Assessing impact, needs and quality-of-life among informal carers of people with pancreatic cancer, a prospective study: the PAN-CARER study protocol.

INTRODUCTION: Approximately 10 300 people are diagnosed with pancreatic cancer each year in the UK. The cancer and its treatment inflict a significant physical, functional and emotional burden on patients. Research suggests that patients have many ongoing needs for support and care, but that these needs are not met by existing services. Family members often step in to fill this gap and provide support and care during and after treatment. Research in other cancers shows that this informal caregiving can place a very heavy burden on carers. However, there are few studies in the international literature that have focused on informal carers in pancreatic cancer; none have been conducted in the UK. METHODS AND ANALYSIS: Two complementary research methods will be utilised. First, a longitudinal quantitative study of 300 carers investigating, using validated questionnaires to assess the impact of caregiving (Caregiver Reaction Assessment), the unmet needs of carers (Supportive Care Needs Survey) and the quality-of-life (Short Form 12-item health survey), will be conducted. Second, qualitative interviews will be conducted with up to 30 carers to explore their experiences in more depth. Mixed-effects regression models will be applied to survey results to determine how impact, needs and quality-of-life vary over time, compare outcomes between carers of patients with operable and inoperable disease and identify social factors which affect outcomes. Interview data will undergo reflexive thematic analysis. ETHICS AND DISSEMINATION: The protocol has been approved by the Health Research Authority of the UK (Ethical approval IRAS ID 309503). Findings will be published in peer-reviewed journals and presented at national and international conferences.

Delayed Gastric Emptying and Gastric Remnant Function After Pancreaticoduodenectomy: A Systematic Review of Objective Assessment Modalities.

BACKGROUND: Delayed gastric emptying (DGE) is a frequent complication after pancreaticoduodenectomy (PD). The diagnosis of DGE is based on International Study Group for Pancreatic Surgery (ISGPS) clinical criteria and objective assessments of DGE are infrequently used. The present literature review aimed to identify objective measures of DGE following PD and determine whether these measures correlate with the clinical definition of DGE. METHODS: A systematic search was performed using the MEDLINE Ovid, EMBASE, Google Scholar and CINAHL databases for studies including pancreatic surgery, delayed gastric emptying and gastric motility until June 2022. The primary outcome was modalities undertaken for the objective measurement of DGE following PD and correlation between objective measurements and clinical diagnosis of DGE. Relevant risk of bias analysis was performed. RESULTS: The search revealed 4881 records, of which 46 studies were included in the final analysis. There were four objective modalities of DGE assessment including gastric scintigraphy (n = 28), acetaminophen/paracetamol absorption test (n = 10), fluoroscopy (n = 6) and the 13C-acetate breath test (n = 3). Protocols were inconsistent, and reported correlations between clinical and objective measures of DGE were variable; however, amongst these measures, at least one study directly or indirectly inferred a correlation, with the greatest evidence accumulated for gastric scintigraphy. CONCLUSION: Several objective modalities to assess DGE following PD have been identified and evaluated, however are infrequently used. Substantial variability exists in the literature regarding indications and interpretation of these tests, and there is a need for a real-time objective modality which correlates with ISGPS DGE definition after PD.

Systematic review of caregiver burden, unmet needs and quality-of-life among informal caregivers of patients with pancreatic cancer.

PURPOSE: Informal caregivers play an important supportive care role for patients with cancer. This may be especially true for pancreatic cancer which is often diagnosed late, has a poor prognosis and is associated with a significant symptom burden. We systematically reviewed the evidence on caregiver burden, unmet needs and quality-of-life of informal caregivers to patients with pancreatic cancer. METHOD: PubMed, Medline, CINAHL and Embase databases were systematically searched on 31 August 2021. Qualitative and quantitative data on informal caregivers' experiences were extracted and coded into themes of burden, unmet needs or quality-of-life with narrative synthesis of the data undertaken. RESULTS: Nine studies (five qualitative, four quantitative), including 6023 informal caregivers, were included in the review. We categorised data into three key themes: caregiver burden, unmet needs and quality-of-life. Data on caregiver burden was organised into a single subtheme relating to symptom management as a source of burden. Data on unmet needs was organised into three subthemes need for: better clinical communication; support and briefings for caregivers; and help with navigating the health care system. Data on quality-of-life indicate large proportions of informal caregivers experience clinical levels of anxiety (33%) or depression (12%-32%). All five qualitative studies were graded as good quality; three quantitative studies were poor quality, and one was fair quality. CONCLUSION: High-quality pancreatic cancer care should consider the impacts of informal caregiving. Prospective longitudinal studies examining multiple dimensions of caregiver burden, needs, and quality-of-life would be valuable at informing supportive care cancer delivery to pancreatic cancer informal caregivers.

Body surface gastric mapping to determine gastric motility patterns associated with delayed gastric emptying after pancreaticoduodenectomy. Gastric Electric Mapping after Pancreatoduodenectomy study protocol.

INTRODUCTION: Delayed gastric emptying (DGE) is frequent after pancreaticoduodenectomy (PD). Although often associated with postoperative pancreatic fistula, the precise pathogenesis in patients with no underlying complications remains unclear. There is evidence to suggest that, after surgery, aberrant electrical pathways are formed in the stomach which could contribute to the development of DGE.Gastric Alimetry is a novel technology which measures the electrical activity of the stomach non-invasively using an array of electrodes applied to the skin of the abdomen. This technique, termed body surface gastric mapping (BSGM), has been validated in normal controls and in patients with functional dyspepsia syndromes. This study will investigate the efficacy and feasibility of using BSGM to assess gastric motility in patients who undergo PD. METHODS AND ANALYSIS: This prospective cohort study will be conducted at a single large volume hepatobiliary unit in the UK. 50 patients who are planned to undergo PD will be included. BSGM measurement will be performed at four timepoints viz: preoperatively, day 4 postoperatively, at discharge and 6 months postoperatively. Key parameters of BSGM measurement, including wave amplitude, frequency and directional vector, will be measured at each timepoint and compared between different patient subgroups. Symptoms will be self-reported by patients during the recording using an iPad application designed for this purpose. Quality of life and patient experience will be assessed using standardised questionnaires at the end of the follow-up period. ETHICS AND DISSEMINATION: The protocol has been approved by the research ethics committees of Newcastle University and the Health Research Authority (HRA) of the UK (ethical approval IRAS ID 305302). Findings will be published in peer-reviewed journals and presented at national and international conferences. TRIAL REGISTRATION NUMBER: This study will automatically be registered with the ISRCTN registry by the HRA as part of the ethics approval process.

A scoring system for predicting malignancy in intraductal papillary mucinous neoplasms of the pancreas: a multicenter EUROPEAN validation.

PURPOSE: A preoperative estimate of the risk of malignancy for intraductal papillary mucinous neoplasms (IPMN) is important. The present study carries out an external validation of the Shin score in a European multicenter cohort. METHODS: An observational multicenter European study from 2010 to 2015. All consecutive patients undergoing surgery for IPMN at 35 hospitals with histological-confirmed IPMN were included. RESULTS: A total of 567 patients were included. The score was significantly associated with the presence of malignancy (p < 0.001). In all, 64% of the patients with benign IPMN had a Shin score < 3 and 57% of those with a diagnosis of malignancy had a score ≥ 3. The relative risk (RR) with a Shin score of 3 was 1.37 (95% CI: 1.07-1.77), with a sensitivity of 57.1% and specificity of 64.4%. CONCLUSION: Patients with a Shin score ≤ 1 should undergo surveillance, while patients with a score ≥ 4 should undergo surgery. Treatment of patients with Shin scores of 2 or 3 should be individualized because these scores cannot accurately predict malignancy of IPMNs. This score should not be the only criterion and should be applied in accordance with agreed clinical guidelines.

Meta-Analysis and Meta-Regression of Risk Factors for Surgical Site Infections in Hepatic and Pancreatic Resection.

BACKGROUND: The risk factors for surgical site infection (SSI) after HPB surgery are poorly defined. This meta-analysis aimed to quantify the SSI rates and risk factors for SSI after pancreas and liver resection. METHODS: The PUBMED, MEDLINE and EMBASE databases were systematically searched using the PRISMA framework. The primary outcome measure was pooled SSI rates. The secondary outcome measure was risk factor profile determination for SSI. RESULTS: The overall rate of SSI after pancreatic and liver resection was 25.1 and 10.4%, respectively (p < 0.001). 32% of pancreaticoduodenectomies developed SSI vs 23% after distal pancreatectomy (p < 0.001). The rate of incisional SSI in the pancreatic group was 9% and organ/space SSI 16.5%. Biliary resection during liver surgery was a risk factor for SSI (25.0 vs 15.7%, p = 0.002). After liver resection, the incisional SSI rate was 7.6% and the organ space SSI rate was 10.2%. Pancreas-specific SSI risk factors were pre-operative biliary drainage (p < 0.001), chemotherapy (p < 0.001) and radiotherapy (p = 0.007). Liver-specific SSI risk factors were smoking (p = 0.046), low albumin (p < 0.001) and significant blood loss (p < 0.001). The rate of organ/space SSI in patients with POPF was 47.7% and in patients without POPF 7.3% (p < 0.001). Organ/space SSI rate was 43% in patients with bile leak and 10% in those without (p < 0.001). CONCLUSIONS: The risk factors for SSI following pancreatic and liver resections are distinct from each other, with higher SSI rates after pancreatic resection. Pancreaticoduodenectomy has increased risk of SSI compared to distal pancreatectomy. Similarly, biliary resections during liver surgery increase the rates of SSI.

Haemostatic Efficacy of Topical Agents During Liver Resection: A Network Meta-Analysis of Randomised Trials.

BACKGROUND: Hepatic resection carries a high risk of parenchymal bleeding both intra- and post-operatively. Topical haemostatic agents are frequently used to control bleeding during hepatectomy, with multiple products currently available. However, it remains unknown which of these is most effective for achieving haemostasis and improving peri-operative outcomes. METHODS: A systematic review and random-effects Bayesian network meta-analysis of randomised trials investigating topical haemostatic agents in hepatic resection was performed. Interventions were analysed by grouping into similar products; fibrin patch, fibrin glue, collagen products, and control. Primary outcomes were the rate of haemostasis at 4 and 10 min. RESULTS: Twenty randomized controlled trials were included in the network meta-analysis, including a total of 3267 patients and 7 different interventions. Fibrin glue and fibrin patch were the most effective interventions for achieving haemostasis at both 4 and 10 min. There were no significant differences between haemostatic agents with respect to blood loss, transfusion requirements, bile leak, post-operative complications, reoperation, or mortality. CONCLUSIONS: Amongst the haemostatic agents currently available, fibrin patch and fibrin glue are the most effective methods for reducing time to haemostasis during liver resection, but have no effect on other peri-operative outcomes. Topical haemostatic agents should not be used routinely, but may be a useful adjunct to achieve haemostasis when needed.

Lactate-Mediated Acidification of Tumor Microenvironment Induces Apoptosis of Liver-Resident NK Cells in Colorectal Liver Metastasis.

Colorectal cancer is the third most common malignancy worldwide, with 1.3 million new cases annually. Metastasis to the liver is a leading cause of mortality in these patients. In human liver, metastatic cancer cells must evade populations of liver-resident natural killer (NK) cells with potent cytotoxic capabilities. Here, we investigated how these tumors evade liver NK-cell surveillance. Tissue biopsies were obtained from patients undergoing resection of colorectal liver metastasis (CRLM, n = 18), from the tumor, adjacent tissue, and distal resection margin. The number and phenotype of liver-resident NK cells, at each site, were analyzed by flow cytometry. Tumor-conditioned media (TCM) was generated for cytokine and metabolite quantification and used to treat healthy liver-resident NK cells, isolated from donor liver perfusate during transplantation. Liver-resident NK cells were significantly depleted from CRLM tumors. Healthy liver-resident NK cells exposed to TCM underwent apoptosis in vitro, associated with elevated lactate. Tumor-infiltrating liver-resident NK cells showed signs of mitochondrial stress, which was recapitulated in vitro by treating liver-resident NK cells with lactic acid. Lactic acid induced apoptosis by decreasing the intracellular pH of NK cells, resulting in mitochondrial dysfunction that could be prevented by blocking mitochondrial ROS accumulation. CRLM tumors produced lactate, thus decreasing the pH of the tumor microenvironment. Liver-resident NK cells migrating toward the tumor were unable to regulate intracellular pH resulting in mitochondrial stress and apoptosis. Targeting CRLM metabolism provides a promising therapeutic approach to restoring local NK-cell activity and preventing tumor growth.