Five-year recurrence/survival after pancreatoduodenectomy for pancreatic adenocarcinoma: does pre-existing diabetes matter? Results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Diabetes mellitus (DM) has a complex relationship with pancreatic cancer. This study examines the impact of preoperative DM, both recent-onset and pre-existing, on long-term outcomes following pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multi-centre cohort of PD for pancreatic head malignancy (2012-2015). Recurrence and five-year survival rates of patients with DM were compared to those without, and subgroup analysis performed to compare patients with recent-onset DM (less than one year) to patients with established DM. RESULTS: Out of 758 patients included, 187 (24.7%) had DM, of whom, 47 of the 187 (25.1%) had recent-onset DM. There was no difference in the rate of postoperative pancreatic fistula (DM: 5.9% vs no DM 9.8%; p = 0.11), five-year survival (DM: 24.1% vs no DM: 22.9%; p = 0.77) or five-year recurrence (DM: 71.7% vs no DM: 67.4%; p = 0.32). There was also no difference between patients with recent-onset DM and patients with established DM in postoperative outcomes, recurrence, or survival. CONCLUSION: We found no difference in five-year recurrence and survival between diabetic patients and those without diabetes. Patients with pre-existing DM should be evaluated for PD on a comparable basis to non-diabetic patients.

Predictors of actual five-year survival and recurrence after pancreatoduodenectomy for ampullary adenocarcinoma: results from an international multicentre retrospective cohort study.

BACKGROUND: Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD patients with a confirmed head of pancreas or periampullary malignancy (June 1st, 2012-May 31st, 2015). Patients with AA who developed recurrence/died within five-years were compared to those who did not. RESULTS: 394 patients were included and actual five-year survival was 54%. Recurrence affected 45% and the median time-to-recurrence was 14 months. Local only, local and distant, and distant only recurrence affected 34, 41 and 94 patients, respectively (site unknown: 7). Among those with recurrence, the most common sites were the liver (32%), local lymph nodes (14%) and lung/pleura (13%). Following multivariable tests, number of resected nodes, histological T stage > II, lymphatic invasion, perineural invasion (PNI), peripancreatic fat invasion (PPFI) and ≥1 positive resection margin correlated with increased recurrence and reduced survival. Furthermore, ≥1 positive margin, PPFI and PNI were all associated with reduced time-to-recurrence. CONCLUSIONS: This multicentre retrospective study of PD outcomes identified numerous histopathological predictors of AA recurrence. Patients with these high-risk features might benefit from adjuvant therapy.

COVID-19-Related Reduction in Emergency Health Care Utilization Among Febrile Pediatric Oncology Patients.

The severe acute respiratory syndrome coronavirus (SARS-CoV-2) pandemic has disrupted normal health care utilization patterns worldwide, including decreasing emergency department (ED) visits for various medical emergencies. We examined whether this pattern was present in febrile pediatric oncology patients. In this single-center cohort study, we conducted a retrospective chart review of ED visits of febrile pediatric oncology patients during the first 4 months of the global SARS-CoV-2 pandemic and compared those data to the same time periods in the previous 2 years. During the first 5 months of the pandemic, 25 pediatric oncology patients with fever visited our ED; 65 children visited during the same time period in 2018; and 60 visited in 2019. Compared with 2018 and 2019, encounters for 2020 were decreased by 62% and 58%, respectively. A significantly higher percentage of febrile pediatric oncology patients (84%) were admitted to our hospital during the pandemic compared the previous years (58%). Of concern is the possibility that fear of exposure to coronavirus disease-19 (COVID-19) at our health care facility prompted caregivers of pediatric oncology patients to avoid seeking care for their child with fever. Consistent communication with families about the life-threatening nature of fever should be prioritized among pediatric oncology providers.

Implementation of a provider-focused intervention for maximizing human papillomavirus (HPV) vaccine uptake in young cancer survivors receiving follow-up care in pediatric oncology practices: protocol for a cluster-randomized trial of the HPV PROTECT intervention.

BACKGROUND: Childhood cancer survivors are at high risk for developing new cancers (such as cervical and anal cancer) caused by persistent infection with the human papillomavirus (HPV). HPV vaccination is effective in preventing the infections that lead to these cancers, but HPV vaccine uptake is low among young cancer survivors. Lack of a healthcare provider recommendation is the most common reason that cancer survivors fail to initiate the HPV vaccine. Strategies that are most successful in increasing HPV vaccine uptake in the general population focus on enhancing healthcare provider skills to effectively recommend the vaccine, and reducing barriers faced by the young people and their parents in receiving the vaccine. This study will evaluate the effectiveness and implementation of an evidence-based healthcare provider-focused intervention (HPV PROTECT) adapted for use in pediatric oncology clinics, to increase HPV vaccine uptake among cancer survivors 9 to 17 years of age. METHODS: This study uses a hybrid type 1 effectiveness-implementation approach. We will test the effectiveness of the HPV PROTECT intervention using a stepped-wedge cluster-randomized trial across a multi-state sample of pediatric oncology clinics. We will evaluate implementation (provider perspectives regarding intervention feasibility, acceptability and appropriateness in the pediatric oncology setting, provider fidelity to intervention components and change in provider HPV vaccine-related knowledge and practices [e.g., providing vaccine recommendations, identifying and reducing barriers to vaccination]) using a mixed methods approach. DISCUSSION: This multisite trial will address important gaps in knowledge relevant to the prevention of HPV-related malignancies in young cancer survivors by testing the effectiveness of an evidence-based provider-directed intervention, adapted for the pediatric oncology setting, to increase HPV vaccine initiation in young cancer survivors receiving care in pediatric oncology clinics, and by procuring information regarding intervention delivery to inform future implementation efforts. If proven effective, HPV PROTECT will be readily disseminable for testing in the larger pediatric oncology community to increase HPV vaccine uptake in cancer survivors, facilitating protection against HPV-related morbidities for this vulnerable population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04469569, prospectively registered on July 14, 2020.

Do some patients receive unnecessary parenteral nutrition after pancreatoduodenectomy? Results from an international multicentre study.

Backgrounds/Aims: After pancreatoduodenectomy (PD), an early oral diet is recommended; however, the postoperative nutritional management of PD patients is known to be highly variable, with some centers still routinely providing parenteral nutrition (PN). Some patients who receive PN experience clinically significant complications, underscoring its judicious use. Using a large cohort, this study aimed to determine the proportion of PD patients who received postoperative nutritional support (NS), describe the nature of this support, and investigate whether receiving PN correlated with adverse perioperative outcomes. Methods: Data were extracted from the Recurrence After Whipple's study, a retrospective multicenter study of PD outcomes. Results: In total, 1,323 patients (89%) had data on their postoperative NS status available. Of these, 45% received postoperative NS, which was "enteral only," "parenteral only," and "enteral and parenteral" in 44%, 35%, and 21% of cases, respectively. Body mass index < 18.5 kg/m2 (p = 0.03), absence of preoperative biliary stenting (p = 0.009), and serum albumin < 36 g/L (p = 0.009) all correlated with receiving postoperative NS. Among those who did not develop a serious postoperative complication, i.e., those who had a relatively uneventful recovery, 20% received PN. Conclusions: A considerable number of patients who had an uneventful recovery received PN. PN is not without risk, and should be reserved for those who are unable to take an oral diet. PD patients should undergo pre- and postoperative assessment by nutrition professionals to ensure they are managed appropriately, and to optimize perioperative outcomes.

Patterns, timing and predictors of recurrence following pancreaticoduodenectomy for distal cholangiocarcinoma: An international multicentre retrospective cohort study.

INTRODUCTION: Patients undergoing pancreaticoduodenectomy for distal cholangiocarcinoma (dCCA) often develop cancer recurrence. Establishing timing, patterns and risk factors for recurrence may help inform surveillance protocol strategies or select patients who could benefit from additional systemic or locoregional therapies. This multicentre retrospective cohort study aimed to determine timing, patterns, and predictive factors of recurrence following pancreaticoduodenectomy for dCCA. MATERIALS AND METHODS: Patients who underwent pancreaticoduodenectomy for dCCA between June 2012 and May 2015 with five years of follow-up were included. The primary outcome was recurrence pattern (none, local-only, distant-only or mixed local/distant). Data were collected on comorbidities, investigations, operation details, complications, histology, adjuvant and palliative therapies, recurrence-free and overall survival. Univariable tests and regression analyses investigated factors associated with recurrence. RESULTS: In the cohort of 198 patients, 129 (65%) developed recurrence: 30 (15%) developed local-only recurrence, 44 (22%) developed distant-only recurrence and 55 (28%) developed mixed pattern recurrence. The most common recurrence sites were local (49%), liver (24%) and lung (11%). 94% of patients who developed recurrence did so within three years of surgery. Predictors of recurrence on univariable analysis were cancer stage, R1 resection, lymph node metastases, perineural invasion, microvascular invasion and lymphatic invasion. Predictors of recurrence on multivariable analysis were female sex, venous resection, advancing histological stage and lymphatic invasion. CONCLUSION: Two thirds of patients have cancer recurrence following pancreaticoduodenectomy for dCCA, and most recur within three years of surgery. The commonest sites of recurrence are the pancreatic bed, liver and lung. Multiple histological features are associated with recurrence.

Anticoagulation after pancreatic surgery with venous resection (TIGRESS): What should we do? Results from an international survey.

Backgrounds/Aims: Patients who undergo pancreatic surgery with venous resection have high rates of morbidity/mortality. Also, they are high-risk for postoperative venous thromboembolism. Whether this group should be routinely anticoagulated is unknown. This study aimed to establish current anticoagulation practices. Methods: A survey (https://form.jotform.com/220242489107048) was sent out to pancreatic surgeons. Questions covered center volume, venous resection/reconstruction techniques and anticoagulation policies. Results: Sixty-five centers from 17 countries responded. Following a "side-bite" venous resection with a patch repair, 40% used an autologous vein patch, 27% used peritoneum, and 27% used a bovine patch. After formally resecting a segment of vein, 17% of centers used an interposition graft (IG). Left renal vein (41%) and polytetrafluoroethylene (73%) grafts were the most commonly used autologous and prosthetic IGs, respectively. Following a prosthetic IG, an autologous IG, and a "side-bite" resection, 59%, 28%, and 19% of centers provided therapeutic anticoagulation, respectively (66% used low molecular-weight heparin). The duration of therapy provided varied from inpatient stay only (14%) to six months (32%). Conclusions: Our global survey indicates that anticoagulation practices are highly variable. Centers do not agree on when to anticoagulate, how to anticoagulate, or the duration of therapy. A robust trial is required to provide clarity.

Serious complications of pancreatoduodenectomy correlate with lower rates of adjuvant chemotherapy: Would high-risk patients benefit from neoadjuvant therapy?

INTRODUCTION: Patients who suffer a serious complication of pancreatoduodenectomy (PD) may have their adjuvant chemotherapy (AC) delayed or omitted as a result. We aimed to investigate whether PD complications affected AC rates. MATERIALS AND METHODS: A retrospective analysis of all PD patients with histologically-confirmed pancreatic ductal adenocarcinoma (2006-2015) was performed; 90-day mortality patients were excluded. Patients who commenced AC were compared to those who did not (morbidity rates and survival) and patients who developed selected postoperative complications were compared to those who did not (AC rates and survival). RESULTS: 157 patients were included and 90-day mortality was 3.8%. Of the remaining patients, 102 (68.5%) received AC (AC data unavailable for two patients). Survival was longer in the AC group (p = 0.004). AC patients had less frequently experienced a postoperative chest infection (8.82% vs 34.0%, p = 0.0003) or a postoperative complication which was Clavien-Dindo (CD) grade ≥ II (29.4% vs 57.4%, p = 0.0019) or ≥ III (6.86% vs 21.3%, p = 0.023). Patients who experienced a postoperative chest infection (36.0% vs 75.0%, p = 0.0003) or a postoperative complication which was CD grade ≥ II (48.9% vs 73.1%, p = 0.0099) or ≥ III (29.4% vs 70.3%, p = 0.0018) less frequently commenced AC. CONCLUSION: Patients who received AC had less frequently experienced a serious postoperative complication. Efforts should be made to preoperatively identify those who are high-risk for a serious complication as this cohort may benefit from neoadjuvant therapy.

Serious complications of pancreatoduodenectomy correlate with lower rates of adjuvant chemotherapy: Results from the recurrence after Whipple's (RAW) study.

INTRODUCTION: Adjuvant chemotherapy (AC) can prolong overall survival (OS) after pancreatoduodenectomy (PD) for pancreatic ductal adenocarcinoma (PDAC). However, fitness for AC may be influenced by postoperative recovery. We aimed to investigate if serious (Clavien-Dindo grade ≥ IIIa) postoperative complications affected AC rates, disease recurrence and OS. MATERIALS AND METHODS: Data were extracted from the Recurrence After Whipple's (RAW) study (n = 1484), a retrospective study of PD outcomes (29 centres from eight countries). Patients who died within 90-days of PD were excluded. The Kaplan-Meier method was used to compare OS in those receiving or not receiving AC, and those with and without serious postoperative complications. The groups were then compared using univariable and multivariable tests. RESULTS: Patients who commenced AC (vs no AC) had improved OS (median difference: (MD): 201 days), as did those who completed their planned course of AC (MD: 291 days, p < 0.0001). Those who commenced AC were younger (mean difference: 2.7 years, p = 0.0002), more often (preoperative) American Society of Anesthesiologists (ASA) grade I-II (74% vs 63%, p = 0.004) and had less often experienced a serious postoperative complication (10% vs 18%, p = 0.002). Patients who developed a serious postoperative complication were less often ASA grade I-II (52% vs 73%, p = 0.0004) and less often commenced AC (58% vs 74%, p = 0.002). CONCLUSION: In our multicentre study of PD outcomes, PDAC patients who received AC had improved OS, and those who experienced a serious postoperative complication commenced AC less frequently. Selected high-risk patients may benefit from targeted preoperative optimisation and/or neoadjuvant chemotherapy.

Postoperative complications after pancreatoduodenectomy for malignancy: results from the Recurrence After Whipple's (RAW) study.

BACKGROUND: Pancreatoduodenectomy (PD) is associated with significant postoperative morbidity. Surgeons should have a sound understanding of the potential complications for consenting and benchmarking purposes. Furthermore, preoperative identification of high-risk patients can guide patient selection and potentially allow for targeted prehabilitation and/or individualized treatment regimens. Using a large multicentre cohort, this study aimed to calculate the incidence of all PD complications and identify risk factors. METHOD: Data were extracted from the Recurrence After Whipple's (RAW) study, a retrospective cohort study of PD outcomes (29 centres from 8 countries, 2012-2015). The incidence and severity of all complications was recorded and potential risk factors for morbidity, major morbidity (Clavien-Dindo grade > IIIa), postoperative pancreatic fistula (POPF), post-pancreatectomy haemorrhage (PPH) and 90-day mortality were investigated. RESULTS: Among the 1348 included patients, overall morbidity, major morbidity, POPF, PPH and perioperative death affected 53 per cent (n = 720), 17 per cent (n = 228), 8 per cent (n = 108), 6 per cent (n = 84) and 4 per cent (n = 53), respectively. Following multivariable tests, a high BMI (P = 0.007), an ASA grade > II (P < 0.0001) and a classic Whipple approach (P = 0.005) were all associated with increased overall morbidity. In addition, ASA grade > II patients were at increased risk of major morbidity (P < 0.0001), and a raised BMI correlated with a greater risk of POPF (P = 0.001). CONCLUSION: In this multicentre study of PD outcomes, an ASA grade > II was a risk factor for major morbidity and a high BMI was a risk factor for POPF. Patients who are preoperatively identified to be high risk may benefit from targeted prehabilitation or individualized treatment regimens.

Does an extensive diagnostic workup for upfront resectable pancreatic cancer result in a delay which affects survival? Results from an international multicentre study.

Backgrounds/Aims: Pancreatoduodenectomy (PD) is recommended in fit patients with a carcinoma (PDAC) of the pancreatic head, and a delayed resection may affect survival. This study aimed to correlate the time from staging to PD with long-term survival, and study the impact of preoperative investigations (if any) on the timing of surgery. Methods: Data were extracted from the Recurrence After Whipple's (RAW) study, a multicentre retrospective study of PD outcomes. Only PDAC patients who underwent an upfront resection were included. Patients who received neoadjuvant chemo-/radiotherapy were excluded. Group A (PD within 28 days of most recent preoperative computed tomography [CT]) was compared to group B (> 28 days). Results: A total of 595 patents were included. Compared to group A (median CT-PD time: 12.5 days, interquartile range: 6-21), group B (49 days, 39-64.5) had similar one-year survival (73% vs. 75%, p = 0.6), five-year survival (23% vs. 21%, p = 0.6) and median time-todeath (17 vs. 18 months, p = 0.8). Staging laparoscopy (43 vs. 29.5 days, p = 0.009) and preoperative biliary stenting (39 vs. 20 days, p < 0.001) were associated with a delay to PD, but magnetic resonance imaging (32 vs. 32 days, p = 0.5), positron emission tomography (40 vs. 31 days, p > 0.99) and endoscopic ultrasonography (28 vs. 32 days, p > 0.99) were not. Conclusions: Although a treatment delay may give rise to patient anxiety, our findings would suggest this does not correlate with worse survival. A delay may be necessary to obtain further information and minimize the number of PD patients diagnosed with early disease recurrence.

Procedure-specific morbidity of pancreatoduodenectomy: a systematic review of incidence and risk factors.

BACKGROUND: Pancreatoduodenectomy (PD) remains the only curative-intent treatment option for patients with cancer affecting the head of the pancreas. It is high-risk and overall morbidity is around 40%. Due to the necessary resection and subsequent anastomoses required, multiple procedure-specific complications are possible. An in-depth understanding of the recent evidence on these will guide the consenting process and allow surgeons to evaluate their own performance. We aimed to consolidate the recent literature on preselected PD complications (postoperative pancreatic fistula (POPF), bile leak (BL), gastrojejunal leak, postpancreatectomy haemorrhage (PPH), cholangitis, and chyle leak (CL)). METHODS: A search of the PubMed database was carried out on 1st July 2021. Articles from July 2011 through to July 2021 were included. The initial search returned 297 results. After screening, 226 articles were excluded. The remaining 71 were assessed for eligibility and a further 34 were excluded. 37 were included in the final synthesis (two meta-analyses and 35 single/multicentre studies). RESULTS: Due to recently updated diagnostic criteria, differing definitions among authors and subclinical cases, true incidence rates are difficult to appreciate. The following were obtained: POPF (excluding biochemical leak): 10.0-25.9%, BL: 3.0-7.9%, gastrojejunal anastomotic leak: 0.4-1.2%, PPH: 7.3-13.6%, cholangitis: 0.05-21.1% and CL: 2.6-19.0%. Numerous risk factors, both modifiable and non-modifiable, were identified for each. CONCLUSION: Most of the recent evidence on the studied complications comes from single institution studies of retrospective design. Robust case-control studies are required so predictive models can estimate the likelihood of specific complications in individual patients.

Results from a UK-wide survey: the nutritional assessment and management of pancreatic resection patients is highly variable.

Most patients who undergo curative-intent resection for pancreatic cancer are malnourished. This correlates with poor outcomes. There are no guidelines for the nutritional management of these patients. We aimed to establish current UK practice by surveying all hepatopancreatobiliary (HPB) units. Questions covered: dietetic service, nutrition risk screening (RS), micronutrients, prehabilitation, nutritional support, pancreatic exocrine replacement therapy (PERT), and details of follow-up. Twenty-six units (83.9%) responded. Twenty-three (88.5%) provide a specialist HPB dietetic service. Twelve (52.2%) cover the entire treatment pathway. Thirteen (50.0%) routinely perform RS, eleven (42.3%) check micronutrients, and fourteen (53.8%) provide a prehabilitation programme. Twelve units (46.2%) allow nutritional supplements within 48 h of surgery, and eight (30.8%) do not allow this until at least 72 h. The use of PERT and acid-suppressing agents is highly variable. Seventeen units (65.4%) routinely provide dietitian follow-up. Practice is highly variable; robust studies are required so consensus guidelines can be formulated.

How we do it: Laparoscopic cholecystectomy in patients with severe obesity.

The number of patients with obesity is set to rise, as is the proportion with severe obesity. These patients are a high-risk subgroup who present addi- tional challenges to the surgeon when performing laparoscopic cholecystectomy. It is important that all surgeons who perform this procedure have a safe strategy they can revert to. This article outlines our approach. After obtaining pneumoperitoneum via a supra-umbilical incision, we advise placing a fascial suture before proceeding with the operation. This allows for high-quality closure, reduces the incidence of incisional hernia, and reduces the risk of inadvertent bowel injury. We also advise the repositioning of the patient on the operating table prior to port placement such that an ergonomic set-up can be achieved. In addition to standard ports, we use an additional twelve-millimetre port in the left upper quadrant. A fan retractor can be inserted via this port and used to gently retract the duodenum inferiorly. This provides adequate exposure for Calot's dissection and arguably reduces the risk of injury to a fatty liver. This technique can also be used in non-obese patients in whom Calot's dissection is particularly challenging, for instance in those who undergo delayed cholecystectomy.

Emergency hernia surgery at a high-volume tertiary centre: a 3-year experience.

BACKGROUND: Hernia surgery is often considered minor. However, emergency abdominal wall hernia (AWH) surgery is associated with significant morbidity. This study reviews a high-volume centre's experience. METHODS: This is a retrospective review of all emergency AWH operations performed between 2014 and 2017. The following were analysed: patient demographics, ASA grade, type of hernia, time from admission to surgery, use of pre-operative imaging, sac content, details of bowel resection, rate of admission to high dependency unit (HDU)/intensive care unit (ICU), length of stay and morbidity/mortality. RESULTS: A total of 198 cases were included. Median age was 67.4 years (range 19-95). 52.2% of patients were ASA III or above. Median time from admission to surgery was 13 h (range 1-341) and median length of stay was 4 days (range 1-75). The sac contained bowel in 93 cases (47.0%). These patients had longer length of stay (P < 0.01) and were more frequently admitted to HDU/ICU (P < 0.01). Thirty-one patients underwent bowel resection (33.3% of those with bowel involvement and 15.7% of the total). Twenty-seven patients (13.6%) were admitted to HDU/ICU post-operatively. Six patients (3.0%) had an unplanned return to theatre and 66 patients (33.3%) had a post-operative complication. Inpatient mortality was three (1.51%). CONCLUSIONS: Patients who undergo emergency AWH surgery represent a relatively aged and co-morbid group. This surgery is associated with significant morbidity and consumes considerable hospital resources. Efforts should be made to identify the higher risk subgroup with bowel involvement. Elderly and co-morbid patients should be listed for timely elective surgery wherever suitable.

A date pit induced aorto-oesophageal fistula: a case report and concise literature review.

Aorto-oesophageal fistula (AEF) is rare and fatal without intervention. Having consumed a date pit 2 weeks prior, the patient in this case presented with the 'Chiari' triad of chest pain, sentinel arterial upper gastro-intestinal haemorrhage and exsanguination after an asymptomatic interval. Following resuscitation, the patient was managed with a Blakemore tube with both oesophageal and gastric balloons inflated to systemic pressures. An aortic stent graft was planned but the patient died on the operating table. AEFs can be treated surgically with either open or endovascular repair. Open repair is highly risky and involves combined replacement/bypass of the thoracic aorta along with resection/repair of the involved oesophagus. Endovascular repair can prevent fatal exsanguination and increase the likelihood of survival but is associated with a significant rate of secondary infection, recurrence of fistula, mediastinitis and sepsis. Further studies are required to inform on management.