The Falciform Ligament for Mesenteric and Portal Vein Reconstruction in Local Advanced Pancreatic Tumor: A Surgical Guide and Single-Center Experience

Background. Since local tumor infiltration to the mesenteric-portal axis might represent a challenging assignment for curative intended resectability during pancreatic surgery, appropriate techniques for venous reconstruction are essential. In this study, we acknowledge the falciform ligament as a feasible and convenient substitute for mesenteric and portal vein reconstruction with high reliability and patency for local advanced pancreatic tumor. Methods. A retrospective single-center analysis. Between June 2017 and January 2018, a total of eleven consecutive patients underwent pancreatic resections with venous reconstruction using falciform ligament. Among them, venous resection was performed in nine cases by wedge and in two cases by full segment. Patency rates and perioperative details were reviewed. Results. Mean clamping time of the mesenteric-portal blood flow was 34 min, while perioperative mortality rate was 0%. By means of Duplex ultrasonography, nine patients were shown to be patent on the day of discharge, while two cases revealed an entire occlusion of the mesenteric-portal axis. Orthograde flow demonstrated a mean value of 34 cm/s. All patent grafts on discharge revealed persistent patencywithin various follow-up assessments. Conclusion. The falciform ligament appears to be a feasible and reliable autologous tissue for venous blood flow reconstruction with high postoperative patency. Especially the possibility of customizing graft dimensions to the individual needs based on local findings allows an optimal size matching of the conduit. The risk of stenosis and/or segmental occlusionmay thus be further reduced

Adjuvant nab-Paclitaxel + Gemcitabine in Resected Pancreatic Ductal Adenocarcinoma: Results From a Randomized, Open-Label, Phase III Trial

Pancreatic ductal adenocarcinomaAdenocarcinoma ductal pancreáticoAdenocarcinoma ductal pancreàticPURPOSE This randomized, open-label trial compared the efficacy and safety of adjuvant nab-paclitaxel + gemcitabine with those of gemcitabine for resected pancreatic ductal adenocarcinoma (ClinicalTrials.gov identifier: NCT01964430). METHODS We assigned 866 treatment-naive patients with pancreatic ductal adenocarcinoma to nab-paclitaxel (125 mg/m2) + gemcitabine (1,000 mg/m2) or gemcitabine alone to one 30-40 infusion on days 1, 8, and 15 of six 28-day cycles. The primary end point was independently assessed disease-free survival (DFS). Additional end points included investigator-assessed DFS, overall survival (OS), and safety. RESULTS Two hundred eighty-seven of 432 patients and 310 of 434 patients completed nab-paclitaxel + gemcitabine and gemcitabine treatment, respectively. At primary data cutoff (December 31, 2018; median follow-up, 38.5 [interquartile range [IQR], 33.8-43 months), the median independently assessed DFS was 19.4 (nab-paclitaxel + gemcitabine) versus 18.8 months (gemcitabine; hazard ratio [HR], 0.88; 95% CI, 0.729 to 1.063; P = .18). The median investigator-assessed DFS was 16.6 (IQR, 8.4-47.0) and 13.7 (IQR, 8.3-44.1) months, respectively (HR, 0.82; 95% CI, 0.694 to 0.965; P = .02). The median OS (427 events; 68% mature) was 40.5 (IQR, 20.7 to not reached) and 36.2 (IQR, 17.7-53.3) months, respectively (HR, 0.82; 95% CI, 0.680 to 0.996; P = .045). At a 16-month follow-up (cutoff, April 3, 2020; median follow-up, 51.4 months [IQR, 47.0-57.0]), the median OS (511 events; 81% mature) was 41.8 (nab-paclitaxel + gemcitabine) versus 37.7 months (gemcitabine; HR, 0.82; 95% CI, 0.687 to 0.973; P = .0232). At the 5-year follow-up (cutoff, April 9, 2021; median follow-up, 63.2 months [IQR, 60.1-68.7]), the median OS (555 events; 88% mature) was 41.8 versus 37.7 months, respectively (HR, 0.80; 95% CI, 0.678 to 0.947; P = .0091). Eighty-six percent (nab-paclitaxel + gemcitabine) and 68% (gemcitabine) of patients experienced grade ≥ 3 treatment-emergent adverse events. Two patients per study arm died of treatment-emergent adverse events. CONCLUSION The primary end point (independently assessed DFS) was not met despite favorable OS seen with nab-paclitaxel + gemcitabine

Treatment of Intrahepatic Cholangiocarcinoma—A Multidisciplinary Approach

Intrahepatic cholangiocarcinoma (iCC) is distinguished as an entity from perihilar and distal cholangiocarcinoma and gallbladder carcinoma. Recently, molecular profiling and histopathological features have allowed further classification. Due to the frequent delay in diagnosis, the prognosis for iCC remains poor despite major technical advances and multimodal therapeutic approaches. Liver resection represents the therapeutic backbone and only curative treatment option, with the functional residual capacity of the liver and oncologic radicality being deciding factors for postoperative and long-term oncological outcome. Furthermore, in selected cases and depending on national guidelines, liver transplantation may be a therapeutic option. Given the often advanced tumor stage at diagnosis or the potential for postoperative recurrence, locoregional therapies have become increasingly important. These strategies range from radiofrequency ablation to transarterial chemoembolization to selective internal radiation therapy and can be used in combination with liver resection. In addition, adjuvant and neoadjuvant chemotherapies as well as targeted therapies and immunotherapies based on molecular profiles can be applied. This review discusses multimodal treatment strategies for iCC and their differential use

Cancer-related neuropathic pain in out-patient oncology clinics: a European survey

BACKGROUND: Although pain is frequently experienced by patients with cancer, it remains under-treated. The primary aim of this study was to estimate the prevalence of cancer-related neuropathic pain (CRNP) in patients with chronic pain who attended an outpatient clinic for standard care in Europe (irrespective of the reason or stage of the cancer). The secondary aims of this study were to characterise pain and cancer in patients with CRNP (including treatment) and to evaluate the usefulness of the painDETECT (PD-Q) screening tool to help physicians identify a potential neuropathic component of cancer-related pain. METHODS: An observational, non-interventional, cross-sectional, multi-centre study of adult patients with cancer using patient and physician case report forms (CRFs). Patients with CRNP were identified by physicians’ clinical assessments after examining the completed PD-Q. RESULTS: A total of 951 patients visiting outpatient clinics across Europe were enrolled in this study between August 2010 and July 2011. Of these, 310 patients (32.60%; 95% confidence interval 29.62, 35.58) were identified as having CRNP. Twenty-nine of 39 (74.4%) physicians who completed the CRF relating to the PD-Q considered it a useful tool to help detect CRNP in daily practice and 28 of 39 (71.8%) indicated that they would use this tool in the future for most or some of their patients. Data from physicians before and after review of the completed PD-Qs showed a shift in clinical opinion (either to positive CRNP diagnosis [yes] or negative CRNP diagnosis [no]) in respect of 142 patients; about half of which (74) were categorised with an initial diagnosis of unknown. Opinions also shifted from a no to a yes diagnosis in 10 patients and from a yes to a no diagnosis in 51 patients. CONCLUSIONS: Approximately one-third of adults with cancer experiencing chronic pain attending outpatient clinics as part of routine care were considered to have CRNP in the opinion of the physicians after considering scores on the PD-Q. While physicians did not consider the PD-Q to be a useful tool for all patients, shifts in diagnosis before and after the use of this tool indicate that it may help physicians identify CRNP, especially where there is initial uncertainty

A tailored approach in lymph node-positive perihilar cholangiocarcinoma

Purpose Extended right hepatectomy is associated with wide surgical margins in PHC and often favored for oncological considerations. However, it remains uncertain whether established surgical principles also apply to the subgroup of node-positive patients. The aim of the present study was to define a tailored surgical approach for patients with perihilar cholangiocarcinoma (PHC) and lymph node metastases. Methods We reviewed the course of all consecutive patients undergoing major hepatectomy for PHC between 2005 and 2015 at the Department of Surgery, Charite - Universitatsmedizin Berlin. Results Two hundred and thirty-one patients underwent major hepatectomy for PHC with 1-, 3-, and 5-year overall (OS) and disease-free survival (DFS) rates of 72%, 48%, and 36%, and 60%, 22%, and 12%, respectively. In lymph node-positive patients (n = 109, 47%), extended left hepatectomy was associated with improved OS and DFS, respectively, when compared to extended right hepatectomy (p = 0.008 and p = 0.003). Interestingly, OS and DFS did not differ between R0 and R1 resections in those patients (both p = ns). Patients undergoing extended left hepatectomy were more likely to receive adjuvant chemotherapy (p = 0.022). This is of note as adjuvant chemotherapy, besides grading (p = 0.041), was the only independent prognostic factor in node-positive patients (p=0.002). Conclusion Patients with node-positive PHC might benefit from less aggressive approaches being associated with lower morbidity and a higher chance for adjuvant chemotherapy. Lymph node sampling might help to guide patients to the appropriate surgical approach according to their lymph node status

Features of ZED1227: The first-in-class tissue transglutaminase inhibitor undergoing clinical evaluation for the treatment of celiac disease

ZED1227 is a small molecule tissue transglutaminase (TG2) inhibitor. The compound selectively binds to the active state of TG2, forming a stable covalent bond with the cysteine in its catalytic center. The molecule was designed for the treatment of celiac disease. Celiac disease is an autoimmune-mediated chronic inflammatory condition of the small intestine affecting about 1–2% of people in Caucasian populations. The autoimmune disease is triggered by dietary gluten. Consumption of staple foods containing wheat, barley, or rye leads to destruction of the small intestinal mucosa in genetically susceptible individuals, and this is accompanied by the generation of characteristic TG2 autoantibodies. TG2 plays a causative role in the pathogenesis of celiac disease. Upon activation by Ca2+, it catalyzes the deamidation of gliadin peptides as well as the crosslinking of gliadin peptides to TG2 itself. These modified biological structures trigger breaking of oral tolerance to gluten, self-tolerance to TG2, and the activation of cytotoxic immune cells in the gut mucosa. Recently, in an exploratory proof-of-concept study, ZED1227 administration clinically validated TG2 as a “druggable” target in celiac disease. Here, we describe the specific features and profiling data of the drug candidate ZED1227. Further, we give an outlook on TG2 inhibition as a therapeutic approach in indications beyond celiac disease

Parenteral nutrition support for patients with pancreatic cancer. Results of a phase II study

<p>Abstract</p> <p>Background</p> <p>Cachexia is a common problem in patients (pts) suffering from upper gastrointestinal cancer. In addition, most of these patients suffer from malabsorption and stenosis of the gastrointestinal tract due to their illness. Various methods of supplementary nutrition (enteral, parenteral) are practised. In patients with advanced pancreatic cancer (APC), phase angle, determined by bio-electrical impedance analysis (BIA), seems to be a survival predictor. The positive influence of BIA determinate predictors by additional nutrition is currently under discussion.</p> <p>Methods</p> <p>To examine the impact of additional parenteral nutrition (APN) we assessed outpatients suffering from APC and progressive cachexia. The assessment based on the BIA method. Assessment parameters were phase angle, ECM/BCM index (ratio of extracellular mass to body cell mass), and BMI (body mass index). Patients suffering from progressive weight loss in spite of additional enteral nutritional support were eligible for the study.</p> <p>Results</p> <p>Median treatment duration in 32 pts was 18 [8-35] weeks. Response evaluation showed a benefit in 27 pts (84%) in at least one parameter. 14 pts (43.7%) improved or stabilised in all three parameters. The median ECM/BCM index was 1.7 [1.11-3.14] at start of APN and improved down to 1.5 [1.12-3.36] during therapy. The median BMI increased from 19.7 [14.4-25.9] to 20.5 [15.4-25.0]. The median phase angle improved by 10% from 3.6 [2.3-5.1] to 3.9 [2.2-5.1].</p> <p>Conclusions</p> <p>We demonstrated the positive impact of APN on the assessed parameters, first of all the phase angle, and we observed at least a temporary benefit or stabilisation of the nutritional status in the majority of the investigated patients. Based on these findings we are currently investigating the impact of APN on survival in a larger patient cohort.</p> <p>Trial registration</p> <p>ClinicalTrials.gov Identifier: NCT00919659</p

Perineural Invasion in Pancreatic Ductal Adenocarcinoma (PDAC): A Saboteur of Curative Intended Therapies?

(1) Background: Perineural invasion (PNI) is a common characteristic of pancreatic ductal adenocarcinoma (PDAC) and is present in most resection margins. We hypothesized that curative pancreatic tumor resection with long-term survival could only be achieved in PNI-negative patients. (2) Material and Methods: A retrospective investigation of PDAC patients who underwent curative-intended surgery during the period 2008 to 2019 was performed at our institution. (3) Results: We identified 571 of 660 (86.5%) resected patients with well-annotated reports and complete datasets. Of those, 531 patients (93%) exhibited tumors with perineural invasion (Pn1), while 40 (7%) were negative for PNI (Pn0). The majority of patients in the Pn1 group presented advanced tumor stage and positive lymph node infiltration. Patients in the Pn0 group showed an improved disease-free and long-term survival compared to the Pn1 group (p < 0.001). Subgroup analysis of all R0-resected patients indicated improved long-term survival and disease-free survival of R0 Pn0 patients when compared to R0 Pn1 patients (p < 0.001). (4) Conclusion: Our study confirmed that Pn0 improves the long-term survival of PDAC-resected cancer patients. Furthermore, PNI significantly challenges the long-term survival of formally curative (R0) resected patients. We provide new insights into the dynamics of PNI in pancreatic cancer patients which are needed to define subgroups of patients for risk stratification and multimodal treatment strategies

Exposure to Inhalable, Respirable, and Ultrafine Particles in Welding Fume

This investigation aims to explore determinants of exposure to particle size-specific welding fume. Area sampling of ultrafine particles (UFP) was performed at 33 worksites in parallel with the collection of respirable particles. Personal sampling of respirable and inhalable particles was carried out in the breathing zone of 241 welders. Median mass concentrations were 2.48 mg m−3 for inhalable and 1.29 mg m−3 for respirable particles when excluding 26 users of powered air-purifying respirators (PAPRs). Mass concentrations were highest when flux-cored arc welding (FCAW) with gas was applied (median of inhalable particles: 11.6 mg m−3). Measurements of particles were frequently below the limit of detection (LOD), especially inside PAPRs or during tungsten inert gas welding (TIG). However, TIG generated a high number of small particles, including UFP. We imputed measurements <LOD from the regression equation with manganese to estimate determinants of the exposure to welding fume. Concentrations were mainly predicted by the welding process and were significantly higher when local exhaust ventilation (LEV) was inefficient or when welding was performed in confined spaces. Substitution of high-emission techniques like FCAW, efficient LEV, and using PAPRs where applicable can reduce exposure to welding fume. However, harmonizing the different exposure metrics for UFP (as particle counts) and for the respirable or inhalable fraction of the welding fume (expressed as their mass) remains challenging

Prostate-specific antigen testing in Tyrol, Austria: prostate cancer mortality reduction was supported by an update with mortality data up to 2008

Objectives: The objective of this study was to update an in-depth analysis of the time trend for prostate cancer (PCA) mortality in the population of Tyrol by 5 years, namely to 2008. In Tyrol, prostate-specific antigen (PSA) tests were introduced in 1988/89; more than three-quarters of all men in the age group 45–74 had at least one PSA test in the past decade. Methods: We applied the same model as in a previous publication, i.e., an age-period-cohort model using Poisson regression, to the mortality data covering more than three decades from 1970 to 2008. Results: For Tyrol from 2004 to 2008 in the age group 60+ period terms show a significant reduction in prostate cancer mortality with a risk ratio of 0.70 (95% confidence interval 0.57, 0.87) for Tyrol, and for Austria excluding Tyrol a moderate reduction with a risk ratio of 0.92 (95% confidence interval 0.87, 0.97), each compared to the mortality rate in the period 1989–1993. Conclusions: This update strengthens our previously published results, namely that PSA testing offered to a population at no charge can reduce prostate cancer mortality. The extent of mortality reduction is in line with that reported in the other recent publications. However, our data do not permit us to fully assess the harms associated with PCA screening, and no recommendation for PSA screening can be made without a careful evaluation of overdiagnosis and overtreatment