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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., (Copyright © 2024 International Hepato-Pancreato-Biliary Association Inc. All rights reserved.)

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., (© The Author(s) 2023. Published by Oxford University Press on behalf of BJS Society Ltd.)

Background: The effect of early oral feeding (EOF) after pancreatoduodenectomy (PD) upon perioperative complications and outcomes is unknown, therefore the aim of this systematic review and meta-analysis was to investigate the effect of EOF on clinical outcomes after PD, such as postoperative pancreatic fistula (POPF), delayed gastric emptying (DGE) and length of stay (LOS)., Methods: A systematic review and meta-analysis was performed in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance and assimilated evidence from studies reporting outcomes for patients who received EOF after PD compared to enteral tube feeding (EN) or parenteral nutrition (PN)., Results: Four studies reported outcomes after EOF compared to EN/PN after PD and included 553 patients. Meta-analyses showed no difference in rates of CR-POPF (OR 0.74; 95%CI 0.44-1.24; p = 0.25) or DGE (Grade B/C) (OR 0.83; 95%CI 0.31-2.21; p = 0.70). LOS was significantly shorter in the EOF group compared to the EN/PN group (Mean Difference -3.40 days; 95% -6.11-0.70 days; p = 0.01)., Conclusion: Current available evidence suggests that EOF after PD is not associated with increased risk of DGE, does not exacerbate POPF and appears to reduce length of stay., (Copyright © 2022 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Objectives: Posterior superior mesenteric artery (SMA) first dissection in pancreaticoduodenectomy (PD) may allow for early assessment of resectability and aberrant anatomy. Study objectives were to compare resection margins, perioperative outcomes, disease-free survival (DFS) and overall survival (OS) in patients undergoing a posterior SMA first dissection PD to a classical technique PD., Methods: Patients (n = 77) who underwent a posterior SMA first PD for adenocarcinoma were case matched for patient and tumor characteristics with patients undergoing a classical approach PD from 2006 to 2014 (n = 177)., Results: The SMA first patients had an improved negative resection margin rate (27 [35.1%] vs 14 [18.2%], P = 0.042) and a higher lymph node yield (median 28 [22-34] vs 21 [17-27], P < 0.001) compared with the classical approach group. No difference was demonstrated in serious complications or 30-day mortality between the SMA first and classical approach patients (Clavien-Dindo 3/4 16 [20.8%] vs 11 [14.3%], P = 0.336; 30-day mortality 3 [3.9%] vs 3 [3.9%], P = 1.00 respectively). Median DFS and OS was similar in SMA first compared with classical approach patients (DFS, 1.6 vs 1.1 years, P = 0.122; OS, 2.5 vs 1.5 years, P = 0.220 respectively)., Conclusions: A posterior SMA first approach is a comparably safe technique that may improve oncological results in PD compared with classical approach dissection.

Background: Site of tumour origin, lymph node metastases and lymph node ratio (LNR) are identified as important factors determining prognosis in patients undergoing pancreaticoduodenectomy (PD). This study hypothesised that a prognostic index to predict survival could be developed through statistical modelling based on these pathological variables., Methods: Patients who underwent PD between 2004 and 2013 were included. Univariable and multivariable (Cox regression) analyses were performed to identify predictors of survival, and a prognostic index was derived. The prognostic index was then validated using an external patient cohort., Results: A total of 567 patients who underwent PD were used as a derivation cohort. Tumour site (p < 0.001), tumour size (p = 0.002), T-stage (p < 0.001), vascular involvement (p = 0.002), number of positive nodes (p < 0.001) and LNR (p < 0.001) were significantly associated with survival in univariable analysis. LNR (p < 0.001), tumour site (p < 0.001), T-stage (p = 0.007) remained significant predictors of survival in multivariable analysis, and were combined to derive a prognostic index. The accuracy of the prognostic index was assessed both on the original cohort, and a validation set of 194 patients from another institutional prospective database. The AUROC scores for predicting the overall survival at 3 years were 0.77 in the derivation cohort and 0.74 in the validation cohort., Conclusion: The Pancreaticoduodenectomy Prognostic Index is a validated clinico-pathological model based on tumour site, T-stage and LNR to predict long-term survival following PD., (Copyright © 2016 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: A post-operative pancreatic fistula (POPF) is a major cause of morbidity and mortality after a pancreaticoduodenectomy (PD). This systematic review aimed to identify all scoring systems to predict POPF after a PD, consider their clinical applicability and assess the study quality., Method: An electronic search was performed of Medline (1946-2014) and EMBASE (1996-2014) databases. Results were screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, and quality assessed according to the QUIPS (quality in prognostic studies) tool., Results: Six eligible scoring systems were identified. Five studies used the International Study Group on Pancreatic Fistula (ISGPF) definition. The proposed scores feature between two and five variables and of the 16 total variables, the majority (12) featured in only one score. Three scores could be fully completed pre-operatively whereas 1 score included intra-operative and two studies post-operative variables. Four scores were internally validated and of these, two scores have been subject to subsequent multicentre review. The median QUIPS score was 38 out of 50 (range 16-50)., Conclusion: These scores show potential in calculating the individualized patient risk of POPF. There is, however, much variation in current scoring systems and further validation in large multicentre cohorts is now needed., (© 2015 International Hepato-Pancreato-Biliary Association.)

Introduction: The evidence for improved prognostic assessment and long-term survival for extended pancreatoduodenectomy (EPD) compared to standard pancreatoduodenectomy (SPD) in patients with carcinoma of the head of the pancreas has not been considered from only randomized controlled trials (RCTs)., Methods: The aim of this study was to conduct a systematic review and meta-analysis of the outcomes comparing SPD and EPD in RCTs. Searches were performed on MEDLINE, Embase and Cochrane databases using MeSH keyword combinations: 'pancreatic cancer', 'pancreaticoduodenectomy', 'extended', 'randomized' and 'lymphadenectomy'. RCTs published up to 2014 were included. Overall post-operative survival, morbidity, 30-day mortality and length of hospital stay were the outcomes assessed., Results: Five eligible RCTs with 546 participants were included (EPD = 276 and SPD = 270). EPD was associated with a significantly higher number of excised lymph nodes (LNs) compared to SPD (mean difference = 15.73, 95% confidence interval (CI) = 9.41-22.04; P < 0.00001; I(2) = 88%). LN metastasis was detected in 58-68 and 55-70% of patients who had EPD and SPD, respectively. EPD did not improve overall survival (hazard ratio (HR) = 0.88, 95% CI = 0.75-1.03; P = 0.11) but did worsen post-operative morbidity compared to SPD (risk ratio (RR) = 1.23; 95% CI = 1.01-1.50; P = 0.004; I(2) = 9%). There were no differences in the 30-day mortality (RR = 0.81; 95% CI = 0.32-2.06; P = 0.66; I(2) = 0%) or length of hospital stay (mean difference = 1.39, 95% CI = -2.31 to 5.09; P = 0.46; I(2) = 67%)., Conclusion: SPD is associated with reduced morbidity, but equivalent long-term benefits compared to patients undergoing EPD.

Objective: To validate a preoperative predictive score of postoperative pancreatic fistula (POPF). Other risk factors for POPF were sought in an attempt to improve the score., Background: POPF is the major contributor to morbidity after pancreaticoduodenectomy (PD). A preoperative score [using body mass index (BMI) and pancreatic duct width] to predict POPF was tested upon a multicenter patient cohort to assess its performance., Methods: Patients undergoing PD at 8 UK centers were identified. The association between the score and other pre-, intra-, and postoperative variables with POPF was assessed., Results: A total of 630 patients underwent PD with 141 occurrences of POPF (22.4%). BMI, perirenal fat thickness, pancreatic duct width on computed tomography and at operation, bilirubin, pancreatojejunostomy technique, underlying pathology, T stage, N stage, R status, and gland firmness were all significantly associated with POPF. The score predicted POPF (P < 0.001) with a higher predictive score associated with increasing severity of POPF (P < 0.001). Stepwise multivariate analysis of pre-, intra-, and postoperative variables demonstrated that only the score was consistently associated with POPF. A table correlating the risk score to actual risk of POPF was created., Conclusions: The predictive score performed well and could not be improved. This provides opportunities for individualizing patient consent and selection, and treatment and research applications.

Introduction: Delayed gastric emptying (DGE) is a common complication after a pylorus-preserving pancreatoduodenectomy (PPPD) and is associated with significant morbidity. This study determines whether DGE is affected by antecolic (AC) or retrocolic (RC) reconstruction after a PPPD., Method: An electronic search was performed of the MEDLINE, EMBASE and PubMed databases to identify all articles related to this topic. Pooled risk ratios (RR) were calculated for categorical outcomes, and mean differences (MD) for secondary continuous outcomes using the fixed-effects and random-effects models for meta-analysis., Results: Nine studies including 878 patients met the inclusion criteria. DGE was lower with an AC reconstruction RR 0.31 [0.12, 0.78] Z = 2.47 (P = 0.010). Length of stay (LOS) MD -4 days [-7.63, -1.14] Z = 2.65 (P = 0.008) and days to commence a solid diet MD -5 days [-6.63, -3.15] Z = 5.50 (P ≤ 0.000) were also significantly in favour of the AC group. There was no difference in the incidence of pancreatic fistula, intra-abdominal collection/bile leak or mortality between the two groups., Conclusion: AC reconstruction after PPPD is associated with a lower incidence of DGE. Time to oral intake was significantly shorter with AC reconstruction, with a reduced hospital stay., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Laparoscopic pancreaticoduodenectomy (LPD) is a safe procedure. Oncological safety of LPD is still a matter for debate. This study aimed to compare the oncological outcomes, in terms of adequacy of resection and recurrence rate following LPD and open pancreaticoduodenectomy (OPD)., Methods: Between November 2005 and April 2009, 12 LPDs (9 ampullary and 3 distal common bile duct tumors) were performed. A cohort of 12 OPDs were matched for age, gender, body mass index (BMI) and American Society of Anesthesiologists (ASA) score and tumor site., Results: Mean tumor size LPD vs OPD (19.8 vs 19.2 mm, P=0.870). R0 resection was achieved in 9 LPD vs 8 OPD (P=1.000). The mean number of metastatic lymph nodes and total number resected for LPD vs OPD were 1.1 vs 2.1 (P=0.140) and 20.7 vs 18.5 (P=0.534) respectively. Clavien complications grade I/II (5 vs 8), III/IV (2 vs 6) and pancreatic leak (2 vs 1) were statistically not significant (LPD vs OPD). The mean high dependency unit (HDU) stay was longer in OPD (3.7 vs 1.4 days, P<0.001). There were 2 recurrences each in LPD and OPD (log-rank, P=0.983). Overall mortality for LPD vs OPD was 3 vs 6 (log-rank, P=0.283) and recurrence-related mortality was 2 vs 1. There was one death within 30 days in the OPD group secondary to severe sepsis and none in the LPD group., Conclusions: Compared to open procedure, LPD achieved a similar rate of R0 resection, lymph node harvest and long-term recurrence for tumors less than 2 cm. Though technically challenging, LPD is safe and does not compromise oncological outcome.

Background: Data have indicated that the lymph node ratio (LNR) may be a better prognostic indicator than lymph node status in pancreatic cancer., Objectives: To analyse the value of the LNR in patients undergoing resection for periampullary carcinomas., Methods: A cut off value of 0.2 was assigned to the LNR in accordance with published studies. The impact of histopathological factors including a LNR was analysed using Kaplan-Meier and Cox regression methods., Results: In total, 551 patients undergoing a resection (January 2000 to December 2010) were analysed. The median lymph node yield was 15, and 198 (34%) patients had a LNR > 0.2. In patients with a LNR of > 0.2, the median overall survival (OS) was 18 versus 33 months in patients with an LNR < 0.2 (P < 0.001). Univariate analysis demonstrated a LNR > 0.2, T and N stage, vascular or perineural invasion, grade and resection margin status to be significantly associated with OS. On multivariate analysis, only a LNR > 0.2, vascular or perineural invasion and margin positivity remained significant. In N1 disease, a LNR was able to distinguish survival in patients with a similar lymph node burden, and correlated with more aggressive tumour pathological variables., Conclusion: A LNR > 0.2, and not lymph note status, is an independent prognostic factor for OS indicating the LNR should be utilized in outcome stratification., (© 2012 International Hepato-Pancreato-Biliary Association.)

Background: The pre-operative neutrophil-to-lymphocyte ratio (NLR), when ≥5 has been associated with reduced survival for patients with various gastrointestinal tract cancers, however, it's prognostic value in patients with periampullary tumour has not been reported to date., Objectives: To determine the prognostic value of pre-operative NLR in terms of survival and recurrence of resected periampullary carcinomas., Methods: This was a retrospective cohort study of consecutive patients undergoing pancreatoduodenectomy (PD) for periampullary carcinoma (pancreatic, ampullary, cholangiocarcinoma) identified from a departmental database. The effect of NLR upon survival and recurrence was explored., Results: Overall median survival amongst 228 patients was 24 months (inter-quartile range [IQR]: 12-43). The median survival for those whose NLR was <5 was not significantly greater than those patients whose NLR was ≥5 (24 months [IQR: 14-42] versus 13 months [IQR: 8-48], respectively; p = 0.234). However, for those that developed recurrence, survival was greater in those with an NLR <5 at (20 months [IQR: 12-27] versus 11 months [IQR: 7-22], respectively; p = 0.038). This effect was most marked in those patients with cholangiocarcinoma (p = 0.019) whilst a trend to worse survival was seen in those with pancreatic adenocarcinoma. No effect was seen in patients with ampullary carcinoma (p = 0.516)., Conclusions: This study provides further evidence that pre-operative NLR offers important prognostic information regarding disease-free survival. This effect, however, is dependent upon the tumour type amongst patients undergoing PD., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Background/objectives: Understanding a patient's risk of pancreatic fistula (PF) prior to pancreatoduodenectomy (PD) would permit an individualised approach to patient selection, consent and, potentially, treatment. Various intra and post operative factors including pancreatic duct width and steatosis are associated with PF. We sought to identify whether information available in the pre-operative phase can predict PF., Methods: Associations between patient characteristics, pre-operative blood test results, data from pre-operative CT imaging and PF were explored. Pancreatic density (Hounsfield units, Hu), pancreatic duct size and gland thickness were measured using CT imaging., Results: PF occurred in 42 of 155 cases (types A, B and C: 32, 8, 2 respectively). An inverse relationship between duct width and PF was observed. The odds ratio of PF, for each 1 mm increase in duct width, was 0.639 (95% CI = 0.531-0.769, p < 0.001). The gland thickness and density at the pancreatic resection margin were positively associated with PF (both p = 0.03). No patient variable was associated with PF., Conclusions: Pancreatic duct width has previously been assessed at the time of operation and simply regarded as normal or wide. Consideration of duct width as a continuous variable using pre-operative CT imaging can be used to simply predict risk of PF. The association between pancreatic density and PF is a novel finding. Whether pancreatic density in Hu relates to steatosis, as it does for hepatic steatosis, merits further review given the association between pancreatic steatosis and PF., (Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

Introduction: Pancreatoduodenectomy (PD) has always been regarded as one of the most technically demanding abdominal procedures, even when carried out in high-volume centers by experienced surgeons. The reduction in higher surgical trainees working hours has led to reduced exposure, and consequently less experience in operative procedures. Furthermore, trainees have also become victims as health care systems striving for operating room efficiency, have attempted to reduce procedure duration by encouraging consultant led procedures at the expense of training. A strategy therefore needs to be developed to match the ability of the trainee with the complexity of the surgical procedure. As a PD can be deconstructed into a number of different steps, it may indeed be an ideal training operation for varying levels of ability., Methods: We describe our technique for PD and break it down to nine steps of varying technical ability making it suitable for many different stages of surgical training., Results: The complexity and variety of steps required to perform a PD makes it an ideal training operation from the junior surgical trainee to the most senior fellow, allowing the development of a wide range of skill sets., Discussion: Since the introduction of reduced working hours (48 h per week in Europe and 80 h per week in the USA) the "apprenticeship" model of surgical training has shifted towards a time-limited program with greater emphasis on supervision. Due to the complexity of surgery, and the perception of diminished levels of trainees' competency, a PD is often viewed as a consultant level operation. We believe that PD is an excellent model as it provides opportunities for trainees with varying levels of operative experience so that a PD could be considered the ideal "teaching case". Breaking down PD into a number of different steps may help building up surgical expertise more quickly while maintaining patients' safety and allowing the surgery to be expedited in a timely manner.

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. 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. 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). 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. [ABSTRACT FROM AUTHOR]

Pancreatoduodenectomy (PD) is recommended in fit patients with a resectable ampullary adenocarcinoma (AA). We aimed to identify predictors of five-year recurrence/survival. 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. 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. 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. [ABSTRACT FROM AUTHOR]

Background: In a previous study we reported an 85% R1 rate for pancreatic cancer following the use of the rigorous, fully standardized Leeds Pathology Protocol (LEEPP). As this significantly exceeded R1 rates observed by others, we investigated the reproducibility of margin assessment using the LEEPP in a larger, prospective, observational cohort study and correlated clinicopathological data with survival. Methods: Clinicopathological features, including exact site and multifocality of margin involvement, and survival were collated from a prospective series of 83 pancreatoduodenectomies for pancreatic (n = 27), ampullary (n = 24) and bile duct cancer (n = 32). Data were compared with those of the previous study in which the same pathology protocol, based on axial slicing and extensive tissue sampling from the circumferential margin, had been used. Results: The R1 rate was high in pancreatic (82%) and bile duct (72%) cancer and significantly lower in ampullary cancer (25%). Margin positivity was often multifocal, the posterior margin being most frequently involved. Margin status correlated with survival in the entire cohort (P = 0.006) and the pancreatic subgroup (P = 0.046). These findings were consistent with observations in our previous study. Conclusions: Margin involvement in pancreatic cancer is a frequent and prognostically significant finding when specimens are assessed using the LEEPP. [ABSTRACT FROM AUTHOR]