Outcomes after pancreaticoduodenectomy with or without preoperative hyperbaric oxygen therapy.

Background: Hyperbaric oxygen (HBO2) therapy is an alternative method against the deleterious effects of ischemic/reperfusion (I/R) injury and its inflammatory response. This study assessed the effect of preoperative HBO2 on patients undergoing pancreaticoduodenectomy. Study Design: Patients were randomized via a computer-generated algorithm. Patients in the HBO2 cohort received two sessions of HBO2 the evening before and the morning of surgery. Measurements of inflammatory mediators and self-assessed pain scales were determined pre-and postoperatively. In addition, perioperative variables and long-term survival were collected and analyzed. Data are presented as median (mean ± SD). Results: 33 patients were included; 17 received preoperative HBO2, and 16 did not. There were no intraoperative or postoperative statistical differences between patients with or without preoperative HBO2. Erythrocyte sedimentation rate (ESR), IL-6, and IL-10 increased slightly before returning to normal, while TGF-alpha decreased before increasing. However, there were no differences with or without HBO2. At postoperative day 30, the pain level measured with VAS score (Visual Analog Score) was lower after HBO2 (1 ± 1.3 vs. 3 ± 3.0, p=0.05). Eleven (76%) patients in the HBO2 cohort and 12 (75%) patients in the non- HBO2 had malignant pathology. The percentage of positive lymph nodes in the HBO2 was 7% compared to 14% in the non-HBO2 (p<0.001). Overall survival was inferior after HBO2 compared to the non- HBO2 (p=0.03). Conclusions: Preoperative HBO2 did not affect perioperative outcomes or significantly change the inflammatory mediators for patients undergoing robotic pancreaticoduodenectomy. Long-term survival was inferior after preoperative HBO2. Further randomized controlled studies are required to assess the full impact of this treatment on patients' prognosis.

Oxalate nephropathy after pancreaticoduodenectomy: a case report.

A 75-year-old male developed acute kidney injury KDIGO stage 3 a few weeks after Whipple surgery was performed for a distal cholangiocarcinoma. Kidney biopsy revealed oxalate nephropathy. This was attributed to post-Whipple malabsorption, poor compliance with pancreatic enzyme replacement therapy, and daily intake of vitamin C supplements. Pancreatic enzyme replacement therapy was resumed and calcium carbonate initiated, with an improvement in glomerular filtration rate. Unfortunately, due to oncological progression, best supportive care was initiated.We review the pathophysiology and conditions predisposing to secondary hyperoxaluria and oxalate nephropathy. This diagnosis should be considered among the main causes of acute kidney injury following pancreatectomy, with important therapeutic implications.

Functional sequelae after pancreatic resection for cancer.

The morbidity and mortality of pancreatic cancer surgery has seen substantial improvement due to the standardization of surgical techniques, the optimization of perioperative multidisciplinary management and the organization of specialized care systems. The identification and treatment of postoperative functional and nutritional sequelae have thereby become major issues in patients who undergo pancreatic surgery. This review addresses the functional sequelae of pancreatic resection for cancerous and pre-cancerous lesions (excluding chronic pancreatitis). Its aim is to specify the prevalence and severity of sequelae according to the type of pancreatic resection and to document, where appropriate, the therapeutic management. Exocrine pancreatic insufficiency (ExPI) is observed in nearly one out of three patients at one year after surgery, and endocrine pancreatic insufficiency (EnPI) is present in one out of five patients after pancreatoduodenectomy (PD) and one out of three patients after distal pancreatectomy (DP). In addition, digestive functional disorders may appear, such as delayed gastric emptying (DGE), which affects 10 to 45% of patients after PD and nearly 8% after DP. Beyond these functional sequelae, pancreatic surgery can also induce nutritional and vitamin deficiencies secondary to a lack of uptake for certain vitamins or to the loss of absorption site in the duodenum. In addition to the treatment of ExPI with oral pancreatic enzymes, nutritional management is based on a high-calorie, high-protein diet with normal lipid intake in frequent small feedings, combined with vitamin supplementation adapted to monitored deficiencies. Better knowledge of the functional consequences of pancreatic cancer surgery can improve the overall management of patients.

[The 501st case: elevated blood glucose, chronic pancreatitis, and post- pancreatoduodenectomy malnutrition].

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.

Routes of nutrition for pancreatic fistula after pancreatoduodenectomy: a prospective snapshot study identifies the need for therapy standardization.

The aim of this study is to describe the current utilization of artificial nutrition [enteral (EN) or total parenteral (TPN)] for pancreatic fistula (POPF) after pancreatoduodenectomy (PD). Prospective data of 311 patients who consecutively underwent PD at a tertiary referral center for pancreatic surgery were collected. Data included the use of EN or TPN specifically for POPF treatment, including timing, outcomes, and adverse events related to their administration. POPF occurred in 66 (21%) patients and 52 (79%) of them were treated with artificial nutrition, for a median of 36 days. Forty (76%) patients were treated with a combination of TPN and EN. The median day of artificial nutrition start was postoperative day 7, with a median drain output of 180 cc/24 h. In 33 (63%) patients, artificial nutrition was started while only a biochemical leak was ongoing. Fungal infections and catheter-related bloodstream infection occurred in 13 (28%) and 15 (33%) TPN patients, respectively; among EN patients, 19 (41%) experienced diarrhea not responsive to pancreatic enzymes and 9 (20%) needed multiple endoscopic naso-jejunal tube positioning. The majority of the patients developing POPF after PD were treated with a combination of TPN and EN, with a clinically relevant rate of adverse events related to their administration. Standardization of nutrition routes in patients developing POPF is urgently needed.

The 501st case: elevated blood glucose, chronic pancreatitis, and post- pancreatoduodenectomy malnutrition / 中华内科杂志

A 50-year-old man with a 15-year history of elevated blood glucose and an approximately 2-year history of diarrhea was admitted to the Peking Union Medical College Hospital. The initial diagnosis was type 2 diabetes. After repeated pancreatitis and pancreatoduodenectomy, severe pancreatic endocrine and exocrine dysfunction including alternating high and low blood glucose and fat diarrhea occurred. Tests for type 1 diabetes-related antibodies were all negative, C-peptide levels were substantially reduced, fat-soluble vitamin levels were reduced, and there was no obvious insulin resistance. Therefore, a diagnosis of pancreatic diabetes was clear. The patient was given small doses of insulin and supplementary pancreatin and micronutrients. Diarrhea was relieved and blood glucose was controlled. The purpose of this article is to raise clinicians' awareness of the possibility of pancreatic diabetes after pancreatitis or pancreatic surgery. Timely intervention and monitoring may reduce the occurrence of complications.

Impact of Osteopenia on Pancreatic Fistula in Patients Undergoing Pancreaticoduodenectomy.

BACKGROUND/AIM: This study aimed to identify the potential risk for postoperative pancreatic fistula (POPF), a major complication of pancreaticoduodenectomy. PATIENTS AND METHODS: This retrospective study included 124 patients with biliary and pancreatic disorders who underwent pancreaticoduodenectomy between 2015 and 2020. Bone marrow density (BMD) was determined in the 11th thoracic vertebra using preoperative computed tomographic images. Delta BMD (dBMD=measured BMD - standard BMD) was calculated using standard BMD determined on the basis of age and sex, and dBMD <0 was defined as osteopenia. The relationship between clinicopathological factors and dBMD was investigated. RESULTS: The average BMD level was 140 Hounsfield units. BMD was significantly lower in women than in men (p<0.01) and in older patients than in younger patients (p<0.01). POPF was significantly correlated with low dBMD (p=0.032). Osteopenia was a risk factor for POPF in patients with soft pancreas (p=0.016). CONCLUSION: Osteopenia was an independent risk factor for POPF after pancreaticoduodenectomy in patients with soft pancreas. Preoperative osteopenia assessment may be useful for the prediction of POPF, and preoperative vitamin D supplementation might be considered in patients with osteopenia.

Significance of Zinc Replacement Therapy After Pancreaticoduodenectomy.

BACKGROUND/AIM: Recently, a decrease in serum zinc levels and the need for zinc preparations have been reported in the perioperative period of gastrointestinal surgery. In this study, we examined treatment outcomes among patients supplemented with zinc after pancreaticoduodenectomy (PD) and evaluated the significance of zinc replacement therapy. PATIENTS AND METHODS: From June 2020 to April 2021, 56 patients who received zinc acetate hydrate (50 mg/day) from postoperative day 3 after PD in our department were retrospectively reviewed. Patients' characteristics and preoperative as well as postoperative data, including serum zinc levels and surgical results at 1 month were reviewed. RESULTS: Preoperative zinc deficiency was present in 86.1% (46/56) of the patients. Moreover, despite zinc supplementation, 17.8% (10/56) of patients had postoperative zinc deficiency. A comparison between the low zinc level group (Zn <80 µg/dl) and the normal zinc level group (Zn ≥80 µg/dl) after surgery showed siginificant differences among patients with malignant diseases (vs. benign diseases, p=0.044), those undergoing open surgery (vs. minimally invasive surgery, p=0.036), and those with intraoperative blood loss ≥346 ml (vs. <346 ml: p=0.041) in the univariate analysis. Multivariate analysis revealed that zinc deficiency was significantly associated with open surgery [odds ratio (OR)=15.885, 95% confidence interval (CI)=1.77-142.01, p=0.013] and intraoperative blood loss (OR=9.329, 95% CI=1.50-57.74, p=0.016). CONCLUSION: In patients undergoing open PD for pancreatic cancer, zinc preparations of 50 mg may not be sufficient and further supplementation may be necessary.

Pancreatic exocrine insufficiency following pancreatoduodenectomy: A prospective bi-center study.

BACKGROUND/OBJECTIVES: Pancreatic exocrine insufficiency (PEI) is a common complication following pancreatoduodenectomy (PD) leading to malnutrition. The course of PEI and related symptoms and vitamin deficiencies is unknown. This study aimed to assess the (long-term) incidence of PEI and vitamin deficiencies after PD. METHODS: A bi-centre prospective observational cohort study was performed, including patients who underwent PD for mainly pancreatic and periampullary (pre)malignancies (2014-2018). Two cohorts were formed to evaluate short and long-term results. Patients were followed for 18 months and clinical symptoms were evaluated by questionnaire. PEI was based on faecal elastase-1 (FE-1) levels and/or clinical symptoms. RESULTS: In total, 95 patients were included. After three months, all but three patients had developed PEI and 27/29 (93%) patients of whom stool samples were available showed abnormal FE-1 levels, which did not improve during follow-up. After six months, all patients had developed PEI. During follow-up, symptoms resolved in 35%-70% of patients. Vitamin D and K deficiencies were observed in 48%-79% of patients, depending on the moment of follow-up; 0%-50% of the patients with deficiencies received vitamin supplementation. DISCUSSION: This prospective study found a high incidence of PEI after PD with persisting symptoms in one-to two thirds of all patients. Limited attention was paid to vitamin deficiencies. Improved screening and treatment strategies for PEI and vitamins need to be designed.

Posterior Circular Stapled GastroJejunostomy After Duodenopancreatectomy.

Anastomotic fistulae are the most common and dreaded postoperative complications of pancreaticoduodenectomy. Delayed gastric emptying (DGE) and slow recovery of bowel function are contributing causes for postoperative pancreatic fistula (PoPF) that should be taken into consideration. The present study evaluates data from 17 consecutive cases that underwent pancreaticoduodenectomy for pancreatic adenocarcinoma with pancreaticojejunal anastomosis and circular stapled mechanical gastrojejunal anastomosis instead of the standard terminolateral technique. Three patients developed Grade A DGE (one also developed grade B PoPF) and one patient required reinsertion of the nasogastric tube due to Grade B PoPF. Overall, the incidence of DGE was 23.5%. Three patients developed Grade B pancreatic fistulae that were successfully managed conservatively. Twelve patients resumed early bowel movement within 4 days, two reinterventions were required for postoperative bleeding. Mean hospital stay was 11.5 days. Patients with DGE had a mean hospital stay of 14.5 days. No gastrojejunostomy leak was encountered. Mortality was nil. Therefore we consider the posterior circular stapled gastrojejunostomy a simple, reproducible, safe technical alternative for avoiding DGE and consequently help lower the risk of PoPF, increased costs associated with prolonged hospital stay and an improved postoperative quality of life.

Oral adverse events due to zinc deficiency after pancreaticoduodenectomy requiring continuous intravenous zinc supplementation: a case report and literature review.

BACKGROUND: Zinc is mainly absorbed in the duodenum and proximal jejunum, which are removed during pancreaticoduodenectomy (PD). Little is known about the adverse oral events and skin disorders caused by zinc deficiency after PD. Herein, we reviewed studies on the development of zinc deficiency after PD and reported about a patient with zinc deficiency after PD who required home intravenous zinc replacement. CASE PRESENTATION: A 73-year-old woman with glossitis, taste disorder, and acrodermatitis enteropathica-like eruption on her fingers presented to the Division of Dentistry and Oral Surgery 69 days after PD. Her serum zinc level markedly decreased to 30 µg/dL. Oral zinc administration was inadequate to treat hypozincemia after PD; therefore, multi-trace elements were injected intravenously during readmission. Her serum zinc levels recovered, and her lesions gradually improved. Furthermore, a central venous port was implanted to maintain normal serum zinc levels, and she continued self-injecting zinc at home. CONCLUSIONS: Zinc deficiency after PD rarely occurs. The clinical oncologist community, including dentists responsible for the oral care of cancer patients, should be aware of the oral adverse events, such as dysgeusia, glossitis, and oral pain, associated with zinc deficiency after cancer surgery and that induced by chemotherapy or head and neck radiation therapy.

Dual-Energy CT Iodine Concentration to Evaluate Postoperative Pancreatic Fistula after Pancreatoduodenectomy.

Background Pancreatic fibrosis and fatty infiltration are associated with postoperative pancreatic fistula (POPF), but accurate preoperative assessment remains a challenge. Iodine concentration (IC) and fat fraction derived from dual-energy CT (DECT) may reflect the amount of fibrosis and steatosis, potentially enabling the preoperative prediction of POPF. Purpose To identify multiphasic DECT-derived IC and fat fraction that improve the prediction of POPF risks compared with contrast-enhanced CT attenuation values and to evaluate the underlying histopathologic changes. Materials and Methods This retrospective study included patients who underwent pancreatoduodenectomy and DECT (including pancreatic parenchymal, portal venous, and delayed phase scanning) between January 2020 and December 2020. The relationships of the quantitative DECT-derived IC and fat fraction, along with CT attenuation values from enhanced images with POPF risk, were analyzed with logistic regression analysis. The predictive performance of the IC was compared with that of the CT values. The histopathologic underpinnings of IC were evaluated with multivariable linear regression analysis. Results A total of 107 patients (median age, 65 years; interquartile range, 57-70 years; 56 men) were included. Of these, 23 (21%) had POPF. The pancreatic parenchymal-to-portal venous phase IC ratio (adjusted odds ratio [OR], 13; 95% CI: 2, 162; P < .001) was an independent predictor of POPF occurrence. The accuracy of the pancreatic parenchymal-to-portal venous phase IC ratio in predicting POPF was higher than that of the CT value ratio in the same phases (78% vs 65%, P < .001). The pancreatic parenchymal-to-portal venous phase IC ratio was independently associated with pancreatic fibrosis (ß = -1.04; 95% CI: -0.44, -1.64; P = .001). Conclusion A higher pancreatic parenchymal-to-portal venous phase IC ratio was associated with less histologic fibrosis and greater risk of POPF. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Lee and Yoon in this issue.

Total pancreatectomy as an alternative to high-risk pancreatojejunostomy after pancreatoduodenectomy: a propensity score analysis on surgical outcome and quality of life.

BACKGROUND: Total pancreatectomy (TP) is mentioned as alternative to pancreatoduodenectomy (PD) with high-risk pancreatojejunostomy (PJ) to avoid severe pancreatic fistula-related complications, but its benefit is controversial and comparative studies are scarce. METHODS: Cross-sectional single-center study among patients after PD with high-risk PJ versus patients after single-stage elective TP for any indication (2015-2017), using propensity scores to evaluate surgical outcomes and long-term quality of life (QoL) in three risk strata. EORTC QLQ-C30 and EQ-5D-5L were used for QoL assessment. RESULTS: Overall, 77 patients after TP (68.8%) and 102 patients after high-risk PD (34.5%) were included. Major morbidity (29.9% vs. 41.2%; p = 0.119) and 90-day mortality (5.2% vs. 8.8%; p = 0.354) did not differ significantly between TP and high-risk PD. Interventions for intra-abdominal fluid collections (9.1% vs. 23.5%, p = 0.011) and postpancreatectomy haemorrhage (6.5% vs. 18.6%; p = 0.018) were more often required after high-risk PD, but these differences did not remain after stratification. QoL was comparable after TP and high-risk PD (75% vs. 83%; p = 0.720), even after stratification. CONCLUSIONS: TP seems not to be inferior to high-risk PD regarding surgical outcomes and QoL. TP could be considered as an alternative to a very high-risk PD, but reluctance persists since TP does not appear to reduce mortality.

Optimal Perioperative Nutrition Therapy for Patients Undergoing Pancreaticoduodenectomy: A Systematic Review with a Component Network Meta-Analysis.

Numerous strategies for perioperative nutrition therapy for patients undergoing pancreaticoduodenectomy (PD) have been proposed. This systematic review aimed to summarize the current relevant published randomized controlled trials (RCTs) evaluating different nutritional interventions via a traditional network meta-analysis (NMA) and component network meta-analysis (cNMA). EMBASE, MEDLINE, the Cochrane Library, and ClinicalTrials.gov were searched to identify the RCTs. The evaluated nutritional interventions comprised standard postoperative enteral nutrition by feeding tube (Postop-SEN), preoperative enteral feeding (Preop-EN), postoperative immunonutrients (Postop-IM), preoperative oral immunonutrient supplement (Preop-IM), and postoperative total parenteral nutrition (TPN). The primary outcomes were general, infectious, and noninfectious complications; postoperative pancreatic fistula (POPF); and delayed gastric emptying (DGE). The secondary outcomes were mortality and length of hospital stay (LOS). The NMA and cNMA were conducted with a frequentist approach. The results are presented as odds ratios (ORs) and 95% confidence intervals (CIs). Two primary outcomes, infectious complications and POPF, were positively influenced by nutritional interventions. Preop-EN plus Postop-SEN (OR 0.11; 95% CI 0.02~0.72), Preop-IM (OR 0.22; 95% CI 0.08~0.62), and Preop-IM plus Postop-IM (OR 0.11; 95% CI 0.03~0.37) were all demonstrated to be associated with a decrease in infectious complications. Postop-TPN (OR 0.37; 95% CI 0.19~0.71) and Preop-IM plus Postop-IM (OR 0.21; 95% CI 0.06~0.77) were clinically beneficial for the prevention of POPF. While enteral feeding and TPN may decrease infectious complications and POPF, respectively, Preop-IM plus Postop-IM may provide the best clinical benefit for patients undergoing PD, as this approach decreases the incidence of both the aforementioned adverse effects.

Micronutritional status after pylorus preserving duodenopancreatectomy: analysis of data from a randomized controlled trial.

Physical frailty and nutritional malassimilation are often observed after pancreaticoduodenectomy for pancreatic cancer. But long-term data concerning the course of micronutrient status is still missing. Micronutrient status after pylorus preserving pancreaticoduodenectomy with a follow-up of 12 months was evaluated using data of a randomized controlled trial. 47 patients were randomized with respect to the physiotherapy regimen they received (intensified physiotherapy: n = 22; standard physiotherapy: n = 25). Nutritional status was recorded preoperatively and postoperatively after one week, 3, 6 and 12 months. BMI, body fat measurement and albumin, lipid, iron and bone metabolism parameters, vitamins A, B1 B6 and B12, homocysteine, folic acid, and trace elements were measured. Laboratory values were analyzed descriptively. Differences between the groups were analyzed using the t-test in SPSS. For vitamin D, B1, B6 and iron a deficiency over time could be demonstrated with 50% of all patients or more being below normal range. The other laboratory values were in low normal range after 3 months and later. Significant differences between groups were found in cholesterol, HDL and selenium levels (corrected p-values < 0.033 in all cases). Vitamin D and iron should be supplemented postoperatively in the long term, and vitamin B1 and B6 substitution should be considered in symptomatic patients. Levels of malnutrition induced fatigue should be comparable between both groups. However, the role of nutritional status on other health-related aspects such as quality of life should be the focus of further studies.Trial Registration Number in the German Registry for Clinical Studies: DRKS00006786; Date of Registration: 01.10.2014.

Preoperative Nutrition Support May Reduce the Prevalence of Postoperative Pancreatic Fistula after Open Pancreaticoduodenectomy in Patients with High Nutritional Risk Determined by NRS2002.

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) is a severe complication which may be caused by a perioperative nutrition problem. We aimed to study whether patients with high nutritional risk (NRS2002 score ≥ 5) might benefit from preoperative nutrition support regarding the risk of CR-POPF after open pancreaticoduodenectomy. METHODS: Consecutive patients undergoing open pancreaticoduodenectomy with complete record of NRS2002 at two Chinese institutions between 2013 and 2018 were analysed. CR-POPF was diagnosed following the 2016 ISGPS criteria. Nutrition support included oral nutrition supplement and enteral and parenteral nutrition. Clinical and economic outcomes were analysed. RESULTS: 522 cases were included. 135 cases (25.9%) were at high nutritional risk (NRS2002 score ≥ 5), among which 41 cases (30.4%) received preoperative nutrition support. The CR-POPF rate was significantly lower in the preoperative nutrition support group compared with the no nutrition support group (12.2% versus 28.7%, P = 0.038). Multivariate analysis showed that preoperative nutrition support was a protective factor for CR-POPF in patients at high risk [OR 0.339, 95% CI (0.115-0.965), P = 0.039]. Higher albumin and a larger diameter of the main pancreatic duct were found to be other protectors for CR-POPF. CONCLUSIONS: Patients with high nutritional risk (NRS2002 score ≥ 5) may profit from preoperative nutritional support manifested in the reduction of CR-POPF.

Survival in borderline resectable and locally advanced pancreatic cancer is determined by the duration and response of neoadjuvant therapy.

BACKGROUND: Pancreatic cancer is the 8th commonest cancer and the 5th commonest cause of cancer-related death in Australia, with a 9% average 5-year survival. This study aims to investigate the effects of neoadjuvant treatment on overall survival (OS) and recurrence-free survival (RFS) in borderline resectable (BRPC) and locally advanced (LAPC) pancreatic adenocarcinoma followed by curative resection. MATERIALS AND METHODS: Prospectively-collected demographic, medical, surgical and pathological data of patients with BRPC and LAPC treated with both neoadjuvant therapy (NAT) and surgery at a single tertiary referral centre in Australia were reviewed and analysed. RESULTS: Between 2012 and 2018, 60 patients, 34 with BRPC and 26 with LAPC, were treated with NAT followed by curative resection. The commonest neoadjuvant chemotherapy regimens were Gemcitabine + Abraxane (51.7%) and FOLFIRINOX (35.0%), with 48.3% of patients additionally receiving neoadjuvant radiotherapy. Median RFS was 30 months and median OS was 35 months. On multivariable analysis, inferior OS was predicted by enlarged loco-regional lymph nodes on initial computed tomography (p = 0.032), larger tumour size post-NAT (p = 0.006) and Common Terminology Criteria for Adverse Events post-NAT toxicity greater than grade 2 (p = 0.015). LAPC patients received more neoadjuvant chemotherapy (p = 0.008) and radiotherapy (p = 0.021) than BRPC and achieved a superior pathological response (p = 0.010). CONCLUSION: Patients who respond to NAT likely have a favourable disease biology and will progress well following resection. It is these patients who should be selected for more aggressive upfront management, and those with resistant disease should be spared from high-risk surgery.

Evaluation of robotic versus open partial pancreatoduodenectomy-study protocol for a randomised controlled pilot trial (EUROPA, DRKS00020407).

BACKGROUND: Partial pancreatoduodenectomy (PD) is the indicated surgical procedure for a wide range of benign and malignant diseases of the pancreatic head and distal bile duct and offers the only potential cure for pancreatic head cancer. The current gold standard, open PD (OPD) performed via laparotomy, is associated with morbidity in around 40% of cases, even at specialised centres. Robotic PD (RPD) might offer a viable alternative to OPD and has been shown to be feasible. Encouraging perioperative results have been reported for RPD in a number of small, non-randomised studies. However, since those studies showed a considerable risk of bias, a thorough comparison of RPD with OPD is warranted. METHODS: The EUROPA (EvalUation of RObotic partial PAncreatoduodenectomy) trial is designed as a randomised controlled unblinded exploratory surgical trial with two parallel study groups. A total of 80 patients scheduled for elective PD will be randomised after giving written informed consent. Patients with borderline or non-resectable carcinoma of the pancreatic head as defined by the National Comprehensive Cancer Network guidelines, distant metastases or an American Society of Anaesthesiologists (ASA) score > III will be excluded. The experimental intervention, RPD, will be compared with the control intervention, OPD. An intraoperative dropout of approximately eight patients per group is expected because they may receive another type of surgical procedure than planned. Overall, 64 patients need to be analysed. The primary endpoint of the trial is overall postoperative morbidity within 90 days after index operation, measured using the Comprehensive Complication Index (CCI). The secondary endpoints include the feasibility of recruitment and assessment of clinical, oncological and safety parameters and quality of life and cost-effectiveness. DISCUSSION: The EUROPA trial is the first randomised controlled trial comparing RPD with OPD. Differences in postoperative morbidity will be evaluated to design a future multicentre confirmatory efficacy trial. TRIAL REGISTRATION: German Clinical Trial Register DRKS00020407 . Registered on 9 March 2020.

Effect of preoperative nutritional supplementation on postoperative outcomes for patients undergoing pancreaticoduodenectomy for cancer: a systematic review protocol.

OBJECTIVE: This review aims to present the best available evidence related to the effect of preoperative nutritional supplementation on postoperative outcomes for patients undergoing pancreaticoduodenectomy for cancer. INTRODUCTION: Pancreaticoduodenectomy surgery is the only curative option for early head of pancreas and periampullary cancers. This complex, high-risk procedure is associated with significant morbidity, making opportunities to improve outcomes paramount. Nutritional supplementation in the preoperative period may enhance the body's ability to withstand the stress of major surgery and reduce postoperative complications. INCLUSION CRITERIA: This review will consider studies of patients undergoing pancreaticoduodenectomy for cancer who are provided preoperative nutritional supplementation in any form for a minimum of 48 hours. Randomized and quasi-randomized trials that compare any form of preoperative nutritional supplementation to standard care in these patients will be included. Outcome data will include hospital length of stay, mortality, infections, delayed gastric emptying, pancreatic fistula, anastomotic leak, hemorrhage, weight loss, body mass index, serum albumin, lymphocyte levels, and nutrition risk index score. METHODS: Electronic databases (PubMed, Scopus, CINAHL, and Cochrane Library) and trial registers will be searched for published and unpublished articles. All articles from database inception to present, published in any language will be included. One reviewer will perform the literature search, screen texts for inclusion, and extract data. Two authors will assess methodological quality of the literature using the JBI critical appraisal tool. Authors will be contacted where additional data or clarification is required. Statistical meta-analysis through synthesis and pooling of data for each intervention will be completed where meaningful. SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD42020215307.