Accuracy of optical diagnosis with narrow band imaging in the surveillance of ulcerative colitis: a prospective study comparing Kudo, Kudo-IBD and NICE classifications.

PURPOSE: The diagnostic accuracy of Narrow Band Imaging (NBI) in the endoscopic surveillance of ulcerative colitis (UC) has been disappointing in most trials which used the Kudo classification. We aim to compare the performance of NBI in the lesion characterization of UC, when applied according to three different classifications (NICE, Kudo, Kudo-IBD). METHODS: In a prospective, real-life study, all visible lesions found during consecutive surveillance colonoscopies with NBI (Exera-II CV-180) for UC were classified as suspected or non-suspected for neoplasia according to the NICE, Kudo and Kudo-IBD criteria. The sensitivity (SE), specificity (SP), positive (+LR) and negative (-LR) likelihood ratios of the three classifications were calculated, using histology as the reference standard. RESULTS: 394 lesions (mean size 6 mm, range 2-40 mm) from 84 patients were analysed. Twenty-one neoplastic (5%), 49 hyperplastic (12%), and 324 inflammatory (82%) lesions were found. The diagnostic accuracy of the NICE, Kudo and Kudo-IBD classifications were, respectively: SE 76%-71%-86%; SP 55-69%-79% (p < 0.05 Kudo-IBD vs. both Kudo and NICE); +LR 1.69-2.34-4.15 (p < 0.05 Kudo-IBD vs. both Kudo and NICE); -LR 0.43-0.41-0.18. CONCLUSION: The diagnostic accuracy of NBI in the differentiation of neoplastic and non-neoplastic lesions in UC is low if used with conventional classifications of the general population, but it is significantly better with the modified Kudo classification specific for UC.

Prognostic and Predictive Value of Microsatellite Instability, Inflammatory Reaction and PD-L1 in Gastric Cancer Patients Treated with Either Adjuvant 5-FU/LV or Sequential FOLFIRI Followed by Cisplatin and Docetaxel: A Translational Analysis from the ITACA-S Trial.

BACKGROUND: Patients with high microsatellite instability (MSI) gastric cancer (GC) show improved survival and no benefit or harm from adjuvant and/or perioperative chemotherapy. The role of immune microenvironment in GC is largely unknown. MATERIALS AND METHODS: In the present study, 256 tumor tissue blocks were centrally collected from patients enrolled in ITACA-S, a randomized adjuvant trial of 5-FU/LV versus sequential FOLFIRI and cisplatin-docetaxel. MSI status was assessed by multiplex PCR, inflammatory reaction by H&E morphological assessment, and programmed death-ligand 1 (PD-L1) expression by immunohistochemistry. RESULTS: Overall, 9% patients had MSI-high tumors, 23% had high inflammatory reaction, 11% had tumor PD-L1 ≥ 1%, and 11% had stromal PD-L1 ≥ 1%. A significant association with disease-free survival (DFS) and overall survival (OS) was found for MSI-high (hazard ratio [HR], 0.43; p = .02; HR, 0.40; p = .02) and high inflammatory reaction (HR, 0.55; p = .010; HR, 0.53; p = .008) but not for PD-L1. At multivariable analysis, only MSI showed an independent association with both DFS (p = .02) and OS (p = .01), whereas inflammatory reaction showed an independent association only with OS (p = .04). Patients with tumor PD-L1 ≥ 1% had a significantly longer DFS in sequential chemotherapy than in than 5-FU/LV arm (interaction p = .04) and a trend for OS (interaction p = .12). CONCLUSION: Our data suggest that MSI status could be a useful prognostic biomarker in patients with radically resected stage II-III GC and should be used as stratification factor in future trials. Tumor PD-L1 ≥ 1% should be further investigated as a potential predictor of benefit from intensive chemotherapy. IMPLICATIONS FOR PRACTICE: In this post hoc analysis of patients with radically resected gastric cancer randomized to an intensive sequential chemotherapy regimen versus 5-FU/LV monotherapy as adjuvant treatment in the ITACA-S trial, MSI-high status was independently associated with better disease-free survival and overall survival (OS) and inflammatory reaction was independently associated with better OS. Moreover, tumor PD-L1 expression ≥1% was associated with greater benefit from intensive sequential chemotherapy compared with 5-fluorouracil plus leucovorin (5-FU/LV), whereas PD-L1 expression <1% was not, conditioning a statistically significant interaction between such biomarker and treatment arms. The meta-analysis of individual patients' data from available studies could yield data on the role of MSI status that could inform clinical decisions.

Liver histopathology in severe COVID 19 respiratory failure is suggestive of vascular alterations.

SARS2-CoV-2 breakout in Italy caused a huge number of severely ill patients with a serious increase in mortality. Although lungs seem to be the main target of the infection, very few information are available about liver involvement, possibly evocating a systemic disease. Post-mortem wedge liver biopsies from 48 patients died from severe pulmonary COVID-19 disease with respiratory failure were collected from two main hospitals in northern Italy. No patient had clinical symptoms of liver disease or signs of liver failure before and during hospitalization; for each of them liver function tests were available. All liver samples showed minimal inflammation features. Histological pictures compatible with vascular alterations were observed, characterized by increase in number of portal vein branches associated with lumen massive dilatation, partial or complete luminal thrombosis of portal and sinusoidal vessels, fibrosis of portal tract, focally markedly enlarged and fibrotic. SARS-CoV-2 was found in 15 of 22 samples tested by in situ hybridization method. Our preliminary results confirm the clinical impression that liver failure is not a main concern and this organ is not the target of significant inflammatory damage. Histopathological findings are highly suggestive for marked derangement of intrahepatic blood vessel network secondary to systemic changes induced by virus that could target not only lung parenchyma but also cardiovascular system, coagulation cascade and endothelial layer of blood vessels. It still remains unclear if the mentioned changes are directly related to virus infection or if SARS-CoV-2 triggers a series of reactions leading to striking vascular alterations.

Analysis of Sentinel Node Biopsy and Clinicopathologic Features as Prognostic Factors in Patients With Atypical Melanocytic Tumors.

BACKGROUND: Atypical melanocytic tumors (AMTs) include a wide spectrum of melanocytic neoplasms that represent a challenge for clinicians due to the lack of a definitive diagnosis and the related uncertainty about their management. This study analyzed clinicopathologic features and sentinel node status as potential prognostic factors in patients with AMTs. PATIENTS AND METHODS: Clinicopathologic and follow-up data of 238 children, adolescents, and adults with histologically proved AMTs consecutively treated at 12 European centers from 2000 through 2010 were retrieved from prospectively maintained databases. The binary association between all investigated covariates was studied by evaluating the Spearman correlation coefficients, and the association between progression-free survival and all investigated covariates was evaluated using univariable Cox models. The overall survival and progression-free survival curves were established using the Kaplan-Meier method. RESULTS: Median follow-up was 126 months (interquartile range, 104-157 months). All patients received an initial diagnostic biopsy followed by wide (1 cm) excision. Sentinel node biopsy was performed in 139 patients (58.4%), 37 (26.6%) of whom had sentinel node positivity. There were 4 local recurrences, 43 regional relapses, and 8 distant metastases as first events. Six patients (2.5%) died of disease progression. Five patients who were sentinel node-negative and 3 patients who were sentinel node-positive developed distant metastases. Ten-year overall and progression-free survival rates were 97% (95% CI, 94.9%-99.2%) and 82.2% (95% CI, 77.3%-87.3%), respectively. Age, mitotic rate/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss were factors affecting prognosis in the whole series and the sentinel node biopsy subgroup. CONCLUSIONS: Age >20 years, mitotic rate >4/mm2, mitoses at the base of the lesion, lymphovascular invasion, and 9p21 loss proved to be worse prognostic factors in patients with ATMs. Sentinel node status was not a clear prognostic predictor.

OATPB1/B3 and MRP3 expression in hepatocellular adenoma predicts Gd-EOB-DTPA uptake and correlates with risk of malignancy.

BACKGROUND AND AIMS: Hepatobiliary phase (HBP) Gd-EOB-DTPA-enhanced magnetic resonance imaging (MRI) has increased the accuracy in differentiating focal nodular hyperplasia (FNH) and hepatocellular adenoma (HCA). However, the ability of this technique to distinguish HCA subtypes remains controversial. The aim of this study was to investigate the expression of hepatocyte transporters (OATPB1/B3, MRP2, MRP3) in HCA subtypes, hence to understand their MRI signal intensity on HBP Gd-EOB-DTPA-enhanced MRI. METHODS: By means of immunohistochemistry (IHC), we scored the expression of OATPB1/B3, MRP2 and MRP3, in resected specimens of FNH (n = 40), subtyped HCA (n = 58) and HCA with focal malignant transformation (HCA-HCC, n = 4). Results were validated on a supplementary set of FNH (n = 6), subtyped HCA (n = 17) and HCA-HCC (n = 1) with Gd-EOB-DTPA MR images. RESULTS: All FNH showed a preserved expression of hepatocytes transporters. Beta-catenin-activated HCA (at highest risk of malignant transformation) and HCA-HCC were characterized by preserved/increased OATPB1/B3 expression (predictor of hyperintensity on HBP), as opposed to other HCA subtypes (P < 0.01) that mostly showed OATPB1/B3 absence (predictor of hypointensity on HBP). HCA-HCC showed an additional MRP3 overexpressed profile (P < 0.01). On HBP Gd-EOB-DTPA-enhanced MRI, FNH and HCA signal intensity reflected the profile predicted by their specific OATPB1/B3 tissue expression. The hyperintense vs hypointense HBP signal criterion was able to distinguish all higher risk HCA and HCA-HCC (100% accuracy). CONCLUSIONS: OATPB1/B3 and MRP3 IHC and signal intensity on HBP Gd-EOB-DTPA-enhanced MRI can help to stratify HCA according to their risk of malignant transformation.

Preoperative Capecitabine, Oxaliplatin, and Irinotecan in Resectable Gastric or Gastroesophageal Junction Cancer: Pathological Response as Primary Endpoint and FDG-PET Predictions.

OBJECTIVES: This phase II trial was aimed at assessing the safety and activity of capecitabine, oxaliplatin, and irinotecan (COI regimen) as a preoperative treatment for resectable gastric cancer (GC) or gastroesophageal junction (GEJ) cancer. METHODS: Patients affected by T3-T4/N0-N+/M0 GC/GEJ cancer were treated with the COI regimen for 4 cycles followed by restaging and gastroresection with D2 lymphadenectomy. Four postoperative cycles were scheduled. The primary endpoint was pathological response rate according to Becker et al. [Cancer 2003;98:1521-1530]. The potential role of fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) as a predictive biomarker of pathological tumor response was assessed in a subgroup of 19 evaluable patients. RESULTS: Between January 2011 and October 2015, a total of 40 patients were enrolled. After the preoperative phase, 36 out of 40 patients (90%) were considered eligible for surgery: 12 patients (30%) achieved a pathological response. The most frequent grade 3/4 adverse events were diarrhea (27%), nausea (25%), and fatigue (17%). Grade 3 neutropenia occurred in 7.5% of patients. A lower standard uptake value at baseline FDG-PET/CT was associated with pathological response. CONCLUSION: COI combination is active with a manageable toxicity profile in patients with resectable GC or GEJ cancer. FDG-PET/CT imaging as a surrogate biomarker of pathological response in this setting appears fascinating but should be further investigated.

Osteopontin, E-cadherin, and ß-catenin expression as prognostic biomarkers in patients with radically resected gastric cancer.

A correlation between osteopontin, E-cadherin, ß-catenin, and cyclooxygenase 2 overexpression and poor clinicopathological features and prognosis has been previously suggested in gastric cancer. This translational study was aimed at assessing the correlation of these immunohistochemical biomarkers with outcome in patients with radically resected gastric cancer. We analyzed osteopontin, E-cadherin, ß-catenin, and cyclooxygenase 2 expression by immunohistochemistry in 346 primary gastric tumor tissue samples from patients enrolled in the ITACA-S trial. This phase III study randomized patients with radically resected gastric cancer to receive adjuvant chemotherapy with either 5-fluorouracil and leucovorin or a sequential regimen of infusional 5-fluorouracil and leucovorin plus irinotecan followed by cisplatin and docetaxel. High expression of osteopontin was correlated with high histological grade, diffuse histotype, and peritoneal relapse, but not with TNM stage. Moreover, osteopontin overexpression was associated with higher risk of tumor recurrence and metastases, and was an independent prognostic factor for both relapse-free and overall survival of gastric cancer patients following adjuvant chemotherapy. Abnormal E-cadherin expression and abnormal ß-catenin expression were correlated with more advanced disease stage, and as a consequence, with poor outcome. Our results suggest that osteopontin overexpression is a valuable independent predictor of tumor recurrence and survival in patients with radically resected gastric cancer.

Resection of hepatocellular cancer ≤2 cm: results from two Western centers.

UNLABELLED: Asian series have shown a 5-year survival rate of ≈70% after resection of hepatocellular carcinoma (HCC) ≤2 cm. Western outcomes with resection have not been as good. In addition, ablation of HCC ≤2 cm has been shown to achieve competitive results, leaving the role of resection in these patients unclear. Records of patients undergoing resection at two Western centers between January 1990 and December 2009 were reviewed. Patients with a single HCC ≤2 cm on pathologic analysis were included. Thirty clinical variables including demographics, liver function, tumor characteristics, nature of the surgery, and the surrounding liver were examined. An exploratory statistical analysis was conducted to determine variables associated with recurrence and survival. The study included 132 patients with a median follow-up of 37.5 months. There was one (<1%) 90-day mortality. There were 32 deaths with a median survival of 74.5 months and a 5-year survival rate of 70% (63% in patients with cirrhosis). The median time to recurrence was 31.6 months and the 5-year recurrence rate was 68%. Presence of satellites (hazard ratio [HR], 2.46; P = 0.031) and platelet count <150,000/µL (HR, 2.37; P = 0.026) were independently associated with survival. Presence of satellites (HR, 2.79; P = 0.003), cirrhosis (HR, 2.3; P = 0.010), and nonanatomic resection (HR, 1.79; P = 0.031) were independently associated with recurrence. Patients with a single HCC ≤2 cm and platelet count ≥150,000/µL achieved a median survival of 138 months and a 5-year survival rate of 8%, respectively. CONCLUSION: Resection of HCC ≤2 cm is safe and achieves excellent results in Western centers. Recurrence continues to be a significant problem. Presence of satellites, platelet count, anatomic resection, and cirrhosis are associated with outcomes after resection, even among such early tumors. Resection should continue to be considered a primary treatment modality in patients with small HCC and well-preserved liver function.

Laparoscopic Cholecystectomy in Children: The Experience of Two Centers Focusing on Indications and Timing in the Era of "New Technologies".

BACKGROUND: In children, laparoscopic cholecystectomy (LC) is now considered the gold standard for gallbladder (GB) removal. In the past, hemolytic disorders associated with cholelithiasis represented the most frequent conditions requiring LC; this is being overtaken by cholelithiasis and biliary conditions in overweight or ex-premature children. AIMS: This study aims to describe current indications and timing for LC in pediatric patients. METHODS: Retrospective study. Data on previous medical therapy, ultrasound, pre- and intraoperative aspects, and histology were collected for patients treated in 2020-2023. RESULTS: In total, 45 patients were enrolled: 15 who underwent urgent surgery and 30 electives. Groups differed in terms of obesity rate, symptoms, ultrasound features, and intraoperative status. The most relevant risk factors for surgical complexity were age and pubertal stage, elevated cholestasis indexes, and gallbladder wall thickness > 3 mm at ultrasound. GB wall thickening ≥3 mm, US Murphy sign, fluid collections, and gallbladder distention on ultrasound correlated with high surgical scores. CONCLUSIONS: Indications for laparoscopic cholecystectomy in children seem to evolve caused by changing characteristics of the pediatric population. Patients with overweight/obesity may develop more complex GB diseases. Asymptomatic patients should be considered for surgery after observation, considering age and/or pubertal maturation when other risk factors are absent.

Gastrointestinal tuberculosis presenting as acute abdomen: a case report.

Intestinal tuberculosis (ITB) represents an important diagnostic challenge in the clinical setting, as it generally can occur as a chronic condition often mimicking other diseases such as Crohn's disease (CD), and can present itself with acute onset, which can be life-threatening. A 29-years-old Chinese woman coming to ER with abdominal pain, fever and weight loss. Computed tomography and colonoscopy images were not diagnostic. Despite medical therapy, the patient progressively worsened developing sepsis requiring emergency surgery. Pathological and microbiological examination of the colon both pointed towards gastrointestinal tuberculosis involvement. Although ITB is generally a chronic-wasting condition, it can also occur as acute abdomen representing an absolute surgical emergency. Although caseation and necrosis in granulomas can be used for diagnosis of ITB, preoperative diagnosis is still challenging. Endoscopic biopsies targeted to ulcerous lesions could be an essential diagnostic tool, contrary to those targeted to the ulcers' edges as performed in CD.

Non-syndromic bile duct paucity and non-IgE cow's milk allergy: a case report of challenging nutritional management and maltodextrin intolerance.

BACKGROUND: Cholestasis in extremely premature infants (EPI) constitutes a nutritional challenge and maltodextrins have been reported as a possible strategy for hypoglycaemia. We aim to describe the nutritional management of an EPI with non-syndromic bile duct paucity (NSBDP) and feeding intolerance. CASE PRESENTATION: A patient, born at 27 weeks of gestational age, presented cholestatic jaundice at 20 days of life with a clinical picture of NSBDP. Patient's growth was insufficient with formula rich in medium-chain triglyceride (MCT) and branched-chain amino acids (BCAA). Due to frequent fasting hypoglicemic episodes, maltodextrins supplements were provided. He subsequently presented severe abdominal distension and painful crises, which required hospital admission and withdrawal of maltodextrins. Hypercaloric extensively hydrolysed formula provided weight gain, glycemic control, and parallel improvement in cholestasis. CONCLUSIONS: Our case suggests caution with the use of maltodextrins in infants, especially if premature. Commercial preparations for hepatopatic patients contain higher concentrations of MCTs and BCAAs, but personalized strategies must be tailored to each patient.

Association of high TUBB3 with resistance to adjuvant docetaxel-based chemotherapy in gastric cancer: translational study of ITACA-S.

BACKGROUND: No predictive markers for chemotherapy activity have been validated in gastric cancer (GC). The potential value of class III ß-tubulin (TUBB3) as biomarker for prognosis and resistance to taxane-based therapy was reported. METHODS: We analyzed GC samples of patients enrolled in the Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach (ITACA-S), a randomized adjuvant study comparing 5-fluorouracil/leucovorin (5-FU/LV) and docetaxel-based sequential chemotherapy. TUBB3 was quantitated by selected reaction monitoring mass spectrometry and patients were stratified using a threshold of 750 attomoles per microgram (amol/µg). Cox proportional modeling and Kaplan-Meier survival analysis were used to assess the impact of TUBB3 expression on overall survival (OS) and disease-free survival. RESULTS: Patients with TUBB3 protein levels >750 and <750 amol/µg were 21.9% and 78.1%, respectively, and were well-balanced between treatment arms. TUBB3 protein levels were not prognostic. Whereas no survival differences according to the 2 arms were observed in the subgroup with low TUBB3 expression (5-year OS 47% vs 40%; p = 0.44), patients with high TUBB3 had a clinically meaningful poorer OS when receiving docetaxel-based versus 5-FU/LV chemotherapy (5-year OS 31% vs 54%; p = 0.09), with a statistically significant interaction between TUBB3 and treatment (p = 0.049). CONCLUSIONS: The quantification of TUBB3 might be considered as a negative predictive biomarker of benefit from taxane-based therapy in GC. Studies are needed to evaluate its role in the neoadjuvant setting.

Personalized molecular targeted therapy in advanced, recurrent hepatocellular carcinoma after liver transplantation: a proof of principle.

BACKGROUND & AIMS: The advent of molecular medicine that targets specific pathways is changing the therapeutic approach to hepatocellular carcinoma. For several aberrantly activated pathways in hepatocarcinoma, surrogate markers of activation can be assessed by immunohistochemistry, although associations with in vivo response to targeted therapies are still lacking. METHODS: A patient, who presented with hepatic and extra-hepatic hepatocarcinoma recurrence 11 years after liver transplantation, was assessed for beta-catenin, pERK, and pS6 in primary and secondary tumor specimens, in order to define a possible activation of the Wnt, Ras/MAPK and Akt/mTOR pathways and design a personalized targeted therapy in absence of alternative treatment options. Moreover, mutation analysis of the beta-catenin gene (CTNNB1) and DNA microsatellite analyses were performed. RESULTS: The identification of the same mutation in the beta-catenin gene, as well as the same microsatellite pattern in tumor tissues taken 11 years apart, proved that the observed hepatocarcinoma was a true recurrence. Nuclear beta-catenin and pS6 in tumor cells were positive, whereas pERK was positive only in the peritumoral endothelium. This pattern of immunohistochemistry, after failure of sorafenib alone, lead to the choice to add the mTOR inhibitor, everolimus, to sorafenib. Three months later a 50% tumor reduction was observed, and after 6 months a further reduction of tumor vital components was confirmed, while a grade II gastrointestinal bleeding episode occurred. CONCLUSIONS: A personalized approach aimed to treat recurrent hepatocarcinoma is possible through analysis of tumoral molecular pathways. Partial success of the selected combination of sorafenib and everolimus supports the pivotal role of mTOR signalling and highlights the importance of reliable biomarkers to route the best molecular-based therapeutic options in HCC.

Pulmonary post-mortem findings in a series of COVID-19 cases from northern Italy: a two-centre descriptive study.

BACKGROUND: COVID-19 is characterised by respiratory symptoms, which deteriorate into respiratory failure in a substantial proportion of cases, requiring intensive care in up to a third of patients admitted to hospital. Analysis of the pathological features in the lung tissues of patients who have died with COVID-19 could help us to understand the disease pathogenesis and clinical outcomes. METHODS: We systematically analysed lung tissue samples from 38 patients who died from COVID-19 in two hospitals in northern Italy between Feb 29 and March 24, 2020. The most representative areas identified at macroscopic examination were selected, and tissue blocks (median seven, range five to nine) were taken from each lung and fixed in 10% buffered formalin for at least 48 h. Tissues were assessed with use of haematoxylin and eosin staining, immunohistochemical staining for inflammatory infiltrate and cellular components (including staining with antibodies against CD68, CD3, CD45, CD61, TTF1, p40, and Ki-67), and electron microscopy to identify virion localisation. FINDINGS: All cases showed features of the exudative and proliferative phases of diffuse alveolar damage, which included capillary congestion (in all cases), necrosis of pneumocytes (in all cases), hyaline membranes (in 33 cases), interstitial and intra-alveolar oedema (in 37 cases), type 2 pneumocyte hyperplasia (in all cases), squamous metaplasia with atypia (in 21 cases), and platelet-fibrin thrombi (in 33 cases). The inflammatory infiltrate, observed in all cases, was largely composed of macrophages in the alveolar lumina (in 24 cases) and lymphocytes in the interstitium (in 31 cases). Electron microscopy revealed that viral particles were predominantly located in the pneumocytes. INTERPRETATION: The predominant pattern of lung lesions in patients with COVID-19 patients is diffuse alveolar damage, as described in patients infected with severe acute respiratory syndrome and Middle East respiratory syndrome coronaviruses. Hyaline membrane formation and pneumocyte atypical hyperplasia are frequent. Importantly, the presence of platelet-fibrin thrombi in small arterial vessels is consistent with coagulopathy, which appears to be common in patients with COVID-19 and should be one of the main targets of therapy. FUNDING: None.

Sclerosing angiomatoid nodular transformation (SANT) of the spleen: A case report on CT and MRI.

Solid tumors of the spleen are rare, with an incidence of 0.007% in all operating and autopsy specimens. In terms of microscopic structure and function, the spleen consists of two parts: the white pulp, which plays an important role in the immune system and the red pulp, which filters the blood.Primary splenic neoplasms can be classified into lymphoid neoplasms arising from the white pulp, and vascular neoplasms which arise from the red pulp.Primary tumors arising from vascular elements include benign lesions such as hemangioma, lymphangioma and hamartoma, intermediate lesions such as hemangioendothelioma, hemangiopericytoma and littoral cell angioma as well as the frankly malignant hemangiosarcoma.It is usually difficult to distinguish a benign from a malignant lesion with preoperative imaging studies and cytological exam by fine-needle aspiration (FNA), that is not easily obtained because of the risk of bleeding.Therefore a splenectomy should be necessary for a definitive diagnosis of splenic tumors.Martel and all for the first time described the sclerosing angiomatoid nodular transformation (SANT), like a vascular lesion of the spleen, with benign clinical course consisting by altered red pulp tissue that has been entrapped by a non-neoplastic stromal proliferative process.We describe a rare case of benign splenic mass documented with FDG/PET-CT (referred as equivocal), CT and MRI.

Biomarkers of Primary Resistance to Trastuzumab in HER2-Positive Metastatic Gastric Cancer Patients: the AMNESIA Case-Control Study.

Purpose: Refining the selection of HER2-positive metastatic gastric cancer patient candidates for trastuzumab is a challenge of precision oncology. Preclinical studies have suggested several genomic mechanisms of primary resistance, leading to activation of tyrosine kinase receptors other than HER2 or downstream signaling pathways.Experimental Design: We carried out this multicenter, prospective, case-control study to demonstrate the negative predictive impact of a panel of candidate genomic alterations (AMNESIA panel), including EGFR/MET/KRAS/PI3K/PTEN mutations and EGFR/MET/KRAS amplifications. Hypothesizing a prevalence of candidate alterations of 30% and 0% in resistant and sensitive HER2-positive patients, respectively, 20 patients per group were needed.Results: AMNESIA panel alterations were significantly more frequent in resistant (11 of 20, 55%) as compared with sensitive (0% of 17) patients (P < 0.001), and in HER2 IHC 2+ (7 of 13, 53.8%) than 3+ (4 of 24, 16.7%) tumors (P = 0.028). Patients with tumors bearing no candidate alterations had a significantly longer median progression-free [5.2 vs. 2.6 months; HR, 0.34; 95% confidence interval (CI), 0.07-0.48; P = 0.001] and overall survival (16.1 vs. 7.6 months; HR, 0.38; 95% CI, 0.09-0.75; P = 0.015). The predictive accuracy of the AMNESIA panel and HER2 IHC was 76% and 65%, respectively. The predictive accuracy of the combined evaluation of the AMNESIA panel and HER2 IHC was 84%.Conclusions: Our panel of candidate genomic alterations may be clinically useful to predict primary resistance to trastuzumab in patients with HER2-positive metastatic gastric cancer and should be further validated with the aim of molecularly stratifying HER2-addicted cancers for the development of novel treatment strategies. Clin Cancer Res; 24(5); 1082-9. ©2017 AACR.

Papillary carcinoma of the thyroid gland of childhood and adolescence: Morphologic subtypes, biologic behavior and prognosis: a clinicopathologic study of 42 sporadic cases treated at a single institution during a 30-year period.

Papillary thyroid carcinomas (PTCs) in pediatric age show an excellent outcome, independently of sex, stage at diagnosis, occurrence of relapse, and type of treatment. Our aim was to study the biologic behavior and the impact on survival of PTC subtypes in childhood. From 1968 to 2002, 42 sporadic pediatric PTCs were subclassified into PTC, not otherwise specified and PTC variants. In all cases, sex, age at diagnosis, age of menarche, side, size, TNM/pTNM classification, neoplastic microfoci, vascular invasion, status of the non-neoplastic parenchyma, and treatment (surgery and nonsurgical therapies) were registered. Follow-up was carried on up to May 2005. PTC, solid/trabecular variant was the most frequent subtype. Both extrathyroid local invasion (P < 0.04) and distant metastases (P < 0.01) at onset were significantly associated with PTC, not otherwise specified. After a median follow-up of 16 years, for the whole series overall survival and progression-free survival (PFS) rates were 100% and 77%, respectively. The solid/trabecular variant was at a significantly increased risk of relapse (PFS 50%, P < 0.01). The occurrence of poorly differentiated tall cell morphology did not influence survival. Sensitivity to hormonal manipulation was maintained over time. In conclusion, although overall survival was not influenced by PTC subtypes, the solid/trabecular variant of PTC was at a significantly higher risk of relapse. At variance with adults, presence of the tall cell morphology did not carry a worst prognostic significance.