Malignant PEComa: a case report with emphasis on clinical and morphological criteria

<p>Abstract</p> <p>Background</p> <p>Malignant perivascular epitheliod cell tumor (PEComa) is a very rare entity composed of distinctive perivascular epitheliod cells with variable immunoreactivity for melanocytic and muscle markers. At present this neoplasm does not have a known normal cellular counterpart and the natural history is often unpredictable. Up to now, few cases of PEComa have been described and treatment modalities are still controversial, particularly in advanced conditions.</p> <p>Case presentation</p> <p>We handled the case of a 42-year-old man with unresectable PEComa of the abdomen. A 7 cm hepatic hypodense lesion between segment V and VIII of the liver and diffuse intraperitoneal nodules of 0,3-3,5 cm along the right subcapsular hepatic region, were documented by a CT scan. Radiological images showed abnormal lymph nodes of the right internal mammary chain and anterior mediastinum. The patient underwent an explorative laparotomy for uncontrolled intrabdominal hemorrhage without a well-defined preoperative tumor diagnosis. At surgery, multiple lobulated nodules containing hemorrhagic fluid on the liver surface, peritoneum and omentum were confirmed. The procedure had a palliative intent and consisted of hemostasis, hematomas evacuation and omentectomy. The diagnosis of PEComa was made after surgery on the basis of morphological and immunohystochemical criteria. Radiological and intra operative findings suggest that the mass has an hepatic origin with diffuse involvement of hepatic capsule and suspensory ligaments. The patient received medical support care with blood and plasma transfusions. In our experience, PEComa was clinically malignant, leading to a fatal outcome 25 days after hospital admission of patient.</p> <p>Conclusions</p> <p>Here we report and discuss the peculiar clinical, radiological and morphological presentation of unresectable PEComa. Although in the majority of the reported series, PEComas show a more better prognosis, our case presents with a particular aggressive biological behaviour. The importance of a correct preoperative diagnosis, the need for more effective targeted therapies based on tumor molecular knowledge and evidence-based clinical studies are emphasized together with a revision of the concerning scientific literature.</p

Targeting Wnt/&beta;-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents

Primary liver cancers (PLCs) are steadily increasing in incidence and mortality in the world. They have a poor prognosis due to their silent nature, late discovery and resistance to common chemotherapy. At present, there are limited treatment alternatives, and the understanding of PLC molecular aspects is essential to develop more efficient drugs and therapeutic surgical and loco-regional strategies. A clear causal link with liver damage, inflammation, and regeneration has been found in the occurrence of PLC over the last few decades. Physiologically, Wingless/It (Wnt)-&beta;-catenin signaling plays a key role in liver development, metabolic zonation and regeneration. Loss of functional homeostasis of this pathway appears to be a major driver of carcinogenesis in the liver parenchyma. In the hepatic microenvironment, molecular deregulations that exceed the Wnt signaling biological capacity can induce tumor initiation and progression. Indeed, somatic mutations are identified in key components of canonical and non-canonical Wnt signaling and in PLCs and precancerous lesions. In this review, the altered functions of Wnt/&beta;-catenin signaling are considered in human PLCs, with emphasis on hepatocellular carcinomas (HCC), cholangiocarcinomas (CCA) and hepatoblastomas (HB). Based on recent literature, we also focused on liver cancerogenesis through Wnt deregulation. An overview of preclinical and clinical studies on approved and experimental drugs, targeting the Wnt/&beta;-catenin cascade in PLCs, is proposed. In addition, the clinical implication of molecule inhibitors that have been shown to possess activity against the Wnt pathway in association with conventional surgical and loco-regional therapies are reviewed

Targeting Wnt/β-Catenin Pathways in Primary Liver Tumours: From Microenvironment Signaling to Therapeutic Agents

Primary liver cancers (PLCs) are steadily increasing in incidence and mortality in the world. They have a poor prognosis due to their silent nature, late discovery and resistance to common chemotherapy. At present, there are limited treatment alternatives, and the understanding of PLC molecular aspects is essential to develop more efficient drugs and therapeutic surgical and loco-regional strategies. A clear causal link with liver damage, inflammation, and regeneration has been found in the occurrence of PLC over the last few decades. Physiologically, Wingless/It (Wnt)-β-catenin signaling plays a key role in liver development, metabolic zonation and regeneration. Loss of functional homeostasis of this pathway appears to be a major driver of carcinogenesis in the liver parenchyma. In the hepatic microenvironment, molecular deregulations that exceed the Wnt signaling biological capacity can induce tumor initiation and progression. Indeed, somatic mutations are identified in key components of canonical and non-canonical Wnt signaling and in PLCs and precancerous lesions. In this review, the altered functions of Wnt/β-catenin signaling are considered in human PLCs, with emphasis on hepatocellular carcinomas (HCC), cholangiocarcinomas (CCA) and hepatoblastomas (HB). Based on recent literature, we also focused on liver cancerogenesis through Wnt deregulation. An overview of preclinical and clinical studies on approved and experimental drugs, targeting the Wnt/β-catenin cascade in PLCs, is proposed. In addition, the clinical implication of molecule inhibitors that have been shown to possess activity against the Wnt pathway in association with conventional surgical and loco-regional therapies are reviewed

Laparoscopic colectomy in colon cancer. A single-center clinical experience

Introduction. Aim of our study was to compare the results of the laparoscopic technique to those obtained by traditional open approach in patients with colon cancer. The advantages, disadvantages, and the contraindications (real and presumptive) of this mini-invasive approach are described, by comparing the data obtained from the international literature with our clinical experience. Patients and methods. From February 2000 to May 2006, we performed 73 laparoscopic colectomies for cancer in the Operative Unit of General and Laparoscopic Surgery, Department of Surgical Sciences of the University of Chieti, Italy. The data of these patients were compared with the data obtained from 141 other patients who underwent open procedure for the same pathology in the same period and in the same Unit. Factors such as obesity, previous major abdominal surgery, T4 cancers, perforation and obstruction of the colon, tumor located in the transverse colon or in the left flexure of the colon were considered contraindications to laparoscopic approach. Results. The length of surgical specimens and the number of lymph nodes removed did not show significant differences in the two groups. Two patients in the open procedure group died in the postoperative period. No postoperative death was noted in the group of patients operated by laparoscopic method. Postoperative complications requiring re-operation were observed in 9 patients in the open group and in 3 patients of laparoscopic group. Postoperative complications not requiring re-operation were observed in 16 patients in the open group and in 4 patients in laparoscopic group. Hospital stay was shorter for laparoscopic right or left colectomy compared to corresponding open procedures. At the follow-up (a mean 30 months), the overall survival was 78% for open colectomies and 82.1% for laparoscopic colectomies. Disease-free survival, excluding patients with stage IV tumor and patients died in the postoperative period, was 77.6% for open colectomies and 82.5% for laparoscopic colectomies. In the group of laparoscopic patients, we observed 1 case of port-site recurrence

Development of a SPE-HPLC-PDA Method for the Quantification of Phthalates in Bottled Water and Their Gene Expression Modulation in a Human Intestinal Cell Model

Phthalates are ubiquitous pollutants that are currently classified as endocrine disruptor chemicals causing serious health problems. As contaminants of food and beverages, they come into contact with the epithelium of the intestinal tract. In this work, a SPE-HPLC-PDA method for the determination of phthalates in water from plastic bottles was developed and validated according to the food and drug administration (FDA) guidelines. A chromatographic separation was achieved using a mobile phase consisting of ammonium acetate buffer 10 mM pH 5 (line A) and a mixture of methanol and iso-propanol (50:50 v/v, line B) using gradient elution. Several SPE cartridges and different pH values were investigated for this study, evaluating their performance as a function of recovery. Among these parameters, pH 5 combined with the SPE sep pack C18 cartridge showed the best performance. Finally, the proposed method was applied to the analysis of real samples, which confirmed the presence of phthalates. A colonic epithelial cell model was used to evaluate the effects of these phthalates at the concentrations found in water from plastic bottles. In cells exposed to phthalates, the increased expression of factors, which control the signaling pathways necessary for intestinal epithelium homeostasis, inflammatory response, and stress was detected. The proposed method falls fully within the limits imposed by the guidelines with precision (RSD%) below 7.1% and accuracy (BIAS%) within −4.2 and +6.1

Minimally Invasive Treatment of Sporadic Burkitt’s Lymphoma Causing Ileocaecal Invagination

Introduction. Primary NHL (non-Hodgkin lymphoma) of the colon represents only 0.2% to 1.2% of all colonic malignancies. Burkitt’s lymphoma (BL) is usually a disease reported in children and young people, most of them associated with EBV or HIV infection. We describe a rare case of intestinal obstruction due to sporadic Burkitt’s lymphoma causing ileocaecal invagination explaining our experience Methods. A 31-year-old man presented with diffuse colic pain and weight loss. Clinical examination revealed an abdominal distension with pain in the right iliac fossa. Colonoscopy documented a caecal large lesion with ulcerated mucosa. Computed tomography (CT) have shown a 60 × 50 mm right colic parietal lesion with signs of ileocolic intussusception. Results. Laparoscopic right hemicolectomy was performed. Postoperative period was uneventful. CD20+ high-grade B-cell Burkitt’s lymphoma was confirmed by immunohistochemistry (CD20+, CD79+, and CD10+) and FISH test (t (8;14) (q24; q32). The patient was subsequently treated with adjuvant combination chemotherapy (Hyper-CVAD) and is alive and disease-free at 8 months follow-up. Discussion. Adult sporadic Burkitt’s lymphoma (BL) causing intestinal obstruction due to ileocaecal intussusception is an extremely rare occurrence and a diagnostic dilemma. Despite the surgical approach is selected based on patient’s conditions and surgeon’s expertise, minimally invasive method could be preferred

Struma ovarii with follicular thyroid-type carcinoma and neuroendocrine component: case report

Abstract Struma ovarii (SO) is a slow-growing ovarian neoplasm with thyroid tissue as its predominant component. It is an uncommon neoplasm, usually asymptomatic with an unknown risk of malignant transformation. Due to difficulties in assessing the rare biological nature and the discrepancies in the reported cases, a consensus on the appropriate treatment has not been definitively reached. A 50-year-old female was subjected to upper gut endoscopy which showed a 30-mm mass located in the gastric antrum, suggestive of mesenchimal tumor. Incidentally, a pelvic CT scan also documented a solid mass in the right adnexa, with morphological characteristics of ovarian neoplasm. The patient underwent gastrectomy, total hysterectomy, bilateral salpingo-oophorectomy with lymph node dissection, and omentectomy. Histology documented the presence of gastric cavernous angioma, and, in the right adnexa, foci of follicular thyroid-type carcinoma arising in SO with a well-differentiated neuroendocrine component. Here we report and discuss the clinical and morphological presentation of follicular thyroid-type carcinoma arising in SO. The neoplasm was discovered incidentally and had a favorable clinical outcome at 1-year follow-up.</p

Combined derivatization and high-performance liquid chromatography with fluorescence and ultraviolet detection for simultaneous analysis of octreotide and gabexate mesylate metabolite in human pancreatic juice samples

A simple and sensitive method based on the combination of derivatization and high-performance liquid chromatography with ultraviolet and fluorimetric detection was developed for the simultaneous determination of octreotide and gabexate mesylate metabolite in human pancreatic juice samples. Parameters of the derivatization procedure affecting extraction efficiency were optimized. The developed method was validated according to the International Conference on Harmonization guidelines. The calibration curves were linear over a range of 0.1-15 µg/mL for octreotide and 0.20-15 µg/mL for gabexate mesylate metabolite. Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The limits of detection were 0.025 and 0.05, respectively, for octreotide and gabexate mesylate metabolite. This paper reports the validation of a quantitative high performance liquid chromatography-photodiode array-fluorescence (HPLC-PDA-FL) method for the simultaneous analysis of octreotide and gabexate mesylate metabolite in pancreatic juice by protein precipitation using zinc sulfate-methanol-acetonitrile containing the derivatizing reagent, 4-fluoro-7-nitro-[2,1,3]-benzoxadiazole (NBD-F). Derivatized products of octreotide and gabexate mesylate metabolite were separated on a Luna C18 column (4.6 × 250 mm; 5 µm particle size) using a gradient with a run time of 36 min, without further purification. The method was validated over the concentration ranges 0.1-15 and 0.2-15 µg/mL for octreotide and gabexate mesylate metabolite, respectively, in human pancreatic juice. Biphalin and methyl-p-hydroxybenzoate were used as the internal standards. This method was successfully utilized to support clinical studies in humans. The results from assay validations show that the method is selective, sensitive and robust. The limit of quantification of the method was 0.1 µg/mL for octreotide and 0.2 µg/mL for gabexate mesylate metabolite, and matrix matched standard curves showed a good linearity up to 15 µg/mL. In the entire analytical range the intra- and inter-day precision (RSD%) values were respectively ≤5.9% and ≤3.1% for octreotide and ≤2.0% and ≤3.9% for gabexate mesylate metabolite. For both analytes the intra- and inter-day accuracy (bias) values ranged respectively from -6.8 to -2.5% and from -4.6 to -5.7%. This method utilizes derivatization with NBD-F and provides adequate sensitivity for both drugs

Risultati della terapia nei tumori stromali gastrointestinali operabili: nostra esperienza

Surgery is the treatment of choice for localized Gastrointestinal stromal tumors (GIST). Complete resection, tumor size and biological behavior are the most important factors predicting good prognosis. GIST measuring 2 cm and larger should be treated aggressively, while for tumor smaller then 2 cm it is still under evaluation the role of surgery, the efficacy of chemotherapy and the benefits of followup with radiological surveillance. Methods: We present the experience of managing GIST in our Institute. The clinical-pathological parameters, the histopathological behavior and the outcome of patients that underwent to surgery were examined. Results: This is a retrospective study of 9 patients with diagnosis of GIST observed from January 2000 to February 2009. The median age was 62 years (range: 45 to 74 years). The GIST size was in media 42 mm (range: 14 to 70 mm). Complete resection with microscopically tumor-free margins was archivied in all cases (2 with laparoscopic approach, 1 using video-assisted techniques). In one patient that undergo to hepatic primary tumor resection, the biopsy of 15 mm nodule of the stomach wall has showed GIST lesion. No evidence of recurrence was observed during the median follow-up of 55 months. Conclusions: Our patient’cohort showed a variation in the clinical presentation but not in the disease stages. All GISTs have been completely resected and in according to the benign biological behaviour was not required chemotherapy. However, all patients have been enrolled in follow-up program. Results of ongoing trials will established the role of a multidisciplinary approach for GIST therapy