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Introduction: The objective of this study was to reclassify published germline CDH1 variants identified in gastric cancer (GC) in accordance with the latest ClinVar definition and to correlate their pathogenicity with the established international clinical criteria for genetic testing. Methods: The relevant literature dating from 1998 to 2019 was systematically searched for data on CDH1 germline mutations in accord with PRISMA guidelines. The collected variants were classified according to the latest ClinVar definition into the following classes: benign (B), likely benign (LB), pathogenic (P), likely pathogenic (LP), and variant of unknown significance (VUS). The McNemar test was used to compare the adequacy of current versus previous International GC Linkage Consortium (IGCLC) criteria. Results: We reclassified a total of 247 CDH1 variants, and we identified that about 70% of B/LB variant carriers were not fulfilling the defined clinical criteria. Instead, all P/LP variants (100%) were associated with the hereditary diffuse gastric cancer (HDGC) phenotype fulfilling the 2020 ILGCC criteria, with a significant improvement (p = 0.025) compared to previous version. Conclusions: We conclude that germline CDH1 genetic testing is indicated only in families meeting the clinical criteria for the HDGC syndrome. This observation suggests that clinical phenotypes that do not clearly fulfill these criteria should not be considered for CDH1 genetic testing. [ABSTRACT FROM AUTHOR]

Purpose: The objective of this study was to determine the male and female frequency of diffuse gastric cancer (DGC), the age at diagnosis, and the country of origin in a selected population with germline CDH1 variants from families with the hereditary diffuse gastric cancer (HDGC) syndrome. Methods: Relevant literature dating from 1998 to 2021 was systematically searched for data on CDH1 gene. The Wilcoxon rank sum test and the Chi-square test were used to estimate if the difference observed between patients with gastric cancer (GC) and unaffected individuals was significant. Results: We identified 80 families fulfilling the established clinical criteria for HDGC CDH1 genetic screening. There were more women than men with DGC and germline CDH1 variant (65.5%). Stratifying the age at diagnosis, we identified an association between DGC, positive CDH1 screening and young women (≤ 40 years) (p = 0.015). The mean age at diagnosis was 39.6 ys for women and 42.5 ys for men. There was an association between CDH1 carrier status and DGC (p = 0.021). Conclusions: Young women carrying germline CDH1 variants with DGC are comparatively frequent in the HDGC syndrome, and potentially at higher risk to develop DGC particularly in low-incidence areas for GC. [ABSTRACT FROM AUTHOR]

Purpose: Recent observations regarding long-term outcomes among patients with early-stage breast cancer (BC) who underwent breast-conserving surgery (BCS) plus whole-breast irradiation (WBI) or mastectomy are from a small number of registry-based studies. Therefore, these findings may overestimate differences in survival between the two groups, compared with randomized controlled trials conducted in the 1980s. The aim of this study is to compare long-term outcomes and clinicopathologic characteristics between patients treated with BCS + WBI or mastectomy for BC. Methods: We performed a propensity score–matched analysis in a cohort of 9710 patients aged < 70 years who underwent BCS + WBI or mastectomy without external radiotherapy for a first primary BC (pT1-2, N0-3a) at the European Institute of Oncology between 2000 and 2008. Patients were matched by propensity score. Results: Median follow-up was 8.4 years (interquartile range 6.5–10.2). The cumulative incidence of axillary lymph node recurrence at 10 years was lower in the BCS + WBI group [2.4% (95% CI, 1.7–3.3%)] than in the mastectomy group [4.4% (95% CI, 3.5–5.5%)] (P =.0005), and the cumulative incidence of contralateral BC was higher in the BCS + WBI group [3.9% (95% CI, 2.8–5.1%)] than in the mastectomy group [2.5% (95% CI, 1.7–3.4%)] (P =.01). Among the 366 patients with HER2 subtype BC, BCS + WBI was associated with a fivefold higher risk [hazard ratio 4.97 (95% CI, 2.28–10.8)] of ipsilateral breast tumor recurrence (IBTR), compared with mastectomy (P <.0001); however, among patients with other BC subtypes, the rates of IBTR were not statistically significantly different. Conclusion: Patients with HER2 subtype BC (T1-2, N0-3) who underwent BCS + WBI had a statistically significantly higher risk of IBTR than patients who underwent mastectomy. Survival was not statistically significantly different between the groups. [ABSTRACT FROM AUTHOR]

Background: To assess the clinical usefulness of serum tumor markers for early detection of distant breast cancer recurrence using FDG-PET/CT. Methods: We retrospectively analyzed 561 consecutive patients who underwent surgery for invasive primary breast cancer and had increased tumor markers (CA 15-3 and CEA) after completion of locoregional therapy. FDG-PET/CT data were reviewed for all cases. CA 15-3 and CEA were evaluated both in a continuous and in a quartile (Q) distribution. The Wilcoxon rank-sum test and logistic regression models were used to evaluate the association between increased tumor marker values and the presence (and type) of distant metastases. Results: The median value of CA 15-3 was 35.0 U/mL (IQR, 29.5–43.0) in cases where no distant metastases were detected, and it was 58.9 U/mL (IQR, 40.0–108.0) in cases where metastases were detected (p < 0.001). The median value of CEA was 6.6 U/mL (IQR, 4.4–10.0) in cases of no metastases and 12.4 U/mL (IQR, 6.9–30.0) in cases of metastases (p < 0.001). Increased levels of both tumor markers (Q3 and Q4) were strongly associated with the presence of distant metastases. The association between CA 15-3 and bone/liver metastases was stronger compared with other types of metastases (p heterogeneity between odds ratios [ORs] = 0.03 for Q3 and <0.001 for Q4), while no relevant heterogeneity between ORs emerged for CEA. Conclusion: Increased tumor marker levels detected in asymptomatic breast cancer patients during adjuvant therapies and follow-up are significantly predictive of distant metastases identified on FDG-PET/CT. [ABSTRACT FROM AUTHOR]

Abstract: Granular cell tumor is a rare condition that occasionally affects breast parenchyma: approximately, 5%‐15% of all granular cell tumors represent 1:1000 of breast tumors. In this study, we reported a consecutive series of 12 patients with primary granular cell tumor of the breast observed at our institute, focusing attention on preoperative management, surgical approach, and long‐term follow‐up. Eight cases (8/12; 66.78%) presented with left‐breast tumors; in the majority of patients (11/12; 91.7%), the lesion was identified in one of the upper quadrants. Specifically, upper intern quadrants (10 cases) were more affected. Surgical excision was performed in all patients. Mean diameter at pathologic section was 11.4 mm (range: 5‐22). Tumor relapse was reported only in one case (8.3%). Mean follow‐up was 98.1 months (range: 1‐192). We proposed a model to explain the molecular mechanism of granular cell tumorigenesis associating to the high level of S100 protein. Management of primary granular cell tumor of the breast requires a correct initial diagnosis using breast imaging associated with core biopsy. Surgical procedure with wide resection or quadrantectomy requires a careful evaluation of breast margins. [ABSTRACT FROM AUTHOR]

Objective: The aim of this retrospective study was to assess the risk factors for developing ipsilateral breast tumor reappearance (IBTR) and de novo contralateral breast cancer (BC) after primary BC treatment. Methods: Retrospectively, 15,168 consecutive patients with primary monolateral BC were enrolled in this monocentric study (from June 1994 to December 2006). Clinicopathological features, follow-up, and survival at 15 years were considered for statistical analysis. Results: Significant associations of increased risk for IBTR were verified with metastatic axillary lymph nodes (HR 1.37 [1.15–1.62], p = 0.0004), high tumor grade G2 (HR 1.35 [1.05–1.74], p = 0.02) and G3 (HR 1.35 [1.01–1.79], p = 0.04), luminal B (HR 1.51 [1.25–1.82], p < 0.0001), and HER2-positive (HR1.66 [1.14–2.41], p = 0.008) and triple-negative subtype (HR 1.54 [1.07–2.21], p = 0.02). Older age (HR 1.44 [1.08–1.91], p = 0.01) and positive family history (HR 1.85 [1.47–2.32], p < 0.0001) were risk factors for contralateral BC. Significant protective factors for IBTR were hormonotherapy (HR 0.71 [0.59–0.85], p = 0.0003), chemotherapy (HR 0.72 [0.60–0.87], p = 0.001), and radiotherapy (HR 0.73 [0.61–0.87], p = 0.0005). Hormonotherapy was also confirmed as a protective factor for contralateral second BC (HR 0.43 [0.30–0.60], p < 0.0001). Conclusions: We classified factors for IBTR and contralateral BC in high- and low-risk groups. In the high-risk group, breast surgery still remains more important than in the low-risk group, which seems to benefit more from adjuvant treatments. [ABSTRACT FROM AUTHOR]

Purpose: The aim of this study was to assess the frequency of second primary non-breast cancer after breast cancer diagnosis and treatment, and its correlation with clinicopathological features.Methods: Data from 21,527 patients with primary breast cancer were collected retrospectively in a single cancer centre; 4.1% of the women developed a second non-breast cancer. The most frequently observed second primary tumor affected the digestive tract (27.8%). The frequency of observed cancers was similar to that expected in the general population, excepting for an excess of melanoma [SIR 1.98 (1.52-2.53)], uterine cancers [SIR 1.44 (1.17-1.74)], ovarian cancers [SIR 1.67 (1.31-2.10)], thyroid tumors [SIR 1.54 (1.23-1.92)], and leukemia [SIR 1.57 (1.11-2.16)].Results: Clinicopathological breast cancer stratification showed a general increased risk of developing a second cancer in older patients, excluding ovarian cancer. An increased risk of developing ovarian cancer after breast cancer diagnosis was observed, in particular, in triple-negative [HR 3.47 (1.91-6.29)], G3 tumors [HR 2.54 (1.10-5.83)] and in positive breast cancer family history [HR 2.19 (1.22-3.94)]. Breast cancer survivors in hormonal therapy treatment are at higher risk for developing a second thyroid cancer [HR 4.00 (1.46-10.9)]. Conversely, adjuvant chemotherapy offered a protective effect on thyroid cancer risk development [HR 0.46 (0.28-0.76)].Conclusions: Older age represents the major risk of developing a second primary non-breast cancer, excluding ovarian cancer. Clinical surveillance is required to prevent ovarian and thyroid cancers, respectively, in patients with positive family history, triple negative, G3 breast cancer and during hormonal therapy treatment in postmenopausal status. [ABSTRACT FROM AUTHOR]

Breast conservation among older patients with early-stage breast cancer: locoregional recurrence following adjuvant radiation or hormonal therapy. Impact of radiation and hormonal therapy on the locoregional recurrence of elderly breast cancer: Are these necessary after breast-conserving surgery? Ipsilateral breast tumor reappearance and contralateral breast cancer after primary breast cancer treatment: a comprehensive retrospective study of 15,168 patients. [Extracted from the article]

Background. There is scant population-based information regarding predictors of stroke severity and long-term mortality for first-ever ischemic strokes. The aims of this study were to determine the characteristics of patients who initially presented with first-ever ischemic stroke and to identify predictors of severity and long-term mortality. Methods. Data were collected from the population-based Cerebrovascular Aosta Registry. Between 2004 and 2008, 1057 patients with first-ever ischemic stroke were included. Variables analysed included comorbidities, sociodemographic factors, prior-to-stroke risk factors, therapy at admission and pathophysiologic and metabolic factors. Multivariate logistic regression models, Kaplan-Meier estimates, and Cox proportional Hazards model were used to assess predictors. Results. Predictors of stroke severity at admission were very old age (odds ratio [OR] 2.98, 95% confidence interval [CI] 1.75-5.06), female gender (OR 1.73, 95% CI 1.21-2.40), atrial fibrillation (OR 2.76, 95% CI 1.72-4.44), low ejection fraction (OR 2.22, CI 95% 1.13-4.32), and cardioembolism (OR 2.0, 95% CI 1.36-2.93). Predictors of long-term mortality were very old age (hazard ratio [HR] 2.02, 95% CI 1.65-2.47), prestroke modified Rankin scale 3-5 (HR 1.82; 95% CI 1.46-2.26), Charlson Index ≥2 (HR 1.97; 95% CI 1.62-2.42), atrial fibrillation (HR 1.43, 95% CI 1.04-1.98), and stroke severity (HR 3.54, 95% CI 2.87-4.36). Conclusions. Very old age and cardiac embolism risk factors are the independent predictors of stroke severity. Moreover, these factors associated with other comorbid medical conditions influence independently long-term mortality after ischemic stroke. [ABSTRACT FROM AUTHOR]

In colorectal cancer (CRC) oncogenic mutations such as KRAS alterations, are considered standard molecular biomarkers that predict the clinical benefit for targeted intervention with epidermal growth factor receptor (EGFR) inhibitors. In addition, these mutations are associated with specific anatomical area in colon tumor development, as BRAF mutations with the microsatellite instability (MSI). In this translational study, we aimed to assess the mutation frequencies of the EGFR (hotspot area and polyadenine deletions A13_del), KRAS, BRAFV600E, and PIK3CA oncogenes in a series of 280 CRC patients. MSI phenotypes are also considered in this series. All patients' clinicopathological data were assessed for statistical analysis and its associations were validated. We verified multiple associations between oncogenic mutations and determined clinicopathological tumor features (1) EGFR A13_deletions are associated with right colon carcinoma (P<0.005), mucinous histotype (P=0.042), G3 grading (P=0.024), and MSI status (P<0.005); (2) PIK3CA mutations are related mucinous histotype (P=0.021); (3) KRASG12 and KRASG13 mutations are correlated, respectively, with the left and right colon cancer development (P<0.005), and finally (4) MSI is associated with right colon tumors (P<0.005). Mostly, we verified a higher frequency rate of the KRASG13 and EGFR A13_del oncogene mutations in right colon cancer; whereas KRASG12 codon mutation occurs more frequently in left colon cancers. In particular, we assessed that right vs left colon cancer are associated with specific molecular characteristics. These evidences, in association with clinicopathological data, can delineate novel approaches for the CRC classification and targeted intervention. [ABSTRACT FROM AUTHOR]

Our aim was to prospectively ascertain the incidence of first-ever stroke and ischaemic stroke subtypes, mortality, functional outcome and recurrence in Northern Italy. We identified all possible cases of stroke (1st January 2004 and 31st December 2008). Multiple overlapping sources were used. Standard definitions for incident cases, pathological types and infarction subtypes were used. Patient characteristics were identified and analysed, case-fatality was ascertained from administrative databases, and outcome was assessed in all surviving patients by modified Rankin Scale. We identified 1,326 incident strokes. The pathological diagnosis was confirmed in 94 % of cases. The incidence of first-ever stroke was 80.2 per 100,000 (95 % CI 73-87) when adjusted to world population. The incidence of embolic stroke was significantly greater in women than in men ( p < 0.001) whereas the incidence of atherothrombotic stroke was significantly greater in men than in women ( p < 0.001). The case-fatality of incident strokes was 9.5 % at 7 day, 16.1 % at 28 day, and 29.9 % at 1 year. Case-fatality of ischaemic stroke was lower than that of other pathological types ( p < 0.0001). Hypertension was the most important risk factor, and atrial fibrillation was the most common in embolic stroke. Increasing age, female gender and embolic stroke subtypes were associated with an adverse outcome. Data on stroke incidence and case-fatality were similar to those of other high-income countries. However, differences were found in the distribution of risk factors and prognosis across the stroke types and ischaemic stroke subtypes. Gender differences in long-term functional outcomes were significant. [ABSTRACT FROM AUTHOR]

Background. Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma. Methods. In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines. Results. Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN) was classified as cT4bN3a (IV stage). In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively. Conclusions. Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer's development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members. [ABSTRACT FROM AUTHOR]

Methods: We conducted a longitudinal, retrospective, bottom-up cost of illness study, to evaluate clinical and economic outcomes of a cohort of patients affected by a first cerebrovascular event, including subjects with ischaemic, haemorrhagic or transient episodes. The analysis intended to detect direct costs, within 1, 2 and 3 years from the index event. Clinical patient data collected in regional disease registry were integrated and linked to regional administrative databases to perform the analysis. Results: The analysis of costs within the first year from the index event included 800 patients. The majority of patients (71.5%) were affected by ischaemic stroke. Overall, per patient costs were €7,079. Overall costs significantly differ according to the type of stroke, with costs for haemorrhagic stroke and ischaemic stroke amounting to €9,044 and €7,289. Hospital costs, including inpatient rehabilitation, were driver of expenditure, accounting for 89.5% of total costs. The multiple regression model showed that sex, level of physical disability and level of neurological deficit predict direct healthcare costs within 1 year. The analysis at 2 and 3 years (per patient costs: €7,901 and €8,874, respectively) showed that majority of costs are concentrated in the first months after the acute event. Conclusions: This cost analysis highlights the importance to set up significant prevention programs to reduce the economic burden of stroke, which is mostly attributable to hospital and inpatient rehabilitation costs immediately after the acute episode. Although some limitation typical of retrospective analyses the approach of linking clinical and administrative database is a power tool to obtain useful information for healthcare planning. [ABSTRACT FROM AUTHOR]

Background: Increased C-reactive protein (CRP) is a known predictor of vascular events in asymptomatic individuals and stroke patients. Only a few studies included transient ischaemic attack (TIA) patients. We assessed CRP levels in addition to traditional risk factors in a cohort of patients with TIA to examine the relationship of these parameters to the occurrence of ischaemic stroke. Methods: This is a prospective, longitudinal clinical evaluation of the efficacy of CRP as a prognostic indicator. CRP levels were measured in 194 TIA patients and in 1,024 asymptomatic individuals (recruited from a project on stroke prevention, the PrATO, which was ongoing at the same time in the Aosta Valley). A clinical risk score was determined using the ABCD2 score in TIA patients. The area under the receiver operating characteristic curve (AUC) was used to evaluate the significance of the markers as predictors. Two models were evaluated: model 1 used the ABCD2 score and model 2 used serum CRP levels in addition to the ABCD2 score. The primary outcome was an ischaemic stroke. Results: Within 2 years ischaemic strokes occurred in 33/194 patients. The Cox proportional hazards models, after adjustments for conventional risk factors, identified CRP levels ≥3 mg/l and ABCD2 scores ≥4 as independent predictors of stroke. The corresponding AUCs were 0.565 and 0.636, based on model 1 and model 2, respectively; this represented a statistically significant difference (p = 0.043). The absolute integrated discrimination improvement was 0.0249 (p = 0.007) and the relative integrated discrimination improvement was 2.3710. The net benefit became significant from a predicted probability ≥10% and was 0.077 when based on model 1 and 0.087 when based on model 2. Conclusions: Routine CRP measurements in the acute phase might be a useful tool for identifying TIA patients who are at a higher risk of ischaemic stroke. The additional use of CRP levels for the risk assessment in TIA patients improves risk definition in terms of the ABCD2 score alone. Copyright © 2011 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Aim: CDH1 germline alterations occur in about 40% of hereditary diffuse gastric cancer (HDGC) families. CDH1 germline mutations are also documented in few early onset diffuse gastric cancer patients (EODGC) without family history, but the real frequency in this setting in unknown. In these patients, the advanced stage at the time of diagnosis remains a clinical burden due to the poor long term survival. Methods: The entire coding region and exon flanking sequences of the CDH1 gene was analysed by direct sequencing in 21 EODGC patients aged ⩽50years. The potential deleterious nature for a new CDH1 missense variant was assessed by cell–cell aggregation and invasion assays. Somatic CDH1 mutation, loss of heterozigosity (LOH) and promoter hypermethylation was explored in the tumour from one CDH1 germline mutation carrier. Results: Two novel CDH1 germline variants were identified in 21 EODGC cases, c.670C>T and –63C>A. Functional analysis of the c.670C>T missense variant classified this mutation as non-pathogenic. The analysis of CDH1 somatic second hits failed to demonstrate E-cadherin structural and epigenetic alterations in the tumour sample. Conclusion: Data from the present work and a systematic review of the literature revealed that CDH1 germline mutations occurred in 7.2% of EOGC patients invariably with diffuse of mixed histology. From these, proved CDH1 mutation pathogenicity has been assigned only to 2.3% of the cases who were recurrently diagnosed before 35years old. Germline CDH1 mutation remain the only germline genetic defect described in this type of patients and CDH1 mutation screening should be recommended for patients with these characteristics. [Copyright &y& Elsevier]

Abstract: Aim: Mitogen-activated protein kinase (MAPK) cascade and phosphatidylinositol 3-kinase (PI3K) survival pathways are frequently activated in the progression of gastrointestinal malignancies. In this study, we aimed to determine the frequency of gene mutations in members of these pathways – Epithelial Growth Factor Receptor (EGFR), KRAS, BRAF, PIK3CA and MLK3 in a series of 63 gastric carcinomas with high levels of microsatellite instability (MSI). Methods: Gene mutation analysis was performed by PCR amplification followed by direct sequencing. In selected tumour cases, EGFR expression was evaluated by immunohistochemistry. Association studies between molecular data and clinicopathologic characteristics were performed. Results: Mutations in EGFR (3′-untranslated region [UTR] polyA repeat), KRAS, PIK3CA and MLK3 genes occurred in 30 (47.6%), 11 (17.5%), 9 (14.3%) and 2 (3.2%) of the MSI gastric cancer (GC) cases, respectively. No BRAF or EGFR hotspot mutations were identified. Overall, mutations in at least one of these genes were found in 55.6% (35/63) of gastric carcinomas. From those mutant cases 40.0% (14/35) of them had concomitant gene mutations, always involving EGFR polyA deletions. Interestingly, we observed significant associations between oncogenic mutations and female gender (p =0.046) old age of diagnosis (p =0.001) and intestinal subtype (p =0.043). Conclusion: Our results show that MSI gastric carcinoma frequently shows activation of EGFR-MAPK and PI3K pathways. Within all alterations found, deletions of the A13 repeats of EGFR were common, suggesting this molecular event as an important biomarker for stratification of GC patients for treatment with EGFR inhibitors. [Copyright &y& Elsevier]

Purpose: X-ray repair cross complementing group 1 (XRCC1) is one of the major DNA repair proteins involved in the bas-excision repair pathway. Several single-nucleotide polymorphisms in the XRCC1 gene are identified and related with increased cancer risk development. In particular, the -77T>C polymorphism located on the promoter region relates with lung cancer risk development. The aim of this study is to analyze the -77T>C allelic frequencies in a population composed of 456 primary gastric cancer patients (GC) and 507 blood donor controls.Methods: GC patients were observed at the University of Siena, Italy; clinicopathological data and family history were available for the cancer group. The control group is composed of blood donors. Constitutional genomic DNA was PCR amplified, and XRCC1 -77T>C was detected using restriction enzyme BsrB I and analyzed in a 3% agarose gel.Results: The -77C>C homozygous genotype was significantly associated with increased risk of gastric cardia carcinoma (p = 0.023) with an odds ratio of 1.65 (95% confidence interval 1.14 to 2.4). In the family history stratification, we report a significant association (p = 0.043) between the -77T>C polymorphism and GC cases with familial lung cancer aggregation.Conclusions: Our results suggest that the XRCC1 -77T>C polymorphism is a relevant host susceptibility factor for gastric cardia cancer development and specific subsets of familial clustering of GC. [ABSTRACT FROM AUTHOR]

Objectives: Only 1% of diffuse gastric cancers occur in families with autosomal dominant gastric cancer susceptibility. Germline mutations in the E-cadherin gene account for the hereditary diffuse gastric cancer (HDGC) syndrome. We studied a large cohort of gastric cancer patients from Tuscany, a region in Italy, to evaluate the presence of familial clustering of gastric cancer. Methods: 238 pedigrees were retrospectively studied by structured interviews. All probands with diagnosed gastric cancer were contacted in-person or by phone and tumor types were assessed in first- and second-degree relatives. Familial aggregation was investigated in order to search for families with suspected HDGC. Results: Familial aggregation for gastric cancer was observed in 79 of 238 cases (33.2%). Among these, there were 64 families (81%) with one gastric cancer other than the proband, 10 families with two gastric cancers (12.7%) and 5 families with three gastric cancers (6.3%). Fourteen families fulfilled the HDGC clinical criteria, one of them presenting with a pathogenic germline mutation in the E-cadherin gene (7.1%). Conclusions: The prevalence of familial HDGC appears extremely high. Since only one pathogenic germline mutation was noted in a family fulfilling the HDGC clinical criteria, factors other than E-cadherin gene mutations may contribute to the familial clustering of HDGC. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Simple Summary: E-cadherin (CDH1 gene) germline mutations are associated with the development of the autosomal cancer syndrome known as hereditary diffuse gastric cancer. About 30% of families fulfilling the clinical criteria established by the International Gastric Cancer Linkage Consortium have constitutional alterations of the CDH1 gene. Different patterns of CDH1 germline mutations have described as truncating, deletion, insertion, splice site, non sense, silence, and at last, missense alterations. The frequency of the different E-cadherin germline mutations in countries with different incidence rates for gastric carcinoma has reported extremely variable. In this study we aimed to assess the worldwide frequency of CDH1 germline mutations in gastric cancers coming from different geographical areas, using a systematic approach. Hereditary diffuse gastric cancer (HDGC) is a complex and multifactorial inherited cancer predisposition syndrome caused by CDH1 germline mutations. Nevertheless, current CDH1 genetic screening recommendations disregard an unbalanced worldwide distribution of CDH1 variants, impacting testing efficacy and patient management. In this systematic review, we collected and analyzed all studies describing CDH1 variants in gastric cancer patients originating from both high- and low-prevalence countries. Selected studies were categorized as family study, series study, and unknown study, according to the implementation of HDGC clinical criteria for genetic testing. Our results indicate that CDH1 mutations are more frequently identified in gastric cancer low-incidence countries, and in the family study group that encompasses cases fulfilling criteria. Considering the type of CDH1 alterations, we verified that the relative frequency of mutation types varies within study groups and geographical areas. In the series study, the missense variant frequency is higher in high-incidence areas of gastric cancer, when compared with non-missense mutations. However, application of variant scoring for putative relevance led to a strong reduction of CDH1 variants conferring increased risk of gastric cancer. Herein, we demonstrate that criteria for CDH1 genetic screening are critical for identification of individuals carrying mutations with clinical significance. Further, we propose that future guidelines for testing should consider GC incidence across geographical regions for improved surveillance programs and early diagnosis of disease. [ABSTRACT FROM AUTHOR]

E-cadherin (CDH1 gene) germline mutations are associated with the development of diffuse gastric cancer in the context of the so-called hereditary diffuse gastric syndrome, and with an inherited predisposition of lobular breast carcinoma. In 2019, the international gastric cancer linkage consortium revised the clinical criteria and established guidelines for the genetic screening of CDH1 germline syndromes. Nevertheless, the introduction of multigene panel testing in clinical practice has led to an increased identification of E-cadherin mutations in individuals without a positive family history of gastric or breast cancers. This observation motivated us to review and present a novel multidisciplinary clinical approach (nutritional, surgical, and image screening) for single subjects who present germline CDH1 mutations but do not fulfil the classic clinical criteria, namely those identified as—(1) incidental finding and (2) individuals with lobular breast cancer without family history of gastric cancer (GC). [ABSTRACT FROM AUTHOR]

The article focuses on sentinel lymph-node (SN) biopsy represents the gold standard treatment for axillary node staging in operable breast cancer (BC) with clinically uninvolved axillary lymph nodes and the breast-conserving surgery with lymphoscintigraphy.

Simple Summary: This paper delves into the persistent issue of unequal access to medical imaging, with a particular focus on breast cancer screening and its impact on marginalized communities and racial/ethnic minorities. Central to our discussion is the role of scientific mobility among radiologists in fostering healthcare policy changes that promote diversity and cultural competence. We propose various strategies to bridge this gap, including cultural education, sensitivity training, and diversifying the radiology workforce. These measures aim to improve communication with diverse patient groups and reduce healthcare disparities. Additionally, we explore the challenges and advantages of teleradiology as a means to extend medical imaging services to underserved areas. In the context of artificial intelligence, we emphasize the critical need to validate algorithms across diverse populations to ensure unbiased and equitable healthcare outcomes. Overall, this paper underscores the importance of international collaboration in addressing global access barriers, presenting it as a key to mitigating disparities in medical imaging access and contributing to the pursuit of equitable healthcare. Access to medical imaging is pivotal in healthcare, playing a crucial role in the prevention, diagnosis, and management of diseases. However, disparities persist in this scenario, disproportionately affecting marginalized communities, racial and ethnic minorities, and individuals facing linguistic or cultural barriers. This paper critically assesses methods to mitigate these disparities, with a focus on breast cancer screening. We underscore scientific mobility as a vital tool for radiologists to advocate for healthcare policy changes: it not only enhances diversity and cultural competence within the radiology community but also fosters international cooperation and knowledge exchange among healthcare institutions. Efforts to ensure cultural competency among radiologists are discussed, including ongoing cultural education, sensitivity training, and workforce diversification. These initiatives are key to improving patient communication and reducing healthcare disparities. This paper also highlights the crucial role of policy changes and legislation in promoting equal access to essential screening services like mammography. We explore the challenges and potential of teleradiology in improving access to medical imaging in remote and underserved areas. In the era of artificial intelligence, this paper emphasizes the necessity of validating its models across a spectrum of populations to prevent bias and achieve equitable healthcare outcomes. Finally, the importance of international collaboration is illustrated, showcasing its role in sharing insights and strategies to overcome global access barriers in medical imaging. Overall, this paper offers a comprehensive overview of the challenges related to disparities in medical imaging access and proposes actionable strategies to address these challenges, aiming for equitable healthcare delivery. [ABSTRACT FROM AUTHOR]

Simple Summary: This review provides a comprehensive overview of mammary Paget disease (MPD) from its historical origins to the current diagnostic and treatment strategies while also exploring promising avenues for future advancements in the field. With improved understanding and ongoing research efforts, we aim to enhance the prognosis and quality of life for individuals affected by this relatively uncommon condition. Mammary Paget disease (MPD) is a rare condition primarily affecting adult women, characterized by unilateral skin changes in the nipple–areolar complex (NAC) and frequently associated with underlying breast carcinoma. Histologically, MPD is identified by large intraepidermal epithelial cells (Paget cells) with distinct characteristics. Immunohistochemical profiles aid in distinguishing MPD from other skin conditions. Clinical evaluation and imaging techniques, including magnetic resonance imaging (MRI), are recommended if MPD is suspected, although definitive diagnosis always requires histological examination. This review delves into the historical context, epidemiology, pathogenesis, clinical manifestations, and diagnosis of MPD, emphasizing the need for early detection. The classification of MPD based on pathogenesis is explored, shedding light on its varied presentations. Treatment options, including mastectomy and breast-conserving surgery, are discussed with clear guidelines for different scenarios. Adjuvant therapies are considered, particularly in cases with underlying breast cancer. Prognostic factors are outlined, underlining the importance of early intervention. Looking to the future, emerging techniques, like liquid biopsy, new immunohistochemical and molecular markers, and artificial intelligence-based image analysis, hold the potential to transform MPD diagnosis and treatment. These innovations offer hope for early detection and improved patient care, though validation through large-scale clinical trials is needed. [ABSTRACT FROM AUTHOR]

Simple Summary: Screening mammography reduces mortality from breast malignancy. However, breast cancer screening is, unfortunately, hindered due to the poor sensitivity of mammography in dense breasts: up to 15–30% of all cancers may be missed. Given the rapid development of Contrast-Enhanced Mammography (CEM) and its potential for diagnostic use, even in an asymptomatic population, it seems very important to correctly assess the Average Glandular Dose (AGD) for a single CEM examination. Few studies have compared the AGD of CEM versus Digital Mammography (DM) and protocols, including Digital Breast Tomosynthesis (DBT) plus DM, in the same group of patients. The additional role of tomosynthesis versus digital mammography in asymptomatic patients with dense breasts in screening examinations has been well investigated with encouraging results. In this study, we intend to compare the AGD and the diagnostic performance of CEM versus DM, and of CEM versus DM + DBT, performed in the same group of patients over the same period of time in a screening setting. This study aims to evaluate the Average Glandular Dose (AGD) and diagnostic performance of CEM versus Digital Mammography (DM) as well as versus DM plus one-view Digital Breast Tomosynthesis (DBT), which were performed in the same patients at short intervals of time. A preventive screening examination in high-risk asymptomatic patients between 2020 and 2022 was performed with two-view Digital Mammography (DM) projections (Cranio Caudal and Medio Lateral) plus one Digital Breast Tomosynthesis (DBT) projection (mediolateral oblique, MLO) in a single session examination. For all patients in whom we found a suspicious lesion by using DM + DBT, we performed (within two weeks) a CEM examination. AGD and compression force were compared between the diagnostic methods. All lesions identified by DM + DBT were biopsied; then, we assessed whether lesions found by DBT were also highlighted by DM alone and/or by CEM. We enrolled 49 patients with 49 lesions in the study. The median AGD was lower for DM alone than for CEM (3.41 mGy vs. 4.24 mGy, p = 0.015). The AGD for CEM was significantly lower than for the DM plus one single projection DBT protocol (4.24 mGy vs. 5.55 mGy, p < 0.001). We did not find a statistically significant difference in the median compression force between the CEM and DM + DBT. DM + DBT allows the identification of one more invasive neoplasm one in situ lesion and two high-risk lesions, compared to DM alone. The CEM, compared to DM + DBT, failed to identify only one of the high-risk lesions. According to these results, CEM could be used in the screening of asymptomatic high-risk patients. [ABSTRACT FROM AUTHOR]

Gastric cancer (GC) has long been a 'Cinderella' among hereditary cancers. Until recently, single-gene testing (SGT) was the only approach to identify high-risk individuals. With the spread of multigene panel testing (MGPT), a debate arose on the involvement of other genes, particularly those pertaining to homologous recombination (HR) repair. We report our mono-institutional experience in genetic counseling and SGT for 54 GC patients, with the detection of nine pathogenic variants (PVs) (9/54:16.7%). Seven out of fifty (14%) patients who underwent SGT for unknown mutations were carriers of a PV in CDH1 (n = 3), BRCA2 (n = 2), BRCA1 (n = 1), and MSH2 (n = 1), while one patient (2%) carried two variants of unknown significance (VUSs). CDH1 and MSH2 emerged as genes involved in early-onset diffuse and later-onset intestinal GCs, respectively. We additionally conducted MGPT on 37 patients, identifying five PVs (13.5%), including three (3/5:60%) in an HR gene (BRCA2, ATM, RAD51D) and at least one VUS in 13 patients (35.1%). Comparing PV carriers and non-carriers, we observed a statistically significant difference in PVs between patients with and without family history of GC (p-value: 0.045) or Lynch-related tumors (p-value: 0.036). Genetic counseling remains central to GC risk assessment. MGPT appeared advantageous in patients with unspecific phenotypes, although it led to challenging results. [ABSTRACT FROM AUTHOR]

Simple Summary: Germline BRCA2 pathogenic variant carriers are associated with prostate cancer risk. Ashkenazi Jewish people are at higher risk of breast cancer due to the high prevalence of specific founder germline BRCA1/2 variants. The distribution of these variants (BRCA1 vs. BRCA2) in Ashkenazi men with prostate cancer is not clear. This systematic review and meta-analysis indicates that germline BRCA1 variants are higher in the Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi men. Instead, BRCA2 variants present a similar distribution between the two considered groups. Background and aims: International guidelines recommend testing BRCA2 in men with prostate cancer, due to the presence of a strong association with this gene. Some ethnicities present disparities in genetic distribution for the relation with specific founder variants. Ashkenazi Jewish people are, importantly, at high risk of breast cancer for their inherited cluster with germline BRCA1/2 variants. However, in Ashkenazi men with prostate cancer, the prevalence of BRCA1 and/or BRCA2 is not well defined. We assessed the frequency of these variants in Ashkenazi vs. non-Ashkenazi men with prostate cancer. Materials and Methods: In accord with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) statement, we revised all germline BRCA variants reported in MEDLINE from 1996 to 2021 in Ashkenazi and non-Ashkenazi men with prostate cancer. Results: Thirty-five original studies were selected for the analysis. Among populations from Israel and North America, Ashkenazi Jewish men presented higher prevalence of BRCA1 variants [0.9% (0.4–1.5) vs. 0.5% (0.2–1.1), p = 0.09] and a lower prevalence of BRCA2 variants [1.5% (1.1–2.0) vs. 3.5% (1.7–5.9), p = 0.08] in comparison to the non-Ashkenazi population. Conclusions: Since germline BRCA1 variants are more prevalent and BRCA2 variants are less prevalent in PCa patients of Ashkenazi Jewish ethnicity in comparison to non-Ashkenazi patients, prostate cancer genetic screening in Ashkenazi men should not be restricted to the BRCA2 gene. [ABSTRACT FROM AUTHOR]

Hereditary diffuse gastric cancer is associated with the E-cadherin germline mutations, but genetic determinants have not been identified for familial intestinal gastric carcinoma. The guidelines for hereditary diffuse gastric cancer are clearly established; however, there are no defined recommendations for the management of familial intestinal gastric carcinoma.~Background~Background~In this study we describe Pope John XXIII's pedigree that harboured gastric cancer as well as six other family members. Family history was analysed according to the International Gastric Cancer Linkage Consortium criteria, and gastric tumours were classified in accord with the last Japanese guidelines.~Methods~Methods~Seven out of 109 members in this pedigree harboured gastric cancer, affecting two consecutive generations. John XXIII's clinical tumour (cTN) was classified as cT4bN3a (IV stage). In two other cases, gastric carcinomas were classified as intestinal histotype and staged as pT1bN0 and pT2N2, respectively.~Results~Results~Pope John XXIII's family presents a strong aggregation for gastric cancer affecting almost seven members; it spreads through two consecutive generations. In absence of defined genetic causes and considering the increased risk of gastric cancer's development in these families, as well as the high mortality rates and advanced stages, we propose an intensive surveillance protocol for asymptomatic members.~Conclusions~Conclusions [ABSTRACT FROM AUTHOR]

Gastric cancer, a leading worldwide cause of cancer mortality, shows high geographic and ethnic variation in incidence rates, which are highest in East Asia. The anatomic locations and clinical behavior also differ by geography, leading to the controversial idea that Eastern and Western forms of the disease are distinct. In view of these differences, we investigated whether gastric cancers from Eastern and Western patients show distinct genomic profiles. We used high-density profiling of somatic copy-number aberrations to analyze the largest collection to date of gastric adenocarcinomas and utilized genotyping data to rigorously annotate ethnic status. The size of this collection allowed us to accurately identify regions of significant copy-number alteration and separately to evaluate tumors arising in Eastern and Western patients. Among molecular subtypes classified by The Cancer Genome Atlas, the frequency of gastric cancers showing chromosomal instability was modestly higher in Western patients. After accounting for this difference, however, gastric cancers arising in Easterners and Westerners have highly similar somatic copy-number patterns. Only one genomic event, focal deletion of the phosphatase gene PTPRD, was significantly enriched in Western cases, though also detected in Eastern cases. Thus, despite the different risk factors and clinical features, gastric cancer appears to be a fundamentally similar disease in both populations and the divergent clinical outcomes cannot be ascribed to different underlying structural somatic genetic aberrations. [ABSTRACT FROM AUTHOR]

Simple Summary: Which should be the optimal surgical approach to breast cancer in the presence of high penetrance gene mutation represents a current clinical and scientific issue, lively debated and studied. Does inherited breast cancer always mean bilateral mastectomy? Scientific research is questioning the oncological safety of a conservative surgical approach in hereditary breast cancer. The present narrative review aims to explore the scientific panorama on this faceted and significant theme. Recent studies have demonstrated that hereditary breast cancer (BC) has a prevalence of 5–10% among all BC diagnoses. Nowadays, significant technological advances in the identification of an increasingly broad spectrum of genetic mutations allow for the discovery of an ever-growing number of inherited pathogenic (P) or likely pathogenic (LP) variants of breast cancer susceptibility genes. As the management of BC patients carrying mutations in the BRCA1/2 genes or other high-penetrance genes is currently a challenge, extensive research is being carried out and a lively scientific debate has been taking place on what the most appropriate local therapy, especially surgical treatment, of patients with inherited BC should be. In many studies, BC outcomes in BRCA carriers and non-carriers have been compared. A number of them showed that, when compared with mastectomy, breast-conserving surgery in BRCA patients is oncologically safe in terms of overall survival, although an increased risk of ipsilateral recurrence was reported. In these patients, devising a specific therapeutic strategy is an inevitably complex process, as it must take into consideration a series of factors, require a multimodal approach, guarantee personalization, strictly adhere to scientific international guidelines, and consider all available evidence. The present narrative review purposes to identify and illustrate evidence from significant selected studies that discussed those issues, as well as to suggest useful tools to clinicians managing this specific clinical condition in daily clinical practice. [ABSTRACT FROM AUTHOR]

Since ancient times, breast cancer treatment has crucially relied on surgeons and clinicians making great efforts to find increasingly conservative approaches to cure the tumor. In the Halstedian era (mid-late 19th century), the predominant practice consisted of the radical and disfiguring removal of the breast, much to the detriment of women’s psycho-physical well-being. Thanks to enlightened scientists such as Professor Umberto Veronesi, breast cancer surgery has since impressively progressed and adopted a much more conservative approach. Over the last three decades, a better understanding of tumor biology and of its significant biomarkers has made the assessment of genetic and molecular profiles increasingly important. At the same time, neo-adjuvant treatments have been introduced, and great improvements in genetics, imaging technologies and in both oncological and reconstructive surgical techniques have been made. The future of breast cancer management must now rest on an ever more precise and targeted type of surgery that, through an increasingly multidisciplinary and personalized approach, can ensure oncological radicality while offering the best possible quality of life. [ABSTRACT FROM AUTHOR]

In this study, cDNA-amplified fragment length polymorphism (cDNA-AFLP) analysis was employed to identify genes that exhibited a modulated expression following cadmium (Cd) treatment in Brassica juncea grown in hydroponic culture. Plants were treated for 6 h, 24 h, and 6 weeks with 10 μM Cd(NO3)2 and untreated 6-week-old plants were used as controls. Cd content was measured at these four time points. Long exposure to Cd affected root morphology: roots appeared thinner and sent out side roots. Seventy-three transcript-derived fragments were identified as Cd responsive. Fifty-two of them showed significant homology to genes with known or putative function, 10 transcript-derived fragments were homologous to uncharacterized genes, while 11 transcript-derived fragments did not show significant matches. The expression pattern of several of these genes was confirmed by northern blot analysis. Fifty-two genes of known or putative function were transcriptional factors, expression regulators, and stress responding and transport facilitation genes, as well as genes involved in cellular metabolism and organization and the photosynthetic process, suggesting that a multitude of processes are implicated in Cd stress response. The transcription of drought- and abscisic acid-responsive genes observed in this study also suggested that Cd imposes water stress and that abscisic acid may be involved in the Cd plant response. [ABSTRACT FROM PUBLISHER]

A letter to the editor is presented in response to the article about the influence of age on soluble E-cadherin serum levels prevents its utility as a disease marker in gastric cancer patients that was published in the previous issue.

Abstract: Pseudoxanthoma elasticum is a systemic metabolic disease presenting calcifications and progressive fragmentation of elastic fibers. Actually, no targeted therapies are available for the treatment; only prevention of complications is possible. Classically, pseudoxanthoma elasticum is a “benign” disease, without cancer association. Herein, we reported a singular association of pseudoxanthoma elasticum with breast carcinoma, describing the clinical management, in particular intra‐operative treatment, focusing on intra‐operative radiotherapy since no specific guidelines are available in literature. [ABSTRACT FROM AUTHOR]

The article discusses a case report of a supernumerary axillary breast cancer who needed a reconstruction with latissimus dorsi flap. Topics discussed include how presence of an accessory breast with concurrent breast cancer is extremely rare, imaging with mammography and high definition ultrasound revealing a suspicious hypoechoic mass in the right supernumerary breast, and reconstruction with local advancement flaps using the latissumus dorsi muscle.

Gastropleural and gastropericardial fistulas are abnormal communications between the stomach and the pleural cavity or pericardium. They are rare and life-threatening complications, which require prompt surgical intervention. We report the case of a gastro-pleuro-pericardial fistula that developed in a patient treated with radiotherapy and then Sunitinib (Sutent ®), a novel tyrosine-kinase inhibitor, for lung metastases from renal cell carcinoma. To our knowledge, this is the first case of a gastro-pleuro-pericardial fistula developing as a consequence of combined radiation and chemotherapy. [ABSTRACT FROM AUTHOR]

A more detailed understanding of the somatic genetic events that drive gastrointestinal adenocarcinomas is necessary to improve diagnosis and therapy. Using data from high-density genomic profiling arrays, we conducted an analysis of somatic copy-number aberrations in 486 gastrointestinal adenocarcinomas including 296 esophageal and gastric cancers. Focal amplifications were substantially more prevalent in gastric/esophageal adenocarcinomas than colorectal tumors. We identified 64 regions of significant recurrent amplification and deletion, some shared and others unique to the adenocarcinoma types examined. Amplified genes were noted in 37% of gastric/esophageal tumors, including in therapeutically targetable kinases such as ERBB2, FGFR1, FGFR2, EGFR, and MET, suggesting the potential use of genomic amplifications as biomarkers to guide therapy of gastric and esophageal cancers where targeted therapeutics have been less developed compared with colorectal cancers. Amplified loci implicated genes with known involvement in carcinogenesis but also pointed to regions harboring potentially novel cancer genes, including a recurrent deletion found in 15% of esophageal tumors where the Runt transcription factor subunit RUNX1 was implicated, including by functional experiments in tissue culture. Together, our results defined genomic features that were common and distinct to various gut-derived adenocarcinomas, potentially informing novel opportunities for targeted therapeutic interventions. [ABSTRACT FROM AUTHOR]

Background Gastric cancer (GC) is a highly prevalent disease, being the fourth most common cancer and the second leading cause of cancer-associated deaths worldwide. Although many genes have been implicated in its development, many cases remain genetically unexplained. Hence, there is an urgent need to find new disease-related genes. Methods A transgenic Drosophila model was used to screen for novel genes putatively involved in GC. The authors evaluated the expression of the most interesting candidates in GC cell lines and primary tumours by semi-quantitative reverse transcription PCR, dissected the molecular mechanisms responsible for the deregulation of the most relevant one, and analysed its functional role in vitro and in a chicken embryo model. Results Six candidate genes were identified, of which cytoplasmic polyadenylation element binding protein 1 (CPEB1) was downregulated in all GC cell lines and in 11 of 12 primary GC tumours. The pivotal CPEB1 promoter CpG site was determined, and it was found that methylation at this 79th CpG site was associated with CPEB1 silencing in GC cell lines and primary tumours. It was also discovered that methylation of this site was significantly more prevalent in diffuse type GC (p¼0.007) and in cases with lymph node metastases (p¼0.042). In vitro, CPEB1 impaired invasion. Its antiangiogenic role was also discovered, which was associated with downregulation of MMP14 and VEGFA. Conclusions The first evidence of CPEB1 involvement in GC is presented, along with the molecular mechanism underlying the regulation of its expression and its potential role in invasion and angiogenesis. [ABSTRACT FROM AUTHOR]

The aim of this study was to evaluate the prognostic value of the ratio of metastatic to examined lymph nodes (N ratio) in gastric cancer patients who underwent limited lymphadenectomy and had a small number (≤15) of analyzed nodes. The prognostic value of the actual AJCC/UICC pN staging system and the N ratio (0%, 1–25%, > 25%) were analyzed by means of univariate and multivariate analyses for 526 patients who underwent R0 resection for gastric adenocarcinoma at the Latvia Oncology Center. The mean (SD) number of analyzed nodes was 5.6 (2.8). The number of positive nodes significantly increased with the number of analyzed nodes ( p < 0.001). No significant differences in survival ( p = 0.508) and risk of death ( p = 0.224) were observed between pN1 and pN2 subsets. When the N ratio (1–25% vs. > 25%) was taken into account, a significant difference was demonstrated between pNR1 and pNR2 with respect to survival ( p = 0.017) and risk of death ( p = 0.012). Nonetheless, the joint allocation of the two classifications demonstrated that only a minority of patients (28 cases) belonged to the pNR1 subset and none of these belonged to the AJCC/UICC pN2 subset. When a small number of lymph nodes are analyzed, the N ratio can discriminate patients better than TNM classification. However, because a small number of retrieved nodes produced only a small number of pNR1 patients, the N ratio classification cannot be justified for clinical use. [ABSTRACT FROM AUTHOR]

Cervical artery dissection is an important cause of stroke in young patients and accounts of 10%–20% of stroke or TIA in patients aged less than 50 years. Basilar artery occlusion (BAO) is an infrequent cause of acute stroke, which invariably leads to death or long-term disability if not recanalized. We describe three patients with BAO caused by vertebral dissection, successfully treated with intra-arterial thrombolysis. The lysis of the occluding embolus was obtained by injection of the thrombolytic drug directly or near the thrombus without haemor-rhagic complications. Our cases confirm the safety and efficacy of intra-arterial thrombolysis in patients with BAO due to a vertebral artery dissection. [ABSTRACT FROM AUTHOR]

The Fas death receptor is expressed by activated lymphocytes and is involved in switching-off the immune response. Its inherited defects cause auto-immune lymphoproliferative syndrome. Impaired Fas function may also play a role in other auto-immune diseases, such as multiple sclerosis and type 1 diabetes mellitus. The aim of this work was to evaluate Fas function in T cells from patients with chronic inflammatory demyelinating polyneuropathy (CIDP). We evaluated Fas-induced apoptosis in T-cell lines from 27 patients with CIDP, 12 patients with acute inflammatory demyelinating polyneuropathy (AIDP), and 110 controls. CIDP patients displayed lower Fas function than both AIDP patients and controls, whereas no statistically significant difference was found between AIDP patients and controls. Moreover, Fas function was lower in CIDP patients with progressive course than in those with relapsing–remitting course and lower in CIDP patients with axonal damage than in those with pure demyelination. These data suggest that defective Fas function favours CIDP development and aggressive evolution. [ABSTRACT FROM AUTHOR]

Simple Summary: Diffuse gastric cancer is the hallmark of the hereditary diffuse gastric cancer syndrome related with the E-cadherin germline mutations. Other cancers (non-gastric) are described in association with the CDH1 gene germline alterations. In this study, we aimed to assess the overall frequency of CDH1 mutations in non-gastric tumors reported in literature so far. Hereditary Diffuse Gastric Cancer (HDGC) is a complex inherited syndrome caused by CDH1 germline mutations. DGC is the hallmark cancer of this genetic predisposition, but several other cancers are associated with these CDH1 mutations. In this review, we revised all studies reporting CDH1 mutations in non-GC patients. The selected studies included: (a) families aggregating with GC and other cancers, both, and (b) families presenting only non-gastric tumors association. Among non-gastric tumors, our results show that CDH1 mutations are most frequently identified in breast cancer. The frequency of missense mutations is higher in the non-GC group, as the age at diagnosis in this group. Moreover, the predominant CDH1 mutation affects the extracellular domain. Our data suggest that CDH1 genetic testing should be considered also in other cancers, especially breast tumors. [ABSTRACT FROM AUTHOR]

Abstract Misidentification of sentinel lymph node via lymphoscintigraphy for breast cancer is an infrequent event. We analysed 35.022 consecutive procedures from a single institution and tried to find a correlation between failures of sentinel node identification and previous oncologic treatments received by the patients. [ABSTRACT FROM AUTHOR]