Interaction analysis of subgroup effects in randomized trials: the essential methodological points.

Subgroup analysis aims to identify subgroups (usually defined by baseline/demographic characteristics), who would (or not) benefit from an intervention under specific conditions. Often performed post hoc (not pre-specified in the protocol), subgroup analyses are prone to elevated type I error due to multiple testing, inadequate power, and inappropriate statistical interpretation. Aside from the well-known Bonferroni correction, subgroup treatment interaction tests can provide useful information to support the hypothesis. Using data from a previously published randomized trial where a p value of 0.015 was found for the comparison between standard and Hemopatch® groups in (the subgroup of) 135 patients who had hand-sewn pancreatic stump closure we first sought to determine whether there was interaction between the number and proportion of the dependent event of interest (POPF) among the subgroup population (patients with hand-sewn stump closure and use of Hemopatch®), Next, we calculated the relative excess risk due to interaction (RERI) and the "attributable proportion" (AP). The p value of the interaction was p = 0.034, the RERI was - 0.77 (p = 0.0204) (the probability of POPF was 0.77 because of the interaction), the RERI was 13% (patients are 13% less likely to sustain POPF because of the interaction), and the AP was - 0.616 (61.6% of patients who did not develop POPF did so because of the interaction). Although no causality can be implied, Hemopatch® may potentially decrease the POPF after distal pancreatectomy when the stump is closed hand-sewn. The hypothesis generated by our subgroup analysis requires confirmation by a specific, randomized trial, including only patients undergoing hand-sewn closure of the pancreatic stump after distal pancreatectomy.Trial registration: INS-621000-0760.

Implementing an electromagnetic tracking navigation system improves the precision of endoscopic transgastric necrosectomy in an ex vivo model.

Endoscopic transgastric necrosectomy is crucial in the management of complications resulting from necrotizing pancreatitis. However, both real-time and visual-spatial information is lacking during the procedure, thereby jeopardizing a precise positioning of the endoscope. We conducted a proof-of-concept study with the aim of overcoming these technical difficulties. For this purpose, a three-dimensional (3D) phantom of a stomach and pancreatic necroses was 3D-printed based on spatial information from individual patient CT scans and subsequently integrated into a silicone torso. An electromagnetic (EM) sensor was adjusted inside the endoscope´s working channel. A software interface enabled real time visualization. The accuracy of this novel assistant system was tested ex vivo by four experienced interventional endoscopists who were supposed to reach seven targets inside the phantom in six different experimental runs of simulated endoscopic transgastric necrosectomy. Supported by endoscopic camera view combined with real-time 3D visualization, all endoscopists reached the targets with a targeting error ranging between 2.6 and 6.5 mm in a maximum of eight minutes. In summary, the EM tracking system might increase efficacy and safety of endoscopic transgastric necrosectomy at the experimental level by enhancing visualization. Yet, a broader feasibility study and further technical improvements are mandatory before aiming at implementation into clinical setting.

Contrast-enhanced guided endoscopic ultrasound procedures.

Contrast-enhanced endoscopic ultrasound (CH-EUS) can overcome the limitations of endoscopic ultrasound-guided acquisition by identifying microvessels inside inhomogeneous tumours and improving the characterization of these tumours. Despite the initial enthusiasm that oriented needle sampling under CH-EUS guidance could provide better diagnostic yield in pancreatic solid lesions, further studies did not confirm the supplementary values in cases of tissue acquisition guided by CH-EUS. This review details the knowledge based on the available data on contrast-guided procedures. The indications for CH-EUS tissue acquisition include isoechoic EUS lesions with poor visible delineation where CH-EUS can differentiate the lesion vascularisation from the surrounding parenchyma and also the mural nodules within biliopancreatic cystic lesions, which occur in select cases. Additionally, the roles of CH-EUS-guided therapy in patients whose pancreatic fluid collections or bile ducts that have an echogenic content have indications for drainage, and patients who have nonvisualized vessels that need to be highlighted via Doppler EUS are presented. Another indication is represented if there is a need for an immediate assessment of the post-radiofrequency ablation of pancreatic neuroendocrine tumours, in which case CH-EUS can be used to reveal the incomplete tumour destruction.

Effect of artificial or autologous coverage of the pancreatic remnant or anastomosis on postoperative pancreatic fistulas after partial pancreatectomy: meta-analysis of randomized clinical trials.

BACKGROUND: Postoperative pancreatic fistulas remain a driver of major complications after partial pancreatectomy. It is unclear whether coverage of the anastomosis or pancreatic remnant can reduce the incidence of postoperative pancreatic fistulas. The aim of this study was to evaluate the effect of autologous or artificial coverage of the pancreatic remnant or anastomosis on outcomes after partial pancreatectomy. METHODS: A systematic literature search was performed using MEDLINE and the Cochrane Central Register of Controlled Trials (CENTRAL) up to March 2024. All RCTs analysing a coverage method in patients undergoing partial pancreatoduodenectomy or distal pancreatectomy were included. The primary outcome was postoperative pancreatic fistula development. Subgroup analyses for pancreatoduodenectomy or distal pancreatectomy and artificial or autologous coverage were conducted. RESULTS: A total of 18 RCTs with 2326 patients were included. In the overall analysis, coverage decreased the incidence of postoperative pancreatic fistulas by 29% (OR 0.71, 95% c.i. 0.54 to 0.93, P < 0.01). This decrease was also seen in the 12 RCTs covering the remnant after distal pancreatectomy (OR 0.69, 95% c.i. 0.51 to 0.94, P < 0.02) and the 4 RCTs applying autologous coverage after pancreatoduodenectomy and distal pancreatectomy (OR 0.53, 95% c.i. 0.29 to 0.96, P < 0.04). Other subgroup analyses (artificial coverage or pancreatoduodenectomy) showed no statistically significant differences. The secondary endpoints of mortality, reoperations, and re-interventions were each affected positively by the use of coverage techniques. The certainty of evidence was very low to moderate. CONCLUSION: The implementation of coverage, whether artificial or autologous, is beneficial after partial pancreatectomy, especially in patients undergoing distal pancreatectomy with autologous coverage.

Risk assessment for pancreatic fistula by intraoperative image analysis of laparoscopic and robotic gastrectomy.

BACKGROUND: Pancreatic fistula (PF) is one of the most serious postoperative complications of gastrectomy. Misidentification of the boundary between the pancreas and the dissected fat is a primary concern. In this study, we focused on differences in the appearance of the pancreas and the dissected fat in actual surgical images and statistically analyzed the relationship between the pancreas and the dissected fat. METHODS: We analyzed data from 109 gastric cancer patients who underwent curative gastrectomy between November 2018 and March 2023. Intraoperative images were taken from videos of lymph node dissections of Nos.6 and 8a regions, and the mean gray value of the areas was measured using ImageJ software for analysis. The visceral fat area (VFA) was evaluated by preoperative axial CT at the umbilical level using Ziostation software. RESULTS: A significant correlation was observed between the fat/pancreas gray value ratio in the No.8a lymph node region and the drain/serum amylase ratio (P < 0.001). The fat/pancreas gray value ratio in the No.6 lymph node region correlated with VFA (P < 0.001). The VFA and drain/serum amylase ratio were significantly higher in the group with intra-abdominal complications (P = 0.004). CONCLUSIONS: We revealed significant relationships between the fat/pancreas gray value ratio with drain/serum amylase and VFA. Detecting differences in gray values between the pancreas and the dissected fat may lead to a decrease in the drain/serum amylase ratio and PF.

Clinical features and treatment of heterotopic pancreas in children: a multi-center retrospective study.

OBJECTIVE: Heterotopic pancreas, an uncommon condition in children, can present with diagnostic and treatment challenges. This study aimed to evaluate the clinical features and treatment options for this disorder in pediatric patients. METHODS: We conducted a retrospective analysis, including patients diagnosed with heterotopic pancreas at four tertiary hospitals between January 2000 and June 2022. Patients were categorized into symptomatic and asymptomatic groups based on clinical presentation. Clinical parameters, including age at surgery, lesion size and site, surgical or endoscopic approach, pathological findings, and outcome, were statistically analyzed. RESULTS: The study included 88 patients with heterotopic pancreas. Among them, 22 were symptomatic, and 41 were aged one year or younger. The heterotopic pancreas was commonly located in Meckel's diverticulum (46.59%), jejunum (20.45%), umbilicus (10.23%),ileum (7.95%), and stomach (6.82%). Sixty-six patients had concomitant diseases. Thirty-three patients had heterotopic pancreas located in the Meckel's diverticulum, with 80.49% of cases accompanied by gastric mucosa heterotopia (GMH). Patients without accompanying GMH had a higher prevalence of heterotopic pancreas-related symptoms (75%). Treatment modalities included removal of the lesions by open surgery, laparoscopic or laparoscopic assisted surgery, or endoscopic surgery based on patient's age, the lesion site and size, and coexisting diseases. CONCLUSIONS: Only one-fourth of the patients with heterotopic pancreas presented with symptoms. Those located in the Meckel's diverticulum have commonly accompanying GMH. Open surgical, laparoscopic surgical or endoscopic resection of the heterotopic pancreas is recommended due to potential complications. Future prospective multicenter studies are warranted to establish rational treatment options.

Generating Human Pancreatic Tissue Slices to Study Endocrine and Exocrine Pancreas Physiology.

It is crucial to study the human pancreas to understand the pathophysiological mechanisms associated with type 1 (T1D) and 2 diabetes (T2D) as well as the pancreas endocrine and exocrine physiology and interplay. Much has been learned from the study of isolated pancreatic islets, but this prevents examining their function and interactions in the context of the whole tissue. Pancreas slices provide a unique opportunity to explore the physiology of normal, inflamed, and structurally damaged islets within their native environment, in turn allowing the study of interactions between endocrine and exocrine compartments to better investigate the complex dynamics of pancreatic tissue. Thus, the adoption of the living pancreas slice platform represents a significant advancement in the field. This protocol describes how to generate living tissue slices from deceased organ donors by tissue embedding in agarose and vibratome slicing as well as their utilization to assess functional readouts such as dynamic secretion and live cell imaging.

Optimizing prediction models for pancreatic fistula after pancreatectomy: Current status and future perspectives.

Postoperative pancreatic fistula (POPF) is a frequent complication after pancreatectomy, leading to increased morbidity and mortality. Optimizing prediction models for POPF has emerged as a critical focus in surgical research. Although over sixty models following pancreaticoduodenectomy, predominantly reliant on a variety of clinical, surgical, and radiological parameters, have been documented, their predictive accuracy remains suboptimal in external validation and across diverse populations. As models after distal pancreatectomy continue to be progressively reported, their external validation is eagerly anticipated. Conversely, POPF prediction after central pancreatectomy is in its nascent stage, warranting urgent need for further development and validation. The potential of machine learning and big data analytics offers promising prospects for enhancing the accuracy of prediction models by incorporating an extensive array of variables and optimizing algorithm performance. Moreover, there is potential for the development of personalized prediction models based on patient- or pancreas-specific factors and postoperative serum or drain fluid biomarkers to improve accuracy in identifying individuals at risk of POPF. In the future, prospective multicenter studies and the integration of novel imaging technologies, such as artificial intelligence-based radiomics, may further refine predictive models. Addressing these issues is anticipated to revolutionize risk stratification, clinical decision-making, and postoperative management in patients undergoing pancreatectomy.

Pancreaticoureteric fistula following penetrating abdominal trauma: A Case Report.

Pancreaticoureteric Fistula (PUF) is a very rare complication secondary to penetrating abdominal trauma involving the ureter and pancreatic parenchyma. Pancreatic injuries carry h igh morbidity due to the involvem ent of surrounding structures and are d ifficult to diagnose due to thei r retroperitoneal location. A case of a patient is reported at Civil Hospital, Hyderabad who presented with a history of firearm injury and missed pancreatic duct involvement on initial exploration that eventually led to the development of Pan creaticoureteric Fistula. He was managed v ia p erc ut aneous nep hrostomy ( PCN ) for the right ureteric injury and pancreatic duct (PD) stenting was done for distal main pancreatic duct injury (MPD).

Defining distal splenopancreatectomy by the mesopancreas.

BACKGROUND: The implementation of the pathologic CRM (circumferential resection margin) staging system for pancreatic head ductal adenocarcinomas (hPDAC) resulted in a dramatic increase of R1 resections at the dorsal resection margin, presumably because of the high rate of mesopancreatic fat (MP) infiltration. Therefore, mesopancreatic excision (MPE) during pancreatoduodenectomy has recently been promoted and has demonstrated better local disease control, fueling the discussion of neoadjuvant downsizing regimes in MP + patients. However, it is unknown to what extent the MP is infiltrated in patients with distal pancreatic (tail/body) carcinomas (dPDAC). It is also unknown if the MP infiltration status affects surgical margin control in distal pancreatectomy (DP). The aim of our study was to histopathologically analyze MP infiltration and elucidate the influence of resection margin clearance on recurrence and survival in patients with dPDAC. Furthermore, the results were compared to a collective receiving MPE for hPDAC. METHOD: Clinicopathological and survival parameters of 295 consecutive patients who underwent surgery for PDAC (n = 63 dPDAC and n = 232 hPDAC) were evaluated. The CRM evaluation was performed in a standardized fashion and the specimens were examined according to the Leeds pathology protocol (LEEPP). The MP area was histopathologically evaluated for cancerous infiltration. RESULTS: In 75.4% of dPDAC patients the MP fat was infiltrated by vital tumor cells. The rates of MP infiltration and R0CRM- resections were similar between dPDAC and hPDAC patients (p = 0.497 and 0.453 respectively). MP- infiltration status did not correlate with CRM implemented resection status in dPDAC patients (p = 0.348). In overall survival analysis, resection status and MP status remained prognostic factors for survival. In follow up analysis. surgical margin clearance in dPDAC patients was associated with a significant improvement in local recurrence rates (5.2% in R0CRM- resected vs. 33.3 in R1/R0CRM + resected, p = 0.002). CONCLUSION: While resection margin status was not affected by the MP status in dPDAC patients, the high MP infiltration rate, as well as improved survival in MP- dPDAC patients after R0CRM- resection, justify mesopancreatic excision during splenopancreatectomy. Larger scale studies are urgently needed to validate our results and to study the effect on neoadjuvant treatment in dPDAC patients.

CBCT-DRRs superior to CT-DRRs for target-tracking applications for pancreatic SBRT.

Objective.In current radiograph-based intra-fraction markerless target-tracking, digitally reconstructed radiographs (DRRs) from planning CTs (CT-DRRs) are often used to train deep learning models that extract information from the intra-fraction radiographs acquired during treatment. Traditional DRR algorithms were designed for patient alignment (i.e.bone matching) and may not replicate the radiographic image quality of intra-fraction radiographs at treatment. Hypothetically, generating DRRs from pre-treatment Cone-Beam CTs (CBCT-DRRs) with DRR algorithms incorporating physical modelling of on-board-imagers (OBIs) could improve the similarity between intra-fraction radiographs and DRRs by eliminating inter-fraction variation and reducing image-quality mismatches between radiographs and DRRs. In this study, we test the two hypotheses that intra-fraction radiographs are more similar to CBCT-DRRs than CT-DRRs, and that intra-fraction radiographs are more similar to DRRs from algorithms incorporating physical models of OBI components than DRRs from algorithms omitting these models.Approach.DRRs were generated from CBCT and CT image sets collected from 20 patients undergoing pancreas stereotactic body radiotherapy. CBCT-DRRs and CT-DRRs were generated replicating the treatment position of patients and the OBI geometry during intra-fraction radiograph acquisition. To investigate whether the modelling of physical OBI components influenced radiograph-DRR similarity, four DRR algorithms were applied for the generation of CBCT-DRRs and CT-DRRs, incorporating and omitting different combinations of OBI component models. The four DRR algorithms were: a traditional DRR algorithm, a DRR algorithm with source-spectrum modelling, a DRR algorithm with source-spectrum and detector modelling, and a DRR algorithm with source-spectrum, detector and patient material modelling. Similarity between radiographs and matched DRRs was quantified using Pearson's correlation and Czekanowski's index, calculated on a per-image basis. Distributions of correlations and indexes were compared to test each of the hypotheses. Distribution differences were determined to be statistically significant when Wilcoxon's signed rank test and the Kolmogorov-Smirnov two sample test returnedp≤ 0.05 for both tests.Main results.Intra-fraction radiographs were more similar to CBCT-DRRs than CT-DRRs for both metrics across all algorithms, with allp≤ 0.007. Source-spectrum modelling improved radiograph-DRR similarity for both metrics, with allp< 10-6. OBI detector modelling and patient material modelling did not influence radiograph-DRR similarity for either metric.Significance.Generating DRRs from pre-treatment CBCT-DRRs is feasible, and incorporating CBCT-DRRs into markerless target-tracking methods may promote improved target-tracking accuracies. Incorporating source-spectrum modelling into a treatment planning system's DRR algorithms may reinforce the safe treatment of cancer patients by aiding in patient alignment.

[Direct transfistulous ultrasound in minimally invasive surgical treatment of infected pancreatic necrosis]. / Pryamoe chresfistul'noe ul'trazvukovoe issledovanie pri minimal'no invazivnom khirurgicheskom lechenii patsientov s infitsirovannym pankreonekrozom.

OBJECTIVE: To develop a method for direct transfistulous ultrasound in minimally invasive treatment of infected pancreatic necrosis. MATERIAL AND METHODS: There were 148 patients with infected pancreatic necrosis between 2015 and 2019 at the Krasnodar City Clinical Hospital No. 2. Drainage with 28-32 Fr tubes was carried out at the first stage, endoscopic transfistulous sequestrectomy - at the second stage (19 (12.8%) patients). In 84 (56.8%) patients, we applied original diagnostic method (transfistulous ultrasonic assessment of inflammatory focus). RESULTS: There were 3 accesses to omental bursa in 93 (62.8%) patients and 2 in 43 (29.1%) patients. We also performed 2 access to retroperitoneal space in 63 (42.6%) patients and 1 access in 38 (25.8%) cases. Transfistulous ultrasound was used once in 19 (22.6%) patients, twice in 28 (33.3%) and 3 times in 37 (44.1%) patients. Examination was not performed in 18 (12.2%) patients due to the following reasons: migration of drainage catheters - 5, non-rectilinear fistulous tract - 13. No complications were observed. CONCLUSION: Transfistulous ultrasound makes it possible to diagnose pathological changes in the pancreas and parapancreatic tissue at various stages of surgical treatment.

Understanding autoimmune pancreatitis: Clinical features, management challenges, and association with malignancies.

In this editorial we comment on the article by Jaber et al. Autoimmune pancreatitis (AIP) represents a distinct form of pancreatitis, categorized into AIP-1 and AIP-2, characterized by obstructive jaundice, lymphoplasmacytic infiltrate, and fibrosis. AIP-1, associated with elevated immunoglobulin G4 (IgG4) levels, exhibits higher relapse rates, affecting older males, while AIP-2 is less common and linked to inflammatory bowel disease. AIP is considered a manifestation of IgG4-related systemic disease, sharing characteristic histological findings. Steroids are the primary treatment, with emerging biomarkers like interferon alpha and interleukin-33. AIP poses an increased risk of various malignancies, and the association with pancreatic cancer is debated. Surgery is reserved for severe cases, necessitating careful evaluation due to diagnostic challenges. AIP patients may have concurrent PanINs but display favorable long-term outcomes compared to pancreatic cancer patients. Thorough diagnostic assessment, including biopsy and steroid response, is crucial for informed surgical decisions in AIP.

Pancreaticoduodenectomy with Anatomical Vascular Variant in Groove Pancreatitis-A Case Report.

Groove pancreatitis represents a chronic focal form of pancreatitis affecting the zone between the pancreatic head and the duodenal "C" loop, known as the groove area. This is a rare condition that affects the pancreatic periampullary part, including the duodenum and the common bile duct, which is usually associated with long-term alcohol and tobacco misuse, and is more frequent in men than in women. The most common clinical symptoms of groove pancreatitis include weight loss, acute abdominal pain, nausea, and jaundice. This report is about a 66-year-old woman with a history of heavy smoking, presenting with weight loss, nausea, and upper abdominal pain. Contrast-enhanced computed tomography revealed the existence of chronic pancreatitis as well as the dilatation of the main pancreatic duct, a cyst of the pancreatic head, and enlargement of the biliary tract. Conservatory treatment was initiated but with no improvement of symptoms. Since endoscopic retrograde cholangiopancreatography was not possible due to the local changes, we decided to perform pancreatoduodenectomy, as surgery appears to be the single effective treatment.

Efficacy and Safety Evaluation of Energy Devices in Bench Surgery for Pancreas Transplantation.

INTRODUCTION: Bench surgery for the preparation of deceased donor pancreatic grafts is labor-intensive and time-consuming. We hypothesized that energy devices could be used during bench surgery to decrease the bench surgery time. However, because bench surgery has two unique characteristics, wet conditions and no blood flow in the vessels, it is necessary to verify the safety and efficacy under such conditions. METHODS: In an animal tissue model, we validated both ultrasonic and bipolar energy devices: Harmonic Shears and the LigaSure (LS) vessel-sealing device by evaluating heat spread and pressure resistance under bench surgery conditions. In a clinical evaluation of the LS, we compared the outcomes of 22 patients in two different bench surgery groups: with and without the use of the LS. RESULTS: Clinically, the bench surgery time was significantly shorter in the LS group than that in the conventional group (P < 0.001). In the animal tissue experiments, the highest temperature in bench surgery conditions was 60.4°C after 1 s at a 5-mm distance in the LS group. Pressure resistance of ≥ 750 mmHg was achieved in almost all trials in both veins and arteries, with no difference between Harmonic Shears and LS. There was more surgical smoke visually in bench conditions versus in dry conditions and under half bite versus full bite conditions. CONCLUSIONS: The encouraging results of our exploratory clinical and animal studies of the energy devices suggest that they may be useful in the setting of bench surgery.

Malpractice Claims Following Major Liver and Pancreatic Surgeries: What Can we Learn?

INTRODUCTION: General surgery is a highly litigious specialty. Lawsuits can be a source of emotional distress and burnout for surgeons. Major hepatic and pancreatic surgeries are technically challenging general surgical oncology procedures associated with an increased risk of complications and mortality. It is unclear whether these operations are associated with an increased risk of lawsuits. The objective of the present study was to summarize the medical malpractice claims surrounding pancreatic and hepatic surgeries from publicly available court records. METHODS: The Westlaw legal database was searched and analyzed for relevant malpractice claims from the last two decades. RESULTS: Of 165 search results, 30 (18.2%) cases were eligible for inclusion. Appellant cases comprised 53.3% of them. Half involved a patient death. Including co-defendants, a majority (n = 21, 70%) named surgeons as defendants, whereas several claims (n = 13, 43%) also named non-surgeons. The most common cause of alleged malpractice was a delay in diagnosis (n = 12, 40%). In eight of these, surgery could not be performed. The second most common were claims alleging the follow-up surgery was due to negligence (n = 6). Collectively, 20 claims were found in favor of the defendant. Seven verdicts (23.3%) returned in favor of the plaintiff, two of which resulted in monetary awards (totaling $1,608,325 and $424,933.85). Three cases went to trial or delayed motion for summary judgment. There were no settlements. CONCLUSIONS: A defendant verdict was reached in two-thirds of malpractice cases involving major hepatic or pancreatic surgery. A delay in diagnosis was the most cited claim in hepatopancreaticobiliary lawsuits, and defendants may often practice in nonsurgical specialties. While rulings favoring plaintiffs are less frequent, the payouts may be substantial.

Cavitron ultrasonic surgical aspirator (CUSA) compared with conventional pancreatic transection in distal pancreatectomy: study protocol for the randomised controlled CUSA-1 pilot trial.

BACKGROUND: Postoperative pancreatic fistula (POPF) remains the most common and serious complication after distal pancreatectomy. Many attempts at lowering fistula rates have led to unrewarding insignificant results as still up to 30% of the patients suffer from clinically relevant POPF. Therefore, the development of new innovative methods and procedures is still a cornerstone of current surgical research.The cavitron ultrasonic surgical aspirator (CUSA) device is a well-known ultrasound-based parenchyma transection method, often used in liver and neurosurgery which has not yet been thoroughly investigated in pancreatic surgery, but the first results seem very promising. METHODS: The CUSA-1 trial is a randomised controlled pilot trial with two parallel study groups. This single-centre trial is assessor and patient blinded. A total of 60 patients with an indication for open distal pancreatectomy will be intraoperatively randomised after informed consent. The patients will be randomly assigned to either the control group with conventional pancreas transection (scalpel or stapler) or the experimental group, with transection using the CUSA device. The primary safety endpoint of this trial will be postoperative complications ≥grade 3 according to the Clavien-Dindo classification. The primary endpoint to investigate the effect will be the rate of POPF within 30 days postoperatively according to the ISGPS definition. Further perioperative outcomes, including postpancreatectomy haemorrhage, length of hospital stay and mortality will be analysed as secondary endpoints. DISCUSSION: Based on the available literature, CUSA may have a beneficial effect on POPF occurrence after distal pancreatectomy. The rationale of the CUSA-1 pilot trial is to investigate the safety and feasibility of the CUSA device in elective open distal pancreatectomy compared with conventional dissection methods and gather the first data on the effect on POPF occurrence. This data will lay the groundwork for a future confirmatory multicentre randomised controlled trial. ETHICS AND DISSEMINATION: The CUSA-1 trial protocol was approved by the ethics committee of the University of Heidelberg (No. S-098/2022). Results will be published in an international peer-reviewed journal and summaries will be provided in lay language to study participants and their relatives. TRIAL REGISTRATION NUMBER: DRKS00027474.

Quality of life after pancreatic surgery.

BACKGROUND: Pancreatic surgery is challenging owing to the anatomical characteristics of the pancreas. Increasing attention has been paid to changes in quality of life (QOL) after pancreatic surgery. AIM: To summarize and analyze current research results on QOL after pancreatic surgery. METHODS: A systematic search of the literature available on PubMed and EMBASE was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Relevant studies were identified by screening the references of retrieved articles. Studies on patients' QOL after pancreatic surgery published after January 1, 2012, were included. These included prospective and retrospective studies on patients' QOL after several types of pancreatic surgeries. The results of these primary studies were summarized inductively. RESULTS: A total of 45 articles were included in the study, of which 13 were related to pancreaticoduodenectomy (PD), seven to duodenum-preserving pancreatic head resection (DPPHR), nine to distal pancreatectomy (DP), two to central pancreatectomy (CP), and 14 to total pancreatectomy (TP). Some studies showed that 3-6 months were needed for QOL recovery after PD, whereas others showed that 6-12 months was more accurate. Although TP and PD had similar influences on QOL, patients needed longer to recover to preoperative or baseline levels after TP. The QOL was better after DPPHR than PD. However, the superiority of the QOL between patients who underwent CP and PD remains controversial. The decrease in exocrine and endocrine functions postoperatively was the main factor affecting the QOL. Minimally invasive surgery could improve patients' QOL in the early stages after PD and DP; however, the long-term effect remains unclear. CONCLUSION: The procedure among PD, DP, CP, and TP with a superior postoperative QOL is controversial. The long-term benefits of minimally invasive versus open surgeries remain unclear. Further prospective trials are warranted.

Pancreatic quantitative sensory testing to predict treatment response of endoscopic therapy or surgery for painful chronic pancreatitis with pancreatic duct obstruction: study protocol for an observational clinical trial.

INTRODUCTION: Treatment for abdominal pain in patients with chronic pancreatitis (CP) remains challenging in the setting of central nervous system sensitisation, a phenomenon of remodelling and neuronal hyperexcitability resulting from persistent pain stimuli. This is suspected to render affected individuals less likely to respond to conventional therapies. Endotherapy or surgical decompression is offered to patients with pancreatic duct obstruction. However, the response to treatment is unpredictable. Pancreatic quantitative sensory testing (P-QST), an investigative technique of standardised stimulations to test the pain system in CP, has been used for phenotyping patients into three mutually exclusive groups: no central sensitisation, segmental sensitisation (pancreatic viscerotome) and widespread hyperalgesia suggestive of supraspinal central sensitisation. We will test the predictive capability of the pretreatment P-QST phenotype to predict the likelihood of pain improvement following invasive treatment for painful CP. METHODS AND ANALYSIS: This observational clinical trial will enrol 150 patients from the University of Pittsburgh, Johns Hopkins and Indiana University. Participants will undergo pretreatment phenotyping with P-QST. Treatment will be pancreatic endotherapy or surgery for clearance of painful pancreatic duct obstruction. PRIMARY OUTCOME: average pain score over the preceding 7 days measured by Numeric Rating Scale at 6 months postintervention. Secondary outcomes will include changes in opioid use during follow-up, and patient-reported outcomes in pain and quality of life at 3, 6 and 12 months after the intervention. Exploratory outcomes will include creation of a model for individualised prediction of response to invasive treatment. ETHICS AND DISSEMINATION: The trial will evaluate the ability of P-QST to predict response to invasive treatment for painful CP and develop a predictive model for individualised prediction of treatment response for widespread use. This trial was approved by the University of Pittsburgh Institutional Review Board. Data and results will be reported and disseminated in conjunction with National Institutes of Health policies. TRIAL REGISTRATION NUMBER: NCT04996628.