Infectious Agents Induce Wnt/ß-Catenin Pathway Deregulation in Primary Liver Cancers.

Interaction between infectious agents and liver tissue, as well as repeated and extreme biological events beyond adaptive capacities, may result in pathological conditions predisposing people to development of primary liver cancers (PLCs). In adults, PLCs mainly comprise hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA). Various infectious agents in the hepatic microenvironment can destabilize normal liver cell functions by modulating the Wnt/ß-catenin pathway components. Among them, hepatotropic viruses B, C, and D are involved in Wnt/ß-catenin signaling dysregulation. Other microbial agents, including oncogenic viruses such as Epstein-Barr virus (EBV) and human papilloma virus (HPV), bacteria, e.g., Mycoplasma hyorhinis and Salmonella Typhi, the protozoan parasite Toxoplasma gondii, the fungus Aspergillus flavus, and liver flukes such as Clonorchissinensis or Opisthorchis viverrini, may induce malignant transformation in hepatocytes or in target cells of the biliary tract through aberrant Wnt signaling activation. This review focuses on new insights into infectious agents implicated in the deregulation of Wnt signaling and PLC development. Since the Wnt/ß-catenin pathway is a driver of cancer following viral and bacterial infections, molecules inhibiting the complex axis of Wnt signaling could represent novel therapeutic approaches in PLC treatment.

Wingless/It/ß-catenin signaling in liver metastasis from colorectal cancer: A focus on biological mechanisms and therapeutic opportunities.

The liver is the most common site of metastases in patients with colorectal cancer. Colorectal liver metastases (CRLMs) are the result of molecular mechanisms that involve different cells of the liver microenvironment. The aberrant activation of Wingless/It (Wnt)/ß-catenin signals downstream of Wnt ligands initially drives the oncogenic transformation of the colon epithelium, but also the progression of metastatization through the epithelial-mesenchymal transition/mesenchymal-epithelial transition interactions. In liver microenvironment, metastatic cells can also survive and adapt through dormancy, which makes them less susceptible to pro-apoptotic signals and therapies. Treatment of CRLMs is challenging due to its variability and heterogeneity. Advances in surgery and oncology have been made in the last decade and a pivotal role for Wnt/ß-catenin pathway has been re-cognized in chemoresistance. At the state of art, there is a lack of clear understanding of why and how this occurs and thus where exactly the opportunities for developing anti-CRLMs therapies may lie. In this review, current knowledge on the involvement of Wnt signaling in the development of CRLMs was considered. In addition, an overview of useful biomarkers with a revision of surgical and non-surgical therapies currently accepted in the clinical practice for colorectal liver metastasis patients were provided.

Robuvit® reduces fatigue after chemotherapy for colon cancer. A pilot registry study.

BACKGROUND: The aim of this pilot registry study was to evaluate the efficacy of Robuvit® (oak wood extract) on residual fatigue due to convalescence in otherwise healthy subjects within one month after surgery and chemotherapy for colon cancer. Robuvit® has been clinically tested in subjects with fatigue (chronic fatigue syndrome), post-traumatic stress disorder, convalescence and burnout. METHODS: One group of patients followed the standard management (SM) and was designated as control group while the supplementation group followed the SM and additionally took two Robuvit® capsules daily for six weeks (200 mg/day).The main study endpoints were the Karnofsky performance scale index, handgrip strength in kg, fitness test score on a treadmill, self-assessed work ability, fatigue score, oxidative stress and carcinoembryonic antigen (CEA) plasma levels. In addition, the mood of the patients was assessed using the 'brief mood introspection scale', BMIS. RESULTS: Fifty-one subjects with fatigue linked to convalescence within 1 month after chemotherapy for colon cancer completed the study, 29 in the Robuvit® group and 22 as controls. The two management groups were comparable for age and sex distribution. The main investigation parameters were also comparable at inclusion. No side effects or tolerability problems were observed in the six weeks of follow-up. Occasional use of painkillers, antinausea medication or anti-inflammatory agents was accepted. After six weeks, Robuvit® supplementation significantly improved the Karnofsky performance scale index compared to controls. Hand grip strength (dynamometry), treadmill fitness test score and the self-assessed work ability were significantly improved with Robuvit® as well. The fatigue score after six weeks was significantly improved with Robuvit® (P<0.05) in comparison with SM controls. Mood was significantly improved after 6 weeks in the Robuvit® patients compared to the control group. The examined study parameters improved in the patients of the control group as well, during a normal postchemotherapy convalescence, but in a lesser extend when compared to the supplementation group. Oxidative stress was high at inclusion in both groups. The decrease in oxidative stress - as plasma free radicals - was significantly higher with the supplementation (P<0.05). CEA values were within the normal values from inclusion and in the 6 weeks of the registry in all subjects. CONCLUSIONS: In conclusion, Robuvit® helps to reduce fatigue after chemotherapy and improves strength, performance, fitness, work ability and mood in these patients, without exposing them to the risk of side effects.

Perineural Invasion in Pancreatic Ductal Adenocarcinoma: From Molecules towards Drugs of Clinical Relevance.

Pancreatic ductal adenocarcinoma is one of the most threatening solid malignancies. Molecular and cellular mediators that activate paracrine signalling also regulate the dynamic interaction between pancreatic cancer cells and nerves. This reciprocal interface leads to perineural invasion (PNI), defined as the ability of cancer cells to invade nerves, similar to vascular and lymphatic metastatic cascade. Targeting PNI in pancreatic cancer might help ameliorate prognosis and pain relief. In this review, the modern knowledge of PNI in pancreatic cancer has been analysed and critically presented. We focused on molecular pathways promoting cancer progression, with particular emphasis on neuropathic pain generation, and we reviewed the current knowledge of pharmacological inhibitors of the PNI axis. PNI represents a common hallmark of PDAC and correlates with recurrence, poor prognosis and pain in pancreatic cancer patients. The interaction among pancreatic cancer cells, immune cells and nerves is biologically relevant in each stage of the disease and stimulates great interest, but the real impact of the administration of novel agents in clinical practice is limited. It is still early days for PNI-targeted treatments, and further advanced studies are needed to understand whether they could be effective tools in the clinical setting.

Targeting Wnt/ß-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)-ß-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/ß-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/ß-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.

Minimally invasive distal pancreatectomy: mapping surgical maneuvers towards operative standardization.

AIM: To analyze the minimally invasive surgical maneuvers currently performed to remove pancreatic tail, with or without preservation of the spleen, for benign and borderline malignant neoplasms. MATERIAL AND METHODS: We described operative steps and technical pitfalls encountered during laparoscopic and robotic distal pancreatectomy. The methodology of research focused on recruitment of evidence-based surgical strategies and critical analysis of modern minimally invasive techniques. RESULTS: Laparoscopic and robotic distal pancreatectomy have gradually accepted by pancreatic surgeons and clinical evidences document its growing interest. The choice of patient positioning, port placement, surgical dissection and operative techniques used for pancreatic parenchymal transection is not codified and changes according to personal preference. The technical variability in minimally invasive approach to pancreatic surgery strongly depends depends on surgeon's training and to limited application of these procedures in single institutions. CONCLUSIONS: Pancreatic surgeons worldwide accept laparoscopic and robotic distal pancreatectomy but the best intraoperative praxis is not defined in clinical routine. To date, the pancreatic resection adopts hybrid techniques and the conduction of minimally invasive resection depends to surgeon's experience, patient body habitus and location of pancreatic lesion. Although several technical variations have described, no standardization of the operative minimally invasive surgical method is convincingly built. KEY WORDS: Laparoscopy, Minimally invasive surgery, Pancreas, Robotic pancreatectomy.

Laparoscopic and open complete mesocolic excision with central vascular ligation for right colonic adenocarcinoma: a retrospective comparative study.

BACKGROUND: To examine the outcome of patients treated with complete mesocolic excision (CME) with central vascular ligation (CVL) after conventional and laparoscopic surgery. METHODS: We retrospectively evaluated stage I-IV colon adenocarcinoma patients treated by the same surgeon (L.M.) from 2013 to 2018. Postoperative complications, recurrences and survival are assessed. RESULTS: Fifty-one patients (M/F: 24/27) underwent laparoscopic right hemicolectomy with CME (L-CME) or open CME (O-CME) plus CVL. Tumour location was the caecum in 39.2% of cases, the transverse in 23.5%, the hepatic colonic flexure in 21.5%, and the ascending colon in 15.6%. Twenty-four patients underwent L-CME while 27 underwent O-CME. More than 15 harvested lymphnodes are reported in 74.1% of O-CME patients and in 66.7% of L-CME patients (p = 0.562). Postoperative complications occurred in 7 O-CME and 5 L-CME patients, respectively (p = 0.669). Three-year overall survival, including stage IV, was of 75% versus 77.8% for L-CME and O-CME patients, respectively, while for stage I-III, was of 88.9% vs. 80% in L-CME and O-CME, respectively (p = 0.440). The median follow-up was of 2.43 years. CONCLUSION: CME with CVL is a meticulous, complex but feasible technique. In our experience, oncological results in terms of recurrences and overall survival, after conventional and laparoscopic CME plus CVL, are comparable. Patients with stage I-III colon adenocarcinoma have a better prognostic trend especially when more than 15 lymphnodes are removed. The respect of oncological radicality and the correct indication to minimally invasive surgery are the undiscussed key outcome variables.

Acute esophageal necrosis syndrome. The 2021 update from an Italian survey and personal experience.

AIM: Black esophagus, or acute esophageal necrosis, is a rare entity with multifactorial aetiology. Modern theories suggest a combination of ischemia, compromised mucosa defences and corrosive agent's injury. MATERIAL AND METHODS: We investigated black esophagus by means of a retrospective review of 26 cases in literature. A Medline overview is performed until May 2021 by considering the Italian results. The search terms were "black esophageal syndrome in Italy", "black esophagus in Italy", "black esophageal necrosis in Italy", and "Gurvits syndrome in Italy". To complete these case reports, we illustrate our first experience of the syndrome successfully treated with esophagectomy, cervical diversion and gastrostomy. RESULTS: Black esophagus is common in adult males (M/F: 21/5) (Range: 47-89 years; Average: 70.6 year-old). The most common symptoms are hematemesis, epigastric pain and dysphagia. Endoscopically, diffuse involvement of acute esophageal necrosis is diagnosed in 42.3% of cases. The treatment consisted on red blood cell transfusions, sucralfate administration, proton pump-inhibition, enteral nutrition and antimicrobial agents. Overall mortality was 38.4% and only one case underwent surgery for acute bleeding. CONCLUSIONS: Black esophagus is often reversible both anatomically and functionally. Its treatment is based on supported therapies and hemodynamic resuscitation. This syndrome shows high mortality related to the coexisted medical conditions rather than acute esophageal necrosis. Only in selected cases, surgical treatment is indicated. KEY WORDS: Acute necrotizing esophagitis, Black esophagus, Ischemia.

Oxidative Distress Induces Wnt/ß-Catenin Pathway Modulation in Colorectal Cancer Cells: Perspectives on APC Retained Functions.

Colorectal cancer (CRC) is a multistep process that arises in the colic tissue microenvironment. Oxidative stress plays a role in mediating CRC cell survival and progression, as well as promoting resistance to therapies. CRC progression is associated with Wnt/ß-Catenin signaling dysregulation and loss of proper APC functions. Cancer recurrence/relapse has been attributed to altered ROS levels, produced in a cancerous microenvironment. The effect of oxidative distress on Wnt/ß-Catenin signaling in the light of APC functions is unclear. This study evaluated the effect of H2O2-induced short-term oxidative stress in HCT116, SW480 and SW620 cells with different phenotypes of APC and ß-Catenin. The modulation and relationship of APC with characteristic molecules of Wnt/ß-Catenin were assessed in gene and protein expression. Results indicated that CRC cells, even when deprived of growth factors, under acute oxidative distress conditions by H2O2 promote ß-Catenin expression and modulate cytoplasmic APC protein. Furthermore, H2O2 induces differential gene expression depending on the cellular phenotype and leading to favor both Wnt/Catenin-dependent and -independent signaling. The exact mechanism by which oxidative distress can affect Wnt signaling functions will require further investigation to reveal new scenarios for the development of therapeutic approaches for CRC, in the light of the conserved functions of APC.

Strangulated richter's hernia with caecum necrosis. Case report.

AIM: Describe a rare case of Richter's hernia with caecum incarceration into a right femoral hernia and provide a narrative literature review about its surgical management. MATERIAL AND METHODS: A 46-year-old woman presented to the Emergency Department and to our surgical unit with a two-days history of worsening abdominal pain in the right lower quadrant without nausea or vomiting, associated with an irreducible lump. Computed tomography of the abdomen described a right inguinal hernia containing small bowel with perivisceral fluid in it without signs of small bowel occlusion nor perforation. RESULTS: A Richter 's femoral hernia with necrotic caecum wall was found but the appendix was not involved. Through a mini-laparotomy, tangential caecal resection and appendectomy were performed. The femoral defect was repaired with a polypropylene mesh-plug placed in the pre-peritoneal space. Postoperative period was uneventful and the patient was discharged on the fifth post-operative day. DISCUSSION: Femoral hernias account for only 2-4% of all groin hernias and occur through a small fascial defect in the femoral canal. Due to its narrowness, it leads to a high risk of incarceration and strangulation thus explaining the increased mortality in the emergency setting (up to 10 fold compared with the elective repair). In some cases, symptoms are no specific and uncommon findings have been reported. Surgical exploration is mandatory in the presence of signs of bowel strangulation or perforation and different approaches (either open or laparoscopically) have been described in literature. CONCLUSIONS: Caecum wall necrosis secondary to an incarcerated Richter's femoral hernia is a rare but dangerous event. Surgical approach is selected on surgeon's expertise. The use of prosthetic mesh is always recommended. KEY WORDS: Bowel necrosis, Emergency surgery, Hernia repair, Richter's hernia.

Laparoscopic Versus Open Hartmann Reversal: A Case-Control Study.

BACKGROUND: Laparoscopic reversal of Hartmann's procedure (LHR) offers reduced morbidity compared with open Hartmann's reversal (OHR). The aim of this study is to compare the outcome of laparoscopic versus open Hartmann reversal. MATERIALS AND METHODS: Thirty-four patients who underwent Hartmann reversal between January 2017 and July 2019 were evaluated. Patients underwent either LHR (n = 17) or OHR (n = 17). Variables such as numbers of patients, patient's age, sex, body mass index (BMI), comorbidities, ASA (American Society of Anesthesiology) score, indication for previous open sigmoid resection, mean operation time, rate of conversion to open surgery, length of hospital stay, mortality, and morbidity were retrospectively evaluated. RESULTS: The two groups of patients were homogeneous for gender, age, body mass index, cause of primary surgery, time to reversal, and comorbidities. In 97% of the cases, HP was done by open surgery. Our data revealed no difference in mean operation time (LHR: 180.5 ± 35.1 vs. OHR: 225.2 ± 48.4) and morbidity rate, although, in OHR group, there were more severe complications. Less intraoperative blood loss (LHR: 100 ± 40 mL vs. OHR: 450 ± 125 mL; p value <0.001), shorter time to flatus (LHR: 2.4 days vs. OHR: 3.6 days; p value <0.021), and shorter hospitalization (LHR: 4.4 vs. OHR: 11.2 days; p value <0.001) were observed in the LHR group. Mortality rate was null in both groups. Discussion. LHR is feasible and safe even for patients who received a primary open Hartmann's procedure. We suggest careful patient's selection allowing LHR procedures to highly skilled laparoscopy surgeons.

A Case Report on Gallbladder Agenesis: Not a Novelty but Still a Laparoscopic Surprise.

Gallbladder agenesis (GA) is a rare embryological anomaly that presents acute cholecystitis like-symptoms. It is often an incidental finding diagnosed during surgery. We reported a case of GA in a patient who presented with dyspepsia and acute right upper abdomen pain with ultrasonographic signs of acute lithiasic cholecystitis. The preoperative assessment, according to first-level exams, is oriented to the diagnosis of acute lithiasic cholecystitis with atrophy and sclerosis. During laparoscopy, the proximal transverse colon was found strictly adherent to gallbladder fossa. The gallbladder was found to be absent. The surgical procedure consisted of lysis of multiple colo-hepatic adhesions. The diagnosis of congenital GA was made laparoscopically. The postoperative radiological images, based on CT and MR examinations, documented the diagnosis of GA with a biliary duct anatomical variant. The recovery was uneventful and the patient remained symptom-free for more than four years. GA is a clinical challenge that still poses diagnostic and therapeutic dilemmas. Although no diagnostic and therapeutic algorithm is accepted worldwide, due to heterogeneity of clinical scenarios and the variability in hospital facilities, surgeons have to be familiar with this rare entity, and conversion in laparotomy or unnecessary operative procedures should be avoided in the same operative setting.

Solitary fibrous tumor of the anterior abdominal wall. A case report and review of the literature.

BACKGROUND: Solitary fibrous tumor (SFT) is a rare mesenchymal neoplasm affecting soft tissues with a not well defined biological behavior. SFT occurs mostly in the pleura and the thorax, while extra-thoracic localization is uncommon and abdominal localization is very rare. Histologically, SFT is a well defined mass with splindle-cell proliferation in collagenous matrix with staghorn vascular network and CD34 reactive. CASE REPORT: A 64 years-old man with a history of recurrent gastric cancer previously treated with total gastrectomy, was admitted with contrast enhanced CT-scan diagnosis of a well demarcated oval mass of 4.8 cm with microcysts, vascularized in the arterial phase and with wash out in the tardive phase, located in the peritoneal side of right rectus abdominis muscle, suspected for metastatic gastric tumor. The patient underwent minilaparotomy and en-bloc excision of the lesion. Histologically the tumor was characterized by a hemangiopericitoma like growth pattern and the immunostaining was positive to CD34, CD99, BCL-2 and Vimentin. The definitive diagnosis was SFT with a proliferation index (Ki-67/MIB-1) <3%. In our case, chemotherapy was not indicated. At the 6-month follow-up, the patient is in good clinical conditions with no recurrence or metastasis. CONCLUSIONS: We reported a rare case of primitive SFT located in peritoneal side of the of right rectus abdominis muscle treated surgically, in a patient previously affected by gastric adenocarcinoma. In this case, SFT showed a benign behaviour during a short term follow-up. Dimensional pattern, histopathological features and curative surgery remain the most important indicators of clinical outcome. KEY WORDS: Abdominal wall, Hemangiopericitoma, SFT, Solitary fibrous tumorSpindle cell.

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.

Simultaneous Minimally Invasive Treatment of Colorectal Neoplasm with Synchronous Liver Metastasis.

Purpose. To analyse perioperative and oncological outcomes of minimally invasive simultaneous resection of primary colorectal neoplasm with synchronous liver metastases. Methods. A Medline revision of the current published literature on laparoscopic and robotic-assisted combined colectomy with hepatectomy for synchronous liver metastatic colorectal neoplasm was performed until February 2015. The specific search terms were "liver metastases", "hepatic metastases", "colorectal", "colon", "rectal", "minimally invasive", "laparoscopy", "robotic-assisted", "robotic colorectal and liver resection", "synchronous", and "simultaneous". Results. 20 clinical reports including 150 patients who underwent minimally invasive one-stage procedure were retrospectively analysed. No randomized trials were found. The approach was laparoscopic in 139 patients (92.7%) and robotic in 11 cases (7.3%). The rectum was the most resected site of primary neoplasm (52.7%) and combined liver procedure was in 89% of cases a minor liver resection. One patient (0.7%) required conversion to open surgery. The overall morbidity and mortality rate were 18% and 1.3%, respectively. The most common complication was colorectal anastomotic leakage. Data concerning oncologic outcomes were too heterogeneous in order to gather definitive results. Conclusion. Although no prospective randomized trials are available, one-stage minimally invasive approach seems to show advantages over conventional surgery in terms of postoperative short-term course. On the contrary, more studies are required to define the oncologic values of the minimally invasive combined treatment.

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.

Outcome of superior mesenteric-portal vein resection during pancreatectomy for borderline ductal adenocarcinoma: results of a prospective comparative study.

BACKGROUND: Approximately 20 % of patients affected by pancreatic ductal adenocarcinoma are amenable to surgical resection. Several tumours are reported as "borderline resectable" because of their proximity to the major vessels. In the effort to achieve a radical tumour removal, vein resection has been proposed, but its oncological benefits remain debated. METHODS: Our aim is to investigate morbidity, mortality and survival after pancreatectomy with vein resection. RESULTS: Forty patients underwent pancreatectomy and vein resection (group A), and 20 patients (group B) underwent bilio-enteric and/or gastro-entero bypass. In group A, cancer vein invasion was microscopically proven in 14 cases (35 %). Vein infiltration, tumour differentiation and node-positive disease were not adverse prognostic variables. No difference in survival was seen over a 1-year follow-up. After this period, group A showed significant survival benefits with a longer stabilisation of the disease (p = 0.005). Tumour-free resection margins and adjuvant chemoradiotherapy were the most important prognostic factors (p < 0.05). CONCLUSIONS: Suspicion of vein infiltration should not be a contraindication to resection. Pancreatectomy can be safely performed with an acceptable morbidity and better survival trend.

Caffeine and the analog CGS 15943 inhibit cancer cell growth by targeting the phosphoinositide 3-kinase/Akt pathway.

Caffeine is a naturally occurring methylxanthine that acts as a non-selective adenosine receptor antagonist. Epidemiological studies demonstrated habitual coffee drinking to be significantly associated with liver cancer survival. We aimed to investigate the effects of caffeine and its analog CGS 15943 on hepatocellular carcinoma (HCC) and pancreatic cancer adenocarcinoma (PDAC). We demonstrate that caffeine and CGS 15943 block proliferation in HCC and PDAC cell lines by inhibiting the PI3K/Akt pathway. Importantly a kinase profiling assay reveals that CGS 15943 targets specifically the catalytic subunit of the class IB PI3K isoform (p110γ). These data give mechanistic insight into the action of caffeine and its analogs and they identify these compounds as promising lead compounds to develop drugs that can specifically target this PI3K isoform whose key role in cancer progression is emerging.

Surgical approach for nodular neck lesions mimicking primitive thyroid neoplasms Report of three cases.

AIM: The finding of a neck nodular lesion provides strong suspicion of primary thyroid malignancy. Direct extension into the thyroid parenchyma of carcinomas arising from pharynx, larynx, trachea or esophagus, nervous structures has been also observed in the minority of cases. The intent of our study is to present and discuss rare conditions presenting asymptomatic neck masses, with particular emphasis on pre-operative characteristics and diagnostic criteria. MATERIAL OF STUDY: In our retrospective analysis, we present three cases of nodular neck lesions that have mimicked primitive thyroid pathologies at the first diagnosis. RESULTS: A 53-mm nodular mass in the right thyroid lobe was observed in one patient. The definitive diagnosis was Castleman's disease. The second case presented a 20-mm hypoechoic lesion in the contest of a multinodular goiter. The pre-operative suspect was thyroid carcinoma with lymphnode metastases but the definitive histology documented an 'ancient schwannoma'. A further patient presented bilateral supra-clavear and cervical lymphnodes in a multinodular goiter, initially interpreted as thyroid carcinoma with loco-regional spread. After a total thyroidectomy and cervical lymphadenectomy, the definitive histology documented foci of poorly differentiated carcinoma in cervical lymphnodes and a multinodular goiter without atypical cellularity. The patient is considered to have an occult tumor, probably arising from the breast, and she was scheduled in an oncological program. CONCLUSIONS: Nodular neck lesions are frequently misdiagnosed as primitive thyroid nodules in the common clinical practice. In these rare conditions, surgical exploration is advocated to reach the definitive diagnosis, to indicate the most appropriate treatment and to avoid unnecessary thyroidectomy. KEY WORDS: Ancient Schwannoma, Castleman's disease, Nodular neck lesion, Thyroid nodule.