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Spleen-preserving distal pancreatectomy (SP-DP), for patients with benign or small low-grade malignant tumors of the body or tail of the pancreas, is the ideal procedure although it is technically demanding. The robotic da Vinci system has been introduced to overcome these technical challenges and reduce operative risks. We report our experience of a new variation in surgical technique: the left lateral approach robotic spleen-preserving distal pancreatectomy (RSP-DP) in right lateral decubitus position. We performed this new variant of SP-DP, in five patients, using the da Vinci Xi system. Technical and clinical feasibility are described. The mean age and body mass index were 53.4 years and 31.4 kg/m 2 , respectively. The mean total operative time was 323 min. The estimated mean blood loss was 240 ml. In all patients, the spleen could be preserved. In four patients, the splenic vessels were also preserved. One patient required a Warshaw technique due to significant fibrosis attached to the splenic vein. The postoperative period of all patients was uneventful except the presence of biochemical leak (BL) in two patients that only required maintenance of the drainage at home. The mean length of hospital stay was 6 days after surgery. The left lateral approach robotic SP-DP in right lateral decubitus position is a feasible and safe procedure for distal benign or small low-grade malignant tumors of the left pancreas. The right lateral decubitus position associated to robotic surgery can facilitate this complex procedure, especially when splenic vessels preservation is indicated, with a lower risk of conversion and shortening of the learning curve., (© 2023. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Objectives: A limited repertoire of good pancreatic ductal adenocarcinoma (PDAC) models is one of the main barriers in developing effective new PDAC treatments. We aimed to characterize 6 commonly used PDAC cell lines and compare them with PDAC patient tumor samples using proteomics., Methods: Proteomic methods were used to generate an extensive catalog of proteins from 10 PDAC surgical specimens, 9 biopsies of adjacent normal tissue, and 6 PDAC cell lines. Protein lists were interrogated to determine what extent the proteome of the cell lines reflects the proteome of primary pancreatic tumors., Results: We identified 7973 proteins from the cell lines, 5680 proteins from the tumor tissues, and 4943 proteins from the adjacent normal tissues. We identified 324 proteins unique to the cell lines, some of which may play a role in survival of cells in culture. Conversely, a list of 63 proteins expressed only in the patient samples, whose expression is lost in culture, may place limitations on the degree to which these model systems reflect tumor biology in vivo., Conclusions: Our work offers a catalog of proteins detected in each of the PDAC cell lines, providing a useful guide for researchers seeking model systems for PDAC functional studies.

Purpose: Surgery is the only potentially curative treatment for pancreatic and liver cancer. However, even in high-volume centres, surgical resection is associated with significant morbidity with resultant physical decline. This systematic review explored physical function and its' implications in the management of resectable cancer of the pancreas and liver., Methods: EMBASE, Medline OVID, CINAHL, Cochrane Library and Web of Science were searched up to June 2019 using a predefined search strategy. Screening of titles, abstracts, and full texts, data extraction, and risk of bias assessment was performed independently by two reviewers. A third reviewer resolved disagreements by consensus., Results: Sixteen studies with a total of 1224 participants were included. Heterogeneity of the literature prevented a meta-analysis. Physical function across the pancreatic/liver cancer trajectory has been under investigated. The relationship between physical function and pancreatic/liver cancer resection outcome remains unclear, although anaerobic threshold appears the strongest predictor of postoperative outcomes. Conclusions regarding the impact of rehabilitative interventions on physical function were limited due to risk of bias concerns., Conclusions: High-quality evidence regarding the implications of physical function in resectable pancreatic and liver cancers is lacking. Well-designed trials are required to examine physical function across the pancreatic/liver cancer continuum and to measure the impact of rehabilitation on physical function., Implications for Cancer Survivors: As survival rates for pancreatic and liver cancer slowly improve a greater understanding of the impact of these cancers and their treatments on physical function, and the potential impact of rehabilitative interventions for survivors is required.

Background: Curative treatment for upper gastrointestinal (UGI) and hepatopancreaticobiliary (HPB) cancers, involves complex surgical resection often in combination with neoadjuvant/adjuvant chemo/chemoradiotherapy. With advancing survival rates, there is an emergent cohort of UGI and HPB cancer survivors with physical and nutritional deficits, resultant from both the cancer and its treatments. Therefore, rehabilitation to counteract these impairments is required to maximise health related quality of life (HRQOL) in survivorship. The initial feasibility of a multidisciplinary rehabilitation programme for UGI survivors was established in the Rehabilitation Strategies following Oesophago-gastric Cancer (ReStOre) feasibility study and pilot randomised controlled trial (RCT). ReStOre II will now further investigate the efficacy of that programme as it applies to a wider cohort of UGI and HPB cancer survivors, namely survivors of cancer of the oesophagus, stomach, pancreas, and liver., Methods: The ReStOre II RCT will compare a 12-week multidisciplinary rehabilitation programme of supervised and self-managed exercise, dietary counselling, and education to standard survivorship care in a cohort of UGI and HPB cancer survivors who are > 3-months post-oesophagectomy/ gastrectomy/ pancreaticoduodenectomy, or major liver resection. One hundred twenty participants (60 per study arm) will be recruited to establish a mean increase in the primary outcome (cardiorespiratory fitness) of 3.5 ml/min/kg with 90% power, 5% significance allowing for 20% drop out. Study outcomes of physical function, body composition, nutritional status, HRQOL, and fatigue will be measured at baseline (T0), post-intervention (T1), and 3-months follow-up (T2). At 1-year follow-up (T3), HRQOL alone will be measured. The impact of ReStOre II on well-being will be examined qualitatively with focus groups/interviews (T1, T2). Bio-samples will be collected from T0-T2 to establish a national UGI and HPB cancer survivorship biobank. The cost effectiveness of ReStOre II will also be analysed., Discussion: This RCT will investigate the efficacy of a 12-week multidisciplinary rehabilitation programme for survivors of UGI and HPB cancer compared to standard survivorship care. If effective, ReStOre II will provide an exemplar model of rehabilitation for UGI and HPB cancer survivors., Trial Registration: The study is registered with ClinicalTrials.gov, registration number: NCT03958019, date registered: 21/05/2019.

Pancreatic cancer remains among the most lethal cancers worldwide, with poor early detection rates and poor survival rates. Patient-derived xenograft (PDX) models have increasingly been used in preclinical and clinical research of solid cancers to fulfil unmet need. Fresh tumour samples from human pancreatic adenocarcinoma patients were implanted in severe combined immunodeficiency (SCID) mice. Samples from 78% of treatment-naïve pancreatic ductal adenocarcinoma patients grew as PDX tumours and were confirmed by histopathology. Frozen samples from F1 PDX tumours could be later successfully passaged in SCID mice to F2 PDX tumours. The human origin of the PDX was confirmed using human-specific antibodies; however, the stromal component was replaced by murine cells. Cell lines were successfully developed from three PDX tumours. RNA was extracted from eight PDX tumours and where possible, corresponding primary tumour (T) and adjacent normal tissues (N). mRNA profiles of tumour vs. F1 PDX and normal vs. tumour were compared by Affymetrix microarray analysis. Differential gene expression showed over 5000 genes changed across the N vs. T and T vs. PDX samples. Gene ontology analysis of a subset of genes demonstrated genes upregulated in normal vs. tumour vs. PDX were linked with cell cycle, cycles cell process and mitotic cell cycle. Amongst the mRNA candidates elevated in the PDX and tumour vs. normal were SERPINB5, FERMT1, AGR2, SLC6A14 and TOP2A . These genes have been associated with growth, proliferation, invasion and metastasis in pancreatic cancer previously. Cumulatively, this demonstrates the applicability of PDX models and transcriptomic array to identify genes associated with growth and proliferation of pancreatic cancer., Competing Interests: The authors declare no conflicts of interest

Background: Pancreatic Cancer remains a lethal disease for the majority of patients. New chemotherapy agents such as Folfirinox offer therapeutic potential for patients who present with Borderline Resectable disease (BRPC). However, results to date are inconsistent, with factors such as malnutrition limiting successful drug delivery. We sought to determine the prevalence of sarcopenia in BRPC patients at diagnosis, and to quantify body composition change during chemotherapy., Methods: The diagnostic/restaging CT scans of BRPC patients were analysed. Body composition was measured at L3 using Tomovision Slice-O-Matic™. Total muscle and adipose tissue mass were estimated using validated regression equations. Sarcopenia was defined as per gender- and body mass index (BMI)-specific lumbar skeletal muscle index (LSMI) and muscle attenuation reference values., Results: Seventy-eight patients received neo-adjuvant chemotherapy, and 67 patients underwent restaging CT, at which point a third were deemed resectable. Half were sarcopenic at diagnosis, and sarcopenia was equally prevalent across all BMI categories.. Skeletal muscle and adipose tissue (intra-muscular, visceral and sub-cutaneous) area decreased during chemotherapy (p < 0.0001). Low muscle attenuation was observed in half of patients at diagnosis, and was associated with increased mortality risk. Loss of lean tissue parameters during chemotherapy was associated with an increased mortality risk; specifically fat-free mass, HR 1.1 (95% CI 1.03-1.17, p = 0.003) and skeletal muscle mass, HR 1.21 (95%CI 1.08-1.35, p = 0.001)., Conclusions: Sarcopenia was prevalent in half of patients at the time of diagnosis with BRPC. Low muscle attenuation at diagnosis, coupled with lean tissue loss during chemotherapy, independently increased mortality risk., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background: Giant cell tumors (GCT) of the pancreas are a rare form of pancreatic cancer. Although data are limited, clinical outcomes appear to depend largely on histological subtype with osteoclastic tumors carrying a better prognosis. We report on a homogenous series of patients with osteoclastic-type GCTs of the pancreas presenting to a national pancreatico-biliary gastrointestinal oncology center., Methods: Patients underwent endoscopic, radiological and histopathological assessments. Data were collected in relation to consecutive patients presenting with osteoclastic-type tumors of the pancreas and analyzed with survival as a primary end point., Results: Four patients were treated over a 4-year period. Median age was 77 years with equal gender distribution. Median tumor size was 42 mm. Histology was osteoclast-type giant cells in all 4 patients. Two patients underwent surgery with curative intent. Median overall survival was 13.1 months., Conclusion: This is the largest reported series of osteoclast-type histology in GCTs of the pancreas., (© 2016 S. Karger AG, Basel.)

According to the international guidelines, a multidisciplinary approach is currently advised for the optimal care of patients with a gastroenteropancreatic neuroendocrine tumor (GEP NET). In our institution (tertiary care center), a systematic multidisciplinary approach was established in May 2007. In this study, we have aimed to assess the initial impact of establishing a systematic multidisciplinary approach to the management of GEP NET patients. We have collected and compared the biochemical, imaging, and pathological data and the therapeutic strategies in GEP NET patients diagnosed, treated, or followed-up from January 1993 to April 2007 versus GEP NET patients attending our institution after the multidisciplinary approach starting, from May 2007 to October 2008. Data of 91 patients before and 42 patients after the establishment of the multidisciplinary approach (total: 133 consecutive GEP NET patients) have been finally collected and analyzed. Before the establishment of the multidisciplinary approach, a lack of consistency in the biochemical, imaging, and pathological findings before treatment initiation as well as during follow-up of GEP NET patients was identified. These inconsistencies have been reduced by the systematic multidisciplinary approach. In addition, the therapeutic management of GEP NET patients has been altered by the multidisciplinary approach and became more consistent with recommended guidelines. We think that a systematic multidisciplinary approach significantly impacts on GEP NET patient care and should be established in all centers dealing with these tumors.

Pancreatic adenocarcinoma has been reported in kindreds with hereditary nonpolyposis colorectal cancer (HNPCC). Medullary carcinoma of the pancreas is a recently described rare variant of pancreatic adenocarcinoma. We describe a man with colorectal carcinoma who subsequently developed pancreatic medullary carcinoma. The tumor displayed microsatellite instability and loss of expression of the mismatch repair proteins MSH2 and MSH6. Mutational analysis of the mismatch repair genes MLH1 and MSH2 demonstrated a pathogenic nonsense mutation within the MSH2 gene, which is consistent with a diagnosis of HNPCC. This report adds support to an association between HNPCC and pancreatic adenocarcinoma displaying the medullary phenotype, suggesting that medullary features in a pancreatic carcinoma may point toward a genetic cancer predisposition. To our knowledge, this is the first reported case of medullary carcinoma of the pancreas in a patient with HNPCC due to a mutation of the MSH2 gene.