Hemicolectomy versus appendectomy for patients with appendiceal neuroendocrine tumours 1-2 cm in size: a retrospective, Europe-wide, pooled cohort study.

BACKGROUND: Awareness of the potential global overtreatment of patients with appendiceal neuroendocrine tumours (NETs) of 1-2 cm in size by performing oncological resections is increasing, but the rarity of this tumour has impeded clear recommendations to date. We aimed to assess the malignant potential of appendiceal NETs of 1-2 cm in size in patients with or without right-sided hemicolectomy. METHODS: In this retrospective cohort study, we pooled data from 40 hospitals in 15 European countries for patients of any age and Eastern Cooperative Oncology Group performance status with a histopathologically confirmed appendiceal NET of 1-2 cm in size who had a complete resection of the primary tumour between Jan 1, 2000, and Dec 31, 2010. Patients either had an appendectomy only or an appendectomy with oncological right-sided hemicolectomy or ileocecal resection. Predefined primary outcomes were the frequency of distant metastases and tumour-related mortality. Secondary outcomes included the frequency of regional lymph node metastases, the association between regional lymph node metastases and histopathological risk factors, and overall survival with or without right-sided hemicolectomy. Cox proportional hazards regression was used to estimate the relative all-cause mortality hazard associated with right-sided hemicolectomy compared with appendectomy alone. This study is registered with ClinicalTrials.gov, NCT03852693. FINDINGS: 282 patients with suspected appendiceal tumours were identified, of whom 278 with an appendiceal NET of 1-2 cm in size were included. 163 (59%) had an appendectomy and 115 (41%) had a right-sided hemicolectomy, 110 (40%) were men, 168 (60%) were women, and mean age at initial surgery was 36·0 years (SD 18·2). Median follow-up was 13·0 years (IQR 11·0-15·6). After centralised histopathological review, appendiceal NETs were classified as a possible or probable primary tumour in two (1%) of 278 patients with distant peritoneal metastases and in two (1%) 278 patients with distant metastases in the liver. All metastases were diagnosed synchronously with no tumour-related deaths during follow-up. Regional lymph node metastases were found in 22 (20%) of 112 patients with right-sided hemicolectomy with available data. On the basis of histopathological risk factors, we estimated that 12·8% (95% CI 6·5 -21·1) of patients undergoing appendectomy probably had residual regional lymph node metastases. Overall survival was similar between patients with appendectomy and right-sided hemicolectomy (adjusted hazard ratio 0·88 [95% CI 0·36-2·17]; p=0·71). INTERPRETATION: This study provides evidence that right-sided hemicolectomy is not indicated after complete resection of an appendiceal NET of 1-2 cm in size by appendectomy, that regional lymph node metastases of appendiceal NETs are clinically irrelevant, and that an additional postoperative exclusion of metastases and histopathological evaluation of risk factors is not supported by the presented results. These findings should inform consensus best practice guidelines for this patient cohort. FUNDING: Swiss Cancer Research foundation.

Prospective validation of the Israeli Score for the prediction of common bile duct stones in patients with acute calculous cholecystitis.

BACKGROUND: Existing guidelines for predicting common bile duct stones (CBDS) are not specific for acute calculous cholecystitis (ACC). This paper is a posthoc analysis of the S.P.Ri.M.A.C.C study aiming to prospectively validate on a large independent cohort of patients the Israeli Score (IS) in predicting CBDS in patients with ACC. METHODS: The S.P.Ri.M.A.C.C. study is an observational multicenter prospective study endorsed by the World Society of Emergency Surgery (WSES). Between September 1st, 2021, and September 1st, 2022, 1201 participants were included. The Chi-Square test was used to compare categorical data. A Cochran-Armitage test was run to determine whether a linear trend existed between the IS and the presence of CBDS. To assess the accuracy of the prediction model, the receiver operating characteristic (ROC) curve was generated, and the area under the ROC curve (AUC) was calculated. Logistic regression was run to obtain Odds Ratio (OR). A two-tailed p < 0.05 was considered statistically significant. RESULTS: The rate of CBDS was 1.8% in patients with an IS of 0, 4.2% in patients with an IS of 1, 24.5% in patients with 2 and 56.3% in patients with 3 (p < 0.001). The Cochran-Armitage test of trend showed a statistically significant linear trend, p < 0.001. Patients with an IS of 3 had 64.4 times (95% CI 24.8-166.9) higher odds of having associated CBDS than patients with an IS of 0. The AUC of the ROC curve of IS for the prediction of CBDS was 0.809 (95% CI 0.752-0.865, p < 0.001). By applying the highest cut-off point (3), the specificity reached 99%, while using the lowest cut-off value (0), the sensitivity reached 100%. CONCLUSION: The IS is a reliable tool to predict CBDS associated with ACC. The algorithm derived from the IS could optimize the management of patients with ACC.

Role of diffusion-weighted MRI in recurrent rectal cancer treated with carbon ion radiotherapy.

Aim: To evaluate the association between pretreatment diffusion-weighted MRI (DW-MRI) and 12-month radiological response in locally recurrent rectal cancer treated with carbon ion radiotherapy. Methods: Histogram analysis was performed on pretreatment DW-MRI for patients re-irradiated with carbon ion radiotherapy for local recurrence of rectal cancer. Results: A total of 17 patients were enrolled in the study. Pretreatment DW-MRI b-value of 1000 s/mm2 (b1000) and apparent diffusion coefficient (ADC) lesion median values for 1-year nonresponders (six patients) and responders (11 patients) demonstrated a median (interquartile of median values) of 62.5 (23.9) and 34.0 (13.0) and 953.0 (277.0) and 942.5 (339.0) µm2/s, respectively. All b1000 histogram features (h-features) and ADC h-kurtosis showed statistically significant differences, whereas only b1000 h-median, b1000 h-interquartile range and ADC h-kurtosis demonstrated remarkable diagnostic accuracy. Conclusion: DW-MRI showed promising results in predicting carbon ion radiotherapy outcome in local recurrence of rectal cancer, particularly with regard to b1000 h-median, b1000 h-interquartile range and ADC h-kurtosis.

Carbon ion radiotherapy is a form of advanced radiotherapy that is especially suitable for radioresistant and/or difficult-to-irradiate tumors. In case of recurrence of rectal cancer after pelvic photon beam radiotherapy, carbon ion radiotherapy may be an option. In this study, the authors looked at the potential role of specific MRI sequences performed before treatment to predict response to carbon ion radiotherapy. If confirmed in a larger prospective cohort, the findings of this study may drive clinical decisions toward a more tumor- and patient-tailored therapeutic approach.

Doctor@Home: Through a Telemedicine Co-production and Co-learning Journey.

Telemedicine and remote visits are becoming more and more popular in several medical disciplines, including oncology. The Covid-19 pandemic has enhanced the need to continue to meet patients' ambulatory care necessities ensuring social distancing and limiting the access to clinical facilities. The National Cancer Institute of Aviano, Italy, has recently launched a program called "Doctor @ Home" (D@H). The pillars of the program are the co-production of the oncological care and the co-learning approach, which sees the clinical staff "hand in hand" with patients to maximize the outcome of the care, trying to take advantage of the new tools offered by modern technologies.

New frontiers in e-health. Policies and the Doctor@Home case study. / La frontiera delle cure a distanza. Assetto normativo ed il caso Doctor@Home.

INTRODUCTION: In recent years, and even more following the need for social distancing generated by the global COVID-19 pandemic, e-health has become an increasingly widespread reality in clinical practice, especially for those clinicians operating in the front-line, like nurses. Its growing importance has been followed by increasing attention both by the literature as well as in the generation of specific rules aimed at regulating the phenomenon. METHODS: A regulatory review of the literature aims to outline the current regulatory framework relating to telemedicine. Telemedicine, especially in a pandemic context, calls for regulation that runs parallel to the rapid evolution of the phenomenon itself. The paper traces the European, Italian, and Regional legislation, focusing then on a practical experience of telemedicine, called Doctor @ Home, active at the IRCCS National Cancer Center in Aviano (Italy). DISCUSSION: First, the need for regulatory harmonization emerges. Secondly, the potential of co-production and co-learning processes for healthcare professionals and patients arises to adapt to the outpatient needs of patients in a post-pandemic "new normal," exploiting the new technological tools made available by the National Health Service.

One Size Does Not Fit All - Translating Knowledge to Bridge the Gaps to Diversity and Inclusion of Surgical Teams.

Diverse teams have proven their ability to reach superior performance and improve patients' outcomes. Nevertheless, differences in race, gender, age, nationality, skills, education, and experience act as powerful barriers to diversity and inclusion, which negatively impacts multiple healthcare organizations and limit the potential outcome of diverse teams. Knowledge Translation (KT) can help to bridge the gaps among all the various individuals involved, whether they be members of the surgical team or surgical patients.

Non-pharmaceutical Interventions and the Infodemic on Twitter: Lessons Learned from Italy during the Covid-19 Pandemic.

The COVID-19 pandemic changed expectations for information dissemination and use around the globe, challenging accepted models of communications, leadership, and social systems. We explore how social media discourse about COVID-19 in Italy was affected by the rapid spread of the virus, and how themes in postings changed with the adoption of social distancing measures and non-pharmaceutical interventions (NPI). We used topic modeling and social network analysis to highlight critical dimensions of conversations around COVID-19: 1) topics in social media postings about the Coronavirus; 2) the scope and reach of social networks; and 3) changes in social media content as the nation moved from partial to full social distancing. Twitter messages sent in Italy between February 11th and March 10th, 2020. 74,306 Tweets sent by institutions, news sources, elected officials, scientists and social media influencers. Messages were retweeted more than 1.2 million times globally. Non-parametric chi-square statistic with residual analysis to identify categories, chi-square test for linear trend, and Social Network Graphing. The first phase of the pandemic was dominated by social media influencers, followed by a focus on the economic consequences of the virus and placing blame on immigrants. As the crisis deepened, science-based themes began to predominate, with a focus on reducing the spread of the virus through physical distancing and business closures Our findings highlight the importance of messaging in social media in gaining the public's trust and engagement during a pandemic. This requires credible scientific voices to garner public support for effective mitigation. Fighting the spread of an infectious disease goes hand in hand with stemming the dissemination of lies, bad science, and misdirection.

Tissue Engineered Esophageal Patch by Mesenchymal Stromal Cells: Optimization of Electrospun Patch Engineering.

Aim of work was to locate a simple, reproducible protocol for uniform seeding and optimal cellularization of biodegradable patch minimizing the risk of structural damages of patch and its contamination in long-term culture. Two seeding procedures are exploited, namely static seeding procedures on biodegradable and biocompatible patches incubated as free floating (floating conditions) or supported by CellCrownTM insert (fixed conditions) and engineered by porcine bone marrow MSCs (p-MSCs). Scaffold prototypes having specific structural features with regard to pore size, pore orientation, porosity, and pore distribution were produced using two different techniques, such as temperature-induced precipitation method and electrospinning technology. The investigation on different prototypes allowed achieving several implementations in terms of cell distribution uniformity, seeding efficiency, and cellularization timing. The cell seeding protocol in stating conditions demonstrated to be the most suitable method, as these conditions successfully improved the cellularization of polymeric patches. Furthermore, the investigation provided interesting information on patches' stability in physiological simulating experimental conditions. Considering the in vitro results, it can be stated that the in vitro protocol proposed for patches cellularization is suitable to achieve homogeneous and complete cellularizations of patch. Moreover, the protocol turned out to be simple, repeatable, and reproducible.

Trauma Coagulopathy and Its Outcomes.

Background and Objectives: Trauma coagulopathy begins at the moment of trauma. This study investigated whether coagulopathy upon arrival in the emergency room (ER) is correlated with increased hemotransfusion requirement, more hemodynamic instability, more severe anatomical damage, a greater need for hospitalization, and hospitalization in the intensive care unit (ICU). We also analyzed whether trauma coagulopathy is correlated with unfavorable indices, such as acidemia, lactate increase, and base excess (BE) increase. Material and Methods: We conducted a prospective, monocentric, observational study of all patients (n = 503) referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for major trauma from 1 January 2018 to 30 January 2019. Results: Of the 503 patients, 204 had trauma coagulopathy (group 1), whereas 299 patients (group 2) did not. Group 1 had a higher hemotransfusion rate than group 2. In group 1, 15% of patients showed hemodynamic instability compared with only 8% of group 2. The shock index (SI) distribution was worse in group 1 than in group 2. Group 1 was more often hypotensive, tachycardic, and with low oxygen saturation, and had a more severe injury severity score than group 2. In addition, 47% of group 1 had three or more body districts involved compared with 23% of group 2. The hospitalization rate was higher in group 1 than in group 2 (76% vs. 58%). The length of hospitalization was >10 days for 45% of group 1 compared with 28% of group 2. The hospitalization rate in the ICU was higher in group 1 than in group 2 (22% vs. 14.8%). The average duration of ICU hospitalization was longer in group 1 than in group 2 (12.5 vs. 9.78 days). Mortality was higher in group 1 than in group 2 (3.92% vs. 0.98%). Group 1 more often had acidemia and high lactates than group 2. Group 1 also more often had BE <-6. Conclusions: Trauma coagulopathy patients, upon arrival in the ER, have greater hemotransfusion (p = 0.016) requirements and need hospitalization (p = 0.032) more frequently than patients without trauma coagulopathy. Trauma coagulopathy seems to be more present in patients with a higher injury severity score (ISS) (p = 0.000) and a greater number of anatomical districts involved (p = 0.000). Head trauma (p = 0.000) and abdominal trauma (p = 0.057) seem related to the development of trauma coagulopathy. Males seem more exposed than females in developing trauma coagulopathy (p = 0.018). Upon arrival in the ER, the presence of tachycardia or alteration of SI and its derivatives can allow early detection of patients with trauma coagulopathy.

Preoperative chemotherapy and carbon ions therapy for treatment of resectable and borderline resectable pancreatic adenocarcinoma: a prospective, phase II, multicentre, single-arm study.

BACKGROUND: Pancreatic adenocarcinoma is a high-mortality neoplasm with a documented 5-years-overall survival around 5%. In the last decades, a real breakthrough in the treatment of the disease has not been achieved. Here we propose a prospective, phase II, multicentre, single-arm study aiming to assess the efficacy and the feasibility of a therapeutic protocol combining chemotherapy, carbon ion therapy and surgery for resectable and borderline resectable pancreatic adenocarcinoma. METHOD: The purpose of this trial (PIOPPO Protocol) is to assess the efficacy and the feasibility of 3 cycles of FOLFIRINOX neoadjuvant chemotherapy followed by a short-course of carbon ion radiotherapy (CIRT) for resectable or borderline resectable pancreatic adenocarcinoma patients. Primary outcome of this study is the assessment of local progression free survival (L-PFS). The calculation of sample size is based on the analysis of the primary endpoint "progression free survival" according to Fleming's Procedure. DISCUSSION: Very preliminary results provide initial evidence of the feasibility of the combined chemotherapy and CIRT in the neoadjuvant setting for resectable or borderline resectable pancreatic cancer. Completion of the accrual and long term results are awaited to see if this combination of treatment is advisable and will provide the expected benefits. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03822936 registered on January 2019.

Experimental Abdominal Sepsis: Sticking to an Awkward but Still Useful Translational Model.

Animal models are widely used to replicate human intra-abdominal infections. Different methodologies have been described and proposed in the scientific literature, including injection and surgical models. The aim of this review is to recapitulate the advantages and disadvantages of each method to help choose the most appropriate model for individual experimental purposes.

The spleen of patients with myelofibrosis harbors defective mesenchymal stromal cells.

Splenic hematopoiesis is a major feature in the course of myelofibrosis (MF). In fact, the spleen of patients with MF contains malignant hematopoietic stem cells retaining a complete differentiation program, suggesting both a pivotal role of the spleen in maintaining the disease and a tight regulation of hematopoiesis by the splenic microenvironment, in particular by mesenchymal stromal cells (MSCs). Little is known about splenic MSCs (Sp-MSCs), both in normal and in pathological context. In this work, we have in vitro expanded and characterized Sp-MSCs from 25 patients with MF and 13 healthy subjects (HS). They shared similar phenotype, growth kinetics, and differentiation capacity. However, MF Sp-MSCs expressed significant lower levels of nestin, and favored megakaryocyte (Mk) differentiation in vitro at a larger extent than their normal counterpart. Moreover, they showed a significant upregulation of matrix metalloprotease 2 (MMP2) and fibronectin 1 (FN1) genes both at mRNA expression and at protein level, and, finally, developed genetic abnormalities which were never detected in HS-derived Sp-MSCs. Our data point toward the existence of a defective splenic niche in patients with MF that could be responsible of some pathological features of the disease, including the increased trafficking of CD34+ cells and the expansion of the megakaryocytic lineage.

Surgical management of duodenal stump fistula after elective gastrectomy for malignancy: an Italian retrospective multicenter study.

BACKGROUND: Duodenal stump fistula (DSF) is a severe complication of gastrectomy. Although nonsurgical therapy is preferred, surgery is still mandatory in one third of DSF patients. The aim of this article is to analyze the surgical management of DSF and factors related to its outcome. METHODS: We performed a retrospective multicenter study using data from January 1990 to November 2011 in 16 Italian surgery centers. We collected 8,268 elective gastrectomies for malignancies, 7,987 by the laparotomic and 281 by the laparoscopic approach. Two hundred five patients developed a DSF, 75 of whom underwent surgery for DSF. We analyzed mortality and DSF healing time as well as the impact of clinical, oncological, and surgical characteristics. RESULTS: The laparoscopic approach increased the risk of DSF development (odds ratio 5.6, 95% confidence interval 2.7-10.6, P < 0.001). The indication for first DSF surgery was intra-abdominal sepsis; the failure rate was over 30%, associated with the appearance of fistulas of neighboring organs, bleeding, and the need for reoperations. The mortality rate was 28% and was related to the presence of vascular disease (P = 0.04), more than one reoperation (P = 0.05), sepsis (P < 0.001), and renal failure (P < 0.001). Fifty-four patients recovered after a median of 39 days (interquartile range 22-68 days); the need to perform more reoperations (P < 0.01) and the presence of an abdominal abscess (P < 0.01) led to an increase in healing time. CONCLUSIONS: Surgery for DSF has a poor prognosis. Our data will help to identify patients at risk of death, but unfortunately could not establish the best surgical procedure applicable to all cases of DSF.