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Following resection of colorectal liver metastasis, most patients have disease recurrence, most commonly intrahepatic. Although the role of resection in colorectal liver metastasis is well-established, there have been limited investigations assessing the benefit of repeat hepatic resection compared with systemic treatment alone for intrahepatic recurrence.A retrospective single-institution cohort study of patients with recurrent colorectal liver metastasis following curative-intent hepatectomy was performed from 2003 to 2019. The oncologic outcomes, including post-recurrence overall survival, were evaluated using Kaplan-Meier and Cox proportional hazards modeling. Patients undergoing repeat hepatic resection were propensity-matched with patients receiving systemic treatment alone based on relevant clinicopathologic variables.There were 338 patients treated with hepatic resection for colorectal liver metastasis over the study period. Liver recurrence was observed in 147 (43%) patients at a median time of 10 months from prior resection, with a median post-recurrence overall survival of 29 months. There were 37 patients managed with repeat hepatic resection; 33 (89%) received perioperative chemotherapy. On propensity matching, there were no significant clinicopathologic differences between 37 patients having repeat hepatic resection and 37 patients treated with systemic treatment alone. Repeat hepatic resection was independently associated with improved 5-year post-recurrence overall survival compared with systemic treatment alone (median overall survival 41 vs 35 months, 5-year overall survival 19% vs 3%, P = .048).Disease characteristics of patients with intrahepatic recurrence of colorectal liver metastasis, specifically the number of liver lesions and size of the largest lesion, are most predictive of survival and response to systemic therapy. Patients who recur with oligometastatic liver disease experience improved outcomes and derive benefit from curative-intent repeat hepatic resection with integrated perioperative systemic therapy.

Most of the patients with gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (iCCA), and peri-hilar cholangiocarcinoma (pCCA) present with advanced disease. Complete staging with multiphasic liver imaging is essential to determine the extent of disease. Operative goals should include a margin-negative resection, portal lymphadenectomy for staging, and sufficient remnant liver volume. Biliary tract malignancies have distinct mutational drivers (GBC and pCCA = ERBB2 in 20%; iCCA = fibroblast growth factor receptor 2 or isocitrate dehydrogenase 1 in 20%) amenable to therapy with inhibitors. Clinical trials assessing neoadjuvant, peri-operative, and adjuvant treatments continue to evolve and now include targeted inhibitors and the integration of hepatic arterial infusion.

ImportanceTreatment at high-volume centers (HVCs) has been associated with improved overall survival (OS) in patients with pancreatic ductal adenocarcinoma (PDAC); however, it is unclear how patterns of referral affect these findings.ObjectiveTo understand the relative contributions of treatment site and selection bias in driving differences in outcomes in patients with PDAC and to characterize socioeconomic factors associated with referral to HVCs.Design, Setting, ParticipantsA population-based retrospective review of the Oregon State Cancer Registry was performed from 1997 to 2019 with a median 4.3 months of follow-up. Study participants were all patients diagnosed with PDAC in Oregon from 1997 to 2018 (n = 8026).ExposuresThe primary exposures studied were diagnosis and treatment at HVCs (20 or more pancreatectomies for PDAC per year), low-volume centers ([LVCs] less than 20 per year), or both.Main Outcomes and MeasuresOS and treatment patterns (eg, receipt of chemotherapy and primary site surgery) were evaluated with Kaplan-Meier analysis and logistic regression, respectively.ResultsEight thousand twenty-six patients (male, 4142 [52%]; mean age, 71 years) were identified (n = 3419 locoregional, n = 4607 metastatic). Patients receiving first-course treatment at a combination of HVCs and LVCs demonstrated improved median OS for locoregional and metastatic disease (16.6 [95% CI, 15.3-17.9] and 6.1 [95% CI, 4.9-7.3] months, respectively) vs patients receiving HVC only (11.5 [95% CI, 10.7-12.3] and 3.9 [95% CI, 3.5-4.3] months, respectively) or LVC-only treatment (8.2 [95% CI, 7.7-8.7] and 2.1 [95% CI, 1.9-2.3] months, respectively; all P P = .03; metastatic: 3.6 vs 2.7 months, P Conclusions and RelevanceLVC-to-HVC referrals for PDAC experienced improved OS vs HVC- or LVC-only care. While disease-related features prompting referral may partially account for this finding, socioeconomic and geographic disparities in referral worsen OS for disadvantaged patients. Measures to improve access to HVCs are encouraged.

Patients can experience recurrence following curative-intent resection of non-functional pancreatic neuroendocrine tumors (NF-pNETs). We sought to develop a nomogram to risk stratify patients relative to recurrence following resection of NF-pNETs. Patients who underwent curative-intent resection for NF-pNETs between 1997 and 2016 were identified from a multi-institutional database. The impact of clinicopathologic factors, including tumor burden score (TBS) (TBS2 = (maximum tumor diameter)2 + (number of tumors)2), was assessed relative to recurrence-free survival (RFS), and a nomogram was developed and internally validated. With a median follow-up of 31.0 months (IQR 11.3–56.6 months), 66 (15.8%) out of 416 patients in the cohort experienced tumor recurrence. Overall, 3-, 5-, and 10-year RFS following curative-intent resection was 83.2%, 74.0%, and 44.7%, respectively. Several factors were associated with risk of recurrence including tumor grade (referent G1: G2, HR 4.07, 95% CI 2.29–7.26, p

Pancreatic cancer is one of the most aggressive gastrointestinal malignancies despite multimodality therapy. In the last several years, genomic studies have revealed that carcinogenesis is driven largely by key driver mutations that can be targeted for oncologic therapy. In addition, advances in cancer immunology have identified receptors and monoclonal antibodies that can be manipulated into harnessing the power of the host's immune system for antitumor treatment. These strategies have generated a paradigm shift in the management of several cancer types, including those in the gastrointestinal tract. However, there are several complicating factors when translating the results to pancreatic cancer, including the dense, fibrotic stroma unique to this disease that may shield the cancer cells from both cytotoxic and immunologic agents. Although the majority of trials have been performed in the metastatic setting, this review will focus on both the historic studies that have defined this field as well as the emerging data arising from ongoing efforts to exploit newly discovered mutations and their druggable targets.

Background: We sought to define the diagnostic yield and concordance rates between endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) and surgical pathology specimen following resection of pancreatic neuroendocrine tumors (pNET) less than 2 cm. Methods: Patients with a pNET less than 2 cm who underwent EUS-FNA were identified using a multi-institutional international database. Tumor differentiation, and Ki-67 index, as determined through EUS-FNA were examined and concordance rates between EUS-FNA and the surgical pathology were assessed. Results: Among 628 patients with a pNET less than 2 cm, 57.2% of patients had an EUS-FNA performed. Patients who underwent EUS had slightly smaller size tumors (1.3 vs 1.4 cm), and the pNETs were less likely to be functional (15.3% vs 26.8%) or symptomatic (48.5% vs 56.5%) (both P

Intraoperative radiation therapy (IORT) has been shown to reduce local recurrence rates among women with early-stage invasive ductal carcinoma, but data regarding its use among women with in situ carcinoma are limited. In this single-institution study, 50 women with in situ carcinoma were treated with oncoplastic breast-conserving surgery (OPS) and single-dose IORT. All 50 patients had "no tumor on ink," but 9 (16%) had margins

Incidence of neuroendocrine tumors (NETs) is increasing, including those of the gastroenteropancreatic tract. A proper understanding of the management of this disease has become necessary for the general surgeon. This article addresses current guidelines for diagnosis and localization of NETs, including somatostatin receptor PET. Updated treatment and outcomes of NETs by primary tumor site are discussed as well as those metastatic to the liver.

Breast-conserving therapy (BCT) using oncoplastic surgery (OPS) allows for larger resections and improved aesthetics though volume redistribution and tissue rearrangement. Data regarding the impact of OPS on surveillance imaging and need for additional biopsies are limited. This observational cohort underwent BCT at a single institution from 2009 to 2018; standard breast-conserving surgery (BCS) was the predominant approach until OPS was introduced in 2012. Rates of imaging beyond standard diagnostic views, as well as rates of biopsy following both approaches, are reported. A total of 422 consecutive patients were identified. The OPS group comprised 205 patients and the BCS group included 217 patients. There was no difference in need for additional imaging between groups (BCS: 58 patients [26.7%] vs. OPS: 53 patients [25.9%]; p = 0.91). When additional imaging was required, it was on the ipsilateral side in 35 (60.3%) BCS patients compared with 24 (45.3%) OPS patients (p = 0.21). The need for biopsy was higher in the BCS group (BCS: 41 patients [18.9%] with 47 total biopsies vs. OPS: 20 patients [9.3%] with 22 total biopsies; p

BACKGROUND. Insurance status predicts access to medical care in the USA. Previous studies have shown uninsured patients with some malignancies have worse outcomes than insured patients. The impact of insurance status on patients with gastroenteropancreatic neuroendocrine tumors (GEP-NETs) is unclear. PATIENTS AND METHODS. A retrospective cohort study of adult patients with resected GEP-NETs was performed using the US Neuroendocrine Tumor Study Group (USNETSG) database (2000–2016). Demographic and clinical factors were compared by insurance status. Patients C 65 years were excluded, as these patients are almost universally covered by Medicare. Kaplan–Meier and log-rank analyses were used for survival analysis. Logistic regression was used to assess factors associated with overall survival (OS). RESULTS. The USNETSG database included 2022 patients. Of those, 1425 were aged 18–64 years at index operation and were included in our analysis. Uninsured patients were more likely to have an emergent operation (7.9% versus 2.5%, p = 0.01) and less likely to receive postoperative somatostatin analog therapy (1.6% versus 9.9%, p = 0.03). OS at 1, 5, and 10 years was significantly higher for insured patients (96.3%, 88.2%, and 73.8%, respectively) than uninsured patients (87.7%, 71.9%, and 44.0%, respectively) (p < 0.01). On Cox multivariate regression analysis controlling for T/M stage, tumor grade, ASA class, and income level, being uninsured was independently associated with worse OS [hazard ratio (HR) 2.69, 95% confidence interval (CI) 1.32–5.48, p = 0.006]. CONCLUSIONS. Insurance status is an independent predictor of survival in patients with GEP-NETs. Our study highlights the importance of access to medical care, disparities related to insurance status, and the need to mitigate these disparities.

BACKGROUND AND OBJECTIVES We sought to define the incidence and impact of Textbook Outcome (TO) on disease-free survival [DFS] among patients undergoing resection of pancreatic neuroendocrine tumors (PNET). METHODS Patients undergoing resection of a PNET between 2000 and 2016 were identified using a multi-institutional database. TO was defined as no postoperative severe complications (Clavien-Dindo grade ≥ III), no 90-day mortality, no prolonged length-of-hospital stay (LOS) (ie, > 75th percentile), no 90-day readmission after discharge, and R0 resection. The 5-year DFS was calculated and the association with TO was examined. RESULTS Among 821 patients with a PNET, median tumor size was 2.1 cm (IQR 1.4-14.6). Resection consisted of pancreatoduodenectomy (PD) (n = 231, 28.1%), distal pancreatectomy (DP) (n = 492, 59.9%), and enucleation (EN) (n = 98, 11.9%). Overall TO rate was 49.3% (n = 405). The incidence of TO varied by procedure type (PD: 32.5% vs DP: 56.7% vs EN: 52.0%; P

BACKGROUND AND OBJECTIVES Lack of high-level evidence supporting adjuvant therapy for patients with resected gastroenteropancreatic neuroendocrine tumors (GEP NETs) warrants an evaluation of its non-standard of care use. METHODS Patients with primary GEP NETs who underwent curative-intent resection at eight institutions between 2000 and 2016 were identified; 91 patients received adjuvant therapy. Recurrence-free survival (RFS) and overall survival (OS) were compared between adjuvant cytotoxic chemotherapy and somatostatin analog cohorts. RESULTS In resected patients, 33 received cytotoxic chemotherapy, and 58 received somatostatin analogs. Five-year RFS/OS was 49% and 83%, respectively. Cytotoxic chemotherapy RFS/OS was 36% and 61%, respectively, lower than the no therapy cohort (P

Background To define recurrence patterns and time course, as well as risk factors associated with recurrence following curative resection of pNETs. Method Patients who underwent curative-intent resection for pNET between 1997 and 2016 were identified from the US Neuroendocrine Tumor Study Group. Data on baseline and tumor-specific characteristics, overall survival (OS), timing and first-site of recurrence, predictors and recurrence management were analyzed. Results Among 1020 patients, 154 (15.1%) patients developed recurrence. Among patients who experienced recurrence, 76 (49.4%) had liver-only recurrence, while 35 (22.7%) had pancreas-only recurrence. The proportion of liver-only recurrence increased from 54.3% within one-year after surgery to 61.5% from four-to-six years after surgery; whereas the proportion of pancreas-only recurrence decreased from 26.1% to 7.7% over these time periods. While liver-only recurrence was associated with tumor characteristics, pancreas-only recurrence was only associated with surgical margin status. Patients undergoing curative resection of recurrence had comparable OS with patients who had no recurrence (median OS, pancreas-only recurrence, 133.9 months; liver-only recurrence, not attained; no recurrence, 143.0 months, p = 0.499) Conclusions Different recurrence patterns and timing course, as well as risk factors suggest biological heterogeneity of pNET recurrence. A personalized approach to postoperative surveillance and treatment of recurrence disease should be considered.

Preoperative chemotherapy (POC) is often employed for patients with resectable colorectal liver metastasis (CRLM). The time to resection (TTR) following the end of chemotherapy may impact oncologic outcomes; this phenomenon has not been studied in CRLM.We queried our institutional cancer database for patients with resected CRLM after POC from 2003 to 2019. TTR was calculated from date of last cytotoxic chemotherapy. Kaplan-Meier analysis and multivariable Cox proportional hazards modeling were used to analyze recurrence-free survival (RFS) and overall survival (OS).We identified n = 187 patients. One hundred twenty-four (66%) patients had a TTR of2 months, while 63 (33%) had a TTR of ≥2 months. Median follow-up was 36 months. On Kaplan-Meier analysis, patients with TTR ≥ 2 months had shorter RFS (median 11 vs. 17 months, p = 0.002) and OS (median 44 vs. 62 months, p 0.001). On multivariable analysis, TTR ≥ 2 months was independently associated with worse RFS (hazard ratio [HR] = 1.54, 95% confidence interval [CI] = 1.06-2.22, p = 0.02) and OS (HR = 1.75, 95% CI = 1.11-2.77, p = 0.01).TTR ≥ 2 months following POC is independently associated with worse oncologic outcomes in patients with resectable CRLM. We therefore recommend consideration for hepatic resection of CRLM within this window whenever feasible.

Background Somatostatin analog functional imaging with gallium-68 (Ga-68) dotatate positron emission tomography/computed tomography (PET/CT) has demonstrated superiority in lesion detection in patients with neuroendocrine tumors (NETs). The clinical impact of this imaging modality on US surgical and medical oncology practices has not been established. Methods Consecutive patients with NET at our institution who received an initial Ga-68 dotatate PET/CT between July 2017 and September 2018 were included. Ga-68 dotatate PET/CT was compared with prior imaging. Results Among 101 eligible patients, 51 of 50 were female/male, site of origin was gastroenteropancreatic (75%), unknown primary (13%), lung (8%), thymus (2%), and other (2%). All NETs were histologically well/moderately differentiated. Ga-68 dotatate imaging findings altered management in 36 (35.6%) patients: documentation of progression led to the initiation of systemic therapy in 14 patients, obviated the need for biopsy in four patients, and altered surgical plans in 7 of 14 (50%) patients referred for surgery. In 11 patients, decisions regarding peptide receptor radionucleotide therapy and somatostatin analogs were altered. Conclusions In this series, Ga-68 dotatate PET/CT altered diagnosis and management in one-third of patients and changed operative plans in half of the patients who were referred for surgical evaluation. These results support the routine use of this imaging in the care of patients with early-stage and advanced NETs.

BACKGROUND: Appendiceal neuroendocrine tumors (A-NETs) are rare neoplasms of the GI tract. They are typically managed according to tumor size; however, the impact of surgical strategy on the short- and long-term outcomes is unknown. METHODS: All patients who underwent resection of A-NET at 8 institutions from 2000 to 2016 were analyzed retrospectively. Patient clinicopathologic features and outcomes were stratified according to resection type. RESULTS: Of 61 patients identified with A-NET, mean age of presentation was 44.7 ± 16.0 years and patients were predominantly Caucasian (77%) and female (56%). Mean tumor size was 1.2 ± 1.3 cm with a median of 0.8 cm. Thirty-one patients (51%) underwent appendectomy and 30 (49%) underwent colonic resection. The appendectomy group had more T1 tumors (87% vs 42%, p < 0.01) than the colon resection group. Of patients in the colon resection group, 27% had positive lymph nodes and 3% had M1 disease. R0 resections were achieved in 90% of appendectomy patients and 97% of colon resection patients. Complications occurred with a higher frequency in the colon resection group (30%) compared with those in the appendectomy group (6%, p = 0.02). The colon resection group also had a longer length of stay, higher average blood loss, and longer average OR time. Median RFS and OS were similar between groups. CONCLUSION: A-NET RFS and OS are equivalent regardless of surgical strategy. Formal colon resection is associated with increased length of stay, OR time, higher blood loss, and more complications. Further study is warranted to identify patients that are likely to benefit from more aggressive surgery.

BACKGROUND: The current study sought to investigate the impact of tumor size and total number of LN examined (TNLE) on the incidence of lymph node metastasis (LNM) among patients with duodenal neuroendocrine tumor (dNET). METHODS: Patients who underwent curative resection for dNETs between 1997–2016 were identified from 8 high-volume US centers. Risk factors associated with overall survival and LNM were identified and the optimal cut-off of TNLE relative to LNM was determined. RESULTS: Among 162 patients who underwent resection of dNETs, median patient age was 59 (interquartile range [IQR], 51–68) years and median tumor size was 1.2 cm (IQR, 0.7–2.0 cm); a total of 101 (62.3%) patients underwent a concomitant LND at the time of surgery. Utilization of lymphadenectomy (LND) increased relative to tumor size (≤1 cm:52.2% vs 1–2 cm:61.4% vs >2 cm:93.8%; P < .05). Similarly, the incidence of LNM increased with dNET size (≤1 cm: 40.0% vs 1–2 cm:65.7% vs >2 cm:80.0%; P < .05). TNLE ≥ 8 had the highest discriminatory power relative to the incidence of LNM (area under the curve = 0.676). On multivariable analysis, while LNM was not associated with prognosis (hazard ratio [HR] = 0.9; 95% confidence intervals [95%CI], 0.4–2.3), G2/G3 tumor grade was (HR = 1.5; 95%CI, 1.0–2.1). CONCLUSIONS: While the incidence of LNM directly correlated with tumor size, patients with dNETs ≤ 1 cm had a 40% incidence of LNM. Regional lymphadenectomy of a least 8 LN was needed to stage patients accurately.

Melanoma incidence has increased worldwide with a concurrent rise in both primary and metastatic melanomas of the gastrointestinal tract. This retrospective single-center case series includes patients with histopathology-confirmed primary or metastatic melanoma of the GI tract between 1998 and 2018. Thirty-four patients were identified for inclusion, of whom 7 were primary and 27 were metastatic cases of gastrointestinal melanoma. For both primary and metastatic cases, the majority of patients presented with frank or occult GI bleeding (57.1% and 70.4%). Primary and metastatic lesions were predominantly diagnosed endoscopically (100% and 63.0%), with 71.4% of primary lesions found at the anorectal junction and 51.9% of metastatic lesions in the small bowel. Endoscopically diagnosed lesions were either polypoid (50%) or a luminal mass (37.5%) in the majority of cases. Common features included: amelanotic (83%), ulcerated (50%), and friable (33.3%). All primary patients were treated with surgical excision or resection. Of the metastatic patients, 56% were resected. The median interval between initial primary and gastrointestinal metastases was 65 months (ranging from 1 month to 24 years). At the time of data analysis, 85.7% of primary and 29.6% of metastatic patients remained alive. The majority of patients in this series were diagnosed endoscopically while investigating a source of gastrointestinal blood loss. Heightened clinical suspicion and recognition of the endoscopic features of gastrointestinal melanoma during evaluation of GI symptoms in a patient with a personal history of primary melanoma are advised.

BACKGROUND: The current study sought to define the impact of lymph node metastasis (LNM) relative to tumor size on tumor recurrence after curative resection for nonfunctional pancreatic neuroendocrine tumors (NF-pNETs) ≤2 cm. METHODS: Patients who underwent curative resection for ≤2-cm NF-pNETs were identified from a multi-institutional database. Risk factors associated with tumor recurrence as well as LNM were identified. Recurrence-free survival (RFS) was compared among patients with or without LNM. RESULTS: A total of 392 ≤2-cm NF-pNETs patients were identified. Among the 328 patients who had lymph node dissection and evaluation, 42 (12.8%) patients had LNM. LNM was associated with tumor recurrence (hazard ratio, 3.06; P = .026) after surgery. RFS was worse among LNM vs no LNM patients (5-year RFS, 81.7% vs 94.1%; P = .019). Patients with tumors measuring 1.5–2 cm had a two-fold increase in the incidence of LNM vs patients with tumors

Breast-conserving therapy (BCT) has been associated with better quality of life and cosmetic outcomes than mastectomy. However, subareolar cancers abutting the nipple–areolar complex (NAC) present a unique cosmetic and oncologic challenge. Oncoplastic central partial mastectomy and neoareolar reduction mammoplasty with immediate nipple reconstruction is a novel technique that can permit BCT for these patients. This study enrolled consecutive patients with central tumors during 2017–2018 who underwent central partial mastectomy reconstructed with neoareolar reduction mammoplasty and immediate nipple reconstruction. Patient demographics, imaging and pathology size, margin width, mastectomy and reexcision rates, and cosmesis were evaluated. The study identified 23 sequential patients. The average patient age was 60.5 ± 12.3 years, and the average body mass index was 29.4 ± 5.7 kg/m2. The mean lesion size was 51.5 ± 43.0 mm on preoperative imaging, and the average disease span shown by the final pathology was 59.5 ± 45.3 mm. “No ink on tumor” was achieved for 22 patients (95.7%). In 13 patients (56.5%), the margins were inadequate for ductal carcinoma in situ (DCIS) (n = 12) or invasive cancer (n = 1). Good to excellent cosmetic results were achieved for 21 patients (95.5%). Complications occurred for six patients (26.1%), including three patients with ischemia of the reconstructed NAC. The single-stage operation described in this report can allow patients with cancers abutting the NAC to consider BCT. This technique allows patients to avoid mastectomy and to minimize the number of operations required for reconstruction while maximizing cosmetic outcomes. In the study cohort, the presence of extensive DCIS resulted in a significant need for reexcision, which could be performed successfully without compromise to cosmetic outcome.

Objective:Despite heterogeneous biology, similar surveillance schemas are utilized after resection of all pancreatic neuroendocrine tumors (PanNETs). Given concerns regarding excess radiation exposure and financial burden, our aim was to develop a prognostic score for disease recurrence to guide individually tailored surveillance strategies.Methods:All patients with primary nonfunctioning, nonmetastatic well/moderately differentiated PanNETs who underwent curative-intent resection at 9-institutions from 2000 to 2016 were included (n = 1006). A Recurrence Risk Score (RRS) was developed from a randomly selected derivation cohort comprised of 67% of patients and verified on the validation-cohort comprised of the remaining 33%.Results:On multivariable analysis, patients within the derivation cohort (n = 681) with symptomatic tumors (jaundice, pain, bleeding), tumors >2cm, Ki67 >3%, and lymph node (LN) (+) disease had increased recurrence. Each factor was assigned a score based on their weighted odds ratio that formed a RRS of 0 to 10: symptomatic = 1, tumor >2cm = 2, Ki67 3% to 20% = 1, Ki67 >20% = 6, LN (+) = 1. Patients were grouped into low-(RRS = 0-2; n = 247), intermediate-(RRS = 3-5; n = 204), or high (RRS = 6-10; n = 9)-risk groups. At 24 months, 33% of high RRS recurred, whereas only 2% of low and 14% of intermediate RRS recurred. This persisted in the validation cohort (n = 325).Conclusions:This international, novel, internally validated RRS accurately stratifies recurrence-free survival for patients with resected PanNETs. Given their unique recurrence patterns, surveillance intervals of 12, 6, and 3 months are proposed for low, intermediate, and high RRS patients, respectively, to minimize radiation exposure and optimize cost/resource utilization.

Presence of multiple lesions and/or tumor span ≥5 cm are traditional indications for mastectomy. Patient desire for breast conservation has increased the interest in extreme oncoplastic breast conserving surgery (EOBCS) to avoid mastectomy; however, perioperative outcomes in this population have not been well described.This is an observational cohort of breast cancer patients with multiple lesions and disease span ≥5 cm who underwent EOBCS. Patient demographics, disease span, margin width, mastectomy and re-excision rates, and cosmesis were evaluated.One hundred-eleven patients underwent EOBCS between 2012 and 2017. Eighty-two patients presented with multifocal or multicentric disease with an average of 3.2 lesions per breast spanning 57.1 ± 23.6 mm. Eighteen patients presented with unifocal tumors measuring an average of 67.6 mm (range 50-160 mm) on imaging. Eleven patients with an imaging size of5 cm had a disease span ≥5 cm on final pathology. No tumor on ink occurred in 87 (78.3%) patients. Fifty-seven (51.4%) patients had additional surgery for inadequate margins. Fifteen (12.6%) patients elected to have mastectomy while 42 (37.8%) patients opted for re-excision. Good to excellent cosmetic results were reported in 95% of patients who ultimately achieved breast conservation. Recurrence rate was 1.1% in patients who completed EOBCS and adjuvant radiation therapy.EOBCS can allow for breast conservation in patients who are traditionally counseled to undergo mastectomy. Although the re-excision rate was significant, most patients ultimately achieved breast conservation with adequate margins. Further study is warranted to determine the long-term oncologic outcomes of this approach.

Gastric carcinoids are rare neuroendocrine tumors of the gastrointestinal tract. They are typically managed according to their etiology. However, there is little known about the impact of surgical strategy on the long-term outcomes of these patients.All patients who underwent resection of gastric carcinoids at 8 institutions from 2000 to 2016 were analyzed retrospectively. Tumors were stratified according to subtype (I, II, III, IV) and resection type (local resection, LR or formal gastrectomy, FG). Clinicopathological parameters, recurrence-free (RFS) and overall survival (OS) were compared between groups.Of 79 patients identified with gastric carcinoids, 34 had type I lesions associated with atrophic gastritis, 4 had type II lesions associated with a gastrinoma, 37 had type III sporadic lesions, and 4 had type IV poorly-differentiated lesions. The mean age of presentation was 56 years in predominantly Caucasian (77%) and female (63%) patients. Mean tumor size was 2.4 cm and multifocal tumors were found in 24 (30%) of patients with the majority occurring in those with type I tumors. Lymph node positive tumors were seen in 15 (19%) patients and 7 (8%) had M1 disease; both most often in type IV followed by type III tumors. R0 resection was achieved in 56 (71%) patients while 15 (19%) had R1 resections and 6 (8%) R2 resections. Patients with type I and III tumors were equally likely to have a LR (50% and 43% respectively) compared to FG while those with type II and IV all had FG with one exception. Type IV tumors had the poorest RFS and OS while Type II tumors had the most favorable RFS and OS (p 0.04 and p 0.0004, respectively). While there was no difference in RFS in those patients undergoing FG versus LR, OS was worse in the FG group (p 0.017). This trend persisted when type II and type IV groups were excluded (p 0.045).Gastric carcinoid treatment should be tailored to tumor type, as biologic behavior rather than resection technique is the more important factor contributing to long-term outcomes.

Although the most common presentation of biliary disorder in North America is secondary to gallstone disease, an awareness of benign biliary cystic neoplasms is important because of the risk of malignant transformation. The incidence of premalignant cystic neoplasms of the bile duct is not well characterized and they often are detected incidentally for suspicion of other abdominal disorders. This article describes the 4 most common premalignant biliary cystic neoplasms: biliary mucinous cystic neoplasms, intraductal papillary mucinous neoplasms of the bile duct, intraductal tubular papillary neoplasms of the bile duct, and choledochal cysts.

Background The impact of margin status on resection of primary pancreatic neuroendocrine tumors has been poorly defined. The objectives of the present study were to determine the impact of margin status on long-term survival of patients with pancreatic neuroendocrine tumors after curative resection and evaluate the impact of reresection to obtain a microscopically negative margin. Methods Patients who underwent curative-intent resection for pancreatic neuroendocrine tumors between 2000 and 2016 were identified at 8 hepatobiliary centers. Overall and recurrence-free survival were analyzed relative to surgical margin status using univariable and multivariable analyses. Results Among 1,020 patients, 866 (84.9%) had an R0 (>1 mm margin) resection, whereas 154 (15.1%) had an R1 (≤1 mm margin) resection. R1 resection was associated with a worse recurrence-free survival (10-year recurrence-free survival, R1 47.3% vs R0 62.8%, hazard ratio 1.8, 95% confidence interval 1.2–2.7, P = .002); residual tumor at either the transection margin (R1t) or the mobilization margin (R1m) was associated with increased recurrence versus R0 (R1t versus R0: hazard ratio 1.8, 95% confidence interval 1.0–3.0, P = .033; R1m versus R0: hazard ratio 1.3, 95% confidence interval 1.0–1.7, P = .060). In contrast, margin status was not associated with overall survival (10-year overall survival, R1 71.1% vs R0 71.8%, P = .392). Intraoperatively, 539 (53.6%) patients had frozen section evaluation of the surgical margin; 49 (9.1%) patients had a positive margin on frozen section analysis; 38 of the 49 patients (77.6%) had reresection, and a final R0 (secondary R0) margin was achieved in 30 patients (78.9%). Extending resection to achieve an R0 status remained associated with worse overall survival (hazard ratio 3.1, 95% confidence interval 1.6–6.2, P = .001) and recurrence-free survival (hazard ratio 2.6, 95% confidence interval 1.4–5.0, P = .004) compared with primary R0 resection. On multivariable analyses, tumor-specific factors, such as cellular differentiation, perineural invasion, Ki-67 index, and major vascular invasion, rather than surgical margin, were associated with long-term outcomes. Conclusion Margin status was not associated with long-term survival. The reresection of an initially positive surgical margin to achieve a negative margin did not improve the outcome of patients with pancreatic neuroendocrine tumors. Parenchymal-sparing pancreatic procedures for pancreatic neuroendocrine tumors may be appropriate when feasible.

BACKGROUND: The incidence, clinical characteristics, and long-term outcomes of patients with gastroenteropancreatic neuroendrocrine tumors and carcinoid syndrome undergoing operative resection have not been well characterized. METHODS: Patients undergoing resection of primary or metastatic gastroenteropancreatic neuroendrocrine tumors between 2000 and 2016 were identified from an 8-institution collaborative database. Clinicopathologic and postoperative characteristics as well as overall survival and disease-free survival were compared among patients with and without carcinoid syndrome. RESULTS: Among 2,182 patients who underwent resection, 139 (6.4%) had preoperative carcinoid syndrome. Patients with carcinoid syndrome were more likely to have midgut primary tumors (44.6% vs 21.4%, P < .001), lymph node metastasis (63.4% vs 44.3%, P < .001), and metastatic disease (62.8% vs 26.7%, P < .001). There was no difference in tumor differentiation, grade, or Ki67 status. Perioperative carcinoid crisis was rare (1.6% vs 0%, P < .01), and the presence of preoperative carcinoid syndrome was not associated with postoperative morbidity (38.8% vs 45.5%, P = .129). Substantial symptom improvement was reported in 59.5% of patients who underwent curative-intent resection, but occurred in only 22.7% who underwent debulking. Despite an association on univariate analysis (P = .04), carcinoid syndrome was not independently associated with disease-free survival after controlling for confounding factors (hazard ratio 0.97, 95% confidence interval 0.64–1.45). Preoperative carcinoid syndrome was not associated with overall survival on univariate or multivariate analysis. CONCLUSION: Among patients undergoing operative resection of gastroenteropancreatic neuroendrocrine tumors, the prevalence of preoperative carcinoid syndrome was low. Although operative intervention with resection or especially debulking in patients with carcinoid syndrome was disappointing and often failed to improve symptoms, after controlling for markers of tumor burden, carcinoid syndrome was not independently associated with worse disease-free survival or overall survival.

INTRO: Chromogranin A (CgA) may be prognostic for patients with neuroendocrine tumors; however, the clinical utility of this test is unclear. METHODS: Patients undergoing resection for pancreatic neuroendocrine tumors (pNET) were selected from the eight institutions of the US Neuroendocrine Tumor Study Group database. Cox regression was used to identify pre-operative variables that predicted recurrence-free survival (RFS), and those with p < 0.1 were included in a risk score. The risk score was tested in a unique subset of the overall cohort. RESULTS: In the entire cohort of 287 patients, median follow-up time was 37 months, and 5-year RFS was 73%. Cox regression analysis identified four variables for inclusion in the risk score: CgA > 5x ULN (HR 4.3, p = 0.01), tumor grade 2/3 (HR 3.7, p = 0.01), resection for recurrent disease (HR 6.2, p < 0.01), and tumor size > 4 cm (HR 4.5, p = 0.1). Each variable was assigned 1 point. Risk-score testing in the unique validation cohort of 63 patients revealed a 95% negative predictive value for recurrence in patients with zero points. DISCUSSION: This simple pre-operative risk scoring system resulted in a high degree of specificity for identifying patients at low-risk for tumor recurrence. This test can be utilized pre-operatively to aid informed decision-making.

Adjuvant therapy for pancreatic cancer has undergone a paradigm shift in the last 30 years. Before the 1990s, surgery was the main treatment with high morbidity and minimal long-term survival. In the mid-1980s, GITSG showed a doubling of overall survival from 11 to 20 months with 5-fluorouracil-based chemoradiation and now the PRODIGE trial showed the benefit of FOLFIRINOX with the longest overall survival to date approaching 5 years. Further investigation on the agents, duration and sequencing of therapy remains ongoing.

Traditional indications for mastectomy include multiple ipsilateral lesions and/or disease spanning ≥ 5 cm. Neoadjuvant chemotherapy increases breast conservation but does not improve survival. We hypothesized that oncoplastic breast-conserving surgery (OPS) may allow for breast conservation while providing full staging and tumor profiling information to guide systemic therapy decisions, thereby permitting more judicious chemotherapy use. This was an observational cohort of patients with invasive breast cancer with multiple lesions and/or disease spanning ≥ 5 cm who underwent OPS from 2012 to 2018. Clinicopathologic features, mastectomy rate, chemotherapy use, and recurrence were evaluated. Overall, 100 patients were identified. Average disease span was 62.8 ± 20.1 mm, with an average of 2.9 lesions (range 1–13). ‘No ink on tumor’ was achieved at the index operation in 80 patients; 13 patients underwent completion mastectomy to achieve adequate margins. Eighty-one patients completed radiation therapy. Breast conservation was possible in 50/58 (86%) patients who did not receive chemotherapy. Forty-two patients received chemotherapy (8 neoadjuvant, 34 adjuvant), of whom 37 (88%) achieved breast conservation. Twenty-six patients with high-risk features received adjuvant chemotherapy. Oncotype DX testing demonstrated the need for chemotherapy in an additional eight patients. After a median follow-up of 40 months, four patients had a local recurrence, including two who declined radiation therapy. OPS can facilitate breast conservation in most patients with traditional indications for mastectomy. Additionally, OPS may reduce unnecessary chemotherapy, especially in patients who qualify for Oncotype DX testing. Further study evaluating long-term oncologic and cosmetic outcomes is warranted.

OBJECTIVE: To improve the prognostic accuracy of the eighth edition of AJCC staging system for pNETs with establishment and validation of a new staging system. BACKGROUND: Validation of the updated eighth AJCC staging system for pNETs has been limited and controversial. METHODS: Data from the SEER registry (1975–2016) (n = 3303) and a multi-institutional database (2000–2016) (n = 825) was used as development and validation cohorts, respectively. A mTNM was proposed by maintaining the eighth AJCC T and M definitions, and the recently proposed N status as N0 (noLNM), N1 (1–3 LNM), and N2 (≥4 LNM), but adopting a new stage classification. RESULTS: The eighth TNM staging system failed to stratify patients with stage I versus IIA, stage IIB versus IIIA, and overall stage I versus II relative to long-term OS in both database. There was a monotonic decrement in survival based on the proposed mTNM staging classification among patients derived from both the SEER (5-year OS, stage I 87.0% vs stage II 80.3% vs stage III 72.9% vs stage IV 57.2%, all P < 0.001), and multi-institutional (5-year OS, stage I 97.6% vs stage II 82.7% vs stage III 78.4% vs stage IV 50.0%, all P < 0.05) datasets. On multivariable analysis, mTNM staging remained strongly associated with prognosis, as the hazard of death incrementally increased with each stage among patients in the 2 cohorts. CONCLUSION: A mTNM pNETs clinical staging system using N0, N1, N2 nodal categories was better at stratifying patients relative to long-term OS than the eighth AJCC staging.

BACKGROUND. Pancreatic neuroendocrine tumors (PNETs) are often indolent; however, identifying patients at risk for rapidly progressing variants is critical, particularly for those with small tumors who may be candidates for expectant management. Specific growth rate [Formula: see text] has been predictive of survival in other malignancies but has not been examined in PNETs. METHODS. A retrospective cohort study of adult patients who underwent PNET resection from 2000 to 2016 was performed utilizing the multi-institutional United States Neuroendocrine Study Group database. Patients with ≥ 2 preoperative cross-sectional imaging studies at least 30 days apart were included in our analysis (N = 288). Patients were grouped as “high [Formula: see text] ” or “low [Formula: see text].” Demographic and clinical factors were compared between the groups. Kaplan–Meier and log-rank analysis were used for survival analysis. Cox proportional hazard analysis was used to assess the impact of various clinical factors on overall survival (OS). RESULTS. High [Formula: see text] was associated with higher T stage at resection, shorter doubling time, and elevated HbA1c (all P ≤ 0.01). Patients with high [Formula: see text] had significantly decreased 5-year OS (63 vs 80%, P = 0.01) and disease-specific survival (72 vs 91%, P = 0.03) compared to those with low [Formula: see text]. In patients with small (≤ 2 cm) tumors (N = 106), high [Formula: see text] predicted lower 5-year OS (79 vs 96%, P = 0.01). On multivariate analysis, high [Formula: see text] was independently associated with worse OS (hazard ratio 2.67, 95% confidence interval 1.05–6.84, P = 0.04). CONCLUSION. High [Formula: see text] is associated with worse survival in PNET patients. Evaluating PNET [Formula: see text] may enhance clinical decision-making, particularly when weighing expectant management versus surgery in patients with small tumors.

Background To investigate the short- and long-term outcomes of patients undergoing pancreaticoduodenectomy (PD) for duodenal neuroendocrine tumors (dNETs) vs pancreatic neuroendocrine tumors (pNETs). Method Patients undergoing PD for dNETs or pNETs between 1997 and 2016 were identified from a multi-institutional database. Overall survival (OS) and recurrence-free survival (RFS) were evaluated. Results Among 276 patients who underwent PD, 244 (88.4%) patients had a primary pNET, whereas 32 (11.6%) patients had a dNET. Following PD, postoperative morbidity and mortality were comparable. While the total number of lymph nodes examined was similar between the two groups (median, dNETs 15.0 vs pNETs 13.0; P= .648), patients with dNETs had a higher incidence of lymph node metastasis (LNM) (60.0% vs 38.2%; P = .022) and a larger number of metastatic nodes (median, 3.5 vs 2.0; P = .039). No differences in OS or RFS were noted among patients with dNETs vs pNETs in both unadjusted and adjusted analyses. Among patients who recurred after PD, patients with dNETs were more likely to recur early (within 2 years, 100% vs 49.2%; P = .029) and at an extrahepatic site (intrahepatic-only recurrence, 20.0% vs 54.1%; P = 0.142) vs patients with pNETs. Conclusions Patients with dNETs and pNETs had a similar prognosis following PD. Data on differences in the incidence of LNM, as well as in recurrence time and patterns may help to inform the treatment of these patients.

BACKGROUND: The risk of recurrence for patients undergoing curative-intent surgery for non-metastatic gastro-entero-pancreatic neuroendocrine tumors (GEP-NET) is currently poorly defined. We sought to develop and validate a nomogram to predict the risk of recurrence after curative-intent resection. METHODS: Using a pseudo-randomization technique, a training set to develop a predictive nomogram and a test set to validate the nomogram were identified. The predictive ability of the nomogram to predict recurrence was assessed using the c-index. RESULTS: Among 1,477 patients, 673 (46%) patients were included in the training set and 804 (54%) patients were included in the test set to validate the nomogram. On multivariable analysis, Ki-67, tumor size, nodal status, and invasion of adjacent organs were independent predictors of DFS. The risk of death increased by 8% for each percentage increase in the Ki-67 index (HR 1.08, 95% CI, 1.05–1.10; p3 lymph node metastasis had a 2.5-fold increased risk of death (HR 2.51, 95% CI, 1.50–4.24; p80%, which correlated with disease free-survival at 10-year of 87%, 68%, 37%, and 0%, respectively. CONCLUSION: A nomogram based on four variables (i.e. Ki-67, tumor size, invasion of adjacent organs and lymph node status) was able to predict the risk of recurrence after surgery for GEP-NET. The nomogram demonstrated a good ability to identify patients at risk of recurrence and can be easily applied in the clinical setting.

Gemcitabine-taxane combination chemotherapy has demonstrated a survival benefit clinically in metastatic pancreatic cancer (PC). The authors present their experience with gemcitabine and docetaxel (gem/tax)-based adjuvant treatment (Rx) after surgery with curative intent. Patients with de novo resectable PC from January 2010 to December 2015 were identified from the authors’ institutional database and registry. The study included only patients who received gem/tax as their initial Rx administered exclusively at the authors’ institution with or without chemoradiation (CRTx). Survival analysis was performed using Kaplan–Meier methods, and prognostic factors were investigated by Cox proportional hazard modeling. Of 102 patients identified, 58 met the study criteria. The median age at diagnosis was 65 years, with 55% of the patients undergoing an R1 resection (margin ≤ 1 mm). Tumor characteristics included a median tumor size of 28 mm, a poor differentiation rate of 54%, and a lymph node positivity of 67%. Most of the patients (90%, 52/58) completed 80% or more of the 24 week Rx. Of these patients, 71% received post-gem/tax CRTx Rx. Grade 3 or 4 toxicity was observed in 52% of the patients. The median follow-up period was 51.2 months, and the observed median overall survival (OS) was 52 months [95% confidence interval (CI) 27.4–not reached]. The actuarial 5-year OS was 49% (95% CI 33.7–63.4%). In the multivariate analysis, an R1 resection and American Joint Committee on Cancer (AJCC) stage 2 versus stage 1 disease were negatively associated with OS, whereas administration of CRTx was positively associated with OS. Adjuvant gem/tax with or without CRTx is feasible, with a favorable OS. Future prospective studies of gem/taxane-based adjuvant Rx for PC are warranted.

Many patients with pancreatic cancer are not candidates for surgical resection due to involvement of critical mesenteric vascular structures. We compare and contrast the commonly used classification systems for borderline resectable and locally advanced pancreatic cancer. We describe the current strategies in managing venous and arterial involvement, as well as the role of neoadjuvant chemotherapy and chemoradiation, before explanding on a novel clinical trial in this patient population.