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This review presents a comprehensive comparative analysis of international guidelines for managing advanced, non-functioning, well-differentiated pancreatic neuroendocrine tumors (panNETs). PanNETs, which represent a significant proportion of pancreatic neuroendocrine neoplasms, exhibit diverse clinical behaviors and prognoses based on differentiation, grading, and other molecular markers. The varying therapeutic strategies proposed by different guidelines reflect their distinct emphases and regional considerations, such as the ESMO guideline\'s focus on advanced disease management and the ENETS guidance paper\'s multidisciplinary approach. This review examines the most recent guidelines from ESMO, NCCN, ASCO, ENETS, and NANETS, analyzing the recommendations for first-line therapies and subsequent treatment pathways in different clinical scenarios. Significant variations are observed in the recommendations, particularly concerning the choice and sequence of systemic therapies, the role of tumor grading and the Ki-67 index in therapeutic decisions, and the integration of regional regulatory and clinical practices. The analysis highlights the need for a tailored approach to managing advanced NF panNETs, advocating for flexibility in applying guidelines to account for individual patient circumstances and the evolving evidence base. This work underscores the complexities of managing this patient population and the critical role of a multidisciplinary team in optimizing treatment outcomes.

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BACKGROUND: A large proportion of patients with foregut cancers do not receive guideline-concordant treatment (GCT). This study sought to understand underlying barriers to GCT through a root cause analysis approach.
METHODS: A single-institution retrospective review of 498 patients with foregut (gastric, pancreatic, and hepatobiliary) adenocarcinoma from 2018 to 2022 was performed. Guideline-concordant treatment was defined based on National Comprehensive Cancer Network guidelines. The Ishikawa cause and effect model was used to establish main contributing factors to non-GCT.
RESULTS: Overall, 34% did not receive GCT. Root causes of non-GCT included Patient, Physician, Institutional Environment and Broader System-related factors. In decreasing order of frequency, the following contributed to non-GCT: receipt of incomplete therapy (N = 28, 16.5%), deconditioning on chemotherapy (N = 26, 15.3%), delays in care because of patient resource constraints followed by loss to follow-up (N = 19, 11.2%), physician factors (N = 19, 11.2%), no documentation of treatment plan after referral to oncologic expertise (N = 19, 11.2%), loss to follow-up before oncology referral (N = 17, 10%), nonreferral to medical oncologic expertise (N = 16, 9.4%), nonreferral to surgical oncology in patients with resectable disease (N = 15, 8.8%), and complications preventing completion of treatment (N = 11, 6.5%). Non-GCT often was a function of multiple intersecting patient, physician, and institutional factors.
CONCLUSIONS: A substantial percentage of patients with foregut cancer do not receive GCT. Solutions that may improve receipt of GCT include development of automated systems to improve patient follow-up; institutional prioritization of resources to enhance staffing; financial counseling and assistance programs; and development and integration of structured prehabilitation programs into cancer treatment pathways.

Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis, with a 5-year overall survival rate of 10%. In November 2018, NCCN recommended that all patients with PDAC receive genetic counseling (GC) and germline testing regardless of family history. We hypothesized that patients with PDAC were more likely to be referred for testing after this change to the guidelines, regardless of presumed predictive factors, and that compliance would be further improved following the implementation of a hereditary cancer clinic (HCC).
We conducted a single-institution retrospective analysis of patients diagnosed with PDAC from June 2017 through December 2021 at University of California, Irvine. We compared rates of genetics referral among patients in different diagnostic eras: the 18-month period before the NCCN Guideline change (pre-NCCN era: June 2017 through November 2018), 14 months following the change (post-NCCN era: December 2018 through January 2020), and 18 months after the creation of an HCC (HCC era: June 2020 through December 2021). Family and personal cancer history, genetics referral patterns, and results of GC were recorded. Data were compared using chi-square, Fisher exact, and multivariate analyses.
A total of 335 patients were treated for PDAC (123 pre-NCCN, 109 post-NCCN, and 103 HCC) at University of California, Irvine. Demographics across groups were comparable. Prior to the guideline changes, 30% were referred to GC compared with 54.7% in the post-NCCN era. After the implementation of the HCC, 77.4% were referred to GC (P<.0001). The odds ratio (OR) for referral to GC among patients with a positive family history of cancer progressively decreased following the change (pre-NCCN era: OR, 11.90 [95% CI, 3.00-80.14]; post-NCCN era: OR, 3.39 [95% CI, 1.13-10.76]; HCC era: OR, 3.11 [95% CI, 0.95-10.16]).
The 2018 updates to the NCCN Guidelines for PDAC recommending germline testing for all patients with PDAC significantly increased GC referral rates at our academic medical center. Implementation of an HCC further boosted compliance with guidelines.

Pancreatic cancer is a highly malignant tumor in the digestive system, and radical surgery is the only possible means to cure pancreatic cancer at present. In the past decade, pancreatic surgery has been developing rapidly, with various new technologies and concepts emerging, among which the use of minimally invasive techniques and the popularization of neoadjuvant therapy concepts are the most notable. At the same time, the surgical treatment of pancreatic cancer still has a long way to go, and many problems need to be solved urgently. This article introduces the surgical treatment of pancreatic cancer in the 2024 edition of the NCCN guidelines, focusing on minimally invasive and open surgical treatments, expanded lymph node dissection, combined vascular resection and reconstruction, surgical treatment of pancreatic neck cancer and neoadjuvant therapy, and briefly discussing the unresolved issues.
胰腺癌是消化系统恶性程度较高的肿瘤，根治性手术是目前唯一可能治愈胰腺癌的手段。近十年来，胰腺外科发展迅速，各类新技术、新理念不断涌现，其中以微创技术的运用和新辅助治疗理念的普及最为引人注目；同时，胰腺癌的外科治疗仍有很长的道路要走，许多问题亟待解决。本文对2024版NCCN指南中胰腺癌外科治疗部分进行介绍，重点解读微创入路和开腹手术治疗、扩大淋巴结清扫、联合血管切除重建、胰颈癌的手术治疗和新辅助治疗这几方面，同时对其中尚未解决的问题做简要讨论。.

OBJECTIVE: The purpose of this study was to compare the different versions of the National Comprehensive Cancer Network (NCCN) guidelines for defining resectability of pancreatic ductal adenocarcinoma (PDAC) in predicting margin-negative (R0) resection, and to assess inter-reader agreement.
METHODS: This retrospective study included 283 patients (mean age, 65.1 years ± 9.4 [SD]; 155 men) who underwent upfront pancreatectomy for PDAC between 2017 and 2019. Two radiologists independently determined the resectability on preoperative CT according to the 2017, 2019, and 2020 NCCN guidelines. The sensitivity and specificity for R0 resection were analyzed using a multivariable logistic regression analysis with generalized estimating equations. Inter-reader agreement was assessed using kappa statistics.
RESULTS: R0 resection was accomplished in 239 patients (84.5%). The sensitivity and specificity averaged across two readers were, respectively, 76.6% and 29.5% for the 2020 guidelines, 74.1% and 32.9% for the 2019 guidelines, and 72.6% and 34.1% for the 2017 guidelines. Compared with the 2020 guidelines, both 2019 and 2017 guidelines showed significantly lower sensitivity for R0 resection (p ≤ .009). Specificity was significantly higher with the 2017 guidelines (p = .043) than with the 2020 guidelines. Inter-reader agreements for determining the resectability of PDCA were strong (k ≥ 0.83) with all guidelines, being highest with the 2020 guidelines (k = 0.91).
CONCLUSIONS: The 2020 NCCN guidelines showed significantly higher sensitivity for prediction of R0 resection than the 2017 and 2019 guidelines.

OBJECTIVE: To perform a comparative analysis of surgically resected mucinous cystic neoplasm (MCN) of pancreas and branch-duct type intraductal papillary mucinous neoplasms (BD-IPMN) considering clinico-radiological high-risk predictors for malignant tumors using the current management guidelines.
METHODS: 224 patients who underwent surgical resection and had histopathologically confirmed MCNs (benign 73; malignant 17) or BD-IPMNs (benign 110; malignant 24) and had pre-operative CT or MRI were retrospectively reviewed. Tumors classified as either high-grade dysplasia or invasive carcinoma were considered malignant, whereas those with low-grade dysplasia were considered benign. Imaging features were analyzed by two radiologists based on selected high-risk stigmata or worrisome features proposed by prevalent guidelines except tumors with main pancreatic duct dilatation (> 5 mm) were excluded.
RESULTS: MCNs and BD-IPMNs showed significant differences in aspects like tumor size, location, the presence and size of enhancing mural nodules, the presence of wall or septal thickening, and multiplicity. Multivariate analyses revealed tumor size (OR, 1.336; 95% CI, 1.124-1.660, p = 0.002) and the presence of enhancing mural nodules (OR, 67.383; 95% CI, 4.490-1011.299, p = 0.002) as significant predictors of malignant MCNs. The optimal tumor size differentiating benign from malignant tumor was 8.95 cm, with a 70.6% sensitivity, 89% specificity, PPV of 27.6%, and NPV of 96.9%, demonstrating superior specificity than the guideline-suggested threshold of 4.0 cm. For malignant BD-IPMNs, the presence of enhancing mural nodules (OR, 15.804; 95% CI, 4.439-56.274, p < 0.001) and CA 19 - 9 elevation (OR, 19.089; 95%CI, 2.868-127.068, p = 0.002) as malignant predictors, with a size of enhancing mural nodule threshold of 5.5 mm providing the best malignancy differentiation.
CONCLUSIONS: While current guidelines may be appropriate for managing BD-IPMNs, our results showed a notably larger optimal threshold size for malignant MCNs than that suggested by current guidelines. This warrants reconsidering existing guideline thresholds for initial risk stratification and management of MCNs.

BACKGROUND: Robotic pancreatoduodenectomy (RPD) is a newly introduced procedure, which is still evolving and lacks standardization. An objective assessment is essential to investigate the feasibility of RPD. The current study aimed to assess our initial ten cases of RPD based on IDEAL (Idea, Development, Exploration, Assessment, and Long-term study) guidelines.
METHODS: This was a prospective phase 2a study following the IDEAL framework. Ten consecutive cases of RPD performed by two surgeons with expertise in open procedures at a single center were assigned to the study. With objective evaluation, each case was classified into four grades according to the achievements of the procedures. Errors observed in the previous case were used to inform the procedure in the next case. The surgical outcomes of the ten cases were reviewed.
RESULTS: The median total operation time was 634 min (interquartile range [IQR], 594-668) with a median resection time of 363 min (IQR, 323-428) and reconstruction time of 123 min (IQR, 107-131). The achievement of the whole procedure was graded as A, \"successful\", in two patients. In two patients, reconstruction was performed with a mini-laparotomy due to extensive pneumoperitoneum, probably caused by insertion of a liver retractor from the xyphoid. Major postoperative complications occurred in two patients. One patient, in whom the jejunal limb was elevated through the Treitz ligament, had a bowel obstruction and needed to undergo re-laparotomy.
CONCLUSIONS: RPD is feasible when performed by surgeons experienced in open procedures. Specific considerations are needed to safely introduce RPD.