The pan - COVID - AGICT study. The impact of COVID-19 pandemic on surgically treated pancreatic cancer patients. A multicentric Italian study.

BACKGROUND: In this article we aimed to perform a subgroup analysis using data from the COVID-AGICT study, to investigate the perioperative outcomes of patients undergoing surgery for pancreatic cancers (PC) during the COVID-19 pandemic. METHODS: The primary endpoint of the study was to find out any difference in the tumoral stage of surgically treated PC patients between 2019 and 2020. Surgical and oncological outcomes of the entire cohort of patients were also appraised dividing the entire peri-pandemic period into six three-month timeframes to balance out the comparison between 2019 and 2020. RESULTS: Overall, a total of 1815 patients were surgically treated during 2019 and 2020 in 14 Italian surgical Units. In 2020, the rate of patients treated with an advanced pathological stage was not different compared to 2019 (p = 0.846). During the pandemic, neoadjuvant chemotherapy (NCT) has dropped significantly (6.2% vs 21.4%, p < 0.001) and, for patients who didn't undergo NCT, the latency between diagnosis and surgery was shortened (49.58 ± 37 days vs 77.40 ± 83 days, p < 0.001). During 2020 there was a significant increase in minimally invasive procedures (p < 0.001). The rate of postoperative complication was the same in the two years but during 2020 there was an increase of the medical ones (19% vs 16.1%, p = 0.001). CONCLUSIONS: The post-pandemic dramatic modifications in healthcare provision, in Italy, did not significantly impair the clinical history of PC patients receiving surgical resection. The present study is one of the largest reports available on the argument and may provide the basis for long-term analyses.

Epidemiology of gastroenteropancreatic neuroendocrine neoplasms: a review and protocol presentation for bridging tumor registry data with the Italian association for neuroendocrine tumors (Itanet) national database.

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).

Feasibility and outcome of spleen and vessel preserving total pancreatectomy (SVPTP) in pancreatic malignancies - a retrospective cohort study.

INTRODUCTION: Total pancreatectomy (TP) is most commonly performed to avoid postoperative pancreatic fistula (POPF) in patients with high-risk pancreas or to achieve tumor-free resection margins. As part of TP, a simultaneous splenectomy is usually performed primarily for the reason of oncologic radicality. However, the benefit of a simultaneous splenectomy remains unclear. Likewise, the technical feasibility as well as the safety of spleen and vessel preserving total pancreatectomy in pancreatic malignancies has hardly been evaluated. Thus, the aims of the study were to evaluate the feasibility as well as the results of spleen and vessel preserving total pancreatectomy (SVPTP). MATERIAL AND METHODS: Patient characteristics, technical feasibility, perioperative data, morbidity, and mortality as well as histopathological results after SVPTP, mainly for pancreatic malignancies, from patient cohorts of two European high-volume-centers for pancreatic surgery were retrospectively analyzed. Mortality was set as the primary outcome and morbidity (complications according to Clavien-Dindo) as the secondary outcome. RESULTS: A SVPTP was performed in 92 patients, predominantly with pancreatic adenocarcinoma (78.3%). In all cases, the splenic vessels could be preserved. In 59 patients, the decision to total pancreatectomy was made intraoperatively. Among these, the most common reason for total pancreatectomy was risk of POPF (78%). The 30-day mortality was 2.2%. Major complications (≥ IIIb according to Clavien-Dindo) occurred in 18.5% within 30 postoperative days. There were no complications directly related to the spleen and vascular preservation procedure. A tumor-negative resection margin was achieved in 71.8%. CONCLUSION: We could demonstrate the technical feasibility and safety of SVPTP even in patients mainly with pancreatic malignancies. In addition to potential immunologic and oncologic advantages, we believe a major benefit of this procedure is preservation of gastric venous outflow. We consider SVPTP to be indicated in patients at high risk for POPF, in patients with multilocular IPMN, and in cases for extended intrapancreatic cancers.

Acid suppression therapy, gastrointestinal bleeding and infection in acute pancreatitis - An international cohort study.

BACKGROUND: Acid suppressing drugs (ASD) are generally used in acute pancreatitis (AP); however, large cohorts are not available to understand their efficiency and safety. Therefore, our aims were to evaluate the association between the administration of ASDs, the outcome of AP, the frequency of gastrointestinal (GI) bleeding and GI infection in patients with AP. METHODS: We initiated an international survey and performed retrospective data analysis on AP patients hospitalized between January 2013 and December 2018. RESULTS: Data of 17,422 adult patients with AP were collected from 59 centers of 23 countries. We found that 23.3% of patients received ASDs before and 86.6% during the course of AP. ASDs were prescribed to 57.6% of patients at discharge. ASD administration was associated with more severe AP and higher mortality. GI bleeding was reported in 4.7% of patients, and it was associated with pancreatitis severity, mortality and ASD therapy. Stool culture test was performed in 6.3% of the patients with 28.4% positive results. Clostridium difficile was the cause of GI infection in 60.5% of cases. Among the patients with GI infections, 28.9% received ASDs, whereas 24.1% were without any acid suppression treatment. GI infection was associated with more severe pancreatitis and higher mortality. CONCLUSIONS: Although ASD therapy is widely used, it is unlikely to have beneficial effects either on the outcome of AP or on the prevention of GI bleeding during AP. Therefore, ASD therapy should be substantially decreased in the therapeutic management of AP.

Computer-aided assessment of the extra-cellular matrix during pancreatic carcinogenesis: a pilot study.

BACKGROUND: A hallmark of pancreatic ductal adenocarcinoma is the desmoplastic reaction, but its impact on the tumor behavior remains controversial. Our aim was to introduce a computer -aided method to precisely quantify the amount of pancreatic collagenic extra-cellular matrix, its spatial distribution pattern, and the degradation process. METHODS: A series of normal, inflammatory and neoplastic pancreatic ductal adenocarcinoma formalin-fixed and paraffin-embedded Sirius red stained sections were automatically digitized and analyzed using a computer-aided method. RESULTS: We found a progressive increase of pancreatic collagenic extra-cellular matrix from normal to the inflammatory and pancreatic ductal adenocarcinoma. The two-dimensional fractal dimension showed a significant difference in the collagenic extra-cellular matrix spatial complexity between normal versus inflammatory and pancreatic ductal adenocarcinoma. A significant difference when comparing the number of cycles necessary to degrade the pancreatic collagenic extra-cellular matrix in normal versus inflammatory and pancreatic ductal adenocarcinoma was also found. The difference between inflammatory and pancreatic ductal adenocarcinoma was also significant. Furthermore, the mean velocity of collagenic extra-cellular matrix degradation was found to be faster in inflammatory and pancreatic ductal adenocarcinoma than in normal. CONCLUSION: These findings demonstrate that inflammatory and pancreatic ductal adenocarcinomas are characterized by an increased amount of pancreatic collagenic extra-cellular matrix and by changes in their spatial complexity and degradation. Our study defines new features about the pancreatic collagenic extra-cellular matrix, and represents a basis for further investigations into the clinical behavior of pancreatic ductal adenocarcinoma and the development of therapeutic strategies.

Matricellular proteins and survival in patients with pancreatic cancer: A systematic review.

Extracellular matrix (ECM) plays a fundamental role in tissue architecture and homeostasis and modulates cell functions through a complex interaction between cell surface receptors, hormones, several bioeffector molecules, and structural proteins like collagen. These components are secreted into ECM and all together contribute to regulate several cellular activities including differentiation, apoptosis, proliferation, and migration. The so-called "matricellular" proteins (MPs) have recently emerged as important regulators of ECM functions. The aim of our review is to consider all different types of MPs family assessing the potential relationship between MPs and survival in patients with pancreatic ductal adenocarcinoma (PDAC). A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement issued in 2009 was conducted through Ovid interface, and literature review was performed in May 2017. The search text words were identified by means of controlled vocabulary, such as the National Library of Medicine's MESH (Medical Subject Headings) and Keywords. Collected data showed an important role of MPs in carcinogenesis and in PDAC prognosis even though the underlying mechanisms are still largely unknown and data are not univocal. Therefore, a better understanding of MPs role in regulation of ECM homeostasis and remodeling of specific organ niches may suggest potential novel extracellular targets for the development of efficacious therapeutic strategies.

Characterization of malignant gastrointestinal stromal tumors-a single center experience.

BACKGROUND: The recurrence rate, related to the unpredictable behavior of gastrointestinal stromal tumors (GISTs), continues to be a major topic of investigation, since no actual risk evaluation scales have proven to be exceedingly effective in predicting prognosis. We therefore focus in this study on investigating the predictive variables of disease recurrence. METHODS: Between September 2004 and January 2011, 34 patients, 18 males and 16 females with a median age of 62 (range, 27-87) years, underwent operations for primary, localized and advanced GISTs. Immunohistochemical profile, KIT and the platelet-derived growth factor receptor-alpha (PDGFR-α) gene mutations, tumor size, tumor site, mitotic index, synchronous tumors, adjuvant therapy, symptoms and gender were considered and analyzed as predictive variables. The receiver operating characteristic (ROC) analysis was used to determine the optimal cut-off value for tumor dimension to predict recurrence. RESULTS: The median follow-up (FU) was 20 months (range, 6-86 months). A first-line adjuvant therapy was performed in nine patients. Disease relapse occurred in five cases. The tumor size and the mitotic index were the strongest predictive factors (P<0.001). The optimal maximum value for the tumor size was 7 cm [area under the curve (AUC) =0.955]. CONCLUSIONS: In light of the most recent evidence, a tumor size of 7 cm should be considered the threshold value for malignancy, and smaller GISTs with low mitotic counts as tumors with a low-grade risk.

MicroRNAs as possible biomarkers for diagnosis and prognosis of hepatitis B- and C-related-hepatocellular-carcinoma.

Aim of the present review is to summarize the current knowledge about the potential relationship between miRNAs and hepatitis B virus (HBV)-hepatitis C virus (HCV) related liver diseases. A systematic computer-based search of published articles, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis Statement, was performed to identify relevant studies on usefulness of serum/plasma/urine miRNAs, as noninvasive biomarkers for early detection of HBV and HCV-induced hepatocellular carcinoma (HCC) development, as well as for its prognostic evaluation. The used Medical Subject Headings terms and keywords were: "HBV", "HCV", "hepatocellular carcinoma", "microRNAs", "miRNAs", "diagnosis", "prognosis", "therapy", "treatment". Some serum/plasma miRNAs, including miR-21, miR-122, mi-125a/b, miR-199a/b, miR-221, miR-222, miR-223, miR-224 might serve as biomarkers for early diagnosis/prognosis of HCC, but, to date, not definitive results or well-defined panels of miRNAs have been obtained. More well-designed studies, focusing on populations of different geographical areas and involving larger series of patients, should be carried out to improve our knowledge on the potential role of miRNAs for HCC early detection and prognosis.

Possible association between hepatitis C virus and malignancies different from hepatocellular carcinoma: A systematic review.

AIM: To summarize the current knowledge about the potential relationship between hepatitis C virus (HCV) infection and the risk of several extra-liver cancers. METHODS: We performed a systematic review of the literature, according to the Preferred Reporting Items for Systematic reviews and Meta-Analysis (PRISMA) Statement. We extracted the pertinent articles, published in MEDLINE and the Cochrane Library, using the following search terms: neoplasm/cancer/malignancy/tumor/carcinoma/adeno-carcinoma and non-Hodgkin lymphomas, kidney/renal-, cholangio-, pancreatic-, thyroid-, breast-,oral-, skin-, prostate-, lung-, colon-, stomach-, haematologic. Case series, case-series with control-group, case-control, cohort-studies as well as meta-analyses, written in English were collected. Some of the main characteristics of retrieved trials, which were designed to investigate the prevalence of HCV infection in each type of the above-mentioned human malignancies were summarised. A main table was defined and included a short description in the text for each of these tumours, whether at least five studies about a specific neoplasm, meeting inclusion criteria, were available in literature. According to these criteria, we created the following sections and the corresponding tables and we indicated the number of included or excluded articles, as well as of meta-analyses and reviews: (1) HCV and haematopoietic malignancies; (2) HCV and cholangiocarcinoma; (3) HCV and pancreatic cancer; (4) HCV and breast cancer; (5) HCV and kidney cancer; (6) HCV and skin or oral cancer; and (7) HCV and thyroid cancer. RESULTS: According to available data, a clear correlation between regions of HCV prevalence and risk of extra-liver cancers has emerged only for a very small group of types and histological subtypes of malignancies. In particular, HCV infection has been associated with: (1) a higher incidence of some B-cell Non-Hodgkin-Lymphoma types, in countries, where an elevated prevalence of this pathogen is detectable, accounting to a percentage of about 10%; (2) an increased risk of intra-hepatic cholangiocarcinoma; and (3) a correlation between HCV prevalence and pancreatic cancer (PAC) incidence. CONCLUSION: To date no definitive conclusions may be obtained from the analysis of relationship between HCV and extra-hepatic cancers. Further studies, recruiting an adequate number of patients are required to confirm or deny this association.

Improvement in perioperative and long-term outcome after surgical treatment of hilar cholangiocarcinoma: results of an Italian multicenter analysis of 440 patients.

OBJECTIVE: To evaluate improvements in operative and long-term results following surgery for hilar cholangiocarcinoma. DESIGN: Retrospective multicenter study including 17 Italian hepatobiliary surgery units. PATIENTS: A total of 440 patients who underwent resection for hilar cholangiocarcinoma from January 1, 1992, through December 31, 2007. MAIN OUTCOME MEASURES: Postoperative mortality, morbidity, overall survival, and disease-free survival. RESULTS: Postoperative mortality and morbidity after liver resection were 10.1% and 47.6%, respectively. At multivariate logistic regression, extent of resection (right or right extended hepatectomy) and intraoperative blood transfusion were independent predictors of postoperative mortality (P = .03 and P = .006, respectively); in patients with jaundice, mortality was also higher without preoperative biliary drainage than with biliary drainage (14.3% vs 10.7%). During the study period, there was an increasingly aggressive approach, with more frequent caudate lobectomies, vascular resections, and resections for advanced tumors (T stage of 3 or greater and tumors with poor differentiation). Despite the aggressive approach, the blood transfusion rate decreased from 81.0% to 53.2%, and mortality slightly decreased from 13.6% to 10.8%. Median overall survival significantly increased from 16 to 30 months (P = .05). At multivariate analysis, R1 resection, lymph node metastases, and T stage of 3 or greater independently predicted overall and disease-free survival. CONCLUSIONS: Surgery for hilar cholangiocarcinoma has improved with decreased operative risk despite a more aggressive surgical policy. Long-term survival after liver resection has also increased, despite the inclusion of cases with more advanced hilar cholangiocarcinoma. Preoperative biliary drainage was a safe strategy before right or right extended hepatectomy in patients with jaundice. Pathologic factors independently predicted overall and disease-free survival at multivariate analysis.

Analysis of prognostic factors in metastatic tumors of the pancreas: a single-center experience and review of the literature.

OBJECTIVES: Pancreatic metastases are rare. The role of surgery is poorly defined, and data on long-term survival are lacking. METHODS: Data from patients with pancreatic metastases observed in our division from 2003 to 2008 were retrospectively analyzed. In addition, the recent English medical literature was reviewed regarding series of patients with pancreatic secondary tumors. RESULTS: Data from 234 patients including 9 consecutive patients observed in our division were retrieved. Metastasis from renal cell carcinoma accounted for 67.9% of all cases. Factors predictive of worse survival, as determined by multivariate analysis, were symptoms at diagnosis, synchronous tumors, radical-intent surgery not performed, and pathologic diagnosis of the primary tumor. Compared with pancreatic metastases from renal cell cancer, metastases from melanoma (P < 0.001) and lung cancer (P = 0.002) were associated with worse survival. The differences in survival of patients with renal cell cancer metastases and those with breast cancer, colorectal, or sarcoma metastases did not reach statistical significance. CONCLUSIONS: There may be a subset of patients with pancreatic metastases who are able to benefit from surgery with respect to improved long-term survival. Symptoms at diagnosis, presentation with primary tumor, surgical resection, and pathologic diagnosis seem to be important prognostic factors.

[Laparoscopic colorectal surgery: is the "learning curve" necessary?]. / Chirurgia colo-rettale laparoscopica: e necessaria la "curva di apprendimento"?

AIM OF THE STUDY: To present the early experience of the Authors' division in the field of colorectal laparoscopic surgery, in order to evaluate the so-called "learning curve". MATERIALS AND METHOD: From February 2003 to May 2004, we have performed 220 surgical procedures for colorectal pathology: 63 were conducted by a laparoscopic approach with 10 patients who, converted to a laparotomic procedure in theatre, were not taken under consideration. The present work is thus based on a population of 53 patients, 27 men and 26 women, at a median age of 64.4 y.o. (range 42-81). RESULTS: We performed 1 total colectomy, 24 right hemicolectomy, 1 resection of the splenic flexure, 12 left hemicolectomy (in 1 case a left hepatic lobectomy was associated), 11 anterior resection of the rectum, 1 Hartmann' sigmoid resection and 3 abdomino-perineal resection. Mean operative time was 200.34 +/- 64.17 min, while the mean hospital stay was 6.44 +/- 2.68 days. Peri-operative mortality was 0%, 30-days mortality was 1/53 patients (9%) while morbidity was 5/53 patients (9.4%): in 2 cases reintervention was necessary. DISCUSSION: From the evaluation of the results, we found some significant data: first, the conversion rate was similar to those reported by other authors, so also the mortality and morbidity rates. CONCLUSIONS: The advantages of the laparoscopic technique, indirectly documented by shorter in-hospital stay. At least for patients submitted to right or left hemicolectomy without complications (5.5 e 5.7 days, respectively), could be seen also after only a 1 year of activity. As far as the "learning curve" is concerned, dividing our activity into 3 times, we verified a progressive shortening of the operative time and, at least for the patients submitted to a right emicolecomy, also of the morbidity rates.

Liver damage in obese patients.

BACKGROUND: Hepatic steatosis, nonalcoholic steatohepatitis and cryptogenetic cirrhosis are frequent in an obese population. Therefore, it is wise to submit all obese patients with significant alterations in hepatic function tests to transparietal liver biopsy. The aim of this study is to determine the hepatic conditions of morbidly obese patients during bariatric surgery by means of a wedge liver biopsy, to avoid any eventual hepatic damage being ascribed to the surgical procedure. METHODS: This prospective study entails 216 consecutive patients, whose work-up included liver function tests, before undergoing vertical gastroplasty and wedge liver biopsy. Histology was assessed for hepatic steatosis, necroinflammatory activity and liver fibrosis/cirrhosis. RESULTS: Abnormal preoperative liver function tests were detected in 65 patients, in 52 unexpectedly. Histologically, significant steatosis was found in 168 patients (77.8%); necroinflammatory activity in 13 (6.0%); liver fibrosis in 46 (21.3%), 5 of whom (2.3%) were found to have an asymptomatic and unknown liver cirrhosis. CONCLUSION: In morbidly obese patients, the incidence of histological liver damage is very high, despite acceptable liver function tests. In addition to steatosis, however, a "second hit" to induce necrosis and inflammation, favoring the development of significant fibrosis, is not essential. Being obese is an independent risk factor for liver damage and could contribute to liver fibrosis either alone or in association with other insulting factors. The identification of obese patients with septal fibrosis/cirrhosis, at surgery, is of considerable interest in clinical practice, mainly under the aspect of prognosis and liability.