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Neuroendocrine neoplasms (NENs) are rare tumors with diverse clinical behaviors. Large databases like the Surveillance, Epidemiology, and End Results (SEER) program and national NEN registries have provided significant epidemiological knowledge, but they have limitations given the recent advancements in NEN diagnostics and treatments. For instance, newer imaging techniques and therapies have revolutionized NEN management, rendering older data less representative. Additionally, crucial parameters, like the Ki67 index, are missing from many databases. Acknowledging these gaps, the Italian Association for Neuroendocrine Tumors (Itanet) initiated a national multicenter prospective database in 2019, aiming to gather data on newly-diagnosed gastroenteropancreatic neuroendocrine (GEP) NENs. This observational study, coordinated by Itanet, includes patients from 37 Italian centers. The database, which is rigorously maintained and updated, focuses on diverse parameters including age, diagnostic techniques, tumor stage, treatments, and survival metrics. As of October 2023, data from 1,600 patients have been recorded, with an anticipation of reaching 3600 by the end of 2025. This study aims at understanding the epidemiology, clinical attributes, and treatment strategies for GEP-NENs in Italy, and to introduce the Itanet database project. Once comprehensive follow-up data will be acquired, the goal will be to discern predictors of treatment outcomes and disease prognosis. The Itanet database will offer an unparalleled, updated perspective on GEP-NENs, addressing the limitations of older databases and aiding in optimizing patient care. STUDY REGISTRATION: This protocol was registered in clinicaltriasl.gov (NCT04282083)., (© 2024. The Author(s).)

Background: We aimed to assess the ability of comprehensive complication index (CCI) and Clavien-Dindo complication (CDC) scale to predict excessive length of hospital stay (e-LOS) in patients undergoing liver resection for hepatocellular carcinoma., Methods: Patients were identified from an Italian multi-institutional database and randomly selected to be included in either a derivation or validation set. Multivariate logistic regression models and ROC curve analysis including either CCI or CDC as predictors of e-LOS were fitted to compare predictive performance. E-LOS was defined as a LOS longer than the 75th percentile among patients with at least one complication., Results: A total of 2669 patients were analyzed (1345 for derivation and 1324 for validation). The odds ratio (OR) was 5.590 (95%CI 4.201; 7.438) for CCI and 5.507 (4.152; 7.304) for CDC. The AUC was 0.964 for CCI and 0.893 for CDC in the derivation set and 0.962 vs. 0.890 in the validation set, respectively. In patients with at least two complications, the OR was 2.793 (1.896; 4.115) for CCI and 2.439 (1.666; 3.570) for CDC with an AUC of 0.850 and 0.673, respectively in the derivation cohort. The AUC was 0.806 for CCI and 0.658 for CDC in the validation set., Conclusions: When reporting postoperative morbidity in liver surgery, CCI is a preferable scale.

The epidemic phase of Coronavirus disease 2019 (COVID-19) made the Worldwide health system struggle against a severe interstitial pneumonia requiring high-intensity care settings for respiratory failure. A rationalisation of resources and a specific treatment path were necessary. The study suggests a predictive model drawing on clinical data gathered by 119 consecutive patients with laboratory-confirmed COVID-19 admitted in Busto Arsizio hospital. We derived a score that identifies the risk of clinical evolution and in-hospital mortality clustering patients into four groups. The study outcomes have been compared across the derivation and validation samples. The prediction rule is based on eight simple patient characteristics that were independently associated with study outcomes. It is able to stratify COVID-19 patients into four severity classes, with in-hospital mortality rates of 0% in group 1, 6-12.5% in group 2, 7-20% in group 3 and 60-86% in group 4 across the derivation and validation sample. The prediction model derived in this study identifies COVID-19 patients with low risk of in-hospital mortality and ICU admission. The prediction model that the study presents identifies COVID-19 patients with low risk of in-hospital mortality and admission to ICU. Moreover, it establishes an intermediate portion of patients that should be treated accurately in order to avoid an unfavourable clinical evolution. A further validation of the model is important before its implementation as a decision-making tool to guide the initial management of patients.

Background: Christmas and New Year's holidays are risk factors for hospitalization, but the causes of this "holiday effect" are uncertain. In particular, clinical complexity (CC) has never been assessed in this setting. We therefore sought to determine whether patients admitted to the hospital during the December holiday period had greater CC compared to those admitted during a contiguous non-holiday period., Methods: This is a prospective, longitudinal study conducted in an academic ward of internal medicine in 2017-2019. Overall, 227 consecutive adult patients were enrolled, including 106 cases (mean age 79.4±12.8 years, 55 females; 15 December-15 January) and 121 controls (mean age 74.3±16.6 years, 56 females; 16 January-16 February). Demographic characteristics, CC, length of stay, and early mortality rate were assessed. Logistic regression analyses for the evaluation of independent correlates of being a holiday case were computed., Results: Cases displayed greater CC (17.7±5.5 vs 15.2±5.9; p = 0.001), with greater impact of socioeconomic (3.51±1.7 vs 2.9±1.7; p = 0.012) and behavioral (2.36±1.6 vs 1.9±1.8; p = 0.01) CC components. Cases were also significantly frailer according to the Edmonton Frail Scale (8.0±2.8 vs 6.4±3.1; p<0.001), whilst having similar disease burden, as measured by the CIRS comorbidity index. Age (OR 1.02; p = 0.039), low income (OR 1.97, 95% CI 1.10-3.55; p = 0.023), and total CC (OR 1.06; p = 0.014) independently correlated with the cases. Also, cases showed a longer length of stay (median 15.5 vs 11 days; p = 0.0016) and higher in-hospital (12 vs 4 events; p = 0.021) and 30-day (14 vs 6 events; p = 0.035) mortality., Conclusions: Patients hospitalized during the December holiday period had worse health outcomes, and this could be attributable to the grater CC, especially related to socioeconomic (social deprivation, low income) and behavioral factors (inappropriate diet). The evaluation of all CC components could potentially represent a useful tool for a more rational resource allocation over this time of the year., Competing Interests: The authors have declared that no competing interests exist.

Background  It remains unclear whether the distal location of deep vein thrombosis (DVT) is independently associated with a lower risk of recurrence in all patients, or represents a marker of the presence and severity of provoking factors for venous thromboembolism (VTE). Methods  We investigated the impact of distal (vs. proximal) DVT location on the risk of developing symptomatic, objectively confirmed recurrent VTE in 831 patients with a first acute symptomatic DVT not associated with pulmonary embolism (PE), who were stratified by the presence of transient or persistent risk factors at baseline. The primary outcome was symptomatic, objectively diagnosed recurrent VTE, including proximal DVT and PE. Results  A total of 205 (24.7%) patients presented with a transient risk factor, 189 (22.7%) with a minor persistent risk factor, 202 (24.3%) with unprovoked DVT, and 235 (28.3%) with cancer-associated DVT. One-hundred twenty-five patients (15.0%) experienced recurrent DVT or PE. The largest relative difference between patients with distal (vs. proximal) DVT was observed in the absence of identifiable risk factors (adjusted hazard ratio [aHR]: 0.11; 95% CI [confidence interval]: 0.03-0.45). In patients with cancer, distal and proximal DVT had a comparable risk of recurrence (aHR: 0.70; 95% CI: 0.28-1.78]). Conclusions  The distal (vs. proximal) location of first acute symptomatic DVT represented, in the absence of any identifiable transient or persistent risk factors, a favorable prognostic factor for recurrence. In contrast, the prognostic impact of DVT location was weaker if persistent provoking risk factors for VTE were present, notably cancer.

In myelodysplastic syndrome (MDS), vascular endothelial growth factor (VEGF) may have regulatory effects on the hematopoietic system and contribute to disease progression. We analyzed by immunocytochemistry VEGF expression in bone marrow (BM) cells from 188 patients with MDS and 96 non-hemopathic subjects. We also measured VEGF BM plasma levels and in vitro VEGF release. Our aims were to evaluate whether VEGF expression abnormalities were associated with relevant laboratory or clinical findings and their possible prognostic value. In MDS, VEGF expression was higher than in controls (p < .0001) and VEGF release was significantly higher in the low-risk cases. A trend to a positive correlation between VEGF myeloid expression and apoptotic rate was observed. High myeloid VEGF levels were independently associated with longer overall survival (p < .0001) and progression-free survival (p = .0002). Our findings suggest that, in MDS, VEGF production and release may contribute to ineffective hematopoiesis, with a potential prognostic role.

Enteral nutrition, as demonstrated by the many published papers, is not only safer and cheaper than parenteral supply of nutrients, but modulates an exaggerated cytokine response related to surgical trauma that leads to an increase in intestinal permeability, bacterial translocation and infection. The aim of enteral nutrition is to reduce the impact of cytokines on surgical patients and the related infectious complications. Via the enteral route the nutrients can reach the bowel lumen where enterocytes draw upon their fuel, preserving the barrier effect and modulating the cytokine response. Parenteral supply does not achieve this target since the blood supply of nutrients is not as important as the luminal supply. It is only via the enteral supply route that we can preserve the barrier effect. Since the cytokine response sets in immediately after a trauma such as surgery, we implement uninterrupted enteral nutrition, which means before, during and after surgery, plus parenteral support till the full calorie intake is achieved. In a hepatic resection study, we have demonstrated that enteral nutrition modulates the interleukin-6 immunological response and shortens both the period to bowel movement resumption and the duration of hospital stay. Aggressive enteral nutrition has also been implemented in severe pancreatitis, allowing control of the disease without the onset of septic complications. The most important target is not to achieve full calorie intake rapidly, but to supply the enteric mucosa continuously with useful immuno-nutrients, such as glutamine and fibres, to preserve the barrier effect, the mucus layer, and immunological status of the mucosa. In this way we have obtained significant results in the surgical treatment of these patients, reducing the infection rate and hospital stay. New prospects may be,possible in the fight against surgical infections by adding probiotics to enteral nutrition in order to improve the microenvironment of the colon.

Background/aims: Liver metastases are a very common event. Multiple choices of therapies can be used. The aim of this paper is to analyze results and methods of a single institution series of 228 consecutive patients with colorectal liver metastases., Methodology: 228 consecutive patients underwent hepatic resection for colorectal liver metastases. From different periods intraoperative ultrasound, intraoperative histological examination, locoregional intra-arterial chemotherapy, and radiofrequency thermal ablation were introduced., Results: Operative mortality was 0.9%. Mean follow-up was 29.5 months. Overall survival was 16% and 9% at 5 and 10 years. 5-year survival was 23% and 6% for patients with single and multiple metastases respectively. For patients with extrahepatic metastatic single lesion 5-year survival was 15%. From the start of intraoperative ultrasound use, 5-year survival was 9% and 27% for patients with multiple and single metastases. Five-year survival for re-resected patients was 13%. Overall survival at 1 and 3 years was 90% and 58% in patients treated with HAI and systemic chemotherapy (disease-free 70% and 47%) and 94% and 12% in patients treated with systemic chemotherapy alone after radical resection (disease-free 53% and 0%)., Conclusions: Aggressive approach, re-resections, intraoperative ultrasound staging, intra-arterial chemotherapy and radiofrequency thermal ablation are justified in multimodal therapeutic strategy of colorectal metastases and seem to improve patients' survival.

Background: Radiofrequency ablation (RFA) is a novel technique for the treatment of liver malignancies that is becoming increasingly more popular because of its feasibility, effectivity, repeatability, and safety. However, an increased number of complications after RFA has been reported in literature. The aim of this paper is to discuss the possible role of RFA in rapid intrahepatic spreading of hepatocellular carcinoma (HCC)., Patients and Methods: We treated a 66-year-old woman who had a 3.5-cm HCC with two courses of percutaneous RFA using a modified needle with seven hooks. The effectiveness of the treatment was assessed 1 month later by enhanced computed tomography., Results: Two courses of treatment were needed owing to the nodule position (close to the inferior vena cava). Computed tomography scan performed 1 month after the second RFA showed an intrahepatic arteriovenous fistula. Angiography performed after 1 month showed a rapid intrahepatic spreading of HCC., Conclusions: Radiofrequency ablation can create an arteriovenous fistula that can facilitate migration of tumoral cells from the nodule to the hepatic portal system and rapid intrahepatic dissemination of HCC.

A mammographic screening program was started in 1999 in the Province of Verona and was offered to women aged 50-69. The purpose of this study was to analyse and compare our data, particularly the type of surgery and histotype, with the literature data where no screening program was implemented. During the first three years of the screening, 113 patients underwent surgical treatment in our Institute. The histology of the mammary lesions was benign neoplasia in 28 (24.7%) and breast cancer in 85 (75.3%) patients. Seventy-three women (85.9%) with malignant neoplasms were submitted to conservative treatment. Mastectomy was performed in 12 (14.1%) patients, 8 of whom with immediate breast reconstruction. Patients coming from screening programs benefit in a high percentage of cases from conservative treatment, which, together with the reduced aggressiveness of the cancers, permits alternative treatments for the axillary lymph nodes and a reduction in adjuvant chemotherapy.

During recent years, there has been considerable debate as to the nutritional supply that needs to be established for a patient with acute pancreatitis. The main problem is still infection of the pancreatic necrosis, which has a decisive bearing on the indication for surgery and is the main cause of mortality. Infection stems from bacterial translocation from the patient's gut. Enteral nutrition with its known potential for reducing this type of infection constitutes an attempt to prevent it by preserving the enteric mucosal barrier. Today, the concept of pancreatic rest is no longer considered mandatory in the guidelines of many Surgical and Nutritional Societies, whilst enteral nutrition is the gold standard for acute pancreatitis. Assuring an integrated parenteral and enteral supply before reaching the full regimen of enteral nutrition is the most reliable policy during the early days of the disease. Moreover, outcomes being equal, enteral nutrition is cheaper than parenteral nutrition, as has been extensively demonstrated in many clinical trials in severe acute pancreatitis.

Postoperative infectious complications are nowadays a major problem in liver surgery. Better surgical outcomes with a consequent reduction in treatment and hospitalisation costs are a primary objective. The aim of this prospective, randomised study was to evaluate the cytokine response during and after portal clamping in patients undergoing liver resection and continuously fed with enteral nutrition as compared to patients receiving parenteral nutritional support. Forty patients with liver tumours were divided into two groups of 20 on the basis of the presence or absence of chronic liver disease. Furthermore, the latter group of 20 were randomised to two subgroups A and B of 10 patients on the basis of the different perioperative nutrition modalities. Group A patients were fed by so-called uninterrupted enteral nutrition, which means without interruption from the day before surgery with a nutritional solution delivered via a nasojejunal tube. The patients in group B were submitted to hepatic resection with parenteral nutritional support. Liver resection had to consist in resection of at least 30% of the parenchyma in non-cirrhotic patients or in segmental resection in cirrhotic ones. Ten milliliter blood samples were harvested before operation, and 10, 30 and 60 min after declamping and at 24 h. Interleukin 6 and a-tumour necrosis factor values were detected in blood samples. The values of C reactive protein and of prealbumin were recorded at 72 h postoperatively. We also evaluated postoperative complications, resumption of bowel movements, oral intake of nourishment, and patient discharge. Values in blood samples in the two groups showed a statistically significant difference in interleukin 6 values only after 24 h (10 min: group A 121 +/- 25.3, group B 156 +/- 31.4; after 24 h: group A 31.5 +/- 12, group B 105.1 +/- 24.1), while the a-tumour necrosis factor assay showed no significant difference between the two groups. However, there was an appreciably longer hospital stay (group A 10.9 +/- 3.1 days (range: 7-21 days), group B 13.2 +/- 2.7 days (range: 8-19 days) (P < 0.02) and a quicker resumption of bowel movements in group A. The data available show that uninterrupted enteral nutrition produces a modulation of the cytokine response following portal clamping. A lower cytokine activation cascade reduces the impact of the action of cytokines on the hepatic parenchyma with consequent enhancement of the hepatic Kupffer cell component. These factors thus substantially reduce the length of the patient's hospital stay and consequently the cost of medical care.

Colic anastomoses are still affected by a high incidence of leakage. We speculate that a supply of fibres and probiotic bacteria improves the healing of colic anastomoses due to a higher production of short-chain fatty acids. These are known to improve the anastomotic healing of colic sutures. Sixty Lewis rats, weighing from 250 g to 350 g, were divided into 6 groups. Groups A + A1 were fed with a low-fibre diet (less than 0.1%), Groups B + B1 with normal rat chow and groups C + C1 with normal rat chow + Lactobacillus plantarum 299v. Transections and re-anastomosis of the distal colon were performed. Groups A1, B1 and C1 were sacrificed after 3 days, and groups A, B, and C after 7 days. The bursting pressure of colic anastomoses was measured. All data are expressed as mean (+/- S.D.). The pH of the colon contents was evaluated by means of a fine needle plastic electrode only in groups A1, B1 and C1. The results were studied by analysis of variance followed by the Student Newman Keuls test for multiple comparisons (significance level P < 0.05). Three days postoperatively, the pH of the colic lumen was lower in animals fed with a normal diet (pH 7.1 +/- 0.3 without Lp supplementation, 6.5 +/- 0.2 with Lp supplementation) than in animals fed with a low-fibre diet (pH 8.0 +/- 0.3). Bursting pressures were significantly higher in the groups fed with fibre and fibre + Lactobacilli than in animals on a low-fibre diet, both on day 3 and day 7. On the basis of these data there seems to be no support for the belief that a supply of fibre-rich food might impair healing and promote development of anastomotic leakage. On the contrary, short-chain fatty acids and fibres would seem to facilitate the healing of colic anastomoses.

Enteral nutrition (EN) is increasingly used to minimize the rate of septic complications related to bacterial translocation, due to its effectiveness and low cost. Bengmark's self-propelling auto-positioning feeding tube (SPT) absorbs and uses gut motility for rapid transport to the upper small intestine, thereby allowing uninterrupted EN both in surgical and critically ill patients. We report on our experience with 175 SPTs applied over the period from December 1996 to February 2000, and analyse the safety, compliance, and indications of SPT in surgical and ICU practice. Open study: feasibility of insertion, time and rate of placement, compliance and complications related to the tube or to EN were studied. SPTs were successfully placed in 40 patients before liver resection, in 32 patients before extensive maxillo-facial surgery MFS and prior to colon resections in 10 cases. SPTs were also applied in 56 patients with acute vascular neurological diseases, 22 in pancreatic diseases and in another 15 critically ill patients. 92.5% of SPT's crossed the pylorus, while only 7.5% stopped in the stomach and 3.4% in the duodenum; 89.14% reached the first jejunal loop. The tip of the tube reached its final position within a mean period of 5.2 hours, 8% instantly and all within 24 hours. Enteral nutrition was started immediately after introduction of the tube into the stomach. The compliance was excellent, even in maxillo-facial surgery patients: only 2/76 patients (2.6%) showed poor compliance. There were no cases of aspiration pneumonia or other complications related to SPT. Polymeric nutrition was usually supplied at a starting flow rate of 45 ml/hour and rapidly increasing over the following 48 h. Eleven patients experienced diarrhoea and 6 abdominal distension, leading to a temporary reduction of the EN flow rate. Clogging of the SPT occurred in 13 patients: 7/13 were cleansed with pancreatic enzymes, but 6 had to be replaced. SPT is ideal for intensive EN and is characterised by minimal complications and excellent patient compliance.