Predictive factors for functional failure of ventral mesh rectopexy in the treatment of rectal prolapse and obstructed defecation.

BACKGROUND: Ventral mesh rectopexy (VMR) is widely accepted for the treatment of rectal prolapse or obstructed defecation. However, despite good anatomical results, the improvement of functional symptoms (constipation or incontinence) cannot always be obtained and in some cases these symptoms may even worsen. The aim of the present study was to identify possible predictors of functional failure after VMR. METHODS: Data of all consecutive patients who had VMR for the treatment of rectal prolapse and/or obstructed defecation between January 2017 and December 2020 in three different pelvic floor surgical centres in Italy were analysed to identify possible predictors of functional failure, intended as persistence, worsening or new onset of constipation or faecal incontinence. Symptom severity was assessed pre- and postoperatively with the Wexner Constipation score and Obstructed Defecation Syndrome score. Quality of life was assessed, also before and after treatment, with the Patients Assessment of Constipation Quality of Life questionnaire, the Pelvic Floor Disability Index and the Pelvic Floor Impact Questionnaire. Faecal incontinence was evaluated with the Cleveland Clinic Incontinence Score. The functional outcomes before and after surgery were compared. RESULTS: Sixty-one patients were included (M:F ratio 3:60, median age 64 years [range 33-88 years]). Forty-two patients (68.9%) had obstructed defecation syndrome, 12(19.7%) had faecal incontinence and 7 patients (11.5%) had both. A statistically significant reduction between pre- and postoperative Obstructed Defecation Syndrome and Wexner scores was reported (p < 0.0001 in both cases). However, the postoperative presence of constipation occurred in 22 patients (36.1%) (this included 3 cases of new-onset constipation). The presence of redundant colon and the pre-existent constipation were associated with an increased risk of persistence of constipation postoperatively or new-onset constipation (p = 0.004 and p < 0.0001, respectively). The use of postoperative pelvic floor rehabilitation (p = 0.034) may reduce the risk of postoperative constipation. CONCLUSIONS: VMR is a safe and effective intervention for correcting the anatomical defect of rectal prolapse. The degree of prolapse, the presence of dolichocolon and pre-existing constipation are risk factors for the persistence or new onset of postoperative constipation. Postoperative rehabilitation treatment may reduce this risk.

Long-term results after stapled hemorrhoidopexy: a survey study with mean follow-up of 12 years.

BACKGROUND: Hemorrhoidal prolapse is a common benign disease. The introduction of circular-stapled hemorrhoidopexy as an alternative to the conventional hemorrhoidectomy led to a new spectrum of postoperative outcomes and complications. The aim of the present study was to evaluate long-term results after stapled hemorrhoidopexy. METHODS: All the patients who had stapled hemorrhoidopexy using a PPH03 stapler, from January 2003 to December 2005, were retrospectively collected in a dedicated database. Between March and May 2016, all the patients were asked by phone to complete a questionnaire. The study evaluated anatomical recurrence, symptom recurrence and frequency, and satisfaction after surgery. The postoperative complications recorded were hemorrhage, hematoma, urinary retention, anastomotic stenosis, persistent anal pain, tenesmus, and impaired anal continence evaluated also with the Faecal Incontinence Severity Index score. RESULTS: One hundred and ninety four patients were identified and 171 completed the questionnaire. The mean follow-up was 12 ± 0.8 years (range 11-13 years). Anatomical self-reported prolapse recurrence was 40.9% (n = 70). In 75.6% (n = 129) of patients, the severity and frequency of symptoms improved. The overall complication rate was 56.7% (n = 40) with a serious adverse event rate of 8.7% (n = 15). The overall tenesmus rate was 38.2% (n = 65) and the overall impaired continence rate was 39.1% (n = 67). Medical therapy was still required occasionally by 40.3% (n = 69) of the patients and 9.3% (n = 16) of the patients underwent surgery for recurrence. Patient satisfaction rate was good (≥ 3 on a scale of 1 to 5) in 81.2% (n = 139) of cases. CONCLUSIONS: The study showed that stapled hemorrhoidopexy using the first-generation devices is safe and feasible but associated with a high recurrence and incontinence rate. More stringent selection criteria in association with the use of large volume devices can lead to better results in the future.

Micro-fragmented adipose tissue injection for the treatment of complex anal fistula: a pilot study accessing safety and feasibility.

BACKGROUND: The aim of the present study was to evaluate the safety and efficacy of autologous, micro-fragmented and minimally manipulated adipose tissue injection associated closure of the internal opening in promoting healing of complex anal fistula. METHODS: A pilot study was conducted on patients referred to our center with anal fistula, from April 2015-December 2016. Inclusion criteria were age over 16 years old and a diagnosis of complex anal fistula according to the American Gastroenterological Association classification The patients were divided into 2 groups; the "first time group" (Group I) in which micro-fragmented adipose tissue injection with closure of the internal opening was the first sphincter-saving procedure, and the "recurrent group" (Group II) consisting of patients who had failed prior sphincter-saving procedures. The procedure was carried out 4-6 weeks after seton placement. Follow-up visits were scheduled at 7 days, and 1, 3, 6 and 12 months after surgery. Fistula healing was defined as the closure of the internal and external openings without any discharge. RESULTS: Out of 47 patients with complex transsphincteric anal fistula, 19 met the inclusion criteria and were selected to undergo the procedure. Twelve of these patients (Group I) had micro-fragmented adipose tissue injection as first-line treatment, and 7 (Group II) had failed previous sphincter-saving procedures. The mean operative time was 55 ± 6 min (range 50-70 min). The mean postoperative pain score measured with the visual analog pain scale was 2 ± 1.4 (range 0-4). No intraoperative difficulties related to the use of the kit were recorded. There were no cases of postoperative fever or abdominal sepsis related to the procedure and no post-treatment perianal bleeding or impaired anal continence. Only 3 cases of minor abdominal wall hematoma that did not require any treatment and 1 case of perianal abscess were observed. Patients were evaluated for a mean follow-up time of 9 ± 3.1 months (range 3-12 months). The overall healing rate was 73.7, 83.3% for Group I and 57.1% for Group II. CONCLUSIONS: The injection of autologous, micro-fragmented and minimally manipulated adipose tissue associated with closure of the internal opening is a safe, feasible and reproducible procedure and may enhance complex anal fistula healing.

Treatment of obstructed defecation syndrome due to rectocele and rectal intussusception with a high volume stapler (TST STARR-plus).

BACKGROUND: In recent years, stapled transanal resection (STARR) has been adopted worldwide with convincing short-term results. However, due to the high recurrence rate and some major complications after STARR, there is still controversy about when the procedure is indicated. The aim of this study was to assess the safety, efficacy and feasibility of STARR performed with a new dedicated device for tailored transanal stapled surgery. METHODS: All the consecutive patients affected by obstructed defecation syndrome (ODS) due to rectocele or/and rectal intussusception, who underwent STARR with the TST STARR-Plus stapler, were included in a prospective study. Pain, Cleveland Clinic Score for Constipation (CCCS) and incontinence, patient satisfaction, number of hemostatic stitches, operative time, hospital stay and perioperative complications were recorded. Postoperative complications and recurrence were also reported. RESULTS: Forty-five consecutive patients (median age 50; range 24-79) were included in the study. Median resected volume was 15 cm3 (range 12-19 cm3) with a median height of surgical specimen of 5.6 cm (range 4.5-10 cm). The mean CCCS decreased from 17.26 (± 3.77) to 5.42 (± 2.78) postoperatively (p < 0.001). Patient satisfaction grade was excellent in 14 patients (31.1%), good in 25 (55.5%), sufficient in three (6.7%) and poor in three patients (6.7%). No major complications occurred. Five patients (11%) reported urgency after 30 days and two patients (4%) after 12 months. The Cleveland Clinic Incontinence score did not significantly change. At a median follow-up of 23 months (range 12-30 months), only three patients (6.7%) reported recurrent symptoms of obstructed defecation comparable to those reported at baseline. CONCLUSIONS: TST STARR-Plus seems to be safe and effective for the treatment of ODS due to rectocele and rectal intussusception, and technical improvement could reduce the risk of some complications. However, careful patient selection is still the best means of preventing complications.

EZH2 alterations in follicular lymphoma: biological and clinical correlations.

The histone methyltransferase EZH2 has an essential role in the development of follicular lymphoma (FL). Recurrent gain-of-function mutations in EZH2 have been described in 25% of FL patients and induce aberrant methylation of histone H3 lysine 27 (H3K27). We evaluated the role of EZH2 genomic gains in FL biology. Using RNA sequencing, Sanger sequencing and SNP-arrays, the mutation status, copy-number and gene-expression profiles of EZH2 were assessed in a cohort of 159 FL patients from the PRIMA trial. Immunohistochemical (IHC) EZH2 expression (n=55) and H3K27 methylation (n=63) profiles were also evaluated. In total, 37% of patients (59/159) harbored an alteration in the EZH2 gene (mutation n=46, gain n=23). Both types of alterations were associated with highly similar transcriptional changes, with increased proliferation programs. An H3K27me3/me2 IHC score fully distinguished mutated from wild-type samples, showing its applicability as surrogate for EZH2 mutation analysis. However, this score did not predict the presence of gains at the EZH2 locus. The presence of an EZH2 genetic alteration was an independent factor associated with a longer progression-free survival (hazard ratio 0.58, 95% confidence interval 0.36-0.93, P=0.025). We propose that the copy-number status of EZH2 should also be considered when evaluating patient stratification and selecting patients for EZH2 inhibitor-targeted therapies.

BCL2 expression but not MYC and BCL2 coexpression predicts survival in elderly patients with diffuse large B-cell lymphoma independently of cell of origin in the phase 3 LNH03-6B trial.

BACKGROUND: Our aim was to evaluate whether the cell of origin (COO) as defined by the Hans algorithm and MYC/BCL2 coexpression, which are the two main biological risk factors in elderly patients treated with rituximab, cyclophosphamide, doxorubicin hydrochloride, vincristine, and prednisolone (R-CHOP), maintain their prognostic value in a large prospective clinical trial. PATIENTS AND METHODS: We evaluated 285 paraffin-embedded samples from patients (60-80 years of age) enrolled in the Lymphoma Study Association trial LNH03-6B who were treated with R-CHOP. We correlated the COO defined by the transcriptome according to the Wright algorithm with that defined by the Hans algorithm in a subset of 62 tumors with available frozen tissue samples. RESULTS: The non-germinal center B-cell-like phenotype according to the Hans algorithm and BCL2 expression (but not MYC and BCL2 coexpression) predicted worse progression-free survival [hazard ratio (HR)=1.78, P = 0.003 and HR = 1.79, P = 0.003, respectively] and overall survival (HR = 1.85, P = 0.005 and HR = 1.67, P = 0.02, respectively) independently of the International Prognostic Index. The correlation between the Hans algorithm and the Wright algorithm was 91%, with an almost perfect concordance according to a kappa test (0.81). CONCLUSIONS: Our results suggest that immunohistochemically defined COO remains a useful tool for predicting prognosis in diffuse large B-cell lymphoma when performed under optimized standardized conditions and that BCL2 expression may help to identify elderly patients at risk for relapse and who could potentially respond to anti-BCL2 targeted agents. In this prospective phase III trial, the coexpression of MYC and BCL2 does not appear to predict worse survival. CLINICAL TRIAL NUMBER: NCT00144755.

Clinical characteristics and prognostic factors of plasmablastic lymphoma patients: analysis of 135 patients from the LYSA group.

Background: Plasmablastic lymphoma (PBL), initially described in 1997 in the oral cavity of HIV positive patients, is now recognized as a distinct aggressive and rare entity of diffuse large B-cells lymphoma by the World Health Organization (WHO) classification. Since the original description, others cases have been reported. However, these are largely derived from case reports or small series limiting any definitive conclusions on clinical characteristics and outcome. Patients and methods: The clinical, biological, pathological features and outcome of a cohort including 135 patients with PBL, from LYSA centers in France and Belgium, were reported and analyzed. Results: The median age was 58 years, with a male predominance. The cohort was divided into 56 HIV-positive patients, 17 post-transplant patients and 62 HIV-negative/non-transplanted patients. Within HIV-negative/non-transplanted, a relative immunosuppression was found in most cases (systemic inflammatory disease, history of cancer, increased age associated with weakened immune system). We have also described a new subtype, PBL arising in a chronic localized inflammatory site, without any sign of immunosuppression. At presentation, 19% of patients showed oral involvement. Immunophenotype showed CD138 positivity in 88% of cases and CD20 negativity in 90% of cases. Chemotherapy was administered to 80% of patients, with a complete response (CR) rate of 55%. The median overall survival (OS) was 32 months. In univariate analysis, HIV positive status showed better OS when compared with HIV negative status. In multivariate analysis, International Prognostic Index score, chemotherapy and CR were associated with survival benefit. Conclusion(s): This cohort, the largest reported to date, increases the spectrum of knowledge on PBL, rarely described. However, specific guidelines to clarify treatment are lacking, and may improve the poor prognosis of this rare disease.

Tailored prolapse surgery for the treatment of hemorrhoids with a new dedicated device: TST Starr plus.

PURPOSE: The aim of the study was to assess the results of the stapled transanal procedure in the treatment of hemorrhoidal prolapse in terms of postoperative complications and recurrence rate using a new dedicated device, TST Starr plus. METHODS: Patients affected by III-IV degree hemorrhoidal prolapsed that underwent stapled transanal resection with the TST Starr plus were included in the present study. Results of the procedure with perioperative complications, postoperative complications, and recurrence rate were reported. RESULTS: From November 2012 to October 2014, 52 patients (19 females) were enrolled in the study. The main symptoms were prolapse (100 %) and bleeding (28.8 %). Transanal rectal resection was performed with parachute technique in 24 patients (46.2 %) and purse string technique in 23 patients (53.8 %). A mild hematoma at the suture line occurred in one patient (1.9 %). Postoperative bleeding was reported in three patients (5.7 %), in one of which, reoperation was necessary (1.9 %). Tenesmus occurred in one patient (1.9 %), and it was resolved with medical therapy. Urgency was reported in nine patients (17.1 %) at 7 days after surgery. Of these, three patients (5.7 %) complained urgency at the median follow-up of 14.5 months. Reoperation was performed in one patient (1.9 %) for chronic anal pain for rigid suture fixed on the deep plans. Occasional bleeding was reported in four patients (7.7 %). No recurrence of prolapse was reported at a median of 14.5 months after surgery, even if one patient (1.9 %) had a partial recurrent prolapse of a downstaged single pile. CONCLUSIONS: TST Starr plus seems to be safe and effective for a tailored transanal stapled surgery for the treatment of III-IV degree hemorrhoidal prolapse. The new conformation and innovative technology of the stapler seems to reduce some postoperative complications and recurrence rate.

[Macrophage activation syndrome as the presenting manifestation of intravascular lymphoma]. / Lymphome intravasculaire révélé par un syndrome d'activation macrophagique.

INTRODUCTION: Intravascular large B cell lymphoma is a neoplastic cell proliferation leading to the occlusion of the lumen of small vessels. This is a rare haematological malignancy, which is difficult to diagnose because of a heterogeneous clinical presentation. CASE REPORT: We report a 62-year-old man who presented a macrophage activation syndrome as the presenting manifestation of an intravascular lymphoma. This association is frequently marked by a greater severity and clinical care requires an early and appropriate treatment. CONCLUSION: Due to the polymorphism and the systemic presentation of intravascular large B cell lymphoma, the internist may be confronted with this disease, which is considered to be more severe if associated with a macrophage activation syndrome. Awareness of the intravascular large B cell lymphoma is important because the prognosis depends on the rapidity of the initiation of chemotherapy associated with rituximab.

Phase III study of ACVBP versus ACVBP plus rituximab for patients with localized low-risk diffuse large B-cell lymphoma (LNH03-1B).

BACKGROUND: The superiority of a chemotherapy with doxorubicin, cyclophosphamide, vindesine, bleomycin and prednisone (ACVBP) in comparison with cyclophosphamide, doxorubicin, vincristin and prednisone plus radiotherapy for young patients with localized diffuse large B-cell lymphoma (DLBCL) was previously demonstrated. We report the results of a trial which evaluates the role of rituximab combined with ACVBP (R-ACVBP) in these patients. PATIENTS AND METHODS: Untreated patients younger than 66 years with stage I or II DLBCL and no adverse prognostic factors of the age-adjusted International Prognostic Index were randomly assigned to receive three cycles of ACVBP plus sequential consolidation with or without the addition of four infusions of rituximab. RESULTS: A total of 223 patients were randomly allocated to the study, 110 in the R-ACVBP group and 113 in the ACVBP group. After a median follow-up of 43 months, our 3-year estimate of event-free survival was 93% in the R-ACVBP group and 82% in the ACVBP group (P = 0.0487). Three-year estimate of progression-free survival was increased in the R-ACVBP group (95% versus 83%, P = 0.0205). Overall survival did not differ between the two groups with a 3-year estimates of 98% and 97%, respectively (P = 0.686). CONCLUSION: In young patients with low-risk localized DLBCL, rituximab combined with three cycles of ACVBP plus consolidation is significantly superior to ACVBP plus consolidation alone.

Diffuse large B-cell lymphoma of Waldeyer's ring has distinct clinicopathologic features: a GELA study.

BACKGROUND: Diffuse large B-cell lymphomas (DLBCLs) arising in specific extranodal sites have peculiar clinicopathologic features. PATIENTS AND METHODS: We analyzed a cohort of 187 primary Waldeyer's ring (WR) DLBCLs retrieved from GELA protocols using anthracyclin-based polychemotherapy. RESULTS: Most patients (92%) had stage I-II disease. A germinal center B-cell-like (GCB) immunophenotype was observed in 61%, and BCL2 expression in 55%, of WR DLBCLs. BCL2, BCL6, IRF4 and MYC breakpoints were observed in, respectively, 3 of 42 (7%), 9 of 36 (25%), 2 of 26 (8%) and 4 of 40 (10%) contributive cases. A variable follicular pattern was evidenced in 30 of 68 (44%) large biopsy specimens. The 5-year progression-free survival (PFS) and the overall survival (OS) of 153 WR DLBCL patients with survival information were 69.5% and 77.8%, respectively. The GCB immunophenotype correlated with a better OS (P = 0.0015), while BCL2 expression predicted a worse OS (P = 0.037), an effect overcome by the GCB/non-GCB classification. Compared with matched nodal DLBCLs, WR DLBCLs with no age-adjusted international prognostic index factor disclosed a better 5-year PFS rate (77.5% versus 70.7%; P = 0.03). CONCLUSIONS: WR DLBCLs display distinct clinicopathologic features compared with conventional DLBCLs, with usual localized-stage disease, common follicular features and a high frequency of GCB immunophenotype contrasting with a low rate of BCL2 rearrangements. In addition, they seem to be associated with a better outcome than their nodal counterpart.

Is sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp identical to inflammatory pseudotumour? Report of 16 cases.

AIMS: To report 16 cases of sclerosing angiomatoid nodular transformation (SANT) of the splenic red pulp. METHODS AND RESULTS: Patients were selected in two phases. An initial group of seven patients was diagnosed with SANT based on the presence of angiomatoid nodules. Sheets of inflammatory fibrosis were found in three patients, resembling inflammatory pseudotumour (IPT); nine further cases of IPT were reviewed. Angiomatoid nodules were detected, leading to the diagnosis of SANT in all cases. The splenic mass (10-150 mm in diameter) was polycyclic, composed of multiple small nodules of loose connective tissue comprising myofibroblasts and a dense network of capillaries as well as some remnants of sinuses. Collagenous fibrosis surrounded them. Bands or large sheets of fibrosis, infiltrated by various inflammatory cells, particularly polytypic plasmacytes, resembling IPT, were present in 10 cases. CONCLUSIONS: SANT of the red pulp is a distinct benign pseudotumorous lesion of the spleen characterized by the presence of angiomatoid nodules. We observed such angiomatoid nodules in all our cases of splenic IPT, which were not follicular dendritic cell or myofibroblastic tumours. We therefore recommend careful examination for angiomatoid nodules in all suspected cases of splenic IPT.

[CT and MR virtual colonscopy: indications, limits and comparison with conventional colonscopy]. / Colonscopia virtuale TC e RM: indicazioni, limiti e confronto con la colonscopia tradizionale.

Virtual endoscopy is a new method for studying the colon; it consists in acquisition of CT and MR images and to elaborate them with a workstation, to create endoluminal vision as like as traditional colonscopy, permitting the complete exploration of colonic lumen, also with stenotic tumors. The analysis of the differences between CT and MR colography shows like these two techniques present both advantages and disadvantages, such as the impossibility to perform MR in patients with pace-maker or in claustrophobic patients and the impossibility to perform CT with iodated agents in patients with renal failure or with a story of adverse reactions. The increased use of these techniques is due to the high sensitivity of last-generation CT and MR machine, to the increased spatial resolution, to specific softwares for digital cleaning of colon, to the introduction of high-end workstations and to the possibility of computed assisted diagnosis (CAD). So, it is desiderable that the increasing spread of multidetector CT devices and the future technical innovations, should have the effect to increase culture and experience in various diagnostic centers about CT-colography, making possible the spreading of virtual endoscopy as a screening tool.

All aggressive lymphoma subtypes do not share similar outcome after front-line autotransplantation: a matched-control analysis by the Groupe d'Etude des Lymphomes de l'Adulte (GELA).

BACKGROUND: Data are still conflicting on the indication of front-line autologous stem-cell transplantation (ASCT) as consolidation for aggressive lymphoma. To assess the therapeutic effect of ASCT among different aggressive lymphoma subtypes, we conducted a matched-control analysis by pooling the data from two Groupe d'Etude des Lymphomes de l'Adulte (GELA) trials. PATIENTS AND METHODS: Between October 1987 and September 1998, 330 patients received ASCT after achieving complete remission with the ACBVP induction regimen. The histological slides showed: B aggressive non-Hodgkin's lymphoma (B-NHL) in 249 patients (75%), T-NHL in 52 patients (15%) (including 23 T anaplastic) and non-classified NHL in 29 patients. The age-adjusted International Prognostic Index (aaIPI) was 2 or 3 in 66%. Patients were matched with controls from the same GELA database but treated with chemotherapy only. RESULTS: ASCT did not benefit non-anaplastic T-NHL patients [5-year overall survival (OS) 44% (chemotherapy) versus 49% (ASCT), P=0.87; disease-free survival (DFS) 38% versus 45%, P=0.89] in comparison with B-NHL [5-year OS 77% (chemotherapy) versus 79% (ASCT), P=0.64; DFS 67% versus 72%, P=0.13]. However, for B-NHL patients with aaIPI score 2 or 3, the benefit of ASCT was significant. CONCLUSIONS: This cohort study confirms the high efficacy of front-line ASCT in responding aggressive B-NHL patients with adverse prognostic factors.

Prognostic factors in patients with aggressive non-Hodgkin's lymphoma treated by front-line autotransplantation after complete remission: a cohort study by the Groupe d'Etude des Lymphomes de l'Adulte.

PURPOSE: Improved survival has been observed in aggressive non-Hodgkin's lymphoma (NHL) patients with adverse prognostic factors when autotransplantation (ASCT) was performed after complete remission. However, there is no agreement on the prognostic factors for patients treated with ASCT. We aimed to estimate the prognostic effect of clinical and biologic variables on relapse and survival rates by pooling the data from two trials. PATIENTS AND METHODS: Of the patients treated in the LNH87 and LNH93 trials, 330 under age 60 years achieved complete remission after high-dose cyclophosphamide, doxorubicin, vincristine, and prednisone, and received consolidative ASCT; 16% of patients had T-cell NHL. The International Prognostic Index (IPI) score was 0 for 11%, 1 for 23%, 2 for 51%, and 3 for 15%. Univariate and Cox multivariate survival analyses were retrospectively performed on this population. RESULTS: Overall survival was 75 +/- 5% at 5 years and disease-free survival (DFS) 67 +/- 5%. For T-cell NHL, these scores were 54% and 44%, respectively. The IPI score had no prognostic value and only the following parameters adversely affected overall survival and DFS (P <.05): marrow involvement; more than one extranodal site; histology (nonanaplastic T-cell v others); and type of anthracycline (mitoxantrone v doxorubicin, for DFS only). CONCLUSION: These results suggest that ASCT can prevent relapse in patients with adverse IPI factors. However, patients presenting with a nonanaplastic T-cell phenotype, more than one extranodal site, or marrow involvement still have a higher risk of relapse. These factors should be taken into account when designing post-ASCT maintenance studies.

Epstein-Barr virus-associated lymphoproliferative disease occurring in a patient with sarcoidosis treated by methotrexate and methylprednisolone.

We describe the case of a 51-yr-old man with systemic sarcoidosis, complicated by the occurrence of a lymphoproliferative disease following a 36-month (duration) immunosuppressive treatment with methotrexate (MTX) and methylprednisolone. Four years after the onset of sarcoidosis, the patient presented a large necrotizing anal fistula. Pathological examination of this lesion showed a diffuse polymorphic infiltrate containing large Epstein-Barr virus (EBV)-positive lymphoid cells associated with areas of necrosis, all features similar to classical B-cell lymphoproliferative disorders occurring in immunosuppressed solid-organ recipients. MTX has been recently implicated in the development of lymphoproliferative disease in connective tissue diseases. This case supports the hypothesis that immunosuppression therapy may contribute to an increased risk for the development of EBV-associated lymphoproliferative disorders in patients suffering from sarcoidosis.

Collagenous gastritis: a report of six cases.

Collagenous gastritis is an exceptional entity with eight cases documented to date characterized by the presence of a thick subepithelial collagen band associated with an inflammatory infiltrate of the gastric mucosa. The aim of our study was to describe the clinical and histologic characteristics of six new cases of collagenous gastritis. All cases showed a subepithelial collagen band that averaged 30 microm but often measured up to 120 microm. This finding was almost always accompanied by mixed chronic inflammation in the lamina propria and by surface epithelial damage of varying severity. Our study seems to delineate two subsets in patients with collagenous gastritis: 1) collagenous gastritis occurring in children and young adults presenting with severe anemia, a nodular pattern on endoscopy, and a disease limited to the gastric mucosa without evidence of colonic involvement, and 2) collagenous gastritis associated with collagenous colitis occurring in adult patients presenting with chronic watery diarrhea. These findings highlight the fact that subepithelial collagen deposition may be a generalized disease affecting the entire gastrointestinal tract.

Epstein-Barr virus and gastric carcinoma in Western patients: comparison of pathological parameters and p53 expression in EBV-positive and negative tumours.

AIMS: 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. METHODS AND RESULTS: 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. CONCLUSIONS: 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.

[Large cell variant of small cell carcinoma of the ovary with hypercalcemia]. / Variante à grandes cellules d'un carcinome à petites cellules de l'ovaire avec hypercalcémie.

We describe an original distinct type of ovarian small cell carcinoma: large cell variant. The distinctive histologic features of tumor cells were the presence of large nuclei with prominent nucleoli and abundant eosinophilic cytoplasm. Immunohistochemistry revealed strong diffuse vimentin, smooth muscle actin positivity and slight reactivity with epithelial markers. Electron microscopy showed aggregates of intermediate filaments, intercellular attachments and no dense core granules. This tumor is associated with paraendocrine hypercalcemia in two thirds of cases. Parathyroid hormone-related protein was focally positive. This tumor is characterized as a very lethal neoplasm, occurring primarily in young women.