Improved survival of patients receiving immunotherapy and chemotherapy following curative-intent resection of colorectal liver metastases.

BACKGROUND: Despite significant advancements in the treatment of patients with colorectal liver metastases (CRLMs), only a minority will experience long-term survival. This study aimed to determine the effect of chemotherapy (CT) and immunotherapy (IT) compared with that of CT alone on patient survival after surgical resection. METHODS: Patients undergoing curative-intent liver resection followed by adjuvant systemic therapy for stage IV colon cancer were identified using the National Cancer Database. Patients were stratified into type of therapy (CT alone vs CT + IT) and microsatellite status. Propensity score-weighted analysis was performed through 1:1 matching based on the nearest neighbor method. RESULTS: Of 9943 patients who underwent resection of CRLMs, 7971 (80%) received systemic adjuvant therapy. Of 7971 patients, 1432 (18%) received a combination of CT and IT. Microsatellite status was not associated with overall survival (OS). Adjuvant CT + IT was associated with increased 3-year OS compared with that of CT alone in both the unmatched cohort (55% vs 48%, respectively; P < .001) and matched cohort (52% vs 48%, respectively; P = .050). On multivariate analysis, older age, positive resection margins, and KRAS mutation were independent predictors of poor survival, whereas the administration of adjuvant CT + IT was an independent predictor of improved survival. CONCLUSION: IT combined with CT was associated with improved survival compared with that of CT alone after curative-intent resection of CRLMs, regardless of microsatellite instability status. Clinical trials to determine optimal patient selection, IT regimen, and long-term efficacy to improve outcomes of patients with CRLMs are warranted.

Drain Placement After Pancreatic Resection: Friend or Foe For Surgical Site Infections?

BACKGROUND: Despite multiple studies and randomized trials, there remains controversy over whether drains should be placed, and if so for how long, after pancreas resection. The aim was to determine if post-pancreatectomy drain placement and timing of drain removal were associated with differences in infectious outcomes and, if so, which specific procedures and infectious sites were most at risk. METHODS: The ACS-NSQIP targeted pancreatectomy database was utilized to identify patients who underwent pancreatectomies between 2015 and 2020 with postoperative drain placement for retrospective cohort analysis. A propensity score matching analyses was conducted to determine associations between drain placement and surgical site infections (SSI). RESULTS: Of 39,057 pancreatic resections, 66.4% were proximal pancreatectomies, and 33.6% were distal pancreatectomies. After propensity score matching, drain placement was not associated with significantly lower rates of superficial SSI (7% vs 9%, p = 0.755) or organ/space SSI (17% vs 16%, p = 0.647) after proximal pancreatectomy. After distal pancreatectomy, drain placement was associated with higher rates of organ/space SSI (12% vs 9%, p = 0.010). Drain removal on or after postoperative day 3 was significantly associated with higher rates of SSI in both proximal and distal pancreatectomy. CONCLUSIONS: Drain placement is associated with an increased rate of organ/space SSI after distal pancreatectomy and not after pancreaticoduodenectomy. When drains are utilized, early removal is associated with a reduction of SSI after all types of pancreatectomy. In surgical units where post-pancreatectomy SSI is a concern, selective drain placement for high-risk glands or after distal pancreatectomy, combined with early drain removal, may be considered.

Perioperative Broad-spectrum Antibiotics are Associated With Decreased Surgical Site Infections Compared to 1st-3rd Generation Cephalosporins After Open Pancreaticoduodenectomy in Patients With Jaundice or a Biliary Stent.

OBJECTIVE: Compare the effectiveness of 1st-3rd generation cephalosporins (1st-3rdCE) to broad-spectrum antibiotics in decreasing surgical site infections (SSI) after pancreatectomy. SUMMARY OF BACKGROUND DATA: SSI is one of the most common complications after pancreatic surgery. Various antibiotic regimens are utilized nationwide with no clear guidelines for pancreatectomy. As we await results of a recently initiated prospective trial, this study retrospectively evaluates over 15,000 patients using the same administrative data abstraction tools as in the trial. METHODS: All relevant clinical variables were collected from the 2016-2018 targeted-pancreatectomy database from the American College of Surgeon National Surgical Quality Improvement Program. Preoperative antibiotics were initially collected as first-generation cephalosporin, second or third-generation cephalosporin, and broad-spectrum antibiotics (Broad-abx). RESULTS: Of the 15,182 patients who completed a pancreatic surgery between 2016 and 2018, 6114 (40%) received a first-generation cephalosporin, 4097 (27%) received a second or third-generation cephalosporin, and 4971 (33%) received Broad-abx. On multivariate analysis, Broad-abx was associated with a decrease in all-type SSI compared to 1st-3rdCE (odds ratio = 0.73-0.77, P < 0.001) after open pancreaticoduodenectomy (PD). There was no difference in SSI between antibiotic-types after distal pancreatectomy. Subgroup multivariate analysis of open PD revealed decrease in all-type SSI with Broad-abx amongst patients with jaundice and/or biliary stent only, regardless of wound protector use (odds ratio = 0.69-0.70, P < 0.001). Propensity score matching of open PD patients with jaundice and/or biliary stent confirmed a decrease in all-type SSI (19% vs 24%, P = 0.001), and organ-space SSI (12% vs 16%, P < 0.001). CONCLUSION: Broad-abx are associated with decreased SSI after open PD and may be preferred specifically for patients with preoperative biliary stent and/ or jaundice.

Should Drains Suck? A Propensity Score Analysis of Closed-Suction Versus Closed-Gravity Drainage After Pancreatectomy.

BACKGROUND: Post-operative pancreatic fistula (POPF) remains one of the most common complications after pancreatic surgery. We previously reported that the majority of US surgeons leave drains after pancreatectomy. However, there remains controversy and surgeon bias on the use of gravity compared with suction drainage with limited data on patient outcomes to guide management. METHODS: Demographics, comorbidities, perioperative, and outcome data were captured from the most recent ACS National Surgical Quality Improvement Program (NSQIP)-targeted pancreatectomy databases. This is a retrospective cohort analysis comparing closed-suction to closed-gravity drains with multivariate analysis and propensity score matching (PSM). RESULTS: Of 9232 patients that underwent a pancreatectomy with closed drain placement, 1345 (15%) were to gravity and 7887 (85%) were to suction. On multivariate and PSM, stratified by surgery-type, there was no difference in biochemical leak (Whipple, 4 vs. 4%; distal, 8 vs. 6%) or clinically relevant (CR)-POPF (Whipple, 13 vs. 15%; distal, 12 vs. 15%). On multivariate analysis, there was an increase in organ-space surgical site infections with suction drains for patients undergoing Whipple procedure (12 vs. 16%, p = 0.004), which did not persist on PSM (p = 0.088). Finally, there were no significant differences in amylase level, time to drain removal, or superficial surgical site infections for patients undergoing either procedure based on drain type. CONCLUSION: The majority of drains utilized after pancreatectomy in the USA are placed to suction, though a significant proportion are kept to gravity. Neither type of drain is associated with increased CR-POPF or other post-operative outcomes compared with the other; therefore, both types remain reasonable options if drains are to be placed.

Epidural Analgesia Is Associated with Prolonged Length of Stay After Open HPB Surgery in Over 27,000 Patients.

BACKGROUND: The impact of epidural analgesia (EA) on postoperative morbidity and length of stay (LOS) after HPB surgery remains to be determined. These specific outcomes have been highlighted by the implementation of multiple enhanced recovery pathways (ERAS). The authors hypothesized that EA in the current environment may be associated with LOS and other outcomes. METHODS: The American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) databases from 2014 to 2017 for patients undergoing open hepatopancreaticobiliary (HPB) surgery were included in a retrospective cohort analysis with propensity score matching (PSM) comparing EA with control. RESULTS: Twenty-seven thousand two hundred eighteen patients underwent open HPB surgery, of which 6048 (22%) received EA. There was an increase use of EA over time (from 19.3 to 25.5%, p = 0.001). On PSM, EA was associated with more than half of a day increase in LOS for both pancreatic (p < 0.001) and hepatic surgery (p < 0.001). Furthermore, for pancreatic surgery, there was an increase in urinary tract infection (2.5% vs. 3.3%, p = 0.018), time to drain removal (7.8 vs. 8.7 days, p < 0.001), and discharge to rehabilitation (2.9% vs. 4.3%, p = 0.029). For hepatic surgery, there was an increase in blood transfusion requirements (17% vs. 20%, p = 0.019). There were no differences in overall morbidity and mortality. CONCLUSION: In this cohort of over 27,000 patients with granular surgical details, there was a significant increase in LOS associated with EA after HPB surgery, along with increased procedure-specific UTI and blood transfusion. With the ever-increasing need for standardized and efficient patient care pathways that reduce LOS, alternative analgesic adjuncts may be considered to optimize patient outcomes.

A propensity score analysis of over 12,000 pancreaticojejunal anastomoses after pancreaticoduodenectomy: does technique impact the clinically relevant fistula rate?

BACKGROUND: Clinically relevant postoperative pancreatic fistula (CR-POPF) remains a major cause of morbidity in patients undergoing pancreatic surgery. Controversy exists as to whether there is any difference in CR-POPF with a Duct-to-Mucosa (DTM) versus an Invagination (IG) pancreaticojejunostomy (PJ). METHODS: Demographic, perioperative, intraoperative, and postoperative data were captured from the American College of Surgeons (ACS) National Surgical Quality Improvement Program (NSQIP) 2014-2017 databases. Potential confounders were included in a logistic regression and a propensity score model. The primary outcome was CR-POPF. RESULTS: A total of 12,361 pancreaticojejunal anastomoses were performed with 11,168 patients undergoing DTM (90%) and 1193 undergoing IG (10%) after pancreaticoduodenectomy. Amongst all patients, there was no significant difference in CR-POPF between DTM and IG on multivariate (OR = 0.95, p = 0.64) or propensity score analysis (OR = 0.99, p = 0.93). After stratification by pancreatic gland texture and duct size, there was a decrease in CR-POPF with DTM amongst patients with duct size greater than 6 mm on multivariate analysis (OR = 0.35, p = 0.009) and propensity score analysis (OR = 0.40, p = 0.018). There were no significant differences in any other strata. CONCLUSION: DTM or IG technique are not associated with CR-POPF for patients with average size pancreatic ducts; however, DTM is preferable in patients with large pancreatic duct diameter (>6 mm).

Impact of Immunotherapy after Resection of Pancreatic Cancer.

BACKGROUND: Adjuvant immunotherapy has improved outcomes in patients with advanced melanoma; however, the potential benefit for patients with pancreatic ductal adenocarcinoma (PDAC) remains unknown. The aim of this study was to determine the impact of adjuvant chemotherapy and immunotherapy (CTx-IT) compared with CTx alone on patient survival after resection of PDAC. STUDY DESIGN: Patients who underwent resection of PDAC from 2004 to 2015 were identified from the National Cancer Database. Univariate and multivariate Cox proportional hazards models were used to determine predictors of overall survival (OS) based on the type of adjuvant therapy received. Patients who received adjuvant immunotherapy were compared with those who received adjuvant CTx alone by propensity score matching. RESULTS: Of 21,313 patients who received curative-intent resection for PDAC followed by adjuvant systemic therapy, 269 (1.3%) patients were treated with adjuvant CTx-IT. Propensity score matching resulted in a cohort of 477 patients: (229 CTx only and 248 CTx-IT). The 5-year OS was higher in the CTx-IT group compared with CTx alone (29.2% vs 18.3%; p = 0.0045). On multivariate analysis, the addition of adjuvant immunotherapy was associated was improved overall survival (hazard ratio 0.74; p = 0.007). CONCLUSIONS: The addition of adjuvant immunotherapy to chemotherapy is associated with improved survival compared with chemotherapy alone after curative-intent resection of pancreatic adenocarcinoma. Future research is warranted to match specific immunotherapy agents with susceptible patient populations to improve outcomes for this aggressive disease.

What is the Incidence of Malignancy in Resected Intraductal Papillary Mucinous Neoplasms? An Analysis of Over 100 US Institutions in a Single Year.

BACKGROUND: A subset of intraductal papillary mucinous neoplasms (IPMNs) will progress to invasive adenocarcinoma, however identifying invasive from non-invasive disease preoperatively remains challenging. The rate of malignancy in resected IPMNs in the US remains unclear. OBJECTIVE: We aimed to determine the rate of malignancy and factors associated with high-risk pathology in resected IPMNs. METHODS: The most recent annual cohort of patients undergoing pancreatectomy included in the American College of Surgeons National Surgical Quality Improvement Program were assessed, and contributions of demographics, preoperative laboratory values, and outcome data to level of IPMN dysplasia were analyzed. The main outcomes were incidence of invasive carcinoma or high-grade dysplasia. RESULTS: Of 5025 pancreatectomies in 1 year, 478 patients underwent pancreatectomy for IPMN. Invasive carcinoma/high-grade dysplasia was identified in 23% of resected lesions, and there was no difference in patient characteristics or type of resection performed in patients with invasive versus non-invasive pathology. Patients with invasive IPMNs presented significantly more often with high liver function tests, >10% weight loss, clinical jaundice and stent placement, and were more likely to undergo an open operation (p = 0.03). There were no differences in perioperative outcomes. Adjusted logistic regression identified an association between invasive disease and non-soft pancreatic gland texture (odds ratio 0.19, 95% confidence interval 0.05-0.68, p < 0.01). CONCLUSIONS: Approximately 10% of all pancreatectomies in the US are for IPMNs. In these patients, treated after the revised international consensus guidelines, only 23% of IPMNs contained invasive or high-grade histology. Resections carried similar morbidity regardless of pathology. Improved biomarkers are needed to aid in surgical selection.

Isolated Pancreatic Uncinate Duct IPMN.

The ventral pancreas originally forms as an evagination of the common bile duct at 32 days gestation and its duct, the uncinate duct, eventually rotates with the ventral anlage to join the dorsal pancreas and fuse with the main pancreatic duct. Thus, though often considered a "branch" duct of the pancreas, embryologically, the uncinate duct is the "main" pancreatic duct of the ventral pancreas. This concept is not fully addressed in the current definitions of intraductal papillary mucinous neoplasms of the pancreas (IPMN) where international consensus guidelines consider the main-duct IPMN as high risk for malignancy and most small branch-duct IPMN as low risk for malignancy. Thus, it is important to recognize that isolated uncinate-duct IPMN can occur and, based on its embryologic origin and increased association with high-grade dysplasia and invasive cancer, may be managed conceptually as a main duct type of disease rather than a branch duct until better biomarkers of malignancy are discovered. The images provide an example of this unique disease process.

Techniques to perform robotic left adrenalectomy in the obese patient.

INTRODUCTION: Minimally invasive adrenalectomy may be associated with reduction in postoperative pain, morbidity, and length of stay and, as a result, has become a preferred approach for many adrenal tumors. Left-sided adrenal tumors, however, are particularly challenging to address in the morbidly obese patient due to difficulties in maintaining exposure and dissection. The robotic platform offers instruments with greater degrees of freedom that aid in retraction and dissection, especially of the adrenal vein, but fixed patient positioning and the large distance needed between patient ports to avoid arm collisions can be restrictive in patients with a large amount of retroperitoneal fat and small working space. METHODS/RESULTS: We demonstrate robotic left adrenalectomy (RLA) in a consecutive series of patients with a mean weight of 99 kg and mean BMI of 36. Techniques to safely and efficiently perform RLA in obese patients are stepwise demonstrated, including (1) Patient positioning, (2) Management of the pannus, (3) Customized port placement, (4) Medial retraction of the pancreas, (5) Finding the left adrenal vein, and (6) Management of bleeding. Intraoperative videos from multiple patients also show surgical pitfalls, examples of poor port placement, arm collisions, alternative approaches to the vein, and techniques to control unexpected bleeding. All patients in the series underwent successful RLA with negative margins, no major intra- or postoperative complications, and discharge on POD 1-2. CONCLUSION: Though poor exposure due to patient body habitus is a relative contraindication, even large left-sided adrenal tumors can be safely approached robotically while adhering to oncologic principles, as is demonstrated in this video.

Hepatectomy After Yttrium-90 (Y90) Radioembolization-Induced Liver Fibrosis.

An obese 55-year-old woman with nonalcoholic fatty liver disease presented 7 years after resection of a T3N1 ileal carcinoid tumor with an elevated chromogranin A, multifocal metastatic disease to the liver, and carcinoid syndrome. She underwent right hepatic artery yttrium-90 (Y90) radioembolization, followed a month later by selective Y90 treatment to segment IV. She then presented to our clinic 10 months later, remaining symptomatic with flushing, diarrhea, anxiety, myalgia, pain, and persistent night sweats despite Sandostatin administration. At least 11 tumors were identified in the right lobe of the liver and three in segment IV on liver-specific imaging. These lesions were stable over a year with no new lesions. At exploration, there was marked hypertrophy of the left lateral segment due to the yttrium-90 treatment of segments IV-VIII, corresponding with preoperative volumetrics predicting a functional liver remnant (FLR) of 40% after extended right hepatectomy. The right lobe and segment IV were fibrotic, hard, and visibly damaged. The gland had a thick, fibrotic capsule, and the parenchyma was dense, inflexible, and difficult to dissect, consistent with the previously reported morbidity of these operations. Extended right hepatectomy was performed. Final pathology demonstrated 15 foci of metastatic well-differentiated neuroendocrine carcinoma that were negative for necrosis, as was expected given her continued symptoms despite radioembolization. Numerous amorphous spheres, frequently in clusters, were present in segments IV-VIII in vessels and approximating tumors consistent with prior Y90 radioembolization. The patient had an uneventful post-operative recovery and remains symptom free on follow-up. Treatment options for metastatic tumors to the liver have increased in recent years and currently include radioembolization in selected patients. Surgical cytoreduction and complete metastasectomy continue to offer improvement in symptoms, quality of life, and survival in patients with neuroendocrine liver metastases; however, hepatectomy after radioembolization is unique and carries increased morbidity/mortality, likely due to Y90-induced liver fibrosis. We demonstrate images of fibrotic yttrium-90 radiation-affected liver and histological sections of radioembolic microbeads in blood vessels and distributed around resected tumors.

Survival after resection of cutaneous adnexal carcinomas with eccrine differentiation: risk factors and trends in outcomes.

BACKGROUND: Current staging systems do not specifically address cutaneous adnexal carcinomas with eccrine differentiation. Due to their rarity, prognosis and management strategies are not well established. A population-based study was performed to determine prognostic factors and survival. METHODS: Patients diagnosed with cutaneous adnexal carcinomas with eccrine differentiation were identified using the surveillance, epidemiology, and end results population-based cancer registry. Associations between risk factors, treatment modalities, and survival were calculated using logistical regression, Kaplan-Meier estimates and log-rank analysis. RESULTS: The incidence of distinct eccrine subtypes was determined within 1,045 patients with cutaneous adnexal tumors containing eccrine differentiation. All-cause 5-year survival (OS) was 82%, while age-adjusted survival was 94%. Patients with microcystic adnexal carcinoma had improved OS (90%) compared to patients with hidradenocarcinoma (74%), spiradenocarcinoma (77%), porocarcinoma (79%), and eccrine adenocarcinoma (81%). The majority of patients were treated with surgical excision and a small subset with surgery plus radiation, with similar OS. Patients with well-to-moderately differentiated tumors demonstrated improved OS compared to those with poorly differentiated/anaplastic disease. CONCLUSIONS: Histological subtype and grade were associated with survival, and should be specified in biopsies and excised specimens. Surgical excision is appropriate, and the addition of adjuvant radiation may not be associated with survival. These results highlight survival data and high-risk prognostic factors that warrant prospective validation, and may augment current staging systems.

Can we predict which residents are going to pass/fail the oral boards?

OBJECTIVE: Previously, we identified a positive correlation between administration of regularly structured mock oral examinations and successful first time pass rates on the American Board of Surgery Certifying Examination (ABSCE)/oral boards. In this study, we investigated factors associated with test results to determine whether residents at risk of not passing the ABSCE can be identified a priori. DESIGN: All general surgery chief residents who graduated from a large academic/community program between 2001 and 2010 were identified. Residents who did not pass the ABSCE on the first attempt were compared to a control group of chief residents who passed the examination on the first attempt. Evaluation metrics included "knowledge," "professional communication," and "spoken English" scores. Differences between groups were determined using one-way ANOVA and χ(2) calculations. RESULTS: Over the decade, 13 residents made more than 1 attempt to pass the ABSCE. The element of the "knowledge" score associated with ABSCE first-attempt pass rates included United States medical licensing examination (USMLE) Step 2 scores (p = 0.02), and not ABSITE, American Board of Surgery Qualifying examination (ABSQE)/written examination or USMLE Step 1 scores. "Professional communication" scores associated with first-attempt pass rates included in-house mock oral examination scores (p = 0.01) and Citywide mock oral examination scores (p = 0.02). ABSCE pass rates did not differ in native vs. non-native English speakers or graduation from a United States vs. International medical school. CONCLUSIONS: Compared with a control group of residents from the same program, residents who passed the ABSCE examination on the first attempt were more likely to have higher USMLE Step 2 and professional communication scores. USMLE Step 1 scores and English as a native language were not associated with certifying examination pass rates. These criteria may offer guidance for residents preparing to take the ABSCE and may aid in the selection of residents for residency programs. Larger studies to validate these findings and to investigate the role of improving communication skills and conducting interventions between the 1st and 2nd attempt are warranted.