Impact of neoadjuvant chemoradiotherapy on pathologic response in pancreatic ductal adenocarcinoma: A systematic review and meta-analysis.

BACKGROUND: The impact of chemoradiotherapy on pathologic response, resection margin, and survival benefit is still debated. The aim of this study was to compare the rate of pathologic complete response (pCR) in surgical resection following neoadjuvant chemotherapy vs. chemoradiotherapy, and secondarily, to compare the rate of R0 resection and Overall Survival (OS). METHODS: A systematic review on MEDLINE/PubMed, Embase, Cochrane, Web of Science and Google Scholar was conducted for studies published between 2012 and 2024 (PROSPERO CRD42022341467). All studies reporting clinical outcomes of patients with Pancreatic ductal adenocarcinoma (PDAC) following neoadjuvant therapy were considered eligible for inclusion. A meta-analysis comparing the rate of pCR, R0 resection rate, and 3-year OS following Chemotherapy vs chemoradiotherapy in patients was performed. The overall quality of evidence was evaluated using a GRADE approach. RESULTS: Out of 5194 potentially relevant studies, 29 studies were considered eligible for full-text assessment, and 11 studies were included in the systematic review and in the meta-analysis. Of these, five were retrospective single-center, five retrospective multi-center studies, and one was a phase II multi-center RCT. Overall, 1830 Chemotherapy patients and 2299 Chemoradiotherapy patients were included in the meta-analysis. A statistically significant increased rate of pCR and R0 resections were found in chemoradiotherapy patients (OR 3.58, 95 % CI 2.47-5.18, p ≤ 0.00001) (OR 1.49, 95 % CI 1.17-1.90, p = 0.001), whereas 3-year OS (OR 1.07, 95 % CI 0.84-1.36, p = 0.6) did not differ significantly. CONCLUSIONS: Chemoradiotherapy may have a positive impact on pathologic response and R0 resection rate, whereas a survival benefit was not reported.

Prognostic value of major pathological response following neoadjuvant therapy for non resectable pancreatic ductal adenocarcinoma.

BACKGROUND: The aim of this study is to evaluate the impact of major pathological response on overall survival (OS) in borderline resectable and locally advanced pancreatic ductal adenocarcinoma following neoadjuvant treatment, and to identify predictors of major pathological response. METHODS: Patients surgically resected following neoadjuvant treatment between 2010 and 2020 at the Pederzoli Hospital were retrospectively analyzed. Pathologic response was assessed using the College of American Pathologists (CAP) score, and major pathological response was defined as CAP 0-1. OS was estimated and compared using the Kaplan-Meier method and log-rank test. A logistic and Cox regression model were performed to identify predictors of major pathologic response and OS. RESULTS: Overall, 200 patients were included in the study. A major and complete pathological response were observed in 52(26.0%) and 15(7.3%) patients respectively. The 1-, 3-, 5-year OS was 92.7, 67.2, and 41.7%, and 71.0, 37.4, and 20.8% in patients with or without major pathologic response respectively (log-rank test p < 0.001). Major pathologic response was confirmed as independent predictor of OS (OR 0.50 95%CI 0.29-0.88, p = 0.01). Post-treatment CA19-9 normalization (OR 4.20 95%CI 1.14-10.35, p = 0.02) and radiological post-treatment tumor residual size<25 mm (OR 2.71 95%CI 1.27-5.79, p = 0.01) were found to be independent predictors of major pathologic response. CONCLUSION: Patients experienced a major pathological response after neoadjuvant treatment have an increased survival, and major pathologic response is an independent predictor of OS. A normal CA19-9 value and radiological tumor size at restaging are confirmed to be independent predictors of major pathologic response.

Current Role and Future Perspectives of Immunotherapy and Circulating Factors in Treatment of Biliary Tract Cancers.

Biliary tract cancers (BTCs) are a heterogenous group of malignancies arising from the epithelial cells of the biliary tree and the gallbladder. They are often locally advanced or already metastatic at the time of the diagnosis and therefore prognosis remains dismal. Unfortunately, the management of BTCs has been limited by resistance and consequent low response rate to cytotoxic systemic therapy. New therapeutic approaches are needed to improve the survival outcomes for these patients. Immunotherapy, one of the newest therapeutic options, is changing the approach to the oncological treatment. Immune checkpoint inhibitors are by far the most promising group of immunotherapeutic agents: they work by blocking the tumor-induced inhibition of the immune cellular response. Immunotherapy in BTCs is currently approved as second-line treatment for patients whose tumors have a peculiar molecular profile, such as high levels of microsatellites instability, PD-L1 overexpression, or high levels of tumor mutational burden. However, emerging data from ongoing clinical trials seem to suggest that durable responses can be achieved in other subsets of patients. The BTCs are characterized by a highly desmoplastic microenvironment that fuels the growth of cancer tissue, but tissue biopsies are often difficult to obtain or not feasible in BTCs. Recent studies have hence proposed to use liquid biopsy approaches to search the blood circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) to use as biomarkers in BTCs. So far studies are insufficient to promote their use in clinical management, however trials are still in progress with promising preliminary results. Analysis of blood samples for ctDNA to research possible tumor-specific genetic or epigenetic alterations that could be linked to treatment response or prognosis was already feasible. Although there are still few data available, ctDNA analysis in BTC is fast, non-invasive, and could also represent a way to diagnose BTC earlier and monitor tumor response to chemotherapy. The prognostic capabilities of soluble factors in BTC are not yet precisely determined and more studies are needed. In this review, we will discuss the different approaches to immunotherapy and tumor circulating factors, the progress that has been made so far, and the possible future developments.

Telemedicine and Pancreatic Cancer: A Systematic Review.

Introduction: Pancreatic cancer requires a multidisciplinary approach in a high-volume center for all the steps of the diagnostic-therapeutic course. However, the most experienced centers are not evenly distributed throughout the country causing a real "health migration" that involves patients and families with relevant economic, time, and energy costs to bear. The COVID-19 pandemic had a deep impact on surgical and oncological care and the travel limits due to COVID-related restrictions, have delayed the care of cancer patient living far from the referral centers. In this scenario, several telemedicine approaches have been proposed to reduce the distance between clinicians and patients and to allow a fast and effective access to care even for patients distant from referral centers. The aim of the study is to analyze the evidence and describe the current utility of telemedicine tool for patients with pancreatic cancer. Methods: We systematically searched the literature in the following databases: Web of Science, PubMed, Scopus, and MEDLINE. The inclusion criteria were article describing a telemedicine intervention (virtual visits, telephone follow-up/counseling, mobile or online apps, telemonitoring) and focusing on adult patients with pancreatic cancer at any stage of the disease. Results: In total, 846 titles/abstracts were identified. Following quality assessment, the review included 40 studies. Telemedicine has been proposed in multiple clinical settings, demonstrating high levels of patient and health professional satisfaction. Conclusion: Successful telemedicine applications in patients with pancreatic cancer are telerehabilitation and nutritional assessment, remote symptom control, teledischarge after pancreatic surgery, tele-education and medical mentoring regarding pancreatic disease as well as telepathology.

Portal vein stenting in recurrent or locally advanced peri-hilar cholangiocarcinoma.

BACKGROUND: Recurrent or locally advanced peri-hilar cholangiocarcinoma (PHCC) usually involves the portal vein (PV) leading to significant stenosis. With disease progression, clinical symptoms such as ascites, bleeding, and hepatic insufficiency are usually observed. Little is know about the benefit of PV stenting in relieving the symptoms associated to portal hypertension and allowing anticancer therapies. The aim of this study is to review our experience in PV stenting for PHCC patients. METHODS: From 2014 to 2022, data from PHCC patients underwent PV stenting at Verona University Hospital, Italy, were reviewed. The indications were: gastrointestinal bleeding from esophagus-gastric varices, ascites not responsive to medical therapy, severe thrombocytopenia, liver insufficiency (hepatic jaundice, coagulopathy, and/or hyperammoniemia), or asymptomatic high-grade PV stenosis. Cavernous transformation and intrahepatic thrombosis in both sides of the liver were considered contraindication. Systematic anticoagulation therapy was not administered. RESULTS: Technical success was achieved in all 16 (100 %) patients. The improvement of clinical symptoms were observed in 12 (75 %) patients. Anticancer therapy was administrated in 11 (69 %) patients. 2 (13 %) complications were observed: 1 biliary injury and 1 recurrent cholangitis that required a percutaneous trans-hepatic biliary drainage placement. Stent occlusion for tumor progression occurred in 1 patient and a re-stenting procedure was successfully performed. No case of thrombotic stent occlusion was observed during follow up. The 1-year stent patency was 86 % and the median patency period was 8 months (IQR, 4-12). CONCLUSION: PV stenting is a feasible and safe palliative treatment that improves clinical condition, allow anticancer therapies, and provide a better quality of life.

Trends in hospital volume and operative mortality in hepato-biliary surgery in Veneto region, Italy.

Hepatobiliary resections are among the most complex and technically challenging surgical procedures. Even though robust evidence showed that complex surgical procedures such as hepatobiliary surgery have better short- and long-term outcomes and lower mortality rate when performed in high-volume centers, the minimal criteria of centers that can perform hepatobiliary activity are not clearly defined. We conducted a retrospective population study of patients who underwent hepatobiliary surgery for malignant disease in a single Italian administrative region (Veneto) from 2010 to 2021 with the aim to investigate the hospitals annual surgical volume for hepatobiliary malignant diseases and the effect of hospital volume on in-hospital, 30- and 90-day postoperative mortality. The centralization process of hepatobiliary surgery in Veneto is rapidly increasing over the past 10 years (rate of performed in highly specialized centers increased from 62% in 2010 to 78% in 2021) and actually it is really established. The crude and adjusted (for age, sex, Charlson Index) mortality rate after hepatobiliary surgery resulted significantly lower in centers with high-volume activity compared to them with low-volume activity. In the Veneto region, the "Hub and Spoke" model led to a progressive centralization of liver and biliary cancer treatment. High surgical volume has been confirmed to be related to better outcomes in terms of mortality rate after hepatobiliary surgical procedures. Further studies are necessary to clearly define the minimal criteria and associated numerical cutoffs that can help define the characteristics of centers that can perform hepatobiliary activities.

Co-design, co-learning, and co-production of an app for pancreatic cancer patients-the "Pancreas Plus" study protocol.

Background: Pancreatic cancer is a malignant and complex tumor that often leads to an adverse prognosis. Patients need to face a challenging treatment path, which involves highly-specialized multidisciplinary professionals. The complexity of the disease requires the development of dedicated tools to support patients in their care journey. Co-production stands as a valuable strategy in oncological care to engage patients in understanding their care journey and behaving accordingly to get the best possible clinical outcome. Methods: The non-profit association Unipancreas, active in promoting the latest advances in pancreatic cancer care and in supporting pancreatic cancer patients, has partnered with a multidisciplinary group of professionals to conceive the brand new program "Pancreas Plus" to employ a co-design, co-learning, and co-production path to design an app devoted to pancreatic cancer patients to assist them during their treatment and follow-up journey. The app, which is the outcome of a multi-stakeholder engagement project, offers health information and medical advice specifically tailored on the pancreatic cancer disease. The article reports the research protocol, which may be replicated for the design of other e-health tools focusing on different conditions. Discussion: The study's output will be an app that sees the pancreatic cancer patient as the main beneficiary but which can gather and address the interests and needs of all meaningful stakeholders, including clinicians, researchers, healthcare and educational institutions, and non-profit associations. Registration: Given the type of study, no registration is required.

Prognostic value of red cell distribution width (RDW) in colorectal cancer. Results from a single-center cohort on 591 patients.

Increasing evidence advocates the prognostic role of RDW in various tumours. We analysed 591 patients to assess whether RDW is a prognostic factor for overall (OS) and cancer-related survival (CRS) for patients with colorectal cancer (CRC). The data were retrieved from a retrospective database. The optimal cut-off value for RDW was set at 14.1%; accordingly, two groups were considered: those with a value equal or lower than 14.1% (L-RDW), and those with a value higher than 14.1% (H-RDW). The mean value of RDW rose from pT1 to pT4 tumours. H-RDW correlated with age above the mean, colonic location of the lesion, pT and TNM stage. Finally, H-RDW was significantly associated with the intent of surgery: almost 50% of patients who underwent a non-curative resection presented H-RDW, compared to 19.3% in R0 resections. OS was significantly lower in patients with H-RDW. CRS was similar in the two groups. Stratifying patients according to TNM stage worse OS was associated with H-RDW only in early stages, whereas there was no difference for stages II-IV. Multivariate analysis confirmed that H-RDW was not an independent prognostic factor. Although H-RDW correlated with some negative clinical-pathological factors, it did not seem to independently influence OS and CRS.

Quality Versus Costs Related to Gastrointestinal Surgery: Disentangling the Value Proposition.

BACKGROUND: There has been a dramatic increase in worldwide health care spending over the last several decades. Operative procedures and perioperative care in the USA represent some of the most expensive episodes per patient. In view of both the rising cost of health care in general and the rising cost of surgical care specifically, policymakers and stakeholders have sought to identify ways to increase the value-improving quality of care while controlling (or diminishing) costs. In this context, we reviewed data relative to achieving the "value proposition" in the delivery of gastrointestinal surgical care. METHODS: The National Library of Medicine online repository (PubMed) was text searched for human studies including "cost," "quality," "outcomes," "health care," "surgery," and "value." Results from this literature framed by the Donabedian conceptual model (identifying structures, processes, and outcomes), and the resulting impact of efforts to improve quality on costs. RESULTS: The relationship between quality and costs was nuanced. Better quality care, though associated with better outcomes, was not always reported as concomitant with low costs. Moreover, some centers reported higher costs of surgical care commensurate with higher quality. Conversely, higher costs in health care delivery were not always linked to improved outcomes. While higher quality surgical care can lead to lower costs, higher costs of care were not necessarily associated with better outcomes. Strategies to improve quality, reduce cost, or achieve both simultaneously included regionalization of complex operations to high-volume centers of excellence, overall reduction in complications, introducing evidence-based improvements in perioperative care pathways including as enhanced recovery after surgery (ERAS), and elimination of inefficient or low-value care. CONCLUSIONS: The relationship between quality and cost following gastrointestinal surgical procedure is complex. Data from the current study should serve to highlight the various means available to improve the value proposition related to surgery, as well as encourage surgeons to become more engaged in the national conversation around the Triple Aim of better health care quality, lower costs, and improved health care outcomes.

Impact of age on feasibility and short-term outcomes of ERAS after laparoscopic colorectal resection.

BACKGROUND: There is still large debate on feasibility and advantages of fast-track protocols in elderly population after colorectal surgery. AIM: To investigate the impact of age on feasibility and short-term results of enhanced recovery protocol (ERP) after laparoscopic colorectal resection. METHODS: Data from 225 patients undergoing laparoscopic colorectal resection and ERP between March 2014 and July 2018 were retrospectively analyzed. Three groups were considered according to patients' age: Group A, 65 years old or less, Group B, 66 to 75 years old and Group C, 76 years old or more. Clinic and pathological data were compared amongst groups together with post-operative outcomes including post-operative overall and surgery-specific complications, mortality and readmission rate. Differences in post-operative length of stay and adherence to ERP's items were evaluated in the three study groups. RESULTS: Among the 225 patients, 112 belonged to Group A, 57 to Group B and 56 to Group C. Thirty-day overall morbidity was 32.9% whilst mortality was nihil. Though the percentage of complications progressively increased with age (25.9% vs 36.8% vs 42.9%), no differences were observed in the rate of major complications (4.5% vs 3.5% vs 1.8%), prolonged post-operative ileus (6.2% vs 12.2% vs 10.7%) and anastomotic leak (2.7% vs 1.8% vs 1.8%). Significant differences in recovery outcomes between groups were observed such as delayed urinary catheter removal (P = 0.032) and autonomous deambulation (P = 0.013) in elderly patients. Although discharge criteria were achieved later in older patients (3 d vs 3 d vs 4 d, P = 0.040), post-operative length of stay was similar in the 3 groups (5 d vs 6 d vs 6 d). CONCLUSION: ERPs can be successfully and safely applied in elderly undergoing laparoscopic colorectal resection.