The expression of matrix metalloproteinases-2 and -9 and their tissue inhibitor 2 in pancreatic ductal and ampullary carcinoma and their relation to angiogenesis and clinicopathological parameters.

AIM: To investigate the expression of metalloproteinase (MMP) -2, MMP-9 and tissue inhibitor of MMP (TIMP) -2 in pancreatic ductal and ampullary carcinoma and to test the findings for correlation with angiogenesis and several clinicopathological parameters. PATIENTS AND METHODS: Paraffin sections from 32 pancreatic ductal adenocarcinomas and 17 ampullary carcinomas were assessed for the expression of MMP-2, MMP-9 and TIMP-2 by immunohistochemistry. Stromal and epithelial staining was evaluated separately. Moreover, sections stained immunohistochemically with anti-CD34 antibody were evaluated by image analysis for the quantification of microvessel density (MVD). RESULTS: In pancreatic ductal adenocarcinoma, lower levels of glandular TIMP-2 were found in poorly differentiated tumors, while high glandular TIMP-2 expression was significantly associated with better survival. The age of the patients and the degree of differentiation of the tumor were identified as independent prognostic parameters. No relation was found between the expression of MMPs, TIMP or angiogenesis and the parameters under consideration. In ampullary adenocarcinoma, strong expression of glandular MMP-2 was associated with higher MVD values. Moreover, lymph vessel invasion was associated with higher stromal TIMP-2. CONCLUSION: In pancreatic ductal adenocarcinoma, TIMP-2 may have a more crucial role in prognosis than MMP-2, MMP-9 or angiogenesis. In ampullary adenocarcinoma, MMP-2 expression correlated with MVD, supporting its postulated role in angiogenesis.

Large somatostatin-producing endocrine carcinoma of the ampulla of vater in association with GIST in a patient with von Recklinghausen's disease. Case report and review of the literature.

CONTEXT: Somatostatin-producing endocrine tumors of the duodenum are very rare neoplasms of the gastrointestinal tract. These tumors may be associated with von Recklinghausen's disease. CASE REPORT: We present the case of a 49-year-old female patient with von Recklinghausen's disease and an incidentally diagnosed ampullary neoplasm. The patient was treated with a classical pancreaticoduodenectomy. At surgery, a mass was found in the greater curve of the stomach which was resected using the classic Whipple procedure. Histology and immunohistochemistry showed that the duodenal tumor was an ampullary somatostatin-producing endocrine carcinoma while the gastric tumor was a gastrointestinal stromal tumor (GIST). The postoperative course was uneventful and the patient is alive, without tumor recurrence, six years after surgery. CONCLUSION: Somatostatin-producing endocrine tumors of the duodenum are rare tumors, often associated with von Recklinghausen's disease; these neoplasms should be treated aggressively using radical surgical resection. Although local resection may be appropriate for small duodenal somatostatin-producing tumors, a pancreaticoduodenectomy is usually required for larger tumors.

Splenic marginal-zone lymphoma: one or more entities? A histologic, immunohistochemical, and molecular study of 42 cases.

We analyzed 42 splenic marginal-zone lymphoma (SMZL) cases diagnosed on splenectomy specimens after established World Health Organization criteria. A predominantly nodular growth pattern was observed in 24 cases; the remainder showed predominantly (11/42) or exclusively (7/42) diffuse infiltration. Twenty-one cases showed the "classic" biphasic appearance; 13 cases exhibited marginal-zone morphology; finally, 8 cases were composed predominantly of small cells. CD21 and CD35 were expressed by 12/42 and 17/38 cases, respectively. DBA.44 was detected in 24/42 cases. Seventeen of 37 cases were surface IgD (SIgD)-positive. Twenty-one of 22 analyzed cases were SIgM-positive (12/21 coexpressed SIgD). Five of 37 cases were SIgG-positive. CD27 staining was observed in 21/35 cases; 7/18 CD27-positive cases coexpressed SIgD; 7/14 CD27-negative cases were SIgD-positive. Forty IGHV-D-J rearrangements were amplified in 34/42 cases: the IGHV4-34 gene predominated, followed by IGHV1-2. Using the 98% homology cut-off, 25/40 (62.5%) IGHV sequences were considered as "mutated": 10/11 cases with monomorphous, marginal-zone morphology were IGHV-mutated; in contrast, 4/6 cases with monomorphous, small-cell morphology were IGHV-unmutated. Five of 7 cases expressing IGHV1 subgroup genes had biphasic morphology, whereas 6/9 IGHV3-expressing cases had monomorphous, marginal-zone morphology. Most IGHV-mutated cases (14/20; 70%) were SIgD-negative; in contrast, 8/11 IGHV-unmutated cases expressed SIgD. CD27 was detected in 10/17 IGHV-mutated and 6/10 IGHV-unmutated cases. Seven of 11 CD27-negative cases were IGHV-mutated; 5/7 CD27-negative/IGHV-mutated cases expressed DBA.44. These results confirm the considerable histologic, immunohistochemical, and molecular heterogeneity of SMZL and indicate an origin from the diverse resident B-cell populations of the normal SMZ.

Adhesion formation and intraperitoneal catheters: histologic findings in a rat model.

Pieces of polyurethane, Teflon, silicone, and polyvinyl chloride were placed intraperitoneally to compare the histologic findings regarding intraperitoneal adhesion development in a rat model. The overall adhesion score differed significantly among the groups, the highest being in the Teflon group (mean 13.2), followed in descending order by the polyvinyl chloride group (10), the silicone group (9.6), and the polyurethane group (6.8). Thus, polyurethane causes the least adhesion development and can be used more extensively for the construction of catheters for intraperitoneal use.

Favorable response to subcutaneous administration of infliximab in rats with experimental colitis.

AIM: To investigate the influence of infliximab (Remicade) on experimental colitis produced by 2,4,6,trinitrobenzene sulfonic acid (TNBS) in rats. METHODS: Thirty-six Wistar rats were allocated into four groups (three groups of six animals each and a fourth of 12 animals). Six more healthy animals served as normal controls (Group 5). Group 1: colitis was induced by intracolonic installation of 25 mg of TNBS dissolved in 0.25 mL of 50% ethanol and infliximab was subcutaneously administered at a dose of 5 mg/kg BW; Group 2: colitis was induced and infliximab was subcutaneously administered at a dose of 10 mg/kg BW; Group 3: colitis was induced and infliximab was subcutaneously administered at a dose of 15 mg/kg BW; Group 4: colitis was induced without treatment with infliximab. Infliximab was administered on d 2-6. On the 7(th) d, all animals were killed. The colon was fixed in 10% buffered formalin and examined by light microscopy for the presence and activity of colitis and the extent of tissue damage. Tumor necrosis factor-alpha (TNF-alpha) and malondialdehyde (MDA) were also measured. RESULTS: Significant differences concerning the presence of reparable lesions and the extent of bowel mucosa without active inflammation in all groups of animals treated with infliximab compared with controls were found. Significant reduction of the tissue levels of TNF-alpha in all groups of treated animals as compared with the untreated ones was found (0.47+/-0.44, 1.09+/-0.86, 0.43+/-0.31 vs 18.73+/-10.53 respectively). Significant reduction in the tissue levels of MDA was noticed in group 1 as compared to group 4, as well as between groups 2 and 4. CONCLUSION: Subcutaneous administration of infliximab reduces the inflammatory activity as well as tissue TNF-alpha and MDA levels in chemical colitis in rats. Infliximab at a dose of 5 mg/kg BW achieves better histological results and produces higher reduction of the levels of TNF-alpha than at a dose of 10 mg/kg BW. Infliximab at a dose of 5 mg/kg BW produces higher reduction of tissue MDA levels than at a dose of 15 mg/kg BW.

Coexistence of Crohn's disease and inflammatory fibroid polyp of the small bowel. Report of a case and review of the literature.

BACKGROUND/AIM: The Authors report a case of a woman aged 35, with concurrent appearance of Crohns disease and Inflammatory Fibroid Polyp of the terminal ileum. CASE REPORT: The combination of the two disorders was clinically manifested as an obstructive ileus. On the operative table, a 4-cm polypoid mass causing intussusception of the bowel was obvious. The resected specimen of the ileum showed profound distention, several ulcerations and fissures. The histological examination confirmed the diagnosis of Crohn's disease coexisting with an Inflammatory Fibroid Polyp. Immunostaining of the lesion for actin showed focal positivity. However, staining for desmin, CD31, S100-protein, PGM-1 CD34, CD117, and bc1-2, was negative. CONCLUSION: Coexistence of Inflammatory Fibroid Polyp with Crohn's disease causing obstructive ileus could be the first manifestation of the disease. The combination of the two disorders corroborates the reparative character of the lesion. Nevertheless, the exact etiopathogenetic relationship between the two entities remains obscure.

Adhesion formation: intraperitoneal catheters in surgical practice.

To compare the adhesion formation, in a rat model, of commercially available materials used as intraperitoneal catheters in clinical practice, pieces of polyurethane, Teflon, silicone, and polyvinyl chloride (PVC) were placed intraperitoneally in 36 female Wistar rats randomly assigned into four groups. Adhesion development was quantitated according to Nair's classification system (NCS). According to NCS, polyurethane showed the least adhesion formation, while the highest scores were found in the PVC group. Comparing the thickness and the firmness of adhesions in the four groups, significant differences were found, with the polyurethane group developing none or filmy and mild adhesions. In contrast, almost all the rats in the Teflon group developed thick and dense adhesions. Thus, polyurethane caused the least adhesion formation among the four materials evaluated, and can be used more extensively for the construction of catheters for prolonged intraperitoneal use.

Pseudosarcomatous myofibroblastic lesion of the urinary bladder: a rare entity posing a diagnostic challenge and therapeutic dilemma.

BACKGROUND: Pseudosarcomatous myofibroblastic lesions of the urinary bladder are relatively rare entities of an uncertain pathogenesis and benign indolent nature. CASE PRESENTATION: We present an extremely rare case of an ALK-1-positive pseudosarcomatous myofibroblastic lesion of the urinary bladder, which was initially misinterpreted as a low-grade leiomyosarcoma of myxoid subtype on histologic examination owing to prominent atypia, high mitotic activity, abnormal mitotic figures and infiltration of the bladder wall. Although the histologic features were suggestive of a sarcoma, the correct diagnosis was finally established and radical surgical treatment was subsequently avoided. The patient is currently free of disease without any evidence of tumor recurrence or metastasis at 3 years post-operatively. CONCLUSION: The key differentiating point rests in distinguishing the aforementioned mass forming lesion from the myxoid subtype of low-grade leiomyosarcoma in order to avoid unnecessary radical therapy.

Morphometric microvascular characteristics in the prognosis of pancreatic and ampullary carcinoma.

OBJECTIVES: To evaluate multiple morphometric microvascular characteristics in addition to microvascular density (MVD) in pancreatic ductal and ampullary adenocarcinomas and provide a better approach in examining the relationship among angiogenesis, several clinicopathologic parameters, and prognosis. METHODS: Histological sections from 32 pancreatic ductal and 17 ampullary adenocarcinomas, immunostained with CD34, were evaluated by image analysis for the quantification of MVD, total vascular area, and microvascular branching, as well as several morphometric parameters related to the vessel size and shape factor. RESULTS: In pancreatic ductal carcinoma, higher levels of MVD, total vascular area, branching, and shape factor were related to N1 tumors. Moreover, MVD, shape factor, and minor axis length were identified as independent prognostic factors of survival. In the ampullary carcinoma group, higher shape factor values were observed in well-differentiated tumors. CONCLUSIONS: In pancreatic ductal carcinoma patients, the assessment of MVD and several morphometric microvascular characteristics provides significant prognostic information. The biologic behavior of the ampullary carcinomas does not seem to be dependent on any of the above mentioned factors of angiogenesis.

Expression of peroxisome proliferator-activated receptor-gamma in colon cancer: correlation with histopathological parameters, cell cycle-related molecules, and patients' survival.

Peroxisome proliferator-activated receptor gamma (PPAR-gamma), a ligand-activated transcription factor, is a key regulator of adipogenic differentiation and glucose homeostasis. PPAR-gamma ligands have recently been demonstrated to affect proliferation and differentiation in cancer cells lines. The aim of the present work was to examine PPAR-gamma expression in colon cancer cases. PPAR-gamma expression was examined immunohistochemically in 86 colon cancer cases and was correlated with clinicopathological parameters, tumor proliferative capacity, cell cycle-related molecule expression, and patient survival. Positive PPAR-gamma immunostaining was prominent in 48 of 86 cases (56%). PPAR-gamma positivity was not correlated with Dukes' stage, histological grade of differentiation, lymph node and liver metastasis, venous invasion, tumor proliferative capacity, or patient survival. A statistically significant correlation was found between PPAR-gamma and the expression of cell cycle-related molecules pRb (P < 0.016), cyclin D1 (P <0.009), p16 (P<0.032), and p21 (P<0.033), while a positive trend for cyclin E was also noted (P<0.057). The pattern, intensity, and extent of PPAR-gamma expression in positive cases were not correlated with any of the examined variables. Our findings support evidence for participation of this protein in the biological mechanisms underlying carcinogenic evolution in the colon, also suggesting the importance of specific PPAR-gamma ligands as cell cycle modulators for a future therapeutic approach in colon cancer.

Report of an atypical case of leishmaniasis presented as acute tonsillitis in an immunocompetent patient.

Visceral leishmaniasis typically presents with symptoms such as fever, enlargement of the spleen and the liver, hypergammaglobulinaemia and infection of the bone marrow resulting in anaemia and leukopenia. The disease is sporadic in the countries of the Mediterranean basin. We report an unusual case of acute tonsillitis due to tonsillar leishmaniasis, in an immunocompetent 34-y-old male patient. Diagnosis was confirmed by serological tests and histopathological examination following biopsy of the right tonsil. The patient was successfully treated with liposomal amphotericin-B.

Prognostic impact of DNA ploidy pattern, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) in patients with primary gastric lymphoma.

BACKGROUND: DNA ploidy, S-phase fraction (SPF), and proliferating cell nuclear antigen (PCNA) are considered to be significant prognostic factors in non-Hodgkin lymphomas. However, reports on their prognostic importance in gastric lymphoma patients are relatively lacking. METHODS: In the present study, we retrospectively studied the above-mentioned parameters in 29 patients with primary gastric lymphoma; 11/29 had B-low grade mucosa associated lymphoid tissue lymphoma (B-MALT), while 18/29 had diffuse large B-cell lymphoma (DLBCL), according to WHO classification. Proliferative activity was studied by staining against PCNA; in addition, the prognostic significance of DNA ploidy and SPF, as determined by flow cytometry, were investigated and compared to the results of the PCNA stainings. RESULTS: Seven out of 29 patients were found to have aneuploid tumors; DNA index values were >1 for all aneuploid lymphomas. There was no difference in DNA aneuploidy in MALT vs. DLBCL. The mean percentage of SPF was 11.4. SPF was found significantly lower in MALT vs. DLBCL (P < 0.05). The mean percentage of PCNA positive tumor cells was 52.6. PCNA protein expression was significantly lower in MALT vs. DLBCL (P < 0.0001). There was a significant positive correlation between PCNA score and SPF (P < 0.01, by Spearman analysis). DNA ploidy had no impact on survival in the present study. Both SPF and PCNA expression were important prognostic factors in the univariate analysis; however, in the multivariate analysis, the only independent prognostic factor for survival was PCNA expression. CONCLUSIONS: These findings indicate that SPF and PCNA are significant prognostic factors in patients with primary gastric lymphomas. However, in the present study, DNA ploidy had no impact on survival in patients with primary gastric lymphomas.

Immunoglobulin heavy- and light-chain repertoire in splenic marginal zone lymphoma.

The considerable heterogeneity in morphology, immunophenotype, genotype, and clinical behavior of splenic marginal zone lymphoma (SMZL) hinders firm conclusions on the origin and differentiation stage of the neoplastic cells. Immunoglobulin (IG) gene usage and somatic mutation patterns were studied in a series of 43 SMZL cases. Clonal IGHV-D-J rearrangements were amplified in 42/43 cases (4 cases carried double rearrangements). Among IGHV-D-J rearrangements, IGHV3 and IGHV4 subgroup genes were used with the highest frequency. Nineteen IGHV genes were unmutated (> 98% homology to the closest germline IGHV gene), whereas 27/46 were mutated. Clonal IGKV-J and IGLV-J gene rearrangements were amplified in 36/43 cases, including 31 IGKV-J (8/31 in lambda light-chain expressing cases) and 12 IGLV-J rearrangements; 9/31 IGKV and 6/12 IGLV sequences were mutated. IGKV-J and IGLV-J rearrangements used 14 IGKV and 9 IGLV different germline genes. Significant evidence for positive selection by classical T-dependent antigen was found in only 5/27 IGHV and 6/15 IGKV+IGLV mutated genes. These results provide evidence for the diverse B-cell subpopulations residing in the SMZ, which could represent physiologic equivalents of distinct SMZL subtypes. Furthermore, they indicate that in SMZL, as in other B cell malignancies, a complementarity imprint of antigen selection might be witnessed either by IGHV, IGKV, or IGLV rearranged sequences.