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Background: Small bowel adenocarcinoma is a relatively rare cancer, often diagnosed in an advanced stage. In localized and resectable disease, surgery alone or in combination with adjuvant chemotherapy is the mainstay of treatment. In the recently published National Comprehensive Cancer Network Clinical Practice guidelines, criteria for selecting patients with stage II small bowel adenocarcinoma to receive adjuvant chemotherapy are provided, and they are mainly extrapolated from studies on colorectal cancer., Patients and Methods: In the present study, we aimed to verify whether mismatch repair deficiency phenotype, high-risk pathologic features (including T4, positive resection margins and a low number of lymph nodes harvested), as well as tumor histologic subtype, were associated with cancer-specific survival in 66 stage II non-ampullary small bowel adenocarcinoma patients, collected through the Small Bowel Cancer Italian Consortium. A central histopathology review was performed. Mismatch repair deficiency was tested by immunohistochemistry for MLH1, MSH2, MSH6 and PMS2, and confirmed by polymerase chain reaction for microsatellite instability., Results: We identified mismatch repair deficiency, glandular/medullary histologic subtype, and celiac disease as significant predictors of favorable cancer-specific survival using univariable analysis with retained significance in bivariable models adjusted for pT stage. Among the high-risk features, only T4 showed a significant association with an increased risk of death; however, its prognostic value was not independent of mismatch repair status., Conclusions: Mismatch repair protein expression, histologic subtype, association with celiac disease, and, in the mismatch repair proficient subset only, T stage, may help identify patients who may benefit from adjuvant chemotherapy.

Small bowel adenocarcinomas (SBAs) are often associated with poor prognosis and have limited therapeutic options. Programmed cell death protein-1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway blockade is an effective treatment in many microsatellite instability-high (MSI-H) solid tumors. We aimed at investigating PD-L1 and PD-1 expression in non-hereditary, non-ampullary SBAs, associated with celiac disease (CeD), Crohn's disease (CrD), or sporadic, recruited through the Small Bowel Cancer Italian Consortium. We assessed PD-L1 and PD-1 by immunohistochemistry in a series of 121 surgically resected SBAs, including 34 CeD-SBAs, 49 CrD-SBAs, and 38 sporadic SBAs. PD-L1 and PD-1 expression was correlated with several clinico-pathological features, such as the etiology, microsatellite instability status, and tumor-infiltrating lymphocyte (TIL) density. The prevalence of PD-L1 positivity according to combined positive score (CPS) was 26% in the whole cohort of SBAs, with significantly (p = 0.001) higher percentage (35%) in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs (5%). CPS ≥ 1 SBAs were significantly (p = 0.013) more frequent in MSI-H cases (41%) than in non-MSI-H ones (18%); however, 15 CPS ≥ 1 microsatellite stable SBAs were also identified. CPS ≥ 1 SBAs showed higher TIL and PD-1 + immune cell density, more frequently medullary histotype, as well as a better outcome in comparison with CPS < 1 cases. This study demonstrates an increased proportion of PD-L1 + cases in both CeD-SBAs and CrD-SBAs in comparison with sporadic SBAs. In addition, the identification of a subset of PD-L1 + microsatellite stable SBAs supports the need to ascertain additional biomarkers of response to immune checkpoint inhibitors along with MSI-H.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Perianal fistulizing Crohn's disease (PFCD) is a common, disabling and aggressive phenotype that negatively impacts on the quality of life of affected patients. Its successful treatment is still a struggle for both physicians and patients. Significant advances in the management of this condition have occurred in the last two decades holding promise for a better future. This culminated into the concept of a collaborative multidisciplinary approach using the latest medical therapies combined with modern surgical and endoscopic techniques. Despite this, PFCD management and treatment have not been standardized yet. Thus the gastroenterologist and surgeon have to be familiar with several approaches and/or techniques. The positioning of each therapeutic option will certainly evolve with new data, but for the time being it should be driven by patient's characteristics, physician's preference and/or experience, costs and availability in local practice. Additionally, patient's perception of benefits and risks of treatment may differ from those of physicians and recognition of this difference is a starting point for difficult clinical decision-making. In this paper, a multidisciplinary group of Italian IBD experts explore and discuss current medical and surgical therapeutic options, highlighting areas of unmet needs in PFCD, with particular focus on the optimal patient flow within the Italian clinical reality., (Copyright © 2019 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)

Background and Aims: Crohn's disease-associated small bowel carcinoma is a rare event, usually reported to have a severe prognosis. However, in previous investigations we have found a minority of cases displaying a relatively favourable behaviour, thus outlining the need to improve the histopathological prediction of Crohn's disease-associated small bowel carcinoma prognosis., Methods: As in recent studies on colorectal cancer, a substantial improvement in prognostic evaluations has been provided by the histological analysis of the tumour invasive front; we therefore systematically analysed the tumour budding and poorly differentiated clusters in the invasive front of 47 Crohn's disease-associated small bowel carcinomas collected through the Small Bowel Cancer Italian Consortium., Results: Both tumour budding and poorly differentiated cluster analyses proved highly effective in prognostic evaluation of Crohn's disease-associated small bowel carcinomas. In addition, they retained prognostic value when combined with two other parameters, i.e. glandular histology and stage I/II, both known to predict a relatively favourable small bowel carcinoma behaviour. In particular, association of tumour budding and poorly differentiated clusters in a combined invasive front score allowed identification of a minor subset of cancers [12/47, 25%] characterised by combined invasive front low grade coupled with a glandular histology and a low stage [I or II] and showing no cancer-related death during a median follow-up of 73.5 months., Conclusions: The improved distinction of lower- from higher-grade Crohn's disease-associated small bowel carcinomas provided by invasive front analysis should be of potential help in choosing appropriate therapy for these rare and frequently ominous neoplasms., (Copyright © 2019 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background and Aims: An increased risk of small bowel carcinoma [SBC] has been reported in coeliac disease [CD] and Crohn's disease [CrD]. We explored clinico-pathological, molecular, and prognostic features of CD-associated SBC [CD-SBC] and CrD-associated SBC [CrD-SBC] in comparison with sporadic SBC [spo-SBC]., Methods: A total of 76 patients undergoing surgical resection for non-familial SBC [26 CD-SBC, 25 CrD-SBC, 25 spo-SBC] were retrospectively enrolled to investigate patients' survival and histological and molecular features including microsatellite instability [MSI] and KRAS/NRAS, BRAF, PIK3CA, TP53, HER2 gene alterations., Results: CD-SBC showed a significantly better sex-, age-, and stage-adjusted overall and cancer-specific survival than CrD-SBC, whereas no significant difference was found between spo-SBC and either CD-SBC or CrD-SBC. CD-SBC exhibited a significantly higher rate of MSI and median tumour-infiltrating lymphocytes [TIL] than CrD-SBC and spo-SBC. Among the whole SBC series, both MSI─which was the result of MLH1 promoter methylation in all but one cases─and high TIL density were associated with improved survival at univariable and stage-inclusive multivariable analysis. However, only TILs retained prognostic power when clinical subgroups were added to the multivariable model. KRAS mutation and HER2 amplification were detected in 30% and 7% of cases, respectively, without prognostic implications., Conclusions: In comparison with CrD-SBC, CD-SBC patients harbour MSI and high TILs more frequently and show better outcome. This seems mainly due to their higher TIL density, which at multivariable analysis showed an independent prognostic value. MSI/TIL status, KRAS mutations and HER2 amplification might help in stratifying patients for targeted anti-cancer therapy., (Copyright © 2017 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com)

Inflammatory bowel disease (IBD) is a chronic affection, in which the two main phenotypical components are Crohn's disease and ulcerative colitis. In both diseases, medical treatment has the main role; in some phases of the natural history of IBD, surgery becomes an important therapeutic tool. The IBD represents a model of multidisciplinary management. Timing represents the key issue for proper management of IBD patients. For acute and severe IBD, the surgery can be a salvage procedure. Today, the laparoscopic approach plays an important role in armamentarium of the surgeon. Several articles compared the short- and long-term results between laparoscopic and open approaches in IBD. The aim of this review is to focus the role of surgery in IBD as well as the role of laparoscopic approach, and principally, the "state of the art" for surgical treatment, sometimes very challenging for surgeon, in all clinical features of IBD by a review of literature highlighted by the most recent international guidelines.

Background: Colorectal cancer is the third most common and the third most lethal cancer in both men and women in developed countries. About 75% of cases are first diagnosed when the disease is classified as localized or regional, undergo potentially curative treatment and enter a post-treatment surveillance program. Although such programs drain significant resources from health systems, empirical evidence of their efficacy is scanty., Patients and Methods: Dukes B2-C colorectal cancer patients who had no evidence of disease at the end of their front-line treatment (surgery and adjuvant radiochemotherapy, if indicated) were eligible for the trial and randomized to two different surveillance programs. These programs differed greatly in the frequency of diagnostic imaging. They had similar schedules of physical examinations and carcinoembryonic antigen (CEA) assessments. Patients received baseline and yearly health-related quality-of-life (HR-QoL) questionnaires. Primary outcomes were overall survival (OS) and QoL., Results: From 1998 to 2006, 1228 assessable patients were randomized, 933 with colon cancer and 295 with rectal cancer. More than 90% of patients had the expected number of diagnostic procedures. Median follow-up duration was 62 months [interquartile range (IQR) 51-86] in the minimal surveillance group and 62 months (IQR 50-85) in the intensive group. At primary analysis, 250 patients had recurred and 218 had died. Intensive surveillance anticipated recurrence, as shown by a significant difference in mean disease-free survival of 5.9 months. Comparison of OS curves of the whole intention-to-treat population showed no statistically significant differences. HR-QoL of life scores did not differ between regimens., Conclusion: Our findings support the conclusions of other randomized clinical trials, which show that early diagnosis of cancer recurrence is not associated with OS benefit., Clinicaltrialsgov: NCT02409472., (© The Author 2015. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Hand injuries exceed 20% of all occupational injuries. This article reviews the history of 237 hand injuries mostly occurred in craftsmen and farmers. The results allow us to make some considerations on the role of occupational physician in their prevention.

Background: In the last years the real innovation in the treatment of groin hernia is represented by tension-free hernioplasty under local anaesthesia, based on the techniques of Lichtenstein and Trabucco, which use synthetic prosthesis (polypropylene) to restore the floor of inguinal tract and enable an early deambulation and return to work., Methods: In 21 months the authors have treated, only under local anaesthesia, 100 patients, 95 men and 5 women; the age ranged from 18 to 82 years; some of them suffer from systemic pathology (7 patients with cardiovascular diseases, 1 with epilepsy, 3 with pulmonary diseases, 1 with liver cirrhosis). All patients underwent short-term antibiotic prophylaxis. No mortality was recorded. The mean follow-up was 12.5 months with only one little and low recurrence detected., Results: Good results were obtained also in terms of intraoperative complication (nausea, vomiting, bradycardia, pain) and post-operative complications, (ecchymosis of scrotum and penis, edema of the scrotum, swelling of the skin suture, subcutaneous hematoma, inguinal pain, fever), not life-threatening, well tolerated and resolved spontaneously., Conclusions: The authors stress the advantages of local anaesthesia, the economic spare due, to one day hospital stay, the safety of the technique also in patients with severe general diseases (0.9-1% in USA). The authors survey the international literature confirming the great effectiveness of tension-free inguinal hernioplasty, in particular in terms of recurrences (Trabucco 0-0.025%, Amid 0.1%).

The authors described two cases of airborne contact dermatitis caused by 2-amino-2-methyl-1-propanol (AMP 100) in two subjects with periorbital erythema and itching skin. The AMP 100 has been used to replace ammonia as a hair dye component in the cosmetic industry with the purpose to eliminate its smell. Patch tests proved positive only to dilutions of 10% and 20% in the two described patients, as well as in other six asymptomatic subjects operating in the same working environment. The authors have diagnosed an irritative airborne contact dermatitis by AMP 100.

Close postoperative follow-up of patients with breast cancer permits the early detection of possible recurrence of disease. Such follow-up allows for the detection of a tumor mass, that is small enough to permit adequate treatment leading to an increased survival time and better quality of life. Thus we studied 85 patients treated by radical mastectomy in stages I, II, and III during the period from December 1977 to June 1982. Among 82 patients, 41 had axillary node involvement and received adjuvant chemotherapy with C.M.F. All patients received a strict follow-up. Thirty-two patients showed recurrence of the disease, with 28. 1% being discovered while still asymptomatic. Seventy-five percent of the recurrences were in the first 24 months after treatment. The frequency of involved sites was different between the group of patients with involvement and the group without involvement of axillary nodes. We have concluded that in asymptomatic patients certain exams need not be repeated at frequent intervals, and we have proposed a new follow-up protocol.