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Twenty-seven endometrioid stromal sarcomas of the ovary from patients 38 to 76 (mean 56) years of age are reported. The tumors were unilateral in 20 cases and bilateral in 7. They were solid (9), solid and cystic (9), or predominantly cystic (6) when this information was known and ranged from 1 to 20 (mean 9.5) cm. The solid areas typically had a tan-yellow cut surface, with areas of hemorrhage and/or necrosis noted in 6; however, in addition, blood was often present in the cyst lumens. On microscopic examination, the predominant and frequently exclusive pattern was a diffuse growth of small cells with interspersed arterioles, the latter appearing round to elongated. A fibromatous pattern was present in 14 of the tumors but was extensive in only 3. A vague nodular growth was observed in 10 tumors but was never striking; a storiform growth was seen in 2 tumors, being conspicuous in 1. Hyaline plaques were present in 10 tumors but were striking in only 2. Sex cord-like or smooth muscle differentiation was seen in 7 and 6 tumors, respectively, being striking in 2 and 3 of them. Foam cells were present in 6 tumors. The tumors showed minimal cytologic atypia. The mitotic index ranged from <1 to 17/10 high-power fields (HPF), being <1/10 HPF in 12, 1 to 5/10 HPF in 9, 6 to 10/10 HPF in 2, and >10/10 HPF in 4 tumors. Infarct-type necrosis was noted in 12 tumors. Hemorrhage, typically recent, was seen in 20 cases, being conspicuous in 5. Ovarian endometriosis was intimately associated with the tumor in 16 cases. Seven patients had stage I tumors, 5 stage II, 13 stage III, and 2 stage IV. Follow-up information was available for 21 patients; 10 were alive and free of disease from 4 to 21 years postoperatively (follow-up being ≥ 11 y in 5); 6 were alive with disease from 1 to 22 years postoperatively; 5 patients are known to have died of disease, with the interval being unknown in 1, and 2, 4, 13, and 17 years in the others. Follow-up information was unavailable in the remaining 6 patients. These findings indicate that these tumors, as in the uterus, often have an indolent course with a better prognosis than other ovarian sarcomas, indicating the importance of correct diagnosis. The differential diagnosis of these neoplasms is in the first instance with a metastasis from the uterus; knowledge of the status of the uterus is paramount in this distinction. Associated ovarian endometriosis suggests a primary tumor. When a primary ovarian origin is determined, the differential diagnosis is most often with a sex cord-stromal tumor, particularly a granulosa cell tumor because of a diffuse growth of cells with scant cytoplasm.

To focus on and compare the tumor hormone receptor profiles on core needle biopsy (CNB) and subsequent surgical excision specimens in a large clinical series of invasive breast carcinoma patients, with regard to guidelines proposed at the St. Gallen International Expert Consensus on the Primary Therapy of Early Breast Cancer 2011. A total of 993 consecutive patients who had hormone receptors (HR) assays performed on both CNB and subsequent surgical excision specimens of invasive carcinomas were included (1,110 tumors). Concordant tumor HR profiles between CNB and surgical excision specimens were noted in 1,085 of 1,110 tumors (97.75%). Among 138 tumors considered negative on CNB (both HR assays <1%), 10 cases (7.2%) displayed an HR profile positive on surgical excision specimen. Discrepancies between CNBs and surgical excision specimens are very seldom noted. HR assay evaluation on surgical excision specimens should only be considered in patients when both HR assays are negative on CNBs., (© 2013 Wiley Periodicals, Inc.)

Purpose: Androgens stimulate the production of hypoxia-inducible factor (HIF1α) and ultimately vascular endothelial growth factor (VEGF-A). Additionally, epithelial growth factor (EGF) mediates HIF1α production. Carbonic anhydrase IX (CAIX) expression is associated with tumor cell hypoxia in a variety of malignancies. This study assesses the prognostic relation between HIF1α, VEGF-A, EGF Receptor and CAIX expression by immunochemistry in diagnostic samples of patients with intermediate- and high-risk localized prostate cancer treated with radiation therapy, with or without androgen deprivation therapy (ADT)., Materials and Methods: Between 1994 and 2004, 103 prostate cancer patients (mean age, 68.7 ± 6.2), with prostate cancer (mean PSA, 13.3 ± 3.7), were treated with radiation therapy (RT, median dose, 74 Gy). Fifty seven (55.3%) patients received ADT (median duration, 6 months; range, 0 - 24). Median follow-up was 97.6 months (range, 5.9 - 206.8)., Results: Higher EGFR expression was significantly (p = 0.04) correlated with higher Gleason scores. On univariate analysis, HIF1α nuclear expression was a significant (p = 0.02) prognostic factor for biological progression-free survival (bPFS). A trend towards significance (p = 0.05) was observed with EGFR expression and bPFS. On multivariate analysis, low HIF1α nuclear (p = 0.01) and high EGFR (p = 0.04) expression remained significant adverse prognostic factors., Conclusions: Our study suggests that high nuclear expression of HIF1α and low EGFR expression in diagnostic biopsies of prostate cancer patients treated with RT ± ADT is associated with a good prognosis.

Epstein-Barr virus (EBV) is associated with several types of cancers including Hodgkin's lymphoma (HL) and nasopharyngeal carcinoma (NPC). EBV-encoded latent membrane protein 1 (LMP1), a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS) to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.

Recent findings have attested the protective effects of erythropoietin (EPO) in ischemically challenged organs. We therefore aimed at elaborating the underlying mechanism of EPO-mediated protection in musculocutaneous tissue undergoing persistent ischemia after acute injury. Mice were assigned to five experimental groups equipped with a randomly perfused flap fixed in a dorsal skinfold chamber, whereas the sixth group did not undergo flap preparation: EPO, L-Name, EPO and L-Name, EPO and bevacizumab, untreated flap, and nonischemic chamber (control). Intravital fluorescence microscopic analysis of microhemodynamics, apoptotic cell death, macromolecular leakage and angiogenesis was carried out over a 10-day period. Further, immunohistochemical analysis was used to study the protein expression of endothelial nitric oxide synthase (eNOS) and vascular endothelial growth factor (VEGF). Increased expression of eNOS in EPO-administered mice correlated with significant arteriolar dilation and thus increased blood flow resulting in a maintained functional capillary density (FCD) at day 10. In addition, EPO induced a VEGF upregulation, which was associated with newly formed capillaries. In addition, EPO was able to reduce ischemia-induced apoptotic cell death and finally to significantly reduce flap necrosis. In contrast, coadministration of L-Name abolished EPO-mediated tissue protection by abrogating the dilatory effect resulting in reduced FCD and tissue survival, without counteracting angiogenesis and apoptotic cell death, whereas additional administration of bevacizumab did not influence the beneficial effect of EPO on flap survival despite abrogating angiogenesis. Macromolecular leakage was found to be increased in all treatment groups. This study shows that EPO administration prevents musculocutaneous tissue from ischemic necrosis as a consequence of an eNOS-dependent arteriolar hyperperfusion maintaining capillary perfusion, thus representing a promising approach to pharmacologically protect ischemically challenged tissue.

Objective: To identify in cytology, high-grade squamous intraepithelial lesions with endocervical glandular extension in cases previously diagnosed as atypical glandular cells (AGC), analyse possible reasons for the diagnostic pitfall and document the frequency of glandular pathology coexisting with high-grade cervical intraepithelial lesion in histology., Methods: Thirty-nine ThinPrep cervical smear (Pap) tests reported as AGC of undetermined significance and showing high-grade lesions on histology [cervical intraepithelial neoplasia (CIN) 2 or 3, endometrial or extrauterine adenocarcinoma] were reviewed retrospectively to identify the cases of high-grade squamous intraepithelial lesion with endocervical glandular extension, using the Bethesda 2001 system. Cyto-histological correlation was performed., Results: A high frequency of diverse glandular pathologies coexisted with high-grade cervical intraepithelial lesions on histology. This included endocervical glandular extension in 63%, benign glandular pathology in 33% and pre-neoplastic or malignant glandular pathology (endocervical glandular dysplasia, adenocarcinoma in situ and metastatic breast carcinoma) in 17% cases. On cytology, the sensitivity was 40%, specificity was 80% and positive predictive value was 86% for endocervical gland extension in high-grade squamous intraepithelial lesions., Conclusions: Special efforts to recognize endocervical glandular extension in high-grade squamous intraepithelial lesions and glandular neoplasia coexisting with squamous intraepithelial lesions from the heterogeneous category of AGC can contribute to increasing the diagnostic accuracy. The identification of endocervical glandular extension on cervical cytology would alert the gynaecologist to perform a thorough assessment of the endocervix during colposcopy. This could also help to decide on the need to perform deeper conization rather than loop electrosurgical excision procedure to ensure negative margins when colposcopic biopsy shows CIN 2 or 3.

Background: Sentinel lymph node (SLN) biopsy plays a major role in the surgical management of primary breast cancer. The aim of this study was to assess the diagnostic accuracy of the assessment of axillary frozen sections of SLNs for micrometastasis diagnosis., Patients and Methods: This study focused on 278 SLNs from 149 patients. Each lymph node was fully analyzed by frozen section. After fixation, serial sections were cut and stained by hematoxylin and eosin (HE) and for pan-cytokeratins by immunohistochemistry (IHC)., Results: Tumor cells were detected in 63 SLNs, 41 on frozen sections and 22 on controls. Of these 63 positive SLNs, 42 contained metastases, 10 contained micrometastases and 11 contained isolated tumor cells. The specificity and positive predictive value of SLN frozen sections for micrometastasis was 100%. The sensitivity was 83.3% for metastasis, 40% for micrometastasis; the false-negative rate was 16.7% for metastasis and 60% for micrometastasis., Conclusion: Analysis of frozen section of SLNs is an accurate method for metastasis detection, allowing concurrent axillary dissection when positive. The protocol for SLN analyses described herein shows good sensitivity for micrometastasis detection.

Objective: The challenges of imaging posterior deeply infiltrating endometriosis with MRI are to image a small anatomic area encompassing several thin fibromuscular anatomic structures such as uterosacral ligaments, and the vaginal and rectal walls; and to image endometriotic lesions, which are fibromuscular structures and have an MRI signal intensity very close to those of surrounding fibromuscular anatomic structures., Conclusion: We show the capability and potential of MRI in diagnosing and staging of posterior deeply infiltrating endometriosis after vaginal and rectal gel opacification.

The canal of Nuck is the portion of the processus vaginalis within the inguinal canal in women. A hydrocele of the canal of Nuck is equivalent to an encysted hydrocele of the cord in men. The literature reveals very little about this rare condition in the adult female patient. In this paper, we report a case of hydrocele of the canal of Nuck in a young female. The diagnosis was made with ultrasound and magnetic resonance imaging and then confirmed preoperatively and by histopathology. Although rare, a hydrocele of the canal of Nuck has to be included in the differential diagnosis of a groin lump in female patients., (Copyright 2009 S. Karger AG, Basel.)

Objective: To describe the cytological aspect of peritoneal washings in benign multicystic peritoneal mesothelioma (BMPM)., Methods: Three peritoneal washing specimens stained by standard cytological and histological procedures and analysed by light microscopy., Results: The specimens showed an abundance of monomorphous mesothelial cells devoid of atypia or mitoses. The mesothelial cells were calretinin positive. They also showed numerous squamous metaplastic cells arranged in flat sheets or isolated cells. The background contained some inflammatory cells., Conclusion: The combination of cytology of the peritoneal washing, histology (cell block and surgical specimen) and clinical history allow differentiation of BMPM from other cystic lesions (cystic lymphangioma and malignant mesothelioma).

Background: The category "atypical glandular cells" (AGC) in The Bethesda System (TBS) 2001 represents equivocal glandular atypia. The objective was to determine the clinical significance of diagnosing AGC using new TBS 2001 on Thin-Prep. There is scant information on the diagnosis of AGC and its outcome on ThinPrep using TBS 2001., Methods: 174 "ThinPrep" Pap tests reported as atypical glandular cells of unknown significance (AGUS) using TBS 1991 during the period (2001-2004) were reclassified using AGC subcategories of TBS 2001. Follow-up histology was correlated with AGC subcategories of TBS 2001 and in women <40 and >or=40 years of age., Results: The mean AGC rate significantly decreased from 0.7% to 0.3%. (p <0.02). The frequency of clinically significant lesions on followup was higher with AGC diagnosis (51%, 21/41) than AGUS diagnosis (36%, 37/103). It was significantly higher for atypical endocervical cells favouring neoplasia (AEC-FN) (67%, 4/6) and AGC with concurrent squamous intraepithelial lesions (SIL) (67%, 8/12) than for the atypical endocervical cells, not otherwise specified (AECNOS) subcategory (12.5%, 2/16). All clinically significant lesions were high grade squamous intraepithelial lesions (HSIL) in women <40 years but in women >or=40 years, the majority (70%) were glandular. In categories atypical glandular cells favouring neoplasia (AGC-FN) and atypical endometrial cells (AEMC) all women had clinically significant glandular lesions., Conclusions: AEC-FN, AGC-FN, AEMC and AGC with concurrent SIL subcategories represented high risk diagnoses. The sequence of further investigations may vary by age and presence of postmenopausal bleeding.

The rupture of an intra-abdominal testicular neoplasm is a rare cause of acute abdomen and massive intra-abdominal haemorrhage. We report the case of a 70-year-old male presenting a massive intra-abdominal bleeding caused by a Leydig cell tumour in an undescended testis. The clinical details and pathology of this rare testicular tumour are discussed.

The nested variant of urothelial carcinoma is a rare type of urothelial invasive carcinoma. It is characterized by islands of discrete to moderate atypical urothelial cells that strongly simulate von Brunn nests and invade to the lamina propria or deeper. Almost all described cases have been located in the bladder. We report a case of nested variant of urothelial carcinoma of the renal pelvis and ureter, synchronous with high-grade urothelial papillary carcinoma.

Background: A low yield of lymph nodes (LN) in abdominoperineal resection (APR) specimen has been associated with preoperative radiation therapy (XRT) in population-based studies, which may preclude adequate staging of anorectal carcinomas. We hypothesized that the number of LN retrieved in APR specimen was correlated with the dose and the timing of pelvic irradiation., Patients and Methods: We performed a retrospective study of 102 patients who underwent APR in a single institution between 1980 and 2004. Pathological reports were reviewed and the number of lymph nodes retrieved in APR specimens was correlated with: 1) Preoperative radiation; 2) Dose of pelvic irradiation; and 3) Time interval between the end of XRT and surgery., Results: There were 61 men and 41 women, with a median age of 66 (range 25-89) years. There were 12 patients operated for squamous cell carcinoma of the anal canal (SCCA) and 90 for rectal cancer. 83% and 46% of patients with anal and rectal cancer respectively underwent radical/neoadjuvant radiotherapy. The mean +/- SD number of LN in APR specimen was 9.2 +/- 5.9. The mean number of LN in APR specimen was significantly lower in patients who underwent preoperative XRT (8 +/- 5.5 vs. 10.5 +/- 6.1, Mann-Whitney U test, p = 0.02). The mean number of LN was not significantly different after XRT in patients with SCCA than in patients with rectal cancer (6.2 +/- 5.3 vs. 7.8 +/- 5.3, p = 0.33). Finally, there was an inverse correlation between the yield of LN and the time elapsed between XRT and surgery (linear regression coefficient r = -0.32, p = 0.03)., Conclusion: Our data indicate that: 1) radiation therapy affects the yield of LN retrieval in APR specimen; 2) this impact is time-dependent. These findings have important implications with regard to anatomic-pathological staging of anal and rectal cancers and subsequent decision-making regarding adjuvant chemotherapy.

Aim: To analyze GIST outcome after primary resection and to determine if a new grading system could adequately predict there prognosis., Methods: A retrospective review (1993-2002) identified 80 patients who underwent primary surgical resection for, c-KIT positive, GIST. Follow-up was complete for all patients (median follow-up 42, range 1-132, months). GIST were classified as low or high grade according to the following parameters: size, mitotic rate, mitotic index (MiB1), presence of necrosis, invasion of adjacent structure and presence of metastasis., Results: GIST originated from the stomach (46), small bowel (30), colon and rectum two and mesentery two. At surgery, 94% of cases presented with localized disease and 6% blood born metastasis with or without lymph node invasion. Resections were complete (R0) in 72 cases. R0 resection correlated with prognosis (p<0.01). Sixty GIST were classified as low grade (median follow-up 60 months) and 20 as high grade (median follow-up 27 months). Five-year actuarial survival of patients with low or high grade GIST were of 95 and 21%, respectively, (p<0.001)., Conclusion: Prognosis of GIST after surgical treatment is influenced by completeness of primary resection and tumour malignant potential. Low grade GIST have an excellent prognosis after surgery alone, while high grade GIST have a high rate of recurrence after primary resection. Adjuvant treatment should be advocated for patient with either high grade GIST or after incomplete primary resection. The presented grading system can reliably predict GIST outcome after primary surgical treatment. Complete surgical resection offers good chance of cure for low grade GIST, while for high grade GIST surgery alone is not sufficient. The presented grading system could be used to identify patients who may benefit of adjuvant treatment with imatinib mesylate after GIST resection.

Purpose: The feasibility and safety of left-sided colorectal procedures with avoidance of mechanical bowel preparation has recently been demonstrated. Moreover, mechanical preparation has been associated with an increased risk for abdominal septic complications, including anastomotic leakage. This study was designed to determine whether mechanical bowel preparation is associated with histologic alterations in the colon., Methods: Fifty patients (mean age, 61 (range, 45-78) years) scheduled to undergo elective colorectal surgery were prospectively randomized to receive mechanical preparation (polyethylene glycol; Group 1) or no preparation (Group 2) preoperatively. A macroscopically healthy segment of the bowel was excised at the proximal margin of the colectomy piece. A pathologist, blinded to the patient's group allocation, assessed various morphologic parameters., Results: Indications for colectomy (cancer and complicated diverticulosis) did not differ between groups. Bowel wall alterations were more frequent in patients who received a preparation. The most striking alterations associated with mechanical preparation were loss of superficial mucus (moderate-to-severe in 96 and 52 percent in Groups 1 and 2, respectively; P < 0.001) and epithelial cells (moderate-to-severe in 88 and 40 percent in Groups 1 and 2, respectively; P < 0.01). In addition, inflammatory changes, i.e., lymphocytes (severe in 48 and 12 percent in Groups 1 and 2, respectively; P < 0.02) and polymorphonuclear cells infiltration (severe in 52 and 8 percent in Groups 1 and 2, respectively; P < 0.02), were more prevalent after mechanical preparation., Conclusions: Mechanical bowel preparation is associated with structural alteration and inflammatory changes in the large bowel wall. Although bowel wall inflammation is a known risk factor for anastomotic leak, it remains to be elucidated whether these changes have a direct relation to the deleterious effect of mechanical bowel preparation in terms of abdominal morbidity.

Adenocarcinoid of the appendix is an infrequent tumor with histologic features of both adenocarcinoma and carcinoid tumor. Although its malignant potential remains unclear, adenocarcinoids seem to be biologically more aggressive than conventional carcinoids. The aim of this study was to analyze long-term results of surgical treatment for appendiceal adenocarcinoid. A retrospective review (1991-2003) identified seven patients (median age 72, range 27-81 years) treated for appendiceal adenocarcinoid. The clinical data of these patients were reviewed. Follow-up was complete for all patients (median 60 months, range 24-108 months). Most cases presented with associated acute appendicitis (71%). First intention surgery consisted of appendectomy (m = 6) and right hemicolectomy (m = 1). In three patients, additional surgical procedures were performed (right colectomy). Indications for colectomy were tumor size (three cases) associated with appendectomy margin invasion in one case. One patient with lymph node and peritoneal involvement experienced recurrence 9 months after hemicolectomy and died of the disease at 2 years. One patient subsequently died of colon carcinoma 6 years after adenocarcinoid treatment. Five patients were alive without disease at the time of the last follow-up. Synchronous or metachronous colon carcinomas developed in three patients (43%). Our results suggest that appendectomy alone could be used for appendiceal adenocarcinoid provided that the tumor (1) is less than 1 cm; (2) does not extend beyond the appendix adventitia; (3) has less than 2 mitoses/10 high power fields; and (4) has surgical margins that are tumor free. Otherwise, carcinologic right colectomy seems to be indicated. The risk for developing colorectal adenocarcinoma seems to be extremely high in patients treated for appendiceal adenocarcinoid and warrants close follow-up with colonoscopic screening.

We report 2 cases of Langerhans cell histiocytosis (LCH) presenting as a thyroid mass. The first case is a 45-year-old woman with a 13-year history of diabetes insipidus who presented with an enlarging thyroid mass with substernal extension. The second case is a 29-year-old man who presented with an enlarging thyroid mass and skin lesions. Histologic evaluation of the thyroid gland in both cases revealed extensive involvement by LCH, confirmed by immunohistochemical analysis showing Langerhans cells that were positive for CD1a and S-100 protein. Langerhans cell histiocytosis can rarely involve the thyroid gland in adults, and we have identified 30 cases reported in literature. Most patients had evidence of LCH involving other anatomic sites, as was true in these 2 cases, and the diagnosis was initially established by examination of other sites in a subset of patients. Affected patients frequently have diabetes insipidus, as was true in case 1. Thyroid gland involvement as the initial presentation of LCH is a rare phenomenon that can result in misdiagnosis.

Pseudovasculitis, vasculitis-like syndromes, vasculitis look-alikes, or mimics of vasculitis represent a heterogeneous collection of disorders that are capable of simulating vasculitis. Inappropriate diagnosis leads to delay or absence of proper management and exposure to potentially deleterious treatment modalities such as corticosteroids and cytotoxic agents. We report the case of fibromuscular dysplasia suspected to be a polyarteritis nodosa. The progression of the lesions visualized by the ultrasonographic study and computed tomography (CT) scan after 10 days of treatment led to an emergency laparotomy. The possible deleterious role of steroids given to treat the suspected vasculitis is discussed.

Purpose: This study was undertaken to assess which ultrasound-derived parameter was superior for measuring venous reflux quantitatively and to evaluate the importance of popliteal vein valve reflux., Patients and Methods: A retrospective analysis was performed of 244 refluxive limbs in 182 patients who underwent ultrasound scanning, venous pressure measurement, air plethysmography, and clinical classification of severity according to the CEAP score. Reflux time (RT, s), peak reflux velocity (PRV, m/s), time of average rate of reflux (TAF, mL/min), absolute displaced volume retrogradely (ADV, mL) were compared to clinical class, ambulatory venous pressure (% drop), venous filling time (s), and venous filling index (mL/s) using nonparametric statistical tests. A P value of <.05 was considered significant. Limbs were divided into 3 groups: (A) axial great saphenous vein reflux only (n = 68); (B) axial deep reflux including popliteal vein incompetence with or without concomitant gastrocnemius or great or small saphenous vein reflux (all ultrasound reflux parameters of each refluxive vein added at the knee level) (n = 79); and (C) all limbs with popliteal vein reflux (the ultrasound data of the refluxive popliteal vein exclusively was used in comparison regardless of concomitant associated reflux) (n = 103). Limbs were also stratified into limbs with skin changes and ulcer (C-class 4-6) and those without (C-class 1-3) and subsequently compared., Results: No meaningful significant correlation was found between RT and the clinical and hemodynamic results in groups A and B. The PRV and TAF correlated significantly with the hemodynamic parameters. The PRV and TAF and clinical severity trended towards correlation in group A (P =.0554 and P =.0998, respectively), but was significantly correlated in group B. The poor hemodynamic condition in the subset of C-class 4-6 limbs in groups A and B was reflected in a greater PRV, TAF, and ADV in this subset as compared with the limbs in C-class 1-3. RT was not significantly different in the subsets of limbs, further suggesting that RT is not related to hemodynamic or clinical state of the limbs. No meaningful correlations were found in group C. Although the hemodynamic data were significantly poorer in the subset of limbs with C-class 4-6 than in C-class 1-3, the ultrasound-derived parameters were not significantly different., Conclusion: The duration of valve reflux time (or valve closure time) cannot be used to quantify severity of reflux and is purely a qualitative measurement. The PRV and the rate of reflux appeared to better reflect the magnitude of venous incompetence. In the presence of axial reflux, it appeared logical and physiologically correct to sum up these reflux parameters for each venous segment crossing the knee. The popliteal valve reflux (the "gatekeeper" function) was not in itself an important determinant of venous hemodynamics and clinical severity. Additional reflux in other venous segments must be taken into account.

Gastrointestinal stromal tumours (GIST) are the most common mesenchymal tumours of the digestive tract. Most gastrointestinal soft tissue neoplasms, previously classified as leiomyomas, schwannomas, leiomyoblastomas or leiomyosarcomas, are today classified as GIST on the basis of molecular and immunohistological features. They originate from gastrointestinal pacemaker cells and are characterised by over-expression of the tyrosine kinase receptor KIT. Overall 5-year survival after surgical resection of GIST is approximately 60%. However, these tumours span a wide clinical spectrum from benign to highly malignant. Prognostic factors have recently been identified for GIST and include tumour size, mitotic rate and other minor factors. At present, surgery is the standard treatment for primary resectable GIST. Benign GIST have an excellent prognosis after primary surgical treatment, with over 90% 5-year survival. While recurrent or malignant GIST, which are resistant to radiotherapy and chemotherapy, had until recently an extremely poor prognosis even after surgical resection, with median survival of 12 months. The development of a tyrosine kinase inhibitor has changed the management of unresectable malignant cases. This new tyrosine kinase inhibitor, imatinib mesylate, which inhibits the c-kit receptor, has proved highly effective against GIST and has improved survival in metastatic GIST. This paper reviews the literature and our experience of GIST, including: diagnosis, pathology, treatment and prognosis.

Paragangliomas are rare tumours originating from neuroectodermic remnants and are usually considered as benign. We present two cases of paraganglioma of the ampulla of Vater that were treated surgically by pancreaticoduodenectomy. In one case, histopathology revealed malignant characteristics of the tumour with invasion of the pancreas and simultaneous duodenal lymph-node metastases. Both patients had a favourable outcome without disease recurrence at 40 and 44 months postoperatively. Only 21 cases of ampullary paraganglioma have been reported in the literature, 7 of them with malignant characteristics. In conclusion, paragangliomas of the ampulla of Vater have malignant potential. Surgical therapy of these tumours should not be limited to local resection, as disease recurrence and lymph node involvement have been reported. We propose that paragangliomas of the ampulla of Vater should be operated by cephalic pancreaticoduodenectomy, which allows long-term and disease-free survival.

Collagenous colitis is associated with chronic diarrhoea and inflammatory changes detected by colonic biopsy, but no endoscopic abnormalities. Cutaneous polyarteritis nodosa shows the same histopathology as systemic polyarteritis nodosa, but is limited to the skin. Both diseases are rare and of unknown aetiology. Collagenous colitis has been described in association with different autoimmune disorders. We report on a case of collagenous colitis and cutaneous polyarteritis nodosa. To our knowledge, this association has not been reported previously.

Background: There is accumulating evidence, both quantitative and qualitative, that pelvic irradiation affects anorectal function. However, the molecular mechanisms responsible for radiation-induced damage to the anal sphincter remain unclear., Aim: To determine the expression of transforming growth factor-beta 1 (TGF-beta 1) and its downstream effector connective tissue growth factor (CTGF) in the anal sphincter of a patient irradiated for prostate cancer., Patient: A 82 year-old patient developed a rectal adenocarcinoma and underwent an abdomino-perineal resection (APR), four years after receiving pelvic irradiation for prostate carcinoma., Methods: Tissue sections of the anal sphincter were processed for histology. Immunostaining for TGF-beta 1 and CTGF were performed., Results: CTGF and TGF-beta 1 immunoreactivity was detected in the irradiated anal sphincter, and was absent in controls. Immunoreactivity for both cytokines predominated in the internal sphincter. CTGF and TGF-beta 1 were preferentially detected in endothelial cells, myofibroblasts and fibroblasts; in addition, there was strong immunoreactivity for TGF-beta 1, but not for CTGF in smooth muscle cells of the anal canal., Conclusion: Four years after pelvic irradiation, radiation-induced damage appeared to affect predominantly the smooth muscle layer of the anal canal. The molecular mechanisms responsible for radiation-induced fibrosis to these tissues involve prolonged activation of TGF-beta 1 and its downstream effector CTGF.

Development of a soft-tissue sarcoma is an infrequent but well-known long-term complication of radiotherapy. Malignant fibrous histiocytomas, extraskeletal osteosarcomas, fibrosarcomas, malignant peripheral nerve sheath tumors, and angiosarcomas are most frequently encountered. Radiation-associated synovial sarcomas are exceptional. We report the clinicopathologic, immunohistochemical, and molecular features of two radiation-associated synovial sarcomas. One tumor developed in a 42-year-old female 17 years after external irradiation was given for breast carcinoma; the other occurred in a 34-year-old female who was irradiated at the age of 7 years for a nonneoplastic condition of the left hand. Both lesions showed morphologic features of monophasic spindle cell synovial sarcoma, were immunoreactive for cytokeratins, epithelial membrane antigen, CD99, CD117 (c-kit), and bcl-2 and bore the t(X;18) (SYT-SSX1) translocation. We conclude that synovial sarcoma has to be added to the list of radiation-associated soft-tissue sarcomas.

Aim: The aim of this study was to assess the feasibility and success of multidisciplinary approach for the management of hereditary colorectal cancer., Material and Methods: From November 1998 to November 2000, 32 individuals with putative familial/hereditary predisposition to colorectal cancer were investigated for adenomatous polyposis (attenuated or classical familial adenomatous polyposis coli, FAP) or for hereditary nonpolyposis colorectal cancer (HNPCC). Amsterdam criteria (I and II) and Bethesda guidelines were used to select putative HNPCC kindreds. Clinical data including endoscopy, pathological and operative reports as well as family history were collected. Pre- and post-test genetic counseling was offered to at-risk individuals. Genetic testing included microsatellite instability (MSI) and search for germline mutations in the APC, hMSH2 and hMLH1 genes. Immunohistochemistry (IHC) of hMSH2 and hMLH1 protein expression in tumour samples was also performed., Results: 11 APC mutations were characterized, whereas four mutations in HNPCC genes were found in hMSH2 (2) and in hMLH1 (2). MSI and IHC correlated completely for cases with identified pathogenic mutation (100%)., Conclusion: A thorough evaluation and management of hereditary colorectal requires a multidisciplinary approach. Thus, more mutation carriers can be identified and benefit from appropriate genetic counselling, while non-carrier individuals are relieved from unnecessary surveillance.

Malignant melanoma metastasis to the ovary is exceptional. This observation relates the case of a 33 year-old woman who presented with a voluminous unilateral, histologically poorly differentiated, ovarian mass, and discusses the differential diagnosis. Immunohistochemical studies demonstrated strong positivity for S-100 protein, HMB-45 and vimentin. We emphasize the unpredictable clinical and biologic behavior of malignant melanomas and the necessity to perform immunohistochemical study by S-100 protein and HMB-45 in a poorly differentiated metastasis to the ovary, histologically compatible with malignant melanoma; even in the absence of intracytoplasmic pigment and clinical antecedent of cutaneous malignant melanoma.