Colon and Rectal Neuroendocrine Tumors: Are They Really One Disease? A Single-Institution Experience over 15 Years.

Colon and rectal neuroendocrine tumors (NETs) are often studied as one entity. Recent evidence suggests that worse outcomes are associated with colon compared with rectal NETs; direct comparisons are lacking. Our aim was to assess clinicopathologic, treatment, and survival differences between these diseases. All patients who underwent resection of colorectal NETs at one institution from 2000 to 2014 were included and analyzed. Of 29 patients, 12(41%) had colon and 17 (59%) had rectal NETs. Baseline demographics were similar between groups, although colon patients tended to be symptomatic at presentation (67% vs 44%, P = 0.41). Eighty-three per cent of colon patients underwent surgical resection, whereas 77 per cent of rectal patients underwent endoscopic or transanal resection (P = 0.003). Colon patients had larger (3.4 cm vs 0.7 cm, P = 0.03), higher T-stage (T3/T4: 91% vs 14%, P = 0.003), higher grade tumors (42% vs 12%, P = 0.09) with more lymph nodes (58% vs 24%, P = 0.12) and lymphovascular invasion positivity (58% vs 24%, P = 0.32). Five-year disease-specific survival was 53% versus 80 per cent for colon and rectal patients, respectively (P = 0.22). After excluding high-grade tumors, colon NETs were associated with lymphovascular invasion positivity (100% vs 17%, P = 0.05) and advanced T-stage (80% vs 8%, P = 0.01). Colon and rectal 5-year disease-specific survival was 67 versus 80 per cent (P = 0.86). Colon and rectal NETs clinically seem to be distinct entities. Colon tumors have more aggressive clinicopathologic features, which may translate to worse outcomes. These differences in tumor biology may demand distinct management and should be further studied in a multi-institutional setting.

Association of perioperative transfusion with survival and recurrence after resection of gallbladder cancer: A 10-institution study from the US Extrahepatic Biliary Malignancy Consortium.

BACKGROUND AND OBJECTIVES: Perioperative blood transfusion is associated with poor outcomes in several malignancies. Its effect in gallbladder cancer (GBC) is unknown. METHODS: All patients with GBC who underwent curative-intent resection at 10-institutions from 2000 to 2015 were included. The effect of blood transfusion on overall survival (OS) and recurrence-free (RFS) was evaluated. RESULTS: Of 262 patients with curative-intent resection for GBC, 61 patients (23%) received blood transfusions. Radical cholecystectomy was the most common procedure (80%), but major hepatectomy was more frequent in the transfusion versus no-transfusion group (13% vs 4%; P = 0.02). The transfusion group was less likely to have incidentally discovered disease (57% vs 74%) and receive adjuvant therapy (29% vs 48%), but more likely to have preoperative jaundice (23% vs 11%), T3/T4 tumors (60% vs 39%), LVI (71% vs 40%), PNI (71% vs 48%), and major complications (39% vs 12%) (all P < 0.05). Transfusion was associated with lower median OS compared to no-transfusion (20 vs 32 mos; P < 0.001), which persisted on multivariable (MV) analysis (HR:1.9; 95%CI 1.1-3.5; P = 0.035), controlling for comorbidities, serum albumin, INR, preoperative jaundice, major hepatectomy, incidental discovery, margin status, T-Stage, LN status, and major complications. Median RFS of transfused patients was 13mo compared to 49mo for non-transfused patients (P = 0.1). Transfusion, however, was an independent predictor of decreased RFS on MV analysis (HR:2.3; 95%CI 1.1-5.1; P = 0.035). CONCLUSIONS: Perioperative blood transfusion is associated with decreased OS and RFS after resection for GCC, accounting for other adverse factors. Transfusions should thus be administered with well-defined protocols.

The Hand-Assisted Laparoscopic Approach to Resection of Pancreatic Mucinous Cystic Neoplasms: An Underused Technique?

Pancreatic mucinous cystic neoplasms (MCNs) are rare tumors typically of the distal pancreas that harbor malignant potential. Although resection is recommended, data are limited on optimal operative approaches to distal pancreatectomy for MCN. MCN resections (2000-2014; eight institutions) were included. Outcomes of minimally invasive and open MCN resections were compared. A total of 289 patients underwent distal pancreatectomy for MCN: 136(47%) minimally invasive and 153(53%) open. Minimally invasive procedures were associated with smaller MCN size (3.9 vs 6.8 cm; P = 0.001), lower operative blood loss (192 vs 392 mL; P = 0.001), and shorter hospital stay(5 vs 7 days; P = 0.001) compared with open. Despite higher American Society of Anesthesiologists class, hand-assisted (n = 46) had similar advantages as laparoscopic/robotic (n = 76). When comparing hand-assisted to open, although MCN size was slightly smaller (4.1 vs 6.8 cm; P = 0.001), specimen length, operative time, and nodal yield were identical. Similar to laparoscopic/robotic, hand-assisted had lower operative blood loss (161 vs 392 mL; P = 0.001) and shorter hospital stay (5 vs 7 days; P = 0.03) compared with open, without increased complications. Hand-assisted laparoscopic technique is a useful approach for MCN resection because specimen length, lymph node yield, operative time, and complication profiles are similar to open procedures, but it still offers the advantages of a minimally invasive approach. Hand-assisted laparoscopy should be considered as an alternative to open technique or as a successive step before converting from total laparoscopic to open distal pancreatectomy for MCN.

The Oncologic Impact of Postoperative Complications Following Resection of Truncal and Extremity Soft Tissue Sarcomas.

INTRODUCTION: Postoperative complications (POCs) negatively impact oncologic outcomes in some malignancies; however, little is known regarding their effect in soft tissue sarcoma (STS). The aim of this study was to determine the impact of POCs on survival after resection of truncal and extremity STS. METHODS: All patients who underwent resection for a primary truncal or extremity STS at a single academic institution from 2000 to 2015 were included and analyzed. Primary outcome was disease-specific survival (DSS). RESULTS: Among 546 STS patients, POCs occurred in 159 (29%) patients; 57% were major and 55% were surgical site infections. Patients with POCs were older (61 vs. 53 years), had more comorbidities (50 vs. 38%), longer operative time (127 vs. 93 min), higher-grade tumors (93 vs. 86%), and were more likely to receive preoperative radiation (42 vs. 33%; all p < 0.05). There was no difference in receipt of postoperative therapy between the POCs and no POCs groups (19 vs. 18%, p = 0.74). Median follow-up for survivors was 37 months, and the 5-year DSS for the entire cohort was 78%. Compared with patients without POCs, patients with POCs had a worse DSS (68% vs. 81%, p = 0.001). Predictors for decreased DSS on univariate analysis included POCs (hazard ratio [HR] 2.12, 95% confidence interval [CI] 1.37-3.28, p = 0.001), advanced age, neurovascular/bone resection, positive margin, high grade, and preoperative and postoperative therapy (all p < 0.05). POCs (HR 1.76, 95% CI 1.08-2.87, p = 0.02) remained an independent predictor for reduced DSS on multivariate analysis, along with age (HR 1.02, p = 0.046) and tumor grade (HR 7.62, p = 0.046). CONCLUSIONS: POCs following resection of truncal and extremity STS are associated with decreased DSS. Efforts to optimize modifiable risk factors and decrease the rate of POCs warrant further investigation.

The diagnosis of pancreatic mucinous cystic neoplasm and associated adenocarcinoma in males: An eight-institution study of 349 patients over 15 years.

BACKGROUND: Per WHO, 2000 classification, pancreatic mucinous cystic neoplasms (MCN) are defined by presence of ovarian stroma, and are primarily located in the pancreatic body/tail of females. The incidence of MCN and associated malignancy in males, since, standardization of MCN diagnostic-criteria is unknown. METHODS: MCN resections from 2000 to 2014 at eight institutions of the Central-Pancreas-Consortium were included, and divided into early (2000-2007) and late (2008-2014) time-periods. Primary aim was to characterize MCN and associated adenocarcinoma/high-grade-dysplasia (AC/HGD) in males versus females over time. RESULTS: Of 1667 resections for pancreatic cystic lesions, 349 pts (21%) had MCNs: 310 (89%) female, 39 (11%) male. Patients were equally divided between early (n = 173) and late (n = 176) time-periods. MCN in male-patients decreased over time (early: 15%, late: 7%; P = 0.036), as did pancreatic head/neck location (early: 22%, late: 11%; P = 0.01). MCN-associated AC/HGD was more frequent in males versus females (39 vs. 12%; P < 0.001). The overall rate of MCN-associated AC/HGD remained stable (early: 17%, late: 13%; P = 0.4), and was identical in males (39%) over both time-periods. Males with AC/HGD had more LN-positive disease versus females (57 vs. 22%; P = 0.039). CONCLUSIONS: As the diagnostic-criteria of MCN have standardized over time, MCN diagnosis has decreased in males and head/neck location. Despite this, MCN-associated adenocarcinoma/high-grade dysplasia has been stable and remains high in males. Any male with suspected MCN, regardless of location, should undergo resection.

Association of Preoperative Risk Factors With Malignancy in Pancreatic Mucinous Cystic Neoplasms: A Multicenter Study.

Importance: Pancreatic mucinous cystic neoplasms (MCNs) harbor malignant potential, and current guidelines recommend resection. However, data are limited on preoperative risk factors for malignancy (adenocarcinoma or high-grade dysplasia) occurring in the setting of an MCN. Objectives: To examine the preoperative risk factors for malignancy in resected MCNs and to assess outcomes of MCN-associated adenocarcinoma. Design, Setting, and Participants: Patients who underwent pancreatic resection of MCNs at the 8 academic centers of the Central Pancreas Consortium from January 1, 2000, through December 31, 2014, were retrospectively identified. Preoperative factors of patients with and without malignant tumors were compared. Survival analyses were conducted for patients with adenocarcinoma. Main Outcomes and Measures: Binary logistic regression models were used to determine the association of preoperative factors with the presence of MCN-associated malignancy. Results: A total of 1667 patients underwent resection of pancreatic cystic lesions, and 349 (20.9%) had an MCN (310 women [88.8%]; mean (SD) age, 53.3 [14.7] years). Male sex (odds ratio [OR], 3.72; 95% CI, 1.21-11.44; P = .02), pancreatic head and neck location (OR, 3.93; 95% CI, 1.43-10.81; P = .01), increased radiographic size of the MCN (OR, 1.17; 95% CI, 1.08-1.27; P < .001), presence of a solid component or mural nodule (OR, 4.54; 95% CI, 1.95-10.57; P < .001), and duct dilation (OR, 4.17; 95% CI, 1.63-10.64; P = .003) were independently associated with malignancy. Malignancy was not associated with presence of radiographic septations or preoperative cyst fluid analysis (carcinoembryonic antigen, amylase, or mucin presence). The median serum CA19-9 level for patients with malignant neoplasms was 210 vs 15 U/mL for those without (P = .001). In the 44 patients with adenocarcinoma, 41 (93.2%) had lymph nodes harvested, with nodal metastases in only 14 (34.1%). Median follow-up for patients with adenocarcinoma was 27 months. Adenocarcinoma recurred in 11 patients (25%), with a 64% recurrence-free survival and 59% overall survival at 3 years. Conclusions and Relevance: Adenocarcinoma or high-grade dysplasia is present in 14.9% of resected pancreatic MCNs for which risks include male sex, pancreatic head and neck location, larger MCN, solid component or mural nodule, and duct dilation. Mucinous cystic neoplasm-associated adenocarcinoma appears to have decreased nodal involvement at the time of resection and increased survival compared with typical pancreatic ductal adenocarcinoma. Indications for resection of MCNs should be revisited.

Small bowel neuroendocrine tumors: A critical analysis of diagnostic work-up and operative approach.

BACKGROUND: Small bowel neuroendocrine tumors (SB-NETs) are often small, multifocal, difficult to localize preoperatively, and can be overlooked during operative exploration. The optimal work-up and operative approach is unknown. METHODS: Patients who underwent resection of SB-NETs at a single-institution from 2000 to 2014 were included. Primary aim was to describe the diagnostic work-up and compare minimally invasive (MIS) to open resection. RESULTS: Ninety-three patients underwent resection for SB-NETs. About 71% were symptomatic and on average underwent three diagnostic tests: 45% had octreoscans (85% diagnostic yield); 11% had SB-enteroscopy (10% yield); 19% had capsule endoscopy (83% yield, but identified the correct tumor number in only 21%). About 27 pts underwent MIS versus 66 open. MIS pts were younger (56 vs. 61 yrs; P = 0.035), and less likely to have obstruction (4% vs. 24%; P = 0.019) and metastases (19% vs. 44%; P = 0.038). Compared to open, MIS had smaller (1.7 vs. 2.4 cm; P = 0.03) and fewer tumors resected (2 vs. 5; P = 0.049), but similar LN yield (13 vs. 12; P = 0.7). In non-metastatic, curative-intent resections, MIS still resected fewer tumors compared to open (1.5 vs. 4; P = 0.034). CONCLUSION: Capsule endoscopy may be better than small bowel enteroscopy at identifying occult SB-NETs, but may underestimate tumor burden. While MIS may be appropriate in select patients, recognizing the limitations of preoperative evaluation is critical for these tumors, as heightened operative vigilance is often required. J. Surg. Oncol. 2016;114:671-676. © 2016 Wiley Periodicals, Inc.

Pancreatic neuroendocrine tumors: Preoperative factors that predict lymph node metastases to guide operative strategy.

BACKGROUND: Enucleation and anatomic resection (central, distal, or pancreaticoduodenectomy) are surgical options for pancreatic neuroendocrine tumors. Depending on nodal-status, enucleation alone may not be oncologically appropriate. Preoperative factors predictive of nodal-involvement are not well defined. METHODS: Patients who underwent curative-intent enucleation or resection of non-metastatic, well/moderately differentiated tumors at a single institution (2000-2014) were included. The aim was to determine factors associated with nodal-metastases and recurrence-free survival. RESULTS: Of 195 patients undergoing resection, 164 met inclusion-criteria. Lymphadenectomy was performed in 131 (80%), and 32 (24%) had nodal-metastases. Receiver-operative-characteristics analysis revealed tumor size ≥2 cm was associated with nodal-involvement (AUC: 0.689; Sensitivity: 90%; Specificity: 53%). On multivariable analysis, male gender (OR: 3.16; 95%CI: 1.18-8.46; P = 0.02), head/uncinate location (HR: 5.37; 95%CI: 2.07-13.96; P = 0.001), and size ≥2 cm (HR: 6.52; 95%CI: 1.75-24.30; P = 0.005) were associated with nodal-positivity. Nodal-metastases (HR: 3.04; 95%CI: 1.04-8.91; P = 0.043) and advanced T-stage (HR: 5.39; 95%CI: 1.46-19.95; P = 0.012) were independently associated with decreased recurrence-free survival. Enucleation (n = 17; 10%) had more positive margins and similar complication rates, pancreatic fistula rates, and lengths of stay as anatomic resections. CONCLUSION: For pancreatic neuroendocrine tumors, male gender, head/uncinate location, and size ≥2 cm are associated with nodal-metastases. Nodal involvement is associated with decreased recurrence-free survival. Anatomic resection may be preferred in patients with these characteristics, as enucleation alone may under-stage patients and does not appear to be associated with an improved complication profile. J. Surg. Oncol. 2016;114:440-445. © 2016 Wiley Periodicals, Inc.

Symptomatic presentation as a predictor of recurrence in gastroenteropancreatic neuroendocrine tumors: A single institution experience over 15 years.

BACKGROUND AND OBJECTIVES: The prognostic implication of symptomatic presentation of gastroenteropancreatic neuroendocrine tumors (GEP-NETs) remains unclear. METHODS: Patients who underwent resection of nonfunctional GEP-NETs (2000-2014) were analyzed. Primary outcomes were overall survival (OS) and distant recurrence-free survival (RFS). RESULTS: Symptomatic presentation was seen in 208 (61%) of 339 patients and was associated with younger age (55 vs. 59 yrs, P = 0.001), higher tumor grade (38% vs. 21%, P = 0.027), presence of lymphovascular invasion (58% vs. 33%, P < 0.001), presence of perineural invasion (54% vs. 29%, P = 0.002), and advanced disease (T3/T4/N1/M1 [63% vs. 44%, P = 0.002]), but not tumor size (2.6 vs. 2.5 cm, P = 0.74). Symptomatic presentation was associated with decreased 3-yr distant-RFS (80% vs. 89%, P = 0.012), but not OS. When accounting for adverse features, symptomatic presentation remained independently associated with reduced distant-RFS (HR 3.51, P = 0.007). On subgroup-analysis of advanced disease patients, symptomatology was associated with reduced 3-yr distant-RFS (67% vs. 79%, P = 0.012) and persisted as an independent risk-factor for decreased distant-RFS (HR 3.01, P = 0.027). CONCLUSIONS: Symptomatic presentation of GEP-NETs is associated with aggressive features and worse distant-RFS. Trials assessing adjuvant therapy for advanced GEP-NETs are needed, and symptomatic presentation may be considered as one inclusion criterion. Following resection, symptomatic presentation should be taken into account when planning surveillance. J. Surg. Oncol. 2016;114:163-169. © 2016 Wiley Periodicals, Inc.