Geneviève Belleannée

Lymph nodes after preoperative chemoradiotherapy for rectal carcinoma: number, status, and impact on survival.

The number and status of lymph nodes examined is crucial for tumor staging. Impact of preoperative chemoradiotherapy on lymph nodes status and survival is still controversial in rectal carcinoma. The aim of this study was (i) to define the impact of preoperative chemoradiotherapy on the number of both retrieved and positive lymph nodes in rectal cancer specimen, (ii) to evaluate the influence of the number of lymph nodes retrieved on survival in patients treated by preoperative chemoradiotherapy. From 1994 to 2004, 495 patients underwent rectal excision for cancer, of which 332 received long course preoperative radiotherapy. Surgery and pathologic assessment were standardized. Multivariate analysis evaluated the influence of clinical and pathologic variables on the number of both retrieved and positive lymph nodes. Kaplan-Meier method and log-rank test assessed the relation between survival and the number of lymph nodes retrieved in patients treated by preoperative chemoradiotherapy. Compared with surgery alone, preoperative chemoradiotherapy decreased both the mean number of lymph nodes retrieved (17 vs. 13; P<0.001) and the mean number of positive lymph nodes (2.3 vs. 1.2; P=0.001). Multivariate analysis confirmed the independent impact of preoperative chemoradiotherapy on retrieved and positive lymph nodes. In patients treated by preoperative chemoradiotherapy, the 5-year overall (71%) and disease-free (60%) survival was not associated with the number of lymph nodes retrieved. Although long course preoperative chemoradiotherapy decreases by 24%, the mean number of lymph nodes retrieved and by 48% the mean number of positive lymph nodes, survival was not influenced by the number of lymph nodes retrieved in irradiated rectal specimen.

Mucosal healing with methotrexate in Crohn’s disease: a prospective comparative study with azathioprine and infliximab

Aliment Pharmacol Ther 2011; 33: 714–721

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.

Long-term results after neovagina creation in Mayer–Rokitanski–Kuster–Hauser syndrome by Vecchietti’s operation

OBJECTIVES To evaluate the long-term results after Vecchiettis operation. STUDY DESIGN Twenty Mayer-Rokitanski-Kuster-Hauser (MRKH) syndrome patients underwent creation of a neovagina using Vecchiettis operation by laparotomy (17 cases) and laparoscopy (3 cases). RESULTS The mean age of the patients was 21 years (16-34). After 66 months (24-156) of follow-up, the mean length x diameter of the neovagina was 8.2 cm x 2.8 cm. The neovaginal epithelium was macroscopically similar to normal vaginal mucosa, except for one patient who had subsequently undergone insertion of skin graft. Post-operative sexual behavior revealed sexual desire and pleasure (100%), lubrication (94%), clitoral orgasm (87%) and vaginal-mediated orgasm (69%). Finally, 16 patients out of 18 (89%) were completely satisfied with the results of the operation. CONCLUSION Vecchiettis operation may be suggested as one of the choice of treatments to correct vaginal aplasia in young MRKH syndrome patients.

Mucosal Intraepithelial T-lymphocytes in Refractory Celiac Disease : A Neoplastic Population With a Variable CD8 Phenotype

Celiac disease (CD) is characterized by villous atrophy and an increase in intraepithelial lymphocytes (IEL). The IEL usually exhibit a suppressor/cytotoxic phenotype (CD3+ and CD8+) and display a polyclonal profile for T-cell receptor (TCR) rearrangement as opposed to the monoclonality of refractory CD (RCD) with CD8− IEL. A complication of CD is the loss of response to a gluten-free diet called RCD that may progress to an enteropathy-associated T-cell lymphoma. We reviewed 20 uncomplicated CD and 23 complicated CD (19 RCD and 4 diagnosed at the same time as enteropathy-associated T-cell lymphoma). In complicated CD, the IEL phenotype was CD8− in 9 cases and CD8+ in 14 cases. In 100% of cases, IEL showed a monoclonal TCR rearrangement. All the 9 CD8− complicated CD exhibited a monoclonal TCR rearrangement and 3 of them were associated with a T-cell lymphoma (2 at the same time as CD and 1 after 43-mo follow-up) and bore the same monoclonal rearrangement in IEL and in lymphoma. Interestingly, the 13 cases (100%) of CD with a CD8+ phenotype were also found monoclonal and 2 of them were associated with a T-cell lymphoma diagnosed at the same time as CD and exhibiting the same rearrangement in IEL and in lymphoma. An aberrant CD3+ CD8− IEL phenotype is a good criterion for RCD diagnosis. However, cases with a normal CD3+ CD8+ IEL phenotype may correspond to RCD. In such cases, we suggest that molecular analysis of TCR-γ genes is a useful method for identifying cases with RCD.

An evaluation of the accuracy of CT when determining resectability of pancreatic head adenocarcinoma after neoadjuvant treatment

BACKGROUND To evaluate the accuracy of MDCT for determination of resectability R0 after neoadjuvant therapy in patients with pancreatic head adenocarcinoma locally advanced. METHODS From January 2005 to December 2010, 80 patients with pancreatic head adenocarcinoma underwent multidetector CT before surgery. Of these, 38 patients received neoadjuvant therapy because tumor was considered locally advanced on baseline CT scan. We retrospectively correlated imaging interpretations with operative and histological data and compared results in patients without (control group) or with (neoadjuvant group) preoperative treatment. RESULTS 41/42 patients in control group and 31/38 patients in neoadjuvant group finally had curative resection. While resection R0 is similar in both groups (83% and 81%), CT accuracy in determining resectability R0 was significantly decreased in neoadjuvant group (58% versus 83%; p=0.039). CT scan specificity was significantly lower after neoadjuvant therapy (52% versus 88% in control group) due to an overestimation of vascular invasion: 12/31 patients with complete resection in neoadjuvant group were evaluated at high risk of incomplete resection on CT scan. Tumor size tends to be underestimated in control group (-2mm) and overestimated in neoadjuvant group (+10mm). T-staging accuracy was decreased in neoadjuvant group (39% versus 78% in control group; p=0.002). CONCLUSION Neoadjuvant therapy significantly decreases the accuracy of CT scan in determining operability, T-staging, and resectability R0 of pancreatic head carcinoma. Overestimation of tumor size and vascular invasion significantly reduces CT scan specificity after preoperative treatment.

Locally Advanced Pancreatic Adenocarcinoma: Reassessment of Response with CT after Neoadjuvant Chemotherapy and Radiation Therapy

PURPOSE To prospectively evaluate the utility of computed tomography (CT) for determination of tumor response and prediction of resectability after neoadjuvant combined chemotherapy and radiation therapy (CRT) in patients with nonmetastatic locally advanced pancreatic cancer. MATERIALS AND METHODS This study received institutional review board approval, and all participants provided written informed consent. Consecutive patients with cephalic locally advanced pancreatic cancer who underwent surgical exploration and/or resection following neoadjuvant CRT were prospectively enrolled from June 2009 to May 2013. Two radiologists independently analyzed the baseline and post-CRT CT scans for the size, attenuation, and circumferential vascular contacts of the tumor. Associations between the postoperative histologic grade of the tumor response (pTNM) and the clinical, biologic, and CT criteria were assessed by using Spearman correlation coefficients. CT criteria related to the presence of complete (ie, R0) resection were assessed by using logistic regression. RESULTS Forty-seven patients were included, 33 with an R0 resection and 14 with positive margins (ie, R1) or no resection. Variables demonstrating a significant correlation with the histologic tumor classification of tumor response were post-CRT carbohydrate antigen 19-9 level (r = 0.46), post-CRT largest tumor axis (r = 0.44), post-CRT sum of the largest and smallest tumor axes (r = 0.46), change in the largest axis (r = -0.31), change in the sum of the largest and smallest axes (r = -0.39), change in superior mesenteric vein (SMV) and/or portal vein (hereafter, SMV/portal vein) contact (r = -0.38), and post-CRT superior mesenteric artery contact (r = 0.34). Partial regression of tumor contact with the SMV/portal vein was associated in all cases with R0 resection (10 of 10 patients, positive predictive value = 100%), and partial regression of tumor contact with any peripancreatic vascular axis was associated with R0 resection in 91% of cases (20 of 22 patients, positive predictive value = 91%). Persistence of SMV/portal vein stenosis after CRT was not predictive of R1 resection. CONCLUSION Partial regression of tumor-vessel contact indicates suitability for surgical exploration, irrespective of the degree of decrease in tumor size or the degree of residual vascular involvement.

Low prevalence of monoclonal B cells in Helicobacter pylori gastritis patients with duodenal ulcer.

We have studied the prevalence of B-cell clonality among a large group of 320 patients with Helicobacter pylori gastritis and duodenal ulcer. These patients underwent endoscopic examination with multiple gastric biopsies at diagnosis and were followed 2 and 12 months after therapy. Histopathologic examination of 809 sets of biopsy specimens showed lymphoid gastritis with lymphoid aggregates or follicles, but without lymphoepithelial lesion, in 302 samples corresponding to initial biopsy specimens (n=130) or to posttreatment biopsy specimens (n=172). DNA extracted from fresh antral specimens allowed the amplification of Helicobacter pylori DNA in all cases before therapy. The arrangement of the immunoglobulin heavy chain gene was studied by polymerase chain reaction (PCR) in the 302 selected lymphoid gastritis samples. Single or dominant bands were seen only in four specimens from three patients (1.3%), whereas a polyclonal pattern was seen in the other 298 samples. The detection threshold of our PCR technique was approximately 3% of clonal B cells diluted in a polyclonal population. This threshold appeared to be a reliable cutoff between polyclonal gastritis and clonal MALT lymphoma. In our experience, Helicobacter pylori lymphoid gastritis appeared mainly as a benign polyclonal condition.

Cytologic findings in a neovagina created with Vecchietti's technique for treating vaginal aplasia

OBJECTIVE To report long-term cytologic findings after treatment of congenital vaginal aplasia or Mayer-Rokitansky-Küster-Hauser syndrome (MRKH) using progressive traction of the vulvar tissues, or Vecchiettis technique (VT). STUDY DESIGN In eight women with MRKH, neovaginal smears stained by the Harris-Schorr technique were collected 2-12 years after VT. RESULTS Eosinophilic superficial cells observed in all cases indicate that the neovaginal epithelium responds to hormonal variations. The presence of Döderlein bacilli (seven cases) suggests that the regional environment of the neovagina is almost the same as that of the normal vagina. Gardnerella vaginalis (one case) and human papilloma virus infection (low grade squamous intraepithelial lesions) (one case) were also observed. CONCLUSION Neovaginal smears taken after the cicatrization period following construction of a neovagina by VT show a remarkable resemblance to those from normal vaginal mucosa and suggest that these neovaginas are almost the same as normal vaginas.

Characterization of biomarkers of tumorigenic and chemoresistant cancer stem cells in human gastric carcinoma.

Purpose: Gastric carcinomas are heterogeneous, and the current therapy remains essentially based on surgery with conventional chemotherapy and radiotherapy. This study aimed to characterize biomarkers allowing the detection of cancer stem cells (CSC) in human gastric carcinoma of different histologic types. Experimental Design: The primary tumors from 37 patients with intestinal- or diffuse-type noncardia gastric carcinoma were studied, and patient-derived tumor xenograft (PDX) models in immunodeficient mice were developed. The expressions of 10 putative cell surface markers of CSCs, as well as aldehyde dehydrogenase (ALDH) activity, were studied, and the tumorigenic properties of cells were evaluated by in vitro tumorsphere assays and in vivo xenografts by limiting dilution assays. Results: We found that a subpopulation of gastric carcinoma cells expressing EPCAM, CD133, CD166, CD44, and a high ALDH activity presented the properties to generate new heterogeneous tumorspheres in vitro and tumors in vivo. CD44 and CD166 were coexpressed, representing 6.1% to 37.5% of the cells; ALDH activity was detected in 1.6% to 15.4% of the cells; and the ALDH+ cells represented a core within the CD44+/CD166+ subpopulation that contained the highest frequency of tumorigenic CSCs in vivo. The ALDH+ cells possessed drug efflux properties and were more resistant to standard chemotherapy than the ALDH− cells, a process that was partially reversed by verapamil treatment. Conclusions: CD44 and ALDH are the most specific biomarkers to detect and isolate tumorigenic and chemoresistant gastric CSCs in noncardia gastric carcinomas independently of the histologic classification of the tumor. Clin Cancer Res; 23(6); 1586–97. ©2016 AACR.