well circumscribed. The epithelial cells, polygonal or elongated and sharply outlined, have an eosinophilic or clear cytoplasm. The nuclei are oval or elongated, with often non-visible nucleoli. Grooved nuclei are quite frequent. Mitotic figures are very uncommon. The cells are arranged in clusters or trabeculae or pseudofollicles containing colloid material. Characteristically the cells, arranged shoulder to shoulder, can show a palisade pattern. The fibrovascular stroma appears hyaline, pseudoamyloid (Congo red staining is negative). The tumor cells show intense staining for thyroglobulin and no staining for thyrocalcitonin. Immunoreactivity for cytokeratin, vimentin, protein S100, NSE is positive but staining is negative for EMA and desmin. In one case, the tumor cells show little positivity for chromogranin A. The variable patterns of this tumor can lead to diagnostic problems. We can exclude the diagnosis of papillary carcinoma as this tumor lacks any true papillary architecture. We reject the diagnosis of medullary carcinoma because of its thyroglobulin and calcitonin immunoreactivity. Paraganglioma never shows immunoreactivity for thyroglobulin. Very often the surrounding thyroid tissue shows focal thyroiditis. The association of the tumor with Hashimoto's thyroiditis can be explained by an autoimmune process.