Adjuvant chemotherapy for adenocarcinoma arising from intraductal papillary mucinous neoplasia: multicentre ADENO-IPMN study.

BACKGROUND: The clinical impact of adjuvant chemotherapy after resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia is unclear. The aim of this study was to identify factors related to receipt of adjuvant chemotherapy and its impact on recurrence and survival. METHODS: This was a multicentre retrospective study of patients undergoing pancreatic resection for adenocarcinoma arising from intraductal papillary mucinous neoplasia between January 2010 and December 2020 at 18 centres. Recurrence and survival outcomes for patients who did and did not receive adjuvant chemotherapy were compared using propensity score matching. RESULTS: Of 459 patients who underwent pancreatic resection, 275 (59.9%) received adjuvant chemotherapy (gemcitabine 51.3%, gemcitabine-capecitabine 21.8%, FOLFIRINOX 8.0%, other 18.9%). Median follow-up was 78 months. The overall recurrence rate was 45.5% and the median time to recurrence was 33 months. In univariable analysis in the matched cohort, adjuvant chemotherapy was not associated with reduced overall (P = 0.713), locoregional (P = 0.283) or systemic (P = 0.592) recurrence, disease-free survival (P = 0.284) or overall survival (P = 0.455). Adjuvant chemotherapy was not associated with reduced site-specific recurrence. In multivariable analysis, there was no association between adjuvant chemotherapy and overall recurrence (HR 0.89, 95% c.i. 0.57 to 1.40), disease-free survival (HR 0.86, 0.59 to 1.30) or overall survival (HR 0.77, 0.50 to 1.20). Adjuvant chemotherapy was not associated with reduced recurrence in any high-risk subgroup (for example, lymph node-positive, higher AJCC stage, poor differentiation). No particular chemotherapy regimen resulted in superior outcomes. CONCLUSION: Chemotherapy following resection of adenocarcinoma arising from intraductal papillary mucinous neoplasia does not appear to influence recurrence rates, recurrence patterns or survival.

Long-term Outcomes following Resection of Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasm (A-IPMN) versus Pancreatic Ductal Adenocarcinoma (PDAC): A Propensity-score Matched Analysis.

OBJECTIVE: The aim of the present study was to compare long-term post-resection oncological outcomes between A-IPMN and PDAC. SUMMARY BACKGROUND DATA: Knowledge of long term oncological outcomes (e.g recurrence and survival data) comparing between adenocarcinoma arising from intraductal papillary mucinous neoplasms (A-IPMN) and pancreatic ductal adenocarcinoma (PDAC) is scarce. METHODS: Patients undergoing pancreatic resection (2010-2020) for A-IPMN were identified retrospectively from 18 academic pancreatic centres and compared with PDAC patients from the same time-period. Propensity-score matching (PSM) was performed and survival and recurrence were compared between A-IPMN and PDAC. RESULTS: 459 A-IPMN patients (median age,70; M:F,250:209) were compared with 476 PDAC patients (median age,69; M:F,262:214). A-IPMN patients had lower T-stage, lymphovascular invasion (51.4%vs. 75.6%), perineural invasion (55.8%vs. 71.2%), lymph node positivity (47.3vs. 72.3%) and R1 resection (38.6%vs. 56.3%) compared to PDAC(P<0.001). The median survival and time-to-recurrence for A-IPMN versus PDAC were 39.0 versus19.5months (P<0.001) and 33.1 versus 14.8months (P<0.001), respectively (median follow-up,78 vs.73 months). Ten-year overall survival for A-IPMN was 34.6%(27/78) and PDAC was 9%(6/67). A-IPMN had higher rates of peritoneal (23.0 vs. 9.1%, P<0.001) and lung recurrence (27.8% vs. 15.6%, P<0.001) but lower rates of locoregional recurrence (39.7% vs. 57.8%; P<0.001). Matched analysis demonstrated inferior overall survival (P=0.005), inferior disease-free survival (P=0.003) and higher locoregional recurrence (P<0.001) in PDAC compared to A-IPMN but no significant difference in systemic recurrence rates (P=0.695). CONCLUSIONS: PDACs have inferior survival and higher recurrence rates compared to A-IPMN in matched cohorts. Locoregional recurrence is higher in PDAC but systemic recurrence rates are comparable and constituted by their own distinctive site-specific recurrence patterns.

Risk of Recurrence after Surgical Resection for Adenocarcinoma Arising from Intraductal Papillary Mucinous Neoplasia (IPMN) with Patterns of Distribution and Treatment: An International, Multicentre, Observational Study.

OBJECTIVE: This international multicentre cohort study aims to identify recurrence patterns and treatment of first and second recurrence in a large cohort of patients after pancreatic resection for adenocarcinoma arising from IPMN. SUMMARY BACKGROUND DATA: Recurrence patterns and treatment of recurrence post resection of adenocarcinoma arising from IPMN are poorly explored. METHOD: Patients undergoing pancreatic resection for adenocarcinoma from IPMN between January 2010 to December 2020 at 18 pancreatic centres were identified. Survival analysis was performed by the Kaplan-Meier log rank test and multivariable logistic regression by Cox-Proportional Hazards modelling. Endpoints were recurrence (time-to, location, and pattern of recurrence) and survival (overall survival and adjusted for treatment provided). RESULTS: Four hundred and fifty-nine patients were included (median, 70 y; IQR, 64-76; male, 54 percent) with a median follow-up of 26.3 months (IQR, 13.0-48.1 mo). Recurrence occurred in 209 patients (45.5 percent; median time to recurrence, 32.8 months, early recurrence [within 1 y], 23.2 percent). Eighty-three (18.1 percent) patients experienced a local regional recurrence and 164 (35.7 percent) patients experienced distant recurrence. Adjuvant chemotherapy was not associated with reduction in recurrence (HR 1.09;P=0.669) One hundred and twenty patients with recurrence received further treatment. The median survival with and without additional treatment was 27.0 and 14.6 months (P<0.001), with no significant difference between treatment modalities. There was no significant difference in survival between location of recurrence (P=0.401). CONCLUSION: Recurrence after pancreatic resection for adenocarcinoma arising from IPMN is frequent with a quarter of patients recurring within 12 months. Treatment of recurrence is associated with improved overall survival and should be considered.

A pen in the liver.

A 24-year-old woman with anxiety, depression, and emotionally unstable personality disorder was referred to a tertiary center 2 weeks after ingesting multiple foreign bodies. She had undergone a laparoscopic cholecystectomy and a laparotomy for extraction of ingested foreign bodies several years ago. A sagittal CT scan view showed a ballpen and a hair clip in the stomach. A coronal view demonstrated that a second ballpen had penetrated the duodenal wall to enter the liver parenchyma. There was no free intraperitoneal air or fluid or evidence of abscess formation. At laparotomy, a toothbrush, a broken spoon and a ballpen were extracted from the stomach via an anterior gastrotomy. The duodenum was adherent to the liver but the second ballpen had migrated into the distal duodenum, with the tip in the proximal jejunum. This was extracted via an enterotomy and the fistula was not interfered with. The enterotomy and gastrotomy were closed with 3-0 polydioxanone sutures. The hair clip had passed spontaneously and was not detected on intraoperative fluoroscopy. She made an uneventful recovery and postoperative liver function tests remained in the normal range. This is only the fourth reported case of a pen fistulizing between the upper gastrointestinal tract and the liver.

Length of Barrett's esophagus in the presence of low-grade dysplasia, high-grade dysplasia, and adenocarcinoma.

INTRODUCTION: The identification and follow-up of ultra-short Barrett's esophagus (BE) is controversial. BE surveillance guidelines emphasize mainly on long-segment BE. However, in practice a substantial proportion of esophageal adenocarcinoma (EAC) are found close to the gastro-esophageal junction (GEJ). Our study aims to chart the length of BE when low-grade dysplasia (LGD), high-grade dysplasia (HGD) and EAC arise in BE. METHODS: Endoscopic findings from all cases with a diagnosis of LGD and HGD in BE between June 2014 and June 2019, and 100 consecutive cases of EAC diagnosed between June 2018 and August 2019, were reviewed. Additionally, 438 consecutive gastroscopies were reviewed to identify 100 cases of non-dysplastic BE. RESULTS: 99 cases of LGD and 61 cases of HGD were reviewed. LGD and HGD when diagnosed, was located in BE ≤ 1 cm in 20% and 18% cases, respectively. LGD and HGD when diagnosed, was located in BE ≤ 3 cm in 48.5% and 40.9% cases, respectively. LGD and HGD when diagnosed in BE ≤ 3 cm was found at index endoscopy in 67% and 42% cases, respectively. Of the 100 cases of EAC, only 23 had concurrent visible BE, with BE higher than the level of EAC in seven. EAC when found, had its proximal extent ≤ 1 cm from GEJ in 22% and ≤ 3 cm from GEJ in 40% cases. Of the 100 non-dysplastic BE, 53% were ≤ 1 cm and 78% were ≤ 3 cm long. CONCLUSION: Almost 20% of all dysplasia in BE occurs in BE < 1 cm. Over 40% occurs in BE < 3 cm. Similarly, 20% of EAC occurs within 1 cm of GEJ and 40% occur within 3 cm. A majority of dysplasia diagnosed within 3 cm of the GEJ is found on index endoscopy. We propose that all lengths of columnar lined epithelium above the GEJ are recognized as BE and subjected to a thorough biopsy protocol.

Introduction of an electronic patient record (EPR) improves operation note documentation: the results of a closed loop audit and proposal of a team-based approach to documentation.

An operation note is a medicolegal document. The Royal College of Surgeons (RCS) of England's Good Surgical Practice 2014 (GSP) sets out 19 points an operation note should include. This study aimed to assess if the introduction of an electronic patient record (EPR) improved the quality of general surgical operation notes. An annonymised retrospective case note review of general surgical operation notes was undertaken over five separate time periods. The first cycle consisted of periods 1 (prior to EPR implementation), 2 (1 week after EPR) and 3 (4 weeks after EPR). Period 4 was a reaudit 2 weeks after the initial results were presented at the local governance meeting. The cycle was then closed with period 5; 1 year after EPR implementation. A comparison was across all 5 time periods for compliance with the RCS guidelines and with subanalysis of the individual categories. 250 operation notes were reviewed during five time periods. Compliance improved by almost 19% (p=0.0003) between periods 1 and 5. Eleven of the 19 points (57.9%) over the audit period achieved 100% compliance post-EPR compared to 0% prior. Poor compliance were noted in the categories of antibiotic use, venous thromboembolism prophylaxis and estimated blood loss (noting that these are often documented in the anaesthetic record and/or WHO checklist). EPRs do not guarantee compliance with GSP. We propose that GSP standards need to be updated to reflect the modernisation of medical records and a team-based approach with multimodality input sources would achieve better patient records and patient care.

Mis-use of antibiotics in acute pancreatitis: Insights from the United Kingdom's National Confidential Enquiry into patient outcome and death (NCEPOD) survey of acute pancreatitis.

BACKGROUND: International guidelines for the management of acute pancreatitis state that antibiotics should only be used to treat infectious complications. Antibiotic prophylaxis is not recommended. The aim of this study was to analyse antibiotic use, and its appropriateness, from a national review of acute pancreatitis. METHODS: Data were collected from The National Confidential Enquiry into Patient Outcome and Death (NCEPOD) study into the management of acute pancreatitis. Adult patients admitted to hospitals in England and Wales between January and June 2014 with a coded diagnosis of acute pancreatitis were included. Clinical and organisational questionnaires were used to collect data and these submissions subjected to peer review. Antibiotic use, including indication and duration were analysed. RESULTS: 439/712 (62%) patients received antibiotics, with 891 separate prescriptions and 23 clinical indications. A maximum of three courses of antibiotics were prescribed, with 41% (290/712) of patients receiving a second course and 24% (174/712) a third course. For the first antibiotic prescription, the most common indication was "unspecified" (85/439). The most common indication for the second course was sepsis (54/290), "unspecified" was the most common indication for the third course (50/174). In 72/374 (19.38%) the indication was deemed inappropriate by the clinicians and in 72/393 (18.3%) by case reviewers. CONCLUSIONS: Inappropriate use of antibiotics in acute pancreatitis is common. Healthcare providers should ensure that antimicrobial policies are in place as part of an antimicrobial stewardship process. This should include specific guidance on their use and these policies must be accessible, adherence audited and frequently reviewed.

An in vivo analysis of safe laparoscopic grasping thresholds for colorectal surgery.

BACKGROUND: Analysis of safe laparoscopic grasping thresholds for the colon has not been performed. This study aimed to analyse tissue damage thresholds when the colon is grasped laparoscopically, correlating histological changes to mechanical compressive forces. METHODS: An instrumented laparoscopic grasper was used to measure the forces applied to porcine colon, with data captured and plotted as a force-time (f-t) curve. Haematoxylin and eosin histochemistry of tissue subjected to 10, 20, 40, 50 and 70 N for 5, 30 and 60 s was performed, and the area of colonic circular and longitudinal muscle was compared in grasped and un-grasped regions. The area under the f-t curve was calculated as a measure of the accumulated force applied, known as the force-time product (FTP). RESULTS: FTP ranged from 55.7 to 3793 N.s. Significant differences were observed between the muscle area of the grasped and un-grasped regions in both longitudinal and circular muscle at 50 N and above for all grasping times. For the longitudinal muscle, significant differences were observed between grasped and un-grasped areas at 20 N force for 30 s (mean difference = 59 mm2, 95% CI 41-77 mm2, P = 0.04), 20 N force for 60 s (mean difference = 31 mm2, 95% CI 21.5-40.5 mm2, P = 0.006) and 40 N force for 30 s (mean difference 37 mm2, 95% CI 27-47 mm2, P = 0.006). Changes in histology correlated with mechanical forces applied to the longitudinal muscle at a FTP over 300 N s. CONCLUSIONS: This study characterizes the grasping forces that result in histological changes to the colon and correlates these with a mechanical measurement of the applied force. The findings will contribute to the development of smart laparoscopic graspers with active constraints to prevent excessive grasping and tissue injury.

Matched Case-Control Comparative Study of Laparoscopic Versus Open Pancreaticoduodenectomy for Malignant Lesions.

INTRODUCTION: Advances in surgical technologies allowed safe laparoscopic pancreaticoduodenectomy (LPD). The aim of this study is to compare the oncologic outcomes of LPD to open pancreaticoduodenectomy (OPD) in terms of safety and recurrence rate. MATERIALS AND METHODS: A cohort of 30 patients were matched for age, sex, American Society of Anaesthesiologists, tumor size, pancreatic duct diameter, and histopathologic diagnosis on a 1:1 basis (15 LPD, 15 OPD). Comparison between groups was performed on intention-to-treat basis. Survival following resection was compared using the Kaplan-Meier survival analysis. RESULTS: The median operating time for LPD group was longer than for OPD group (470 vs. 310 min; P=0.184). However, estimated blood loss (300 vs. 620 mL; P=0.023), high dependency unit stay (2.0 vs. 6.0 d; P=0.013) and postoperative hospital stay (9.0 vs. 17.4 d; P=0.017) were significantly lower in the LPD group. There was no significant difference in postoperative rates of morbidity (40% vs. 67%; P=0.431) and mortality (0% vs. 6.7%; P=0.99). The surgical resection margins R0 status (87% vs. 73%; P=0.79) and the number of lymph nodes (18 vs. 20; P=0.99) in the resected specimens were comparable between the 2 groups. There was no significant difference in overall survival outcomes. CONCLUSIONS: In selected patients, the laparoscopic approach to pancreaticoduodenectomy in the hands of the experienced offers advantages over open surgery without compromising the oncologic resection.

Is the Use of a Robotic Camera Holder Economically Viable? A Cost Comparison of Surgical Assistant Versus the Use of a Robotic Camera Holder in Laparoscopic Liver Resections.

The laparoscopic approach has gained acceptance in the field of hepatopancreaticobiliary surgery. It offers several advantages including reduced blood loss, reduced postoperative pain, and shorter length of stay. However, long operating times can be associated with surgeon and assistant fatigue and image tremor. Robotic camera holders have been designed to overcome these drawbacks but may come with significant costs. The aim of this study was to economically evaluate their use compared with standard assistants using a single surgeon consecutive series of laparoscopic liver resections from January 2014 to May 2015. Only use of nurse assistants with no advanced training and postgraduate year 2 doctors were cheaper than utilization of the device. We suggest the use of a robotic camera holder is cost-beneficial and may have wider service and educational benefits.

Real-Time Measurement of the Tool-Tissue Interaction in Minimally Invasive Abdominal Surgery: The First Step to Developing the Next Generation of Smart Laparoscopic Instruments.

Introduction Analysis of force application in laparoscopic surgery is critical to understanding the nature of the tool-tissue interaction. The aim of this study is to provide real-time data about manipulations to abdominal organs. Methods An instrumented short fenestrated grasper was used in an in vivo porcine model, measuring force at the grasper handle. Grasping force and duration over 5 small bowel manipulation tasks were analyzed. Forces required to retract gallbladder, bladder, small bowel, large bowel, and rectum were measured over 30 seconds. Four parameters were calculated-T(hold), the grasp time; T(close), time taken for the jaws to close; F(max), maximum force reached; and F(rms), root mean square force (representing the average force across the grasp time). Results Mean F(max) to manipulate the small bowel was 20.5 N (±7.2) and F(rms) was 13.7 N (±5.4). Mean T(close) was 0.52 seconds (±0.26) and T(hold) was 3.87 seconds (±1.5). In individual organs, mean F(max) was 49 N (±15) to manipulate the rectum and 59 N (±13.4) for the colon. The mean F(max) for bladder and gallbladder retraction was 28.8 N (±7.4) and 50.7 N (±3.8), respectively. All organs exhibited force relaxation, the F(rms) reduced to below 25 N for all organs except the small bowel, with a mean F(rms) of less than 10 N. Conclusion This study has commenced the process of quantifying tool-tissue interaction. The static measurements discussed here should evolve to include dynamic measurements such as shear, torque, and retraction forces, and be correlated with evidence of histological damage to tissue.

Minimally Invasive Distal Pancreatectomy: A Single-Center Analysis of Outcome With Experience and Systematic Review of the Literature.

BACKGROUND: The aim of this study is to analyze the learning curve for laparoscopic distal pancreatectomy (LDP) in our series and review the literature on learning curves for LDP and robotic distal pancreatectomy (RDP). METHODS: Learning curve analysis was performed by split group and cumulative sum (CUSUM) analysis of blood loss, operative time, and length of stay. The systematic review identified studies analyzing changes in outcome with experience. RESULTS: A total of 25 resections were performed. CUSUM analysis of operative time found learning curves of 10 cases for LDP and splenectomy and 11 for LDP with splenic preservation. CUSUM analysis of blood loss showed approximately 6 cases. In the literature, values of 10 cases of LDP and approximately 7 RDP were found. CONCLUSIONS: Low numbers of LDP are required to reach proficiency in the hands of expert laparoscopic surgeons. Our results correspond with numbers quoted in the literature.

Attaining surgical competency and its implications in surgical clinical trial design: a systematic review of the learning curve in laparoscopic and robot-assisted laparoscopic colorectal cancer surgery.

BACKGROUND: Laparoscopic surgery is increasingly used in the treatment of colorectal cancer and more recently robotic assistance has been advocated. However, the learning curve to achieve surgical proficiency in laparoscopic surgery is ill-defined and subject to many influences. The aim of this review was to comprehensively appraise the literature on the learning curve for laparoscopic and robotic colorectal cancer surgery, and to quantify attainment of surgical proficiency and its implications in surgical clinical trial design. METHODS: A systematic review using a defined search strategy was performed. Included studies had to state an explicit numerical value of the learning curve evaluated by a single parameter or multiple parameters. RESULTS: Thirty-four studies were included, 28 laparoscopic and 6 robot assisted. Of the laparoscopic studies, nine defined the learning curve on the basis of a single parameter. Nine studies used more than one parameter to define learning, and 11 used a cumulative sum (CUSUM) analysis. One study used both a multiparameter and CUSUM analysis. The definition of proficiency was subjective, and the number of operations to achieve it ranged from 5 to 310 cases for laparoscopic and 15-30 cases for robotic surgery. CONCLUSIONS: The learning curve in laparoscopic colorectal surgery is multifaceted and often ill-defined, with poor descriptions of mentorship/supervision. Further, the quantification to attain proficiency is variable. The use of a single parameter to quantify this is simplistic. Multidimensional assessment is recommended; as part of this, the CUSUM model, which assesses trends in multiple surgical outcomes, is useful and appropriate when assessing the learning curve in a clinical setting.

Reviewing the technological challenges associated with the development of a laparoscopic palpation device.

Minimally invasive surgery (MIS) has heralded a revolution in surgical practice, with numerous advantages over open surgery. Nevertheless, it prevents the surgeon from directly touching and manipulating tissue and therefore severely restricts the use of valuable techniques such as palpation. Accordingly a key challenge in MIS is to restore haptic feedback to the surgeon. This paper reviews the state-of-the-art in laparoscopic palpation devices (LPDs) with particular focus on device mechanisms, sensors and data analysis. It concludes by examining the challenges that must be overcome to create effective LPD systems that measure and display haptic information to the surgeon for improved intraoperative assessment.

Towards evidence-based emergency medicine: best BETs from the Manchester Royal Infirmary. Diagnosis of drug overdose by rapid reversal with naloxone.

A short-cut review was carried out to establish whether naloxone may have an awakening effect in patients who have not taken opiates, thereby clouding its use as a diagnostic manoeuvre. The clinical bottom line is that opioid antagonists are able to reverse symptoms such as altered consciousness in patients who have not taken an overdose of opiates. It is unclear in which conditions or circumstances this occurs.