The optimal surgical management of pancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1 is controversial. This study sought to compare clinicopathologic ...characteristics and outcomes of multiple endocrine neoplasia type 1–associated and sporadic pancreatic neuroendocrine tumors from a large multi-national database.
A multi-institutional, international database of patients with surgically resected pancreatic neuroendocrine tumors was analyzed. The cohort was divided into 2 groups: those with multiple endocrine neoplasia type 1 versus those with sporadic disease. Clinicopathologic comparisons were made. Overall and disease-free survival were analyzed. Propensity score matching was used to reduce bias.
Of 651 patients included, 45 (6.9%) had multiple endocrine neoplasia type 1 and 606 sporadic pancreatic neuroendocrine tumors. Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors were more common in younger patients and associated with multifocal disease at the time of surgery and higher T-stage. Lymph node involvement and the presence of metastasis were similar. Total pancreatectomy rate was 5-fold higher in the multiple endocrine neoplasia type 1 cohort. Median survival did not differ (disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). After matching, survival remained similar (overall survival not reached in either cohort, disease-free survival 126 months multiple endocrine neoplasia type 1 vs 198 months sporadic, P > .5). Equivalence in overall survival and disease-free survival persisted even when patients who underwent subtotal and total pancreatectomy were excluded.
Multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors are more common in younger patients and are associated with multifocality and higher T-stage. Survival for patients with multiple endocrine neoplasia type 1–associated pancreatic neuroendocrine tumors is comparable to those with sporadic pancreatic neuroendocrine tumors, even in the absence of radical pancreatectomy. Consideration should be given to parenchymal-sparing surgery to preserve pancreatic function.
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Aims
To compare outcomes of interrupted (IS) and continuous (CS) suturing techniques for Roux-en-Y hepaticojejunostomy and duct-to-duct choledochocholedochostomy.
Methods
The study protocol was ...prospectively registered in PROSPERO (registration number: CRD42021286294). A systematic search of MEDLINE, CENTRAL, and Web of Science and bibliographic reference lists were conducted (last search: 14th March 2022). All comparative studies reporting outcomes of IS and CS in hepaticojejunostomy and choledochocholedochostomy were included and their risk of bias was assessed using ROBINS-I tool. Overall biliary complications, bile leak, biliary stricture, cholangitis, liver abscess, and anastomosis time were the evaluated outcome parameters.
Results
Ten comparative studies (2 prospective and 8 retrospective) were included which reported 1617 patients of whom 1186 patients underwent Roux-en-Y hepaticojejunostomy (IS: 789, CS: 397) and the remaining 431 patients underwent duct-to-duct choledochocholedochostomy (IS: 168, CS: 263). Although use of IS for hepaticojejunostomy was associated with significantly longer anastomosis time (MD: 14.15 min,
p
=0.0002) compared to CS, there was no significant difference in overall biliary complications (OR: 1.34,
p
=0.11), bile leak (OR: 1.64,
p
=0.14), biliary stricture (OR: 0.84,
p
=0.65), cholangitis (OR: 1.54,
p
=0.35), or liver abscess (OR: 0.58,
p
=0.40) between two groups. Similarly, use of IS for choledochocholedochostomy was associated with no significant difference in risk of overall biliary complications (OR: 0.92,
p
=0.90), bile leak (OR: 1.70,
p
=0.28), or biliary stricture (OR: 1.07,
p
=0.92) compared to CS.
Conclusions
Interrupted and continuous suturing techniques for Roux-en-Y hepaticojejunostomy or duct-to-duct choledochocholedochostomy seem to have comparable clinical outcomes. The available evidence may be subject to confounding by indication with respect to diameter of bile duct. Future high-quality research is encouraged to report the outcomes with respect to duct diameter and suture material.
The aim of this study was to investigate the influence of resection margin status in patients with KRAS mutations (mt-KRAS) when compared to those with wild-type KRAS (wt-KRAS) on long-term outcomes ...in patients with resected CRLM.
All patients who underwent resection of CRLM with curative intent between January 2011 and December 2016 and had a KRAS type recorded were included in the study. Overall survival (OS), as well as death-censored overall (RFS) and liver-specific (LS-RFS) recurrence-free survival between KRAS types and the margin status within KRAS subgroups were compared using Cox regression models.
Data were available for N = 500 patients (30.4% mt-KRAS). mt-KRAS status was independently associated with significantly shorter OS. Within the wt-KRAS subgroup, smaller margins were found to be associated with significantly shorter death-censored LS-RFS (p < 0.001), with HRs of 1.93 (p = 0.005) for 1–4 mm margins and 2.83 (p < 0.001) for <1 mm margins, relative to those with clear margins. No such association was observed in the mt-KRAS subgroup (p = 0.721).
The resection margin status is of greater importance in patients with wt-KRAS. Such information could be useful in the operative planning, especially for those with multiple metastatic deposits, and also in the post-operative counselling and surveillance based on the margin and KRAS status.
BackgroundSurgical resection is a part of the treatment pathways for the management of pancreatic cancer with arterial involvement. Arterial resection in this context is however not widely supported ...due to the paucity and diversity of the reported evidence in the literature. The aim of this systematic review is the presentation and analysis of the current evidence in the field.MethodsA systematic literature search of PubMed, MEDLINE and the Cochrane Library was performed for eligible studies, following the PRISMA guidelines. Information on baseline characteristics, peri-operative outcomes, survival outcomes and histopathological findings were extracted for pooling and analysis.ResultsEight studies with a total of 170 patients were included in the analysis. One hundred and thirty-five patients had a pancreaticoduodenectomy (PD) and 35 had a total pancreatectomy (TP) with arterial resection. Perioperative morbidity was 43.5% and mortality was 4.5%. Median overall survival (OS) was 12.7 months (range, 10.5-22.2 months). Overall 3- and 5-year survival for this cohort was reported at 6.6% (range, 0-42.4%) and 3.3% (range, 0-6.6%) respectively. Resection margins were clear (R0) in a median of 75% of patients. Only a median of 45% of patients received neo-adjuvant chemotherapy.ConclusionsArterial resection can be performed with an acceptable peri-operative morbidity and mortality. However, survival outcomes are still not convincing and future efforts should concentrate on patient and disease biology selection.
To determine whether the short-term benefits associated with an enhanced recovery after surgery programme (ERAS) following pancreaticoduodenectomy (PD) vary with age.
830 consecutive patients who ...underwent PD between January 2009 and March 2019 were divided according to age: elderly (≥75 years) vs. non-elderly patients (<75 years). Within each age group, cohort characteristics and outcomes were compared between patients treated pre- and post-ERAS (ERAS was systematically introduced in December 2012). Univariable and multivariable analysis were then performed, to assess whether ERAS was independently associated with length of hospital stay (LOS).
Of the entire cohort, 577 of 830 patients (69.5%) were managed according to an ERAS protocol, and 170 patients (20.5%) were aged ≥75 years old. Patients treated post-ERAS were significantly more comorbid than those pre-ERAS, with a mean Charlson Comorbidity Index of 4.6 vs. 4.1 (p < 0.001) and 6.0 vs. 5.7 (p = 0.039) for the non-elderly and elderly subgroups, respectively. There were significantly fewer medical complications in non-elderly patients treated post-ERAS compared to pre-ERAS (12.4% vs. 22.4%; p = 0.002), but not in elderly patients (23.6% vs. 14.0%; p = 0.203). On multivariable analysis, ERAS was independently associated with reduced LOS in both elderly (14.8% reduction, 95% CI: 0.7–27.0%, p = 0.041) and non-elderly patients (15.6% reduction, 95% CI: 9.2–21.6%, p < 0.001), with the effect size being similar in each group.
ERAS protocols can be safely applied to patients undergoing pancreaticoduodenectomy irrespective of age. Implementation of an ERAS protocol was associated with a significant reduction in postoperative LOS in both elderly and non-elderly patients, despite higher comorbidity in the post-ERAS period.
In 2017, the WHO updated their 2010 classification of pancreatic neuroendocrine tumors, introducing a well-differentiated, highly proliferative grade 3 tumor, distinct from neuroendocrine carcinomas. ...The aim of this study was to investigate the clinical significance of this update in a large cohort of resected tumors.
Using a multicenter, international dataset of patients with pancreatic neuroendocrine lesions, patients were classified both according to the WHO 2010 and 2017 schema. Multivariable survival analyses were performed, and the models were evaluated for discrimination ability and goodness of fit.
Excluding patients with a known germline MEN1 mutation and incomplete data, 544 patients were analyzed. The performance of the WHO 2010 and 2017 models was similar, however surgically resected grade 3 tumors behaved very similarly to neuroendocrine carcinomas.
The addition of a grade 3 NET classification may be of limited utility in surgically resected patients, as these lesions have similar postoperative survival compared to carcinomas. While the addition may allow for a more granular evaluation of novel treatment strategies, surgical intervention for high grade tumors should be considered judiciously.
Background
The International Study Group on Pancreatic Surgery recommends upfront surgery for resectable pancreatic cancer or borderline resectable‐venous (BR‐V) disease and neoadjuvant therapy (NAT) ...among those with arterial involvement (BR‐A or locally advanced, LA). Though neoadjuvant therapy (NAT) is a promising strategy, outcomes are rarely reported on intention‐to‐treat (ITT) basis. This study presents ITT outcomes where pathways to surgery were in line with International Study Group on Pancreatic Surgery guidelines.
Methods
Patients recommended for potentially curative treatment with PDAC between 2012 and 2017 (n = 345) were classified as resectable, BR‐A/BR‐V or LA, according to NCCN criteria. The primary outcome was overall survival. Secondary outcomes were resection rates, positive margins and toxicity among patients receiving NAT.
Results
At surgery, the resection rates were 78% (172/221), 65% (35/54) and 54% (21/39) for those with resectable, BR‐V and BR‐A/LA disease, respectively (P < 0.0001). The median survival of those resected in the BR‐A/LA cohort was 31 months. However, on an ITT basis, there was no significant difference in survival between resectable, BR‐V and BR‐A/LA disease (median: 19 versus 15 versus 19 months; P = 0.585). On review, some 31 (44%) patients of the BR‐A/LA cohort either did not receive or did not complete NAT.
Conclusion
To realize benefits of NAT, more patients need to complete NAT and to undergo resection. Upfront resection for BR‐V disease is associated with equivalent outcomes to upfront surgery for resectable disease or NAT for BR‐A/LA disease. Strategies to increase the proportion of patients who complete NAT and undergo resection are needed.
Benefits of NAT may become apparent if more patients undergo surgery and/or chemotherapy becomes more effective/tolerable. High‐quality studies are needed to identify approaches to treatment that optimise clinical outcomes, quality of life and patient preference.
The aim of this study is to assess the correlation between the margin status on the specimen side (Rs) and that from the patient side (base of resection) (Rp) and the influence of positive margins ...(R1s and R1p) on cancer related outcomes in patients with colorectal liver metastases (CRLM).
In this prospective study, patients undergoing non-anatomical resection (NAR) of multifocal CRLM, with suspected close resection margins were included. The primary outcome evaluated was the correlation of Rs and Rp.
Twenty-three patients had 89 NARs, and CUSA samples from the base of 36 specimens were analysed. Among 36 specimens where extended histology (EH) was performed, margin status on the specimen side (Rs) was positive in 69.4% (25/36), whereas on the patient side, the margin (Rp) was positive in only 8.3% (3/36) of specimens. On univariate analysis, there was no significant difference in the site-specific recurrence at previous resection with regards to Rs positivity (P = 0.56) and Rp positivity (P = 0.48).
There is a poor correlation between Rs and Rp and the local recurrence rates in the liver. These results might further support that tumour biology is more relevant than the margin status in patients with multifocal CRLM.
The aim of the current study is to investigate the variations of anatomical (LVRem%) and functional remnant volumes (fLVRem%) and the dynamic uptake of Technetium-Mebrofinate (FRLF) measured from 99m ...Technetium-Mebrofinate SPECT-CT scan (TMSCT) in patients at high risk of post-hepatectomy liver failure (PHLF).
Variations in the measures of LVRem% and fLVRem% were assessed. The predictive accuracies of LVRem%, fLVRem% and FRLF with respect to PHLF were reported.
From the N = 92 scans performed, LVRem% and fLVRem% returned identical results in 15% of cases, and ±10 percentage points in 79% of cases. Some patients had larger discrepancies, with difference of >10 percentage points in 21% of cases. The difference was significant in those with primary liver cancers (−4.4 ± 9.2, p = 0.002). For the N = 29 patients that underwent surgery as planned on TMSCT, FRLF was a strong predictor of PHLF, with an AUROC of 0.83 (p = 0.005).
TMSCT is emerging as a useful modality in pre-operative assessment of patients undergoing major liver resection. For those with primary liver cancer, there is a significant variation in the anatomical and functional distributions that needs considered in surgical planning. Reduced FRLF, measured as the dynamic uptake in the future liver remnant, is a strong predictor of PHLF.
Backgrounds/Aims: Postoperative pancreatic fistula (POPF) after pancreaticoduodenectomy (PD) is a source of major morbidity and mortality. Early diagnosis and treatment of POPF is mandatory to ...improve patient outcomes and clinical risk scores may be ombined with postoperative drain fluid amylase (DFA) values to stratify patients. The aim of this pilot study was to etermine if intraoperative fluid amylase (IFA) values correlate with DFA1 and POPF. Methods: In patients undergoing PD from February to November 2020, intraoperative samples of intra-abdominal fluid adjacent to the pancreatic anastomosis were taken and sent for fluid amylase measurement prior to abdominal closure. Data regarding patient demographics, postoperative DFA values, complications, and mortality were prospectively collected. Results: Data were obtained for 52 patients with a median alternative Fistula Risk Score (aFRS) of 9.9. Postoperative complications occurred in 20 (38.5%) patients (five Clavien grade ≥ 3). There were eight POPFs and two patients died (pneumonia/sepsis). There was a significant correlation between IFA and DFA1 (R2 = 0.713; p < 0.001) and DFA3 (p < 0.001), and the median IFA was higher in patients with POPF than patients without (1,232.5 vs. 122; p = 0.0003). IFA > 260 U/L predicted POPF with sensitivity, specificity, positive and negative predictive values of 88.0%, 75.0%, 39.0%, and 97.0%, respectively. The incidence of POPF was 43.0% in high-risk (high aFRS/IFA) and 0% in lowrisk patients (low aFRS/IFA). Conclusions: IFA correlated with POPF and may be a useful adjunct to clinical risk scores to stratify patients during PD. Larger, prospective studies are needed to determine whether IFA has clinical utility.
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