Para-aortic node involvement is not an independent predictor of survival after resection for pancreatic cancer

To analyze the importance of para-aortic node status in a series of patients who underwent pancreaticoduodenectomy (PD) in a single Institution. METHODSBetween January 2000 and December 2012, 151 patients underwent PD with para-aortic node dissection for pancreatic adenocarcinoma in our Institution. Patients were divided into two groups: patients with negative PALNs (PALNs-), and patients with metastatic PALNs (PALNs+). Pathologic factors, including stage, nodal status, number of positive nodes and lymph node ratio, invasion of para-aortic nodes, tumor’s grading, and radicality of resection were studied by univariate and multivariate analysis. Survival curves were constructed with Kaplan-Meier method and compared with Log-rank test: significance was considered as P < 0.05. RESULTSA total of 107 patients (74%) had nodal metastases. Median number of pathologically assessed lymph nodes was 26 (range 14-63). Twenty-five patients (16.5%) had para-aortic lymph node involvement. Thirty-three patients (23%) underwent R1 pancreatic resection. One-hundred forty-one patients recurred and died for tumor recurrence, one is alive with recurrence, and 9 are alive and free of disease. Overall survival was significantly influenced by grading (P = 0.0001), radicality of resection (P = 0.001), stage (P = 0.03), lymph node status (P = 0.04), para-aortic nodes metastases (P = 0.02). Multivariate analysis showed that grading was an independent prognostic factor for overall survival (P = 0.0001), while grading (P = 0.0001) and radicality of resection (P = 0.01) were prognostic parameters for disease-free survival. Number of metastatic nodes, node ratio, and para-aortic nodes involvement were not independent predictors of disease-free and overall survival. CONCLUSIONIn this experience, lymph node status and para-aortic node metastases were associated with poor survival at univariate analysis, but they were not independent prognostic factors.

Role of calcium in polycystic kidney disease:From signaling to pathology

Autosomal dominant polycystic kidney disease （ADPKD） is the most common inherited monogenic kidney disease. Characterized by the development and growth of cysts that cause progressive kidney enlargement, it ultimately leads to end-stage renal disease. Approximately 85% of ADPKD cases are caused by mutations in the PKD1 gene, while mutations in the PKD2 gene account for the remaining 15% of cases. The PKD1 gene encodes for polycystin-1 （PC1）, a large multi-functional memb-rane receptor protein able to regulate ion channel complexes, whereas polycystin-2 （PC2）, encoded by the PKD2 gene, is an integral membrane protein that functions as a calcium-permeable cation channel, located mainly in the endoplasmic reticulum （ER）. In the primary cilia of the epithelial cells, PC1 interacts with PC2 to form a polycystin complex that acts as a mechanosensor, regulating signaling pathways involved in the differentiation of kidney tubular epithelial cells. Despite progress in understanding the function of these proteins, the molecular mechanisms associated with the pathogenesis of ADPKD remain unclear. In this review we discuss how an imbalance between functional PC1 and PC2 proteins may disrupt calcium channel activities in the cilium, plasma membrane and ER, thereby altering intracellular calcium signaling and leading to the aberrant cell proliferation and apoptosis associated with the development and growth of renal cysts. Research in this feld could lead to the discovery of new molecules able to rebalance intracellular calcium, thereby normalizing cell proliferation and reducing kidney cyst progression.

Lymphoepitelioma-like hepatocellular carcinoma: A case report and a review of the literature

Lymphoepitelioma is a particular form of undifferentiat-ed carcinoma, characterized by a prominent lymphoid stroma, originally described in the nasopharynx. Lym-phoid stroma-rich carcinomas arising in other organs have been termed lymphoepithelioma-like carcinoma (LELC). In the liver, primary LELCs are very rare, and the majority has been identified as cholangiocarcino-mas. Here a rare case of lymphoepithelioma-like hepa-tocellular carcinoma (HCC) is described. A 47-year old woman presented with abdominal pain. Ultrasonogra-phy revealed a liver nodule, 2.2 cm in diameter, local-ized in the right lobe, adjacent to the gallbladder. Viral markers for hepatic B virus (HBV), hepatic C virus (HCV) and Epstein-Barr virus (EBV) were negative. The nod-ule was hypoechogenic. The patient underwent sur-gery, with resection of the nodule. Histology showed hepatocellular carcinoma, characterized by a promi-nent lymphoid infiltrate. At immunocytochemistry, tumor cells were reactive for Hep Par1 and glypican 3. Immunophenotyping of tumor infiltrating lymphocytes evidenced the predominance of CD8+ cytotoxic sup-pressor T cells. The postoperative clinical outcome was favorable and the patient was recurrence-free 15 mo after resection. This case, to the best of our knowl-edge, is the first reported non EBV and non cirrhosis-associated lymphoepithelioma-like hepatocellular carci-noma. The association between the lack of EBV infec-tion, the absence of cirrhosis, a "cytotoxic profile" of the inflammatory infiltrate and a good prognosis could identify a variant of lymphoepithelioma-like HCC with a favorable clinical outcome.

Ampulla of Vater carcinoma: Molecular landscape and clinical implications

Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.

Dynamic expression of several grow factors in process of osteoblasts grafts to promote healing of osteoporotic fracuture

AIM:To study the biological function of transforming growth factor a1(TGF-a 1),vascular endothelial growth factor(VEGF),basic fibroblast growth factor(bFGF) during the process of osteoblasts allografts to accelerate fracture healing of osteoporosis rats.METHODS: Set up the fracture models of osteoporosis rats and do osteoblasts grafts; during different periods in the process of fracture heal ing by using immunnohistochemistry to detect the expression of TGF-a1,VEGF,bFG F and in situ hybridization to study the expression of bFGFmRNA,VEGFmRNA,TGF-a 1 mRNA,also using image analysis to deal with it.RESULTS:In experimental group, Osteoblasts can survive, even proliferate in fracture areas;VEGF,bFGF could be s een positive after 7 days of after osteoblast grafts,and there have the highest quantities about 14 days of post-transplantation.TGF-a1 could be seen positiv e after 3 days of post-transplantation,and there have the highest quantities ab out 7-10 days of post-transplantation.However there are not obviously high qua ntities in control.CONCLUSION:Osteoblasts grafts enhance bone fracture healing of osteoporosis rats.TGF-a1, VEGF and bFGF play very important roles in accel erating fracture healing of osteoporosis rats.

In-vivo characterization of DALM in ulcerative colitis with high-resolution probe-based confocal laser endomicroscopy

Recently,the use of confocal laser endomicroscopy(CLE) in the diagnosis of chronic ulcerative colitis(CUC) was reported.In this brief report we aimed to assess the application of probe-based CLE to characterize colonic mucosa and dysplasia in CUC.The study involved a patient presenting long-standing CUC.Confocal imaging of both the inflamed mucosa,a circumscribed lesion(dysplasiaassociated lesional mass),and adjacent colonic mucosa are demonstrated and the correlation between the CLE and histological images.Inflamed mucosa and dysplasia showed specific alteration of crypt architecture,cellular infiltration,and vessel architecture with an excellent correlation between CLE and standard histological examination.

May the assessment of baseline mucosal molecular pattern predict the development of gluten related disorders among microscopic enteritis?

AIM To evaluate mucosal baseline m RNA expression of tissue transglutaminase 2(t TG2), interferon gamma(IFNγ), toll-like receptor 2(TLR2) and Myeloid Differentiation factor 88(MyD 88) in patients with microscopic enteritis(ME).METHODS We retrospectively enrolled 89 patients with ME of different etiology, which was defined within a 2-year mean period of follow-up. Baseline histological examination was performed on Hematoxylin-Eosin stained sections and CD3 lymphocyte immunohistochemistry was used for intraepithelial lymphocyte count(IELs). ME was defined according to the criteria of Bucharest Consensus Conference. For each patient, formalin embedded biopsy samples of the duodenum referred to the period of ME diagnosis were retrieved. Real-time polymerase chain reaction(RT-PCR) was used to detect the amount of mR NA coding for tT G2, IFNγ, TLR2 and My D88, and the quantity was expressed as fold change compared to controls. Control group was represented by duodenal normal specimens from 15 healthy subjects undergoing endoscopy for functional symptoms. Comparisons among continuous variables were performed by One way analysis of variance(ANOVA) and Bonferroni’s test. The χ~2 test was used for categorical variables. Pearson’s test was used to evaluate correlations. Receiver operating curves were drawn for all four markers to estimate sensitivity and specificity in discriminating the development of CD and GS.RESULTS After a period of follow up of 21.7 ± 11.7 mo, the following diagnoses were achieved: gluten related disorders in 48 subjects(31 CD; 17 GS) and non-gluten related ones in 41(29 Irritable Bowel Syndrome- IBS; 12 Others). CD patients had the highest tT G2 levels(8.3 ± 4.5). The ANOVA plus Bonferroni analysis showed that CD > Other ME > GS = IBS > negative controls. A cut off value of 2.258 was able to discriminate between CD and GS with a sensitivity of 52.94% and a specificity of 87.1%. Additionally, CD patients had the highest IFNγ levels(8.5 ± 4.1). ANOVA plus Bonferroni demonstrated CD > Other ME > GS = IBS > negative controls. A cut off of 1.853 was able to differentiate CD and GS with a sensitivity of 47.06% and a specificity of 96.77%. Patients with non gluten-related causes of ME exhibited the highest TLR2 levels(6.1 ± 1.9) as follows: Other ME > CD = GS = IBS > negative controls. TLR2 was unable to discriminate CD from GS. Patients with CD overexpressed MyD 88 levels similarly to non gluten-related causes of DL(7.8 ± 4.9 and 6.7 ± 2.9), thus CD = Other ME > GS = IBS > negative controls. A cut off of 3.722 was able to differentiate CD from GS with a sensitivity of 52.94% and a specificity of 74.19%. IELs count(15-25 and more than 25/100 enterocytes) strongly correlated with mR NA levels of all tested molecules(P < 0.0001).CONCLUSION Our results confirm that a single marker is unable to predict a discrimination among ME underlying conditions as well as between CD and GS. Mucosal high levels of t TG and IFNγ m RNA may predict the development of CD more than GS with high specificity, despite an expected low sensitivity. TLR2 does not discriminate the development of CD from GS. My D88 levels indicate that intestinal permeability is more increased when a severe intestinal damage underlies ME in both gluten related and unrelated conditions. Therefore, the results of the present paper do not seem to show a clear translational value.

Comparison of imaging-based and pathological dimensions in pancreatic neuroendocrine tumors

AIM To establish the ability of magnetic resonance(MR) and computer tomography(CT) to predict pathologic dimensions of pancreatic neuroendocrine tumors(Pan NET) in a caseload of a tertiary referral center.METHODS Patients submitted to surgery for Pan NET at the Surgical Unit of the Pancreas Institute with at least 1 preoperative imaging examination(MR or CT scan) from January 2005 to December 2015 were included and data retrospectively collected. Exclusion criteria were: multifocal lesions, genetic syndromes, microadenomas or mixed tumors, metastatic disease and neoadjuvant therapy. Bland-Altman(BA) and Mountain-Plot(MP) statistics were used to compare size measured by each modality with the pathology size. Passing-Bablok(PB) regression analysis was used to check the agreement between MR and CT.RESULTS Our study population consisted of 292 patients. Seventy-nine(27.1%) were functioning Pan NET. The mean biases were 0.17 ± 7.99 mm, 1 ± 8.51 mm and 0.23 ± 9 mm, 1.2 ± 9.8 mm for MR and CT, considering the overall population and the subgroup of non-functioning-Pan NET, respectively. Limits of agreement(LOA) included the vast majority of observations, indicating a good agreement between imaging and pathology. The MP further confirmed this finding and showed that the two methods are unbiased with respect to each other. Considering ≤ 2 cm non-functioning-Pan NET, no statistical significance was found in the size estimation rate of MR and CT(P = 0.433). PBR analysis did not reveal significant differences between MR, CT and pathology.CONCLUSION MR and CT scan are accurate and interchangeable imaging techniques in predicting pathologic dimensions of Pan NET.

Diagnostic accuracy of confocal laser endomicroscopy in diagnosing dysplasia in patients affected by long-standing ulcerative colitis

AIM:To evaluate the diagnostic accuracy of confocal laser endomicroscopy(CLE) for the detection of dysplasia in long-standing ulcerative colitis(UC).METHODS:We prospectively performed a surveillance colonoscopy in 51 patients affected by long-standing UC.Also,in the presence of macroscopic areas with suspected dysplasia,both targeted contrasted indigo carmine endoscopic assessment and probe-based CLE were performed.Colic mucosal biopsies and histology,utilised as the gold standard,were assessed randomly and on visible lesions,in accordance with current guidelines.RESULTS:Fourteen of the 51 patients(27%) showed macroscopic mucosal alterations with the suspected presence of dysplasia,needing chromoendoscopic and CLE evaluation.In 5 macroscopically suspected cases,the presence of dysplasia was confirmed by histology(3 flat dysplasia;2 DALMs).No dysplasia/cancer was found on any of the outstanding random biopsies.The diagnostic accuracy of CLE for the detection of dysplasia compared to standard histology was sensitivity 100%,specificity 90%,positive predictive value 83% and negative predictive value 100%.CONCLUSION:CLE is an accurate tool for the detection of dysplasia in long-standing UC and shows optimal values of sensitivity and negative predictivity.The scheduled combined application of chromoendoscopy and CLE could maximize the endoscopic diagnostic accuracy for diagnosis of dysplasia in UC patients,thus limiting the need for biopsies.

Nonsense variant of ATP8B1 gene in heterozygosis and benign recurrent intrahepatic cholestasis: A case report and review of literature

BACKGROUND Benign recurrent intrahepatic cholestasis is a genetic disorder with recurrent cholestatic jaundice due to ATP8B1 and ABCB11 gene mutations encoding for hepato-canalicular transporters.Herein,we firstly provide the evidence that a nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygous form is involved in BRIC pathogenesis.CASE SUMMARY A 29-year-old male showed severe jaundice and laboratory tests consistent with intrahepatic cholestasis despite normal gamma-glutamyltranspeptidase.Acute and chronic liver diseases with viral,metabolic and autoimmune etiology were excluded.Normal intra/extra-hepatic bile ducts were demonstrated by magnetic resonance.Liver biopsy showed:Cholestasis in the centrilobular and intermediate zones with bile plugs and intra-hepatocyte pigment,Kupffer’s cell activation/hyperplasia and preserved biliary ducts.Being satisfied benign recurrent intrahepatic cholestasis diagnostic criteria,ATP8B1 and ABCB11 gene analysis was performed.Surprisingly,we found a novel nonsense variant of ATP8B1 gene(c.1558A>T)in heterozygosis.The variant was confirmed by Sanger sequencing following a standard protocol and tested for familial segregation,showing a maternal inheritance.Immunohistochemistry confirmed a significant reduction of mutated gene related protein(familial intrahepatic cholestasis 1).The patient was treated with ursodeoxycholic acid 15 mg/kg per day and colestyramine 8 g daily with total bilirubin decrease and normalization at the 6th and 12th mo.CONCLUSION A genetic abnormality,different from those already known,could be involved in familial intrahepatic cholestatic disorders and/or pro-cholestatic genetic predisposition,thus encouraging further mutation detection in this field.

Risk factors of extraneural spreading in astrocytomas and oligodendrogliomas in donors with gliomas: A systematic review

BACKGROUND Patients with a history of primary brain tumors can be eligible for organ donation under extended criteria.The risk assessment of tumor transmission via organ transplant in primary brain tumors is primarily based on the assessment of tumor histotype and grade.Previous surgeries,chemo-/radiotherapy,and ventriculoperitoneal shunt placement can lead to a disruption of the blood-brain barrier,concurring to an increase in the transmission risk.AIM To investigate the role of tumor transmission risk factors in donors with oligodendrogliomas and astrocytomas.METHODS We searched PubMed and EMBASE databases for studies reporting extraneural spreading of oligoden-drogliomas and astrocytomas and extracted clinical-pathological data on the primary tumor histotype and grade,the elapsed time from the diagnosis to the onset of metastases,sites and number of metastases,prior surgeries,prior radiotherapy and/or chemotherapy,ventriculoatrial or ventriculo-peritoneal shunt placement,and the presence of isocitrate dehydrogenase 1/2 mutation and 1p/19q codeletion.Statistical analysis was performed using R software.Statistical correlation between chemotherapy or radiotherapy and the presence of multiple extra-central nervous system metastases was analyzed usingχ2 and Fischer exact test.The Kaplan-Meier method was used to evaluate the presence of a correlation between the metastasis-free time and:(1)Localization of metastases;(2)The occurrence of intracranial recurrences;and(3)The occurrence of multiple metastases.RESULTS Data on a total of 157 patients were retrieved.The time from the initial diagnosis to metastatic spread ranged from 0 to 325 mo in patients with oligodendrogliomas and 0 to 267 mo in those with astrocytomas.Respectively,19%and 39%of patients with oligodendroglioma and astrocytoma did not receive any adjuvant therapy.The most frequent metastatic sites were bone,bone marrow,and lymph nodes.The lungs and the liver were the most commonly involved visceral sites.There was no significant correlation between the occurrence of multiple metastases and the administration of adjuvant chemo-/radiotherapy.Patients who developed intracranial recurrences/metastases had a significantly longer extraneural metastasis-free time compared to those who developed extraneural metastases in the absence of any intra-central nervous system spread.CONCLUSION A long follow-up time does not exclude the presence of extraneural metastases.Therefore,targeted imaging of bones and cervical lymph nodes may improve safety in the management of these donors.

Physiologically based microenvironment for in vitro neural differentiation of adipose-derived stem cells

The limited capacity of nervous system to promote a spontaneous regeneration and the high rate of neurodegenerative diseases appearance are keys factors that stimulate researches both for defining the molecular mechanisms of pathophysiology and for evaluating putative strategies to induce neural tissue regeneration. In this latter aspect, the application of stem cells seems to be a promising approach, even if the control of their differentiation and the maintaining of a safe state of proliferation should be troubled. Here, we focus on adipose tissue-derived stem cells and we seek out the recent advances on the promotion of their neural differentiation, performing a critical integration of the basic biology and physiology of adipose tissuederived stem cells with the functional modifications that the biophysical, biomechanical and biochemical microenvironment induces to cell phenotype. The pre-clinical studies showed that the neural differentiation by cell stimulation with growth factors benefits from the integration with biomaterials and biophysical interaction like microgravity. All these elements have been reported as furnisher of microenvironments with desirable biological, physical and mechanical properties. A critical review of current knowledge is here proposed, underscoring that a real advance toward a stable, safe and controllable adipose stem cells clinical application will derive from a synergic multidisciplinary approach that involves material engineer, basic cell biology, cell and tissue physiology.

Histo-molecular oncogenesis of pancreatic cancer:From precancerous lesions to invasive ductal adenocarcinoma

Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.

Clinical challenge for gastroenterologists–Gastrointestinal manifestations of systemic mastocytosis:A comprehensive review

Mastocytosis is a rare and heterogeneous disease characterized by various clinical and biological features that affect different prognoses and treatments.The disease is usually divided into 2 principal categories:cutaneous and systemic disease(SM).Clinical features can be related to mast cell(MC)mediator release or pathological MC infiltration.SM is a disease often hard to identify,and the diagnosis is based on clinical,biological,histological,and molecular criteria with different specialists involved in the patient’s clinical work-up.Among all manifestations of the disease,gastrointestinal(GI)symptoms are common,being present in 14%-85% of patients,and can significantly impair the quality of life.Here we review the data regarding GI involvement in SM,in terms of clinical presentations,histological and endoscopic features,the pathogenesis of GI symptoms,and their treatment.

Intestinal amyloidosis:Two cases with different patterns of clinical and imaging presentation

The involvement of the small bowel in systemic forms of amyloidosis may be diffuse or very rarely focal.Some cases of focal amyloidomas of the duodenum and jejunum without extraintestinal manifestations have been reported.The focal amyloidomas consisted of extensive amyloid infiltration of the entire intestinal wall thickness.Radiological barium studies,ultrasound and computed tomography(CT)patterns of diffuse small bowel amyloidosis have been described:the signs are non-specific and may include small-bowel dilatation,symmetric bowel wall thickening,mesenteric infiltration,and mesenteric adenopathy.No data are available about the positron emission tomography (PET)/CT and magnetic resonance imaging(MRI)patterns of intestinal amyloidosis.We report two cases of small bowel amyloidosis:the former characterized by focal deposition of amyloid proteins exclusively within blood vessel walls of the terminal ileum,the latter characterized by diffuse intestinal involvement observed on MRI and PET/CT studies.

Robotically assisted removal of pelvic splenosis fifty-six years after splenectomy: A case report

BACKGROUND‘Splenosis’is defined as the autotransplantation of splenic tissue following trauma or surgery,usually in the form of intraperitoneal nodules.The proliferation of imaging techniques has resulted in increased unexpected discoveries of splenosis nodules,and achieving a differential diagnosis can be challenging.Nuclear medicine studies have been playing an increasingly important role in this process,but the clinical significance of asymptomatic nodules remains uncertain.CASE SUMMARY We present a case of pelvic splenosis in a 73-year-old man diagnosed 56 years after a splenectomy during a computed tomography(CT)follow-up for B-cell lymphoma,presenting intense contrast enhancement of an 18 mm nodule in the right recto-vesical space.18F-fluorodeoxyglucose demonstrated weak metabolic activity.Since histological diagnosis was deemed necessary,the nodule was easily removed with robotically assisted laparoscopy,together with another 6 mm left a paracolic lesion.The latter was previously undiagnosed but retrospectively visible on the CT scan.CONCLUSION In a patient requiring differential diagnosis of splenosis nodules from lymphomarecurrence, the robotic approach provided a safe en bloc removal with shorthospitalization. The Da Vinci Xi robot was particularly helpful because its opticscan be introduced from all ports, facilitating visualization and lysis of multipleintra-abdominal adhesions.

Experimental Study of the Effect of the Bax Gene on Human Hepatocellular Carcinoma and Therapy via Hepatic Artery Delivery

OBJECTIVE To investigate apoptosis induced by Bax in hepatocellular carcinoma cells and to examine the results of 2 different routes for in vivo gene delivery. METHODS The anti-hepatocellular carcinoma activity of the Bax gene transferred to the human hepatocellular carcinoma QGY7703 cell line was examined. In addition the Bax gene was transferred in vivo in mice via the caudal vein or hepatic artery to investigate the differences in target organ and non-target organ transfection. RESULTS 1）The Bax gene mediated by a binary adenoviral vector system induced apoptosis in the human hepatic carcinoma QFY7703 cell line. The cell apoptotic rate in the experimental group （Bax） was 50.2±6.9% but only 32.1 ± 9.7% in the Ad/CMV-p53 group, showing that the Bax-apoptotic rate was significantly higher than the control group. 2） LacZ expression was higher in the target organ （liver） when given through the hepatic artery than through the tail vein. In contrast, LacZ expression in the nontarget organs was higher if given through the tail vein compared to the hepatic artery. CONCLUSION Superselective hepatic artery delivery with Bax gene therapy is safe, specific, effective and has low toxicity. This study provided the basis for Bax-gene therapy via the hepatic artery in vivo.

Conservative Medroxyprogesterone Acetate Therapy in Early Stage of Endometrial Carcinoma Associated with Phosphatase and Tensin Homolog Expression

Young patients with the endometrial cancer IA who desire to preserve fertility, can select the conservative therapy with progestin. However, the therapy involves risks of progression and relapse. We examined immunohistochemical analyses of phosphatase and tension homolog (PTEN) and p53 expressions to predict the early relapse, and pregnancy and delivery. Twenty women with endometrial cancer, FIGO IA (1988) (FIGO staging was essentially defined post-surgically), instead of the pathogical specimen before surgery without myometrial invasion were estimated by MRI under 40 years at Gifu University Hospital, Japan from 1988 to 2009. Patients were treated with medroxyprogesterone acetate (MPA, 400 - 600 mg/day) for 4 - 10 months, with whole wall endometrial curettage performed every four weeks. Response to the therapy, pregnancy, delivery and relapse of disease during follow-up over a 72-month period. Immunohistochemical expression of PTEN and p53 was also evaluated with pregnancy, delivery and relapse rate. All patients had pathological complete remissions within 4 - 10 months. Relapse rate was high (60%) in more than 72 months. Immunohistochemical PTEN retain in tumor cells before MPA treatment (8/10) was significant better correlation with pregnancy and delivery rate than of lost cases (1/5) in non-obese women (P < 0.05). Conservative therapy is feasible in carefully selected young women with endometrial cancer without myometrial invasion. However, the relapse rate was high. In cases who desire to be a pregnant, an earlier infertility treatment may be considered especially for PTEN loss especially in nonobese cases.

Bioactive Fatty Acids Reduce Development of Gastric Cancer Following Duodenogastric Reflux in Rats

Background: Bioactive fatty acids such as the eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and the modified fatty acid analogue, tetradecylthioacetic acid (TTA), are known to influence inflammatory processes in the body. Our aim was to investigate if diets containing fish oil (FO) enriched with bioactive fatty acids could affect inflammation and development of glandular stomach carcinogenesis in a duodenogastric reflux (DGR) animal model. We also wanted to evaluate if a high-fat diet might increase the risk of developing gastric cancer compared to a low-fat diet. Methods: 185 rats operated on with a gastroenterostomy were randomly allocated to 5 different treatment groups given: low-fat, high-fat, high-fat + FO, high-fat + TTA or high-fat + FO + TTA. The stomachs were removed after 50 weeks and examined by light microscopy with hematoxylin and eosin staining (HE). Immunohistochemical staining against COX-2, PCNA and p53 was performed when adenocarcinomas were found. The plasma fatty acid profile was determined. Results: Adenocarcinomas developed in 21% of animals fed the low-fat diet, 35% in the high-fat group, 16% in the high-fat + TTA group, 21% in the high-fat + FO group and 8.6% in the high-fat + FO + TTA treatment group. COX-2 and PCNA were positive whereas p53 was negative in the majority of the samples. The anti-inflammatory fatty acid index increased after treatment with FO and in combination with FO and TTA. Conclusion: FO and TTA in combination with a high-fat diet significantly lower the risk of developing adenocarcinomas in rats subjected to duodenogastric reflux. This is most likely due to a selective modulation of inflammation.

Practical hints for the diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasms of the digestive system

In this editorial,a comment on the article by Díaz-López et al published in the recent issue of the 2024 is provided.We focus on the practical implications critical for providing a correct and complete diagnosis of mixed neuroendocrine-nonneuroendocrine neoplasm(MiNEN)in the gastrointestinal system.The diagnosis of MiNEN begins with the recognition of neuroendocrine features in one component of a biphasic tumor.The non-neuroendocrine counterpart can be virtually represented by any neoplastic type,even though the most frequent histologies are glandular and squamous.However,qualification of the neuroendocrine component requires histological and immunohistochemical confirmation.Neuroendocrine tumors are characterized by a peculiar architectural organization and bland nuclei with granular“salt and pepper”chromatin.Although neuroendocrine carcinomas have multiple and variable presentations,they typically show a solid or organoid architecture.The histological aspect needs to be confirmed by immunohistochemistry,and a diagnosis is confirmed whenever the expression of keratin and neuroendocrine markers is observed.Once both histopathological and immunohistochemical features of neuroendocrine neoplasms are identified,it is important to consider the three major pitfalls of MiNEN diagnostics:(1)Entrapment of neuroendocrine non-neoplastic cells within the tumor mass;(2)Differential diagnosis with amphicrine neoplasms;and(3)Differential diagnosis of tumors that partially express neuroendocrine markers.According to the current guidelines for diagnosing digestive MiNEN,each component must represent at least 30%of the entire neoplastic mass.Although the high-grade histopathological subtype frequently determines disease prognosis,both components can significantly affect prognosis.Thus,if one of the components,either neuroendocrine or non-neuroendocrine,does not fulfill the volumetric criteria,the guidelines still encourage reporting it.These strict criteria are essential for correctly recognizing and characterizing digestive MiNENs.This task is essential because it has prognostic relevance and substantial potential value for guiding further studies in this field.In the future,systematic analyses should be performed to validate or reconsider the current 30%cutoff value.