Prophylactic Antibiotic Duration and Infectious Complications in Pancreatoduodenectomy Patients With Biliary Stents: Opportunity for De-escalation.

OBJECTIVE: The aim of this study was to compare infectious complications in pancreatoduodenectomy (PD) patients with biliary stents treated with short, medium, or long durations of prophylactic antibiotics. BACKGROUND: Pre-existing biliary stents have historically been associated with higher infection risk after PD. Patients are administered prophylactic antibiotics, but the optimal duration remains unknown. METHODS: This single-institution retrospective cohort study included consecutive PD patients from October 2016 to April 2022. Antibiotics were continued past the operative dose per surgeon discretion. Infection rates were compared by short (≤24 h), medium (>24 but ≤96 h), and long (>96 h) duration antibiotics. Multivariable regression analysis was performed to evaluate associations with a primary composite outcome of wound infection, organ-space infection, sepsis, or cholangitis. RESULTS: Among 542 PD patients, 310 patients (57%) had biliary stents. The composite outcome occurred in 28% (34/122) short, 25% (27/108) medium, and 29% (23/80) long-duration ( P =0.824) antibiotic patients. There were no differences in other infection rates or mortality. On multivariable analysis, antibiotic duration was not associated with infection rate. Only postoperative pancreatic fistula (odds ratio 33.1, P <0.001) and male sex (odds ratio 1.9, P =0.028) were associated with the composite outcome. CONCLUSIONS: Among 310 PD patients with biliary stents, long-duration prophylactic antibiotics were associated with similar composite infection rates to short and medium durations but were used almost twice as often in high-risk patients. These findings may represent an opportunity to de-escalate antibiotic coverage and promote risk-stratified antibiotic stewardship in stented patients by aligning antibiotic duration with risk-stratified pancreatectomy clinical pathways.

A Practical Guide to Inflow Control, Retraction, and Exposure for Robotic Hepatectomy.

Establishment of inflow control and gentle effective retraction of the liver for optimal exposure are critical to safe hepatectomy. Multiple methods have been previously reported for inflow control in minimally invasive (MIS) hepatectomy including Huang's Loop.1-3 We describe here the assembly and use of our modified version of Huang's loop that permits adjustable, atraumatic, and totally intracorporeal inflow control. We use a soft 16-French urinary catheter with a single premade opening near the blunt tip, across which a small slit is created. A beveled cut is made to the catheter 12-15 cm from the blunt tip and a suture sewn there that can be grasped to pull this beveled tail through the slit and window around the porta hepatis; this loop can be tightened or loosened with ease. For liver retraction, current techniques can be traumatic, especially when instruments apply traction directly onto the liver.4 Our preferred approach utilizes a liver sling made from a soft, rolled surgical sponge with 15-cm silk ties secured at each end; the length of the sling can be adjusted on the basis of thickness of the liver. The sling applies gentle, atraumatic "pulling" traction and is especially useful for exposure of the right posterior sector. We also use external band retraction to align the transection plane with the camera.5 Both also provide countertraction when advancing instruments into a firm or fibrotic liver. These techniques are commonly used in our MIS practice, and we have found them to be cost-efficient, easily reproducible, and effective.

Local Therapy Improves Survival for Early Recurrence After Resection of Colorectal Liver Metastases.

BACKGROUND: Early recurrence following hepatectomy for colorectal liver metastases (CLM) is associated with worse survival; yet, impact of further local therapy is unclear. We sought to evaluate whether local therapy benefits patients with early recurrence following hepatectomy for CLM. METHODS: Clinicopathologic and survival outcomes of patients managed with hepatectomy for CLM (1/2001-12/2020) were queried from a prospectively maintained database. Timing of recurrence was stratified as early (recurrence-free survival [RFS] < 6 months), intermediate (RFS 6-12 months), and later (RFS > 12 months). Local therapy was defined as ablation, resection, or radiation. RESULTS: Of 671 patients, 541 (81%) recurred with 189 (28%) early, 180 (27%) intermediate, and 172 (26%) later recurrences. Local therapy for recurrence resulted in improved survival, regardless of recurrence timing (early 78 vs. 32 months, intermediate 72 vs. 39 months, later 132 vs. 65 months, all p < 0.001). Following recurrence, treatment with local therapy (hazard ratio [HR] = 0.24), liver and extrahepatic recurrence (HR = 1.81), RAS + TP53 co-mutation (HR = 1.52), and SMAD4 mutation (HR = 1.92) were independently associated with overall survival (all p ≤ 0.002). Among patients with recurrence treated by local therapy, patients older than 65 years (HR 1.79), liver and extrahepatic recurrence (HR 2.05), primary site or other recurrence (HR 1.90), RAS-TP53 co-mutation (HR 1.63), and SMAD4 mutation (HR 2.06) had shorter post-local therapy survival (all p ≤ 0.04). CONCLUSIONS: While most patients recur after hepatectomy for CLM, local therapy may result in long-term survival despite early recurrence. Somatic mutational profiling may help to guide the multidisciplinary consideration of local therapy after recurrence.

Revisiting the Malignant Masquerade at the Liver Hilum: Have We Made Progress?

BACKGROUND: Distinguishing malignant from benign causes of obstruction at the liver hilum can pose a diagnostic dilemma. This study aimed to determine factors that predict benign causes of hilar obstruction and long-term outcomes after resection. METHODS: Consecutive patients who underwent surgery for hilar obstruction at a single institution between 1997 and 2022 were retrospectively analyzed. Median follow-up was 26 months (range 0-281 months). RESULTS: Among 182 patients who underwent surgery for hilar obstruction, 25 (14%) patients were found to have benign disease. Median CA19-9 level after normalization of serum bilirubin was 80 U/mL (range 1-5779) and 21 U/mL (range 1-681) among patients with malignant and benign strictures, respectively (p = 0.001). Cross-sectional imaging features associated with malignancy were lobar atrophy, soft tissue mass/infiltration, and vascular involvement (all p < 0.05). Factors not correlated with malignancy were jaundice upon presentation, peak serum bilirubin, sex, and race. Preoperative bile duct brushing or biopsy had sensitivity and specificity rates of 82% and 55%, respectively. Among patients who underwent resection with curative intent, grade 3-4 complications occurred in 55% and 29% of patients with malignant and benign strictures, respectively (p = 0.028). Postoperative long-term complications of chronic portal hypertension and recurrent cholangitis occurred in ≥ 10% of patients with both benign and malignant disease (p = non-significant). CONCLUSIONS: Strictures at the liver hilum continue to present diagnostic and management challenges. Postoperative complications and long-term sequelae of portal hypertension and recurrent cholangitis develop in a significant number of patients after resection of both benign and malignant strictures.

The benefit of adjuvant chemotherapy following pancreaticoduodenectomy for pancreatic adenocarcinoma depends on response to neoadjuvant therapy.

BACKGROUND: The benefit of adjuvant therapy (AT) remains unclear in pancreatic ductal adenocarcinoma (PDAC) after neoadjuvant therapy (NAT) and surgical resection. METHODS: The 2019 National Cancer Database was queried for patients with non-metastatic PDAC who received NAT followed by pancreaticoduodenectomy. Only patients with data regarding receipt of AT were included. Patients were classified if they had nodal down-staging specifically, or any downstaging (Tumor, Nodal, or overall). Propensity score matching (PSM) adjusted for pretreatment covariate imbalance between groups. The weighted Kaplan-Meier method and log-rank test were used to estimate the cumulative survival. RESULTS: After exclusion criteria and PSM, a total of 2784 patients remained; 1689 (60.7%) received AT and 1095 (39.3%) did not receive AT. Among all, those with additional AT had a significantly improved overall survival (OS) (p < 0.001). Upon evaluation of patients without downstaging after NAT, those who received AT had improved OS (no nodal downstaging or any downstaging; p = 0.002; p = 0.001). When evaluating patients with downstaging after NAT, those receiving AT did not have improved OS (nodal downstaging or any downstaging: p = 0.352; p = 0.99). CONCLUSION: Response to NAT appears to correlate with the benefit of AT following pancreaticoduodenectomy; patients who have a favorable response to NAT may not benefit from AT.

Reproducibility and efficiency of liver volumetry using manual method and liver analysis software.

BACKGROUND: For liver volumetry, manual tracing on computed tomography (CT) images is time-consuming and operator dependent. To overcome these disadvantages, several three-dimensional simulation software programs have been developed; however, their efficacy has not fully been evaluated. METHODS: Three physicians performed liver volumetry on preoperative CT images on 30 patients who underwent formal right hepatectomy, using manual tracing volumetry and two simulation software programs, SYNAPSE and syngo.via. The future liver remnant (FLR) was calculated using each method of volumetry. The primary endpoint was reproducibility and secondary outcomes were calculation time and learning curve. RESULTS: The mean FLR was significantly lower for manual volumetry than for SYNAPSE or syngo.via; there was no significant difference in mean FLR between the two software-based methods. Reproducibility was lower for the manual method than for the software-based methods. Mean calculation time was shortest for SYNAPSE. For the two physicians unfamiliar with the software, no obvious learning curve was observed for using SYNAPSE, whereas learning curves were observed for using syngo.via. CONCLUSIONS: Liver volumetry was more reproducible and faster with three-dimensional simulation software, especially SYNAPSE software, than with the conventional manual tracing method. Software can help even inexperienced physicians learn quickly how to perform liver volumetry.

Targeted exome-based predictors of patterns of progression of colorectal liver metastasis after percutaneous thermal ablation.

BACKGROUND: Percutaneous thermal ablation is a curative-intent locoregional therapy (LRT) for selected patients with unresectable colorectal liver metastasis (CLM). Several factors have been identified that contribute to local tumour control after ablation. However, factors contributing to disease progression outside the ablation zone after ablation are poorly understood. METHODS: In this retrospective study, using next-generation sequencing, we identified genetic biomarkers associated with different patterns of progression following thermal ablation of CLM. RESULTS: A total of 191 ablation naïve patients between January 2011 and March 2020 were included in the analysis, and 101 had genomic profiling available. Alterations in the TGFß pathway were associated with increased risk of development of new intrahepatic tumours (hazard ratio [HR], 2.75, 95% confidence interval [95% CI] 1.39-5.45, P = 0.004); and alterations in the Wnt pathway were associated with increased probability of receiving salvage LRT for any intrahepatic progression (HR, 5.8, 95% CI 1.94-19.5, P = 0.003). CONCLUSIONS: Our findings indicate that genomic alterations in cancer-related signalling pathways can predict different progression patterns and the likelihood of receiving salvage LRT following percutaneous thermal ablation of CLM.

Prognosis Associated With CA19-9 Response Dynamics and Normalization During Neoadjuvant Therapy in Resected Pancreatic Adenocarcinoma.

OBJECTIVE: To characterize associations between carbohydrate antigen 19-9 (CA19-9) dynamics during neoadjuvant therapy (NT) and survival for patients with pancreatic ductal adenocarcinoma (PDAC). BACKGROUND: Although normalization of CA19-9 during NT is associated with improved outcomes following PDAC resection, we hypothesize that CA19-9 dynamics during NT can improve prognostication. METHODS: Characteristics for patients with PDAC undergoing NT (July 2011-October 2018) with ≥3 CA19-9 results (bilirubin<2mg/dL) were collected and grouped by CA19-9 dynamics. Nonproducers (<1 U/ml) were excluded, and normal was ≤35 U/ml. Postresection survival was compared among groups. RESULTS: Of 431 patients, 166 had eligible CA19-9 values. Median baseline CA19-9 was 98 U/ml. Overall 2-year postresection recurrence-free survival (RFS) and overall survival (OS) were 37% and 63%, respectively. Patients with normalization (53%) had improved 2-year RFS (47% vs. 28%, P = 0.01) and OS (75% vs. 49%, P = 0.01). CA19-9 dynamics during NT were analyzed by shape, direction, and normalization creating response types ("A-B-C-D-E"). Type A was "Always" decreasing to normalization, B "Bidirectional" with eventual normalization, C "Consistently" normal, D any "Decrease" without normalization, and E "Elevating" without normalization. Types A and B responses were associated with the longest postresection 2-year RFS (51% and 56%) and OS (75% and 92%, respectively) whereas Types D and E had the worst outcomes. After adjusting for node-positivity, perineural invasion, and margin-positivity, CA19-9 response types were independently associated with both RFS and OS, and predicted outcomes are better than CA19-9 normalization alone (likelihood ratio test RFS P < 0.001, OS P = 0.01). CONCLUSIONS: This novel A-B-C-D-E classification of CA19-9 dynamics during NT was associated with postresection outcomes more precisely than CA19-9 normalization alone.

Classification of Post-Pancreatectomy Readmissions and Opportunities for Targeted Mitigation Strategies.

OBJECTIVE: Within a learning health system paradigm, this study sought to evaluate reasons for readmission to identify opportunities for improvement. SUMMARY BACKGROUND DATA: Post-pancreatectomy readmission rates have remained constant despite improved index hospitalization metrics. METHODS: We performed a single-institution case-control study of consecutive pancreatectomy patients (October 2016 - April 2022). Complications were prospectively graded in biweekly faculty and advanced practice provider meetings. We analyzed risk factors during index hospitalization and categorized indications for 90-day readmissions. RESULTS: A total of 835 patients, median age 65 years and 51% (427/835) males, underwent 64% (534/835) pancreatoduodenectomies, 34% (280/835) distal pancreatectomies, and 3% (21/835) other resections. 24% (204/835) of patients were readmitted. Primary indication for readmission was technical in 51% (105/204), infectious in 17% (35/204), and medical/metabolic in 31% (64/204) of patients. Procedures were required in 77% (81/105) and 60% (21/35) of technical and infectious readmissions, respectively, while 66% (42/64) of medical/metabolic readmissions were managed non-invasively. During the index hospitalization, benign pathology (OR 1.8, P=0.049), biochemical pancreatic leak (OR 2.3, P=0.001), bile/gastric/chyle leak (OR 6.4, P=0.001), organ-space infection (OR 3.4, P=0.007), undrained fluid on imaging (OR 2.4, P=0.045), and increasing white blood cell count (OR 1.7, P=0.045) were independently associated with odds of readmission. CONCLUSIONS: Most readmissions following pancreatectomy were technical in origin. Patients with complications during index hospitalization, increasing white blood cell count, or undrained fluid before discharge were at highest risk for readmission. Pre-discharge risk-stratification of readmission risk factors and augmentation of in-clinic resources may be strategies to reduce readmission rates.

Prospective Study of Perioperative Circulating Tumor DNA Dynamics in Patients Undergoing Hepatectomy for Colorectal Liver Metastases.

OBJECTIVE: To evaluate the association of perioperative ctDNA dynamics on outcomes after hepatectomy for CLM. SUMMARY BACKGROUND DATA: Prognostication is imprecise for patients undergoing hepatectomy for CLM, and ctDNA is a promising biomarker. However, clinical implications of perioperative ctDNA dynamics are not well established. METHODS: Patients underwent curative-intent hepatectomy after preoperative chemotherapy for CLM (2013-2017) with paired prehepatectomy/postoperative ctDNA analyses via plasma-only assay. Positivity was determined using a proprietary variant classifier. Primary endpoint was recurrence-free survival (RFS). Median follow-up was 55 months. RESULTS: Forty-eight patients were included. ctDNA was detected before and after surgery (ctDNA+/+) in 14 (29%), before but not after surgery (ctDNA+/-) in 19 (40%), and not at all (ctDNA-/-) in 11 (23%). Adverse tissue somatic mutations were detected in TP53 (n = 26; 54%), RAS (n = 23; 48%), SMAD4 (n = 5; 10%), FBXW7 (n = 3; 6%), and BRAF (n = 2; 4%). ctDNA+/+ was associated with worse RFS (median: ctDNA+/+, 6.0 months; ctDNA+/-, not reached; ctDNA-/-, 33.0 months; P = 0.001). Compared to ctDNA+/+, ctDNA+/- was associated with improved RFS [hazard ratio (HR) 0.24 (95% confidence interval (CI) 0.1-0.58)] and overall survival [HR 0.24 (95% CI 0.08-0.74)]. Adverse somatic mutations were not associated with survival. After adjustment for prehepatectomy chemotherapy, synchronous disease, and ≥2 CLM, ctDNA+/- and ctDNA-/- were independently associated with improved RFS compared to ctDNA+/+ (ctDNA+/-: HR 0.21, 95% CI 0.08-0.53; ctDNA-/-: HR 0.21, 95% CI 0.08-0.56). CONCLUSIONS: Perioperative ctDNA dynamics are associated with survival, identify patients with high recurrence risk, and may be used to guide treatment decisions and surveillance after hepatectomy for patients with CLM.

Treatment Disparities Partially Mediate Socioeconomic- and Race/Ethnicity-Based Survival Disparities in Stage I-II Hepatocellular Carcinoma.

BACKGROUND: Low socioeconomic status (SES) patients with early-stage hepatocellular carcinoma (HCC) receive procedural treatments less often and have shorter survival. Little is known about the extent to which these survival disparities result from treatment-related disparities versus other causal pathways. We aimed to estimate the proportion of SES-based survival disparities that are mediated by treatment- and facility-related factors among patients with stage I-II HCC. METHODS: We analyzed patients aged 18-75 years diagnosed with stage I-II HCC in 2008-2016 using the National Cancer Database. Inverse odds weighting mediation analysis was used to calculate the proportion mediated by three mediators: procedure type, facility volume, and facility procedural interventions offered. Intersectional analyses were performed to determine whether treatment disparities played a larger role in survival disparities among Black and Hispanic patients. RESULTS: Among 46,003 patients, 15.0% had low SES, 71.6% had middle SES, and 13.4% had high SES. Five-year overall survival was 46.9%, 39.9%, and 35.7% among high, middle, and low SES patients, respectively. Procedure type mediated 45.9% (95% confidence interval [CI] 31.1-60.7%) and 36.7% (95% CI 25.7-47.7%) of overall survival disparities for low and middle SES patients, respectively, which was more than was mediated by the two facility-level mediators. Procedure type mediated a larger proportion of survival disparities among low-middle SES Black (46.6-48.2%) and Hispanic patients (92.9-93.7%) than in White patients (29.5-29.7%). CONCLUSIONS: SES-based disparities in use of procedural interventions mediate a large proportion of survival disparities, particularly among Black and Hispanic patients. Initiatives aimed at attenuating these treatment disparities should be pursued.

Hepatectomy Before Primary Tumor Resection as Preferred Approach for Synchronous Liver Metastases from Rectal Cancer.

BACKGROUND: For patients with synchronous liver metastases (LM) from rectal cancer, a consensus on surgical sequencing is lacking. We compared outcomes between the reverse (hepatectomy first), classic (primary tumor resection first), and combined (simultaneous hepatectomy and primary tumor resection) approaches. METHODS: A prospectively maintained database was queried for patients with rectal cancer LM diagnosed before primary tumor resection who underwent hepatectomy for LM from January 2004 to April 2021. Clinicopathological factors and survival were compared between the three approaches. RESULTS: Among 274 patients, 141 (51%) underwent the reverse approach; 73 (27%), the classic approach; and 60 (22%), the combined approach. Higher carcinoembryonic antigen level at LM diagnosis and higher number of LM were associated with the reverse approach. Combined approach patients had smaller tumors and underwent less complex hepatectomies. More than eight cycles of pre-hepatectomy chemotherapy and maximum diameter of LM > 5 cm were independently associated with worse overall survival (OS) (p = 0.002 and 0.027, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups. Additionally, 82% of incomplete reverse-approach patients ultimately did not require diversion during follow-up. RAS/TP53 co-mutation was independently associated with lack of primary resection with the reverse approach (odds ratio: 0.16, 95% CI 0.038-0.64, p = 0.010). CONCLUSIONS: The reverse approach results in survival similar to that of combined and classic approaches and may obviate primary rectal tumor resections and diversions. RAS/TP53 co-mutation is associated with a lower rate of completion of the reverse approach.

Benchmarks and Geographic Differences in Gallbladder Cancer Surgery: An International Multicenter Study.

BACKGROUND: High-quality surgery plays a central role in the delivery of excellent oncologic care. Benchmark values indicate the best achievable results. We aimed to define benchmark values for gallbladder cancer (GBC) surgery across an international population. PATIENTS AND METHODS: This study included consecutive patients with GBC who underwent curative-intent surgery during 2000-2021 at 13 centers, across seven countries and four continents. Patients operated on at high-volume centers without the need for vascular and/or bile duct reconstruction and without significant comorbidities were chosen as the benchmark group. RESULTS: Of 906 patients who underwent curative-intent GBC surgery during the study period, 245 (27%) were included in the benchmark group. These were predominantly women (n = 174, 71%) and had a median age of 64 years (interquartile range 57-70 years). In the benchmark group, 50 patients (20%) experienced complications within 90 days after surgery, with 20 patients (8%) developing major complications (Clavien-Dindo grade ≥ IIIa). Median length of postoperative hospital stay was 6 days (interquartile range 4-8 days). Benchmark values included ≥ 4 lymph nodes retrieved, estimated intraoperative blood loss ≤ 350 mL, perioperative blood transfusion rate ≤ 13%, operative time ≤ 332 min, length of hospital stay ≤ 8 days, R1 margin rate ≤ 7%, complication rate ≤ 22%, and rate of grade ≥ IIIa complications ≤ 11%. CONCLUSIONS: Surgery for GBC remains associated with significant morbidity. The availability of benchmark values may facilitate comparisons in future analyses among GBC patients, GBC surgical approaches, and centers performing GBC surgery.

Neoadjuvant chemotherapy for high-risk intrahepatic cholangiocarcinoma - does pathologic response mean better outcomes?

BACKGROUND: The role of neoadjuvant chemotherapy (NAC) in the management of intrahepatic cholangiocarcinoma (ICC) remains unknown. We sought to evaluate our experience treating high-risk ICC with NAC and to determine the prognostic significance of pathologic response. METHODS: Patients with ICC treated with NAC and surgery were analyzed using a prospectively maintained database. Pathologic response was graded by a blinded pathologist. Clinicopathologic/treatment variables were evaluated for associations with survival. RESULTS: Among 45 patients who received NAC followed by hepatectomy for high-risk ICC, 32(71%) were considered stage III, and 6(13%) were considered stage IV at time of diagnosis. Major response was identified in 39% of cases, including 2 with pathologic complete response. Patients with major response had a longer median NAC duration than patients with minor response (6 vs 4cycles, P=0.02). Regimen (gemcitabine/cisplatin vs gemcitabine/cisplatin/nab-paclitaxel) was not associated with response rate. Median recurrence-free (RFS) and overall survival (OS) were 11 and 45 months. Pathologic response was not associated with improved survival. CONCLUSION: Pathologic response to NAC was not associated with survival in this highly selected cohort. Nonetheless, the extended OS experienced by these high-risk patients is encouraging and suggests that NAC may help select patients who stand to benefit from aggressive resection.

Evaluating the benefit of surgical resection for hepatocellular carcinoma with multifocality or intrahepatic vascular invasion.

BACKGROUND: The role of hepatectomy for hepatocellular carcinoma (HCC) with multifocality or intrahepatic vascular involvement remains ill-defined. Our objective was to evaluate benefits of surgical resection for patients with these high-risk features. METHODS: The National Cancer Database was used to identify HCC patients with vascular involvement and/or multifocality (T2/T3, N-/M-) from 2011 to 2015. Propensity score matching (k-nearest neighbors, no replacement, 1:1) grouped patients by treatment: surgical resection versus non-surgical modalities. Groups were matched using patient, clinical, and liver-specific characteristics. Median overall survival (OS) was calculated using Kaplan-Meier, and adjusted analyses were performed using shared frailty models. RESULTS: 14,557 patients met inclusion criteria, including 1892 (9.4%) treated with surgical resection. Median cohort OS was 20.5 months. After adjustment, surgical resection was associated with survival advantage compared to non-surgical treatment (37.8 versus 15.7 months, log-rank P < .001; adjusted hazard ratio 0.49, 95% confidence interval, 0.45-0.54). Patients with minimal comorbidity, unifocal disease, and age <54 had highest probability of survival one year post-surgery. CONCLUSIONS: Surgical resection is associated with a survival advantage in HCC with multifocality and/or intrahepatic vascular involvement. The presence of these features should not contraindicate consideration of hepatectomy in suitable surgical candidates.

Impact of cumulative operative time on postoperative complication risk in simultaneous resections of colorectal liver metastases and primary tumors.

BACKGROUND: Simultaneous resection of colorectal liver metastases (CLM) and primary colorectal cancers (CRC) is nuanced without firm rules for selection. This study aimed to identify factors associated with morbidity after simultaneous resection. METHODS: Using a prospective database, patients undergoing simultaneous CLM-CRC resection from 1/1/2017-7/1/2020 were analyzed. Regression modeling estimated impact of colorectal resection type, Kawaguchi-Gayet (KG) hepatectomy complexity, and perioperative factors on 90-day complications. RESULTS: Overall, 120 patients underwent simultaneous CLM-CRC resection. Grade≥2 complications occurred in 38.3% (n = 46); these patients experienced longer length of stay (median LOS 7.5 vs. 4, p < 0.001) and increased readmission (39% vs. 1.4%, p < 0.001) compared to patients with zero or Grade 1 complications. Median OR time was 298 min. Patients within highest operative time quartile (>506 min) had higher grade≥2 complications (57%vs. 23%, p = 0.04) and greater than 4-fold increased odds of grade≥2 morbidity (OR 4.3, 95% CI (Confidence Interval) 1.41-13.1, p = 0.01). After adjusting for Pringle time, KG complexity and colorectal resection type, increasing operative time was associated with grade≥2 complications, especially for resections in highest quartile of operative time (OR 7.28, 95% CI 1.73-30.6, p = 0.007). CONCLUSION: In patients undergoing simultaneous CLM-CRC resection, prolonged operative time is independently associated with grade≥2 complications. Awareness of cumulative operative time may inform intraoperative decision-making by surgical teams.

Robotic Extended Right Hepatectomy for Colorectal Liver Metastasis.

BACKGROUND: Advantages of minimally invasive compared with open hepatobiliary surgery include quicker functional recovery, decreased postoperative length of stay, and decreased postoperative opioid use. As more complex operations are approached in minimally invasive fashion, it is imperative to maintain safety and excellent oncologic outcomes. METHODS: In this video, we demonstrate the key principles in performing a safe robotic extended right hepatectomy for colorectal liver metastasis following sound oncologic principles. RESULTS: Key preoperative considerations include (1) early referral to a hepatobiliary surgeon, (2) careful review of cross-sectional imaging to identify the relationship of tumors to major vasculature and any aberrant vascular anatomy, and (3) liver volumetry for every right hepatectomy to determine the need for future liver remnant volume augmentation. Key intraoperative techniques include (1) liberal use of ultrasound before and during transection to determine the relationship of major vasculature to tumor to preserve liver parenchyma without compromising tumor margins, (2) external retraction with vessel loops placed on either side of the transection line as stay sutures to facilitate parenchymal transection, and (3) a crush clamp technique to safely identify and control crossing vessels while dividing liver parenchyma. CONCLUSIONS: With proper preoperative planning and intraoperative use of these techniques, the benefits of a minimally invasive approach can be achieved while maintaining excellence in surgical quality and safety.

Outcomes of Mixed Pathologic Response in Patients with Multiple Colorectal Liver Metastases Treated with Neoadjuvant Chemotherapy and Liver Resection.

BACKGROUND: Pathologic response to preoperative chemotherapy predicts survival in patients with colorectal liver metastases (CLMs) who undergo hepatectomy. In multiple CLMs, mixed pathologic response, wherein tumors exhibit different degrees of treatment response, is possible. We sought to evaluate survival outcomes of mixed response in patients with multiple CLMs. METHODS: We conducted a retrospective cohort study using a single-institution database of patients with two or more CLMs who underwent preoperative chemotherapy and hepatectomy (2010-2018). Pathologic response of each tumor was measured on pathology. Patients were stratified by pathologic response as complete (pCR) = 0-1% viability; major (pMajR) = 2-49% viability; minor (pMinR) = 50-99% viability; or mixed (pMixR) = at least one pCR/MajR tumor and one pMinR. Recurrence-free survival (RFS) and overall survival (OS) were estimated using the Kaplan-Meier method, and adjusted risk of death was evaluated using Cox regression. RESULTS: Among 444 patients, 6% had pCR, 34% had pMajR, 36% had pMinR, and 24% had pMixR. Median and 5-year RFS for patients with pMixR was 10.4 months and 16%, respectively, compared with pMajR (11.3 months and 18%, respectively), pMinR (7.7 months and 13%, respectively), and pCR (23.1 months and 38%, respectively) [log-rank p < 0.001]. Median and 5-year OS for patients with pMixR was 77.4 months and 60%, respectively, compared with pMajR (80.5 months and 63%, respectively), pMinR (49.9 months and 39%, respectively), and pCR (median OS not reached; median follow-up of 37.1 months and 5-year OS of 65%) [log-rank p = 0.002]. pMixR was associated with a 52% risk of death reduction (hazard ratio 0.48, 95% confidence interval 0.30-0.78 vs. pMinR). CONCLUSIONS: One-quarter of patients with multiple CLMs have pMixR following preoperative chemotherapy and hepatectomy. OS and RFS for patients with pMixR mirror those of pMajR rather than pMinR, suggesting the greatest response achieved in any metastasis best predicts survival.

Opioid Discharge Prescriptions After Inpatient Surgery: Risks of Rebound Refills by Length of Stay.

INTRODUCTION: As inpatient stays become shorter, one concern with standardizing discharge opioid prescriptions is the potential risk of "rebound refills." We sought to compare opioid prescription refill rates and volumes for surgical patients discharged on postoperative day (POD) 2-3, 4-7, and 8+. METHODS: In a prospective quality improvement protocol, faculty volunteered to use either a 5x-multiplier (5x) or usual care (UC) for discharge prescriptions after inpatient (≥48 h stay) surgery from Sep-Dec 2019. The 5x-multiplier is 5-times the patient's last 24-h opioid use (by oral morphine equivalents, OME). Cohorts were compared by POD of discharge: POD 2-3 ("SHORT"), POD 4-7 ("INTERMEDIATE"), and POD 8+ ("LONG"). The primary endpoint was 30-d refill rates. Secondary endpoints included 30-d refill OME and inpatient opioid weaning/discharge metrics. RESULTS: From 22 faculty, 409 patients were included. When stratified by POD, 154 (37.7%) were discharged SHORT, 176 (43.0%) INTERMEDIATE, and 79 (19.3%) LONG. SHORT stay patients had a median last 24-h OME of 10 mg (versus 5 mg INTERMEDIATE, 5 mg LONG; P = 0.268), and a median discharge OME of 55 mg (versus 75 mg INTERMEDIATE, 100 mg LONG; P = 0.221). Patients with SHORT stays did not have higher refill rates (11.7% versus 18.2% INTERMEDIATE, 19.0% LONG; P = 0.193) or higher median refill OME (150 mg versus 300 mg INTERMEDAITE, 339 mg LONG; P = 0.154). CONCLUSIONS: Despite concerns of increased refills, patients discharged by POD 2-3 were not associated with "rebound refills." A patient-centered 5x-multiplier standardization of discharge opioid prescriptions is feasible in all inpatient surgery patients, even those discharged following a short inpatient stay.

Association of Patient Controlled Analgesia and Total Inpatient Opioid Use After Pancreatectomy.

INTRODUCTION: The initial settings on an intravenous patient-controlled analgesia (IV-PCA) pump can represent a significant source of postoperative opioid exposure. The primary aim of this study was to evaluate the impact of first day IV-PCA use on total inpatient opioid use after open pancreatectomy, before and after standardization of initial dosing. METHODS: Inpatient oral morphine equivalents (OMEs) were reviewed for pancreatectomy patients treated with IV-PCA at a single institution before and after (3/2016-8/2017 versus 3/2019-11/2020) implementation of a standardized initial IV-PCA dosing regimen (initial limit 0.1 mg hydromorphone, or 1 mg OME, every 10 min as needed). IV-PCA OME in the first 24 h and the total inpatient OME were compared between cohorts. RESULTS: Of 220 total patients, 132 were in the prestandardization (PRE) historical cohort. A first-24-h IV-PCA use was different (PRE median 95 mg versus poststandardization [POST] 15 mg, P < 0.001). The median total inpatient OME was different (P < 0.001) between PRE (525 mg, interquartile range [IQR] 239-951 mg) and POST patients (129 mg, IQR 65-204 mg) with 77% (median 373 mg) of total inpatient OMEs contributed by IV-PCA in the PRE and 56% (median 64 mg) in the POST cohorts. There were similar patient-reported pain scores between groups. CONCLUSIONS: Standardizing initial IV-PCA settings was associated with a reduced first-24-h opioid exposure, proportional and absolute total IV-PCA use, and total inpatient OMEs. Because of the contribution of an IV-PCA to the total inpatient opioid exposure, purposeful reduction or omission of an IV-PCA is critical to perioperative opioid reduction strategies.