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.

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.

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.

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.

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.

Neoadjuvant chemoradiotherapy versus immediate surgery for resectable and borderline resectable pancreatic cancer: Meta-analysis and trial sequential analysis of randomized controlled trials.

We aimed to compare resection and survival outcomes of neoadjuvant chemoradiotherapy (CRT) and immediate surgery in patients with resectable pancreatic cancer (RPC) or borderline resectable pancreatic cancer (BRPC). In compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards, a systematic review of randomized controlled trials (RCTs) was conducted. Random effects modeling was applied to calculate pooled outcome data. Likelihood of type 1 or 2 errors in the meta-analysis model was assessed by trial sequential analysis. A total of 400 patients from four RCTs were included. When RPC and BRPC were analyzed together, neoadjuvant CRT resulted in a higher R0 resection rate (risk ratio [RR]: 1.55, p = 0.004), longer overall survival (mean difference [MD]: 3.75 years, p = 0.009) but lower overall resection rate (RR: 0.83, p = 0.008) compared with immediate surgery. When RPC and BRPC were analyzed separately, neoadjuvant CRT improved R0 resection rate (RR: 3.72, p = 0.004) and overall survival (MD: 6.64, p = 0.004) of patients with BRPC. However, it did not improve R0 resection rate (RR: 1.18, p = 0.13) or overall survival (MD: 0.94, p = 0.57) of patients with RPC. Neoadjuvant CRT might be beneficial for patients with BRPC, but not for patients with RPC. Nevertheless, the best available evidence does not include contemporary chemotherapy regimens. Patients with RPC and those with BRPC should not be combined in the same cohort in future studies.

A rare case of concomittant pancreatic adenosquamous and neuroendocrine tumours.

Only two cases of concomitantly occurring adenosquamous and neuroendocrine tumours (NET) have been reported in the literature. We report a case where both NET and adenosquamous are simultaneously occurring. A 42-year-old lady was hospitalized following painless jaundice and loss of weight. Computer tomography scan showed 3.0 x 2.9 cm hypo enhancing and hypovascular mass in the uncinate/head process. Another hypervascular mass was seen in the body of the pancreas. Pathological examination showed that the lesion in the uncinate process/neck of pancreas was an adenosquamous in the main pancreatic duct intraductal papillary mucinous neoplasm. The second tumour was a NET measuring 36 mm with no metastatic involvement. These findings suggested concurrently occurring but separated adenocarcinoma and NET tumours. This is the third case in the literature where both NET and adenosquamous are happening concomitantly, and the previous two other cases are also reviewed in the article.

'You know where we are if you need us.' The role of primary care in supporting patients following pancreaticoduodenectomy for cancer: a qualitative study.

BACKGROUND: Ten per cent of patients diagnosed with pancreatic cancer undergo pancreaticoduodenectomy. It is known that these patients have unmet psychological support needs, and GPs are key in enabling effective coordination of care for people living with life-shortening conditions. AIM: To explore patients' perspectives on the role of primary care in their management, and their sources of support. DESIGN & SETTING: Inductive qualitative study of patients who had undergone pancreaticoduodenectomy between 6 months and 6 years previously for pancreatic or distal biliary duct cancers. Participants were recruited by clinical nurse specialists (CNSs) from a single NHS trust in Northwest England. METHOD: Semi-structured interviews, either face-to-face or via video link, were conducted with 20 participants. Interviews were audio-recorded, transcribed, and anonymised. Thematic analysis utilised principles of constant comparison. RESULTS: Participants described immense treatment burden and uncertainty around the role of the GP in their ongoing care. They recognised that GPs may have little experience of patients who have undergone pancreaticoduodenectomy, but felt that GPs can play a vital role in offering support. Participants wished for emotional support postoperatively, and valued support networks including family and friends. However, they found expressing their deepest fears difficult. Participants felt they would value greater recognition by primary care of both physical and psychological sequelae of major pancreatic surgery, and the impact on their families. CONCLUSION: Patients may feel themselves to be a 'burden' to both healthcare professionals and their own support networks following pancreaticoduodenectomy. Primary care is in a key position to proactively offer psychological support.

Level 2a evidence comparing robotic versus laparoscopic left lateral hepatic sectionectomy: a meta-analysis.

OBJECTIVES: To evaluate comparative outcomes of robotic and laparoscopic left lateral hepatic sectionectomy (LLS). METHODS: A systematic search of PubMed, Web of Science, EMBASE and bibliographic reference lists with application of a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits was conducted. Overall, minor (Clavien-Dindo grade < III) and major (Clavien-Dindo grade > III) postoperative complications, mortality, volume of blood loss, conversion to an open procedure, procedure time, length of hospital stay, cost-effectiveness and R1 resection were the evaluated outcome measures. RESULTS: Seven comparative observational studies reporting a total of 319 patients of whom 150 underwent robotic LLS and the remaining 169 patients underwent laparoscopic LLS were included. The robotic approach was associated with significantly longer procedure time (MD: 29.40 min, p = 0.01) and higher cost (MD: $4170, p < 0.00001) compared to the laparoscopic approach. There was no significant difference in overall postoperative morbidity (OR: 1.29, p = 0.62), Clavien-Dindo grade < III (OR: 1.65, p = 0.49), Clavien-Dindo grade > III (OR: 1.18, p = 0.85), perioperative mortality (RD: 0.00, p = 1.00), volume of blood loss (MD: 1.96 mls, p = 0.91), conversion to an open procedure (RD: - 0.02, p = 0.46), length of hospital stay (MD: 0.22 day, p = 0.52) or R1 resection (RD:0.00, p = 1.00) between two groups. CONCLUSIONS: Meta-analysis of the best available evidence (level 2) demonstrated that robotic LLS is associated with significantly longer procedure time and higher cost and similar perioperative outcomes compared to the laparoscopic approach. Future randomised studies are required to evaluate short-term perioperative, long-term oncological and surgeon-centred outcomes.

Is there enough time to train? An audit of core surgical training rotas.

BACKGROUND: The Joint Committee on Surgical Training (JCST) have published a series of quality indicators (QIs) which act as a benchmark against which the quality of surgical training can be assessed. This audit aims to compare core surgical training (CST) rotas in our region against the JCST QI 10's minimum standard of 5 consultant supervised training sessions per week. METHODS: Core surgical trainees in one training region were contacted requesting their on-call rotas from rotations undertaken during the 2019/20 academic year. Rotas were analysed in a protocolised manner, with the number of potential training sessions available calculated and compared against the JCST QI 10 minimum recommendation. RESULTS: Twenty-four rotas were assessed across 17 hospitals. Only six (25%) of rotas achieved the JCST QI 10 standard. There was a mean deficit of 18.5 (±29.5) training sessions per 6-month rotation. Rotas compliant with JCST QI 10 used a mean rota pattern of 1 in 11 compared to 1 in 9 for those failing to meet the target. Further analysis, comprising of the addition of expected consultant led training whilst on call, led to an improvement in compliance to 9 (38%) and 13 (54%) of rotas when there was an addition of 0.5 h and 1 h of consultant supervised training time per on-call session respectively. CONCLUSION: Many core surgical trainee rotas in the region are non-compliant with JCST QI 10, indicating a lack of regular consultant-led training opportunities. A move to a reduced on-call commitment with the use of supporting medical practitioners could be considered to improve this.

'It's always in the back of my mind': understanding the psychological impact of recovery following pancreaticoduodenectomy for cancer: a qualitative study.

OBJECTIVES: Ten per cent of patients diagnosed with pancreatic cancer undergo pancreaticoduodenectomy. There is limited previous research focusing on psychological well-being; unmet support needs impact negatively on quality of life. This paper reports the psychological impact of a pancreatic cancer diagnosis and subsequent pancreaticoduodenectomy, exploring how patients' lives alter following surgery and how they seek support. DESIGN: Inductive qualitative study involving in-depth semistructured interviews with 20 participants who had undergone pancreaticoduodenectomy for pancreatic or distal biliary duct cancer. Interviews were audiorecorded, transcribed and anonymised, and thematic analysis used principles of constant comparison. SETTING: Single National Health Service Trust in Northwest England. PARTICIPANTS: Patients were eligible for inclusion if they had had pancreaticoduodenectomy for head of pancreas cancer, periampullary cancer or distal cholangiocarcinoma between 6 months and 6 years previously, and had completed adjuvant chemotherapy. RESULTS: Analysis identified the following main themes: diagnosis and decision making around surgery; recovery from surgery and chemotherapy; burden of monitoring and ongoing symptoms; adjusting to 'a new normal'; understanding around prognosis; support-seeking. Participants seized the chance to have surgery, often without seeming to absorb the risks or their prognosis. They perceived that they were unable to control their life trajectory and, although they valued close monitoring, experienced anxiety around their appointments. Participants expressed uncertainty about whether they would be able to return to their former activities. There were tensions in their comments about support-seeking, but most felt that emotional support should be offered proactively. CONCLUSIONS: Patients should be made aware of potential psychological sequelae, and that treatment completion may trigger the need for more support. Clinical nurse specialists (CNSs) were identified as key members of the team in proactively offering support; further training for CNSs should be encouraged. Understanding patients' experience of living with cancer and the impact of treatment is crucial in enabling the development of improved support interventions.

Stapled anastomosis versus hand-sewn anastomosis of gastro/duodenojejunostomy in pancreaticoduodenectomy: A systematic review and meta-analysis.

BACKGROUND: Controversy exists regarding the best anastomotic method for pancreaticoduodenectomy (PD). We aimed to evaluate the perioperative outcomes of PD with stapled anastomosis (SA) versus hand-sewn anastomosis (HA) of gastrojejunostomy or duodenojejunostomy. METHODS: We conducted a systematic search of electronic information sources, including MEDLINE; EMBASE; CINAHL; the Cochrane Central Register of Controlled Trials (CENTRAL); the World Health Organization International Clinical Trials Registry; ClinicalTrials.gov; ISRCTN Register, and bibliographic reference lists. We applied a combination of free text and controlled vocabulary search adapted to thesaurus headings, search operators and limits in each of the above databases. Delayed gastric emptying (DGE), postoperative pancreatic fistula (POPF), anastomotic bleeding, anastomotic leak, intra-abdominal abscess and mortality were defined as the outcome parameters. Combined overall effect sizes were calculated using fixed-effect or random-effects models. RESULTS: We identified 1 randomised controlled trial (RCT) and 5 observational studies reporting a total of 890 patients who underwent PD with SA (n = 300) or conventional HA (n = 590). Our analysis demonstrated that SA significantly reduced postoperative DGE (OR: 0.37, 95% CI 0.25-0.54, P < 0.00001) but significantly increased anastomotic bleeding (OR: 13.4, 95% CI 2.96-57.41, P = 0.0007) compared to HA. No significant difference was found in POPF (OR: 0.83, 95% CI 0.56-1.21, P = 0.33); anastomotic leak (OR: 0.50, 95% CI 0.09-3.79, P = 0.58); intra-abdominal abscess (OR: 1.39, 95% CI 0.71-2.70, P = 0.34); or mortality (RD: -0.01, 95% CI 0.03-0.02, P = 0.65) between two groups. CONCLUSIONS: Our analysis demonstrated that compared to conventional HA, SA may be associated with lower incidence of DGE after PD without increasing the risk of clinically significant POPF, anastomotic leak or mortality. However, it is associated with higher rate of anastomotic bleeding which mandates careful and precise haemostasis of the stapled line. Considering the current limited evidence, no definitive conclusion can be drawn. Future research is required.

Ultrasound-guided percutaneous thrombin for the management of superior mesenteric artery pseudoaneurysm.

Visceral aneurysms are a well-recognized and potentially fatal occurrence in the event of rupture. Endovascular occlusion using stent grafting or embolization is often favorable over high-risk open surgical repair. However, interventional mesenteric angiography may not always be feasible or successful. We present an emergency case of successful occlusion of a large peripancreatic pseudoaneurysm using a single percutaneous injection of thrombin under ultrasound guidance alone after both laparotomy and mesenteric angiography had failed to identify and control bleeding. In this case and review of the current evidence, we propose an effective alternative first-line treatment strategy in these complex patients.