SLEEVE GASTRECTOMY INHIBITS TUMOR FORMATION IN A MOUSE MODEL OF FAMILIAL ADENOMATOUS POLYPOSIS

Introduction
The role of lymph node (LN) parameters in pancreatoduodenectomy (PD) for cancer has been mainly investigated in the upfront surgery setting. Yet, due to the impact of neoadjuvant therapy (NAT) on nodal status, these results cannot be directly translated to post-NAT PD. This study aimed to examine LN yields and metastases per anatomical stations and how the extension of LN dissection affects nodal staging in post-NAT PD. Lastly, the prognostic role of LN parameters was investigated.
Methods
An institutional lymphadenectomy protocol was prospectively applied to all post-NAT PDs from June 2013. Lymphadenectomy included stations 5/6/8a-p/12a-b-c-p/13/14a-b/17 and jejunal mesentery LNs. Stations embedded in the PD specimen (13/14/17/jejunal) were defined as first-echelon, those sampled separately (5/6/8/12) as second-echelon. The prognostic impact of LN parameters in N+ patients was evaluated using uni- and multivariable Cox regression. To avoid collinearity, separate multivariable models were designed for each nodal parameter.
Results
Among 288 patients 61% received FOLFIRINOX, 30% Gem-Abraxane. The median number of examined (ELN) and positive LNs (PLN) were 43 and 1, and 185 patients were N+ (64%). The commonest metastatic sites were stations 13 (51%), 14 (34%) and 17 (32%). The overall rates of first and second echelon involvement were 60% and 20%. The median number of ELN and PLN in the first echelon were 29 and 1. The addition of second echelon LNs increased nodal counts by 9 ELN and 0 PLN, resulting in only minor changes in staging.
The median follow-up was 25.1 months, 35.8 in censored cases. At multivariable analysis, second echelon involvement, ≥4 metastatic stations, metastases to station 8 and jejunal mesentery LNs, but not N2 status, were independently associated with survival of N+ patients, along with adjuvant treatment.
The median recurrence-free survival (RFS) was 14.8 months and 176 patients experienced recurrence (71%), among which 41 were local relapses (23%). In N+ patients, nodal echelons, ≥4 metastatic stations and tumor involvement of station 8,14 and jejunal mesentery LNs were independent predictors of RFS, along with Ca 19.9 response, T- and R-status and adjuvant treatment. Distant recurrences incrementally increased with nodal involvement (Figure).
Conclusion
LN metastases most commonly occur in first-echelon LNs, and first-echelon dissection provides an adequate number of ELN for optimal staging. Examining second-echelon LNs does not improve the staging process substantially. Yet, second-echelon involvement is prognostically relevant, as well as metastases to station 8 and jejunal mesentery LNs. These data have potential implications when assessing surgical indication after NAT. Moreover, intraoperative frozen section of station 8 might help decision-making, especially in technically demanding cases or fragile patients.

Background:
The concept of “experience” in surgery remains nebulous and multifactorial, encompassing both the surgeon and the institution as pivotal variables. While a surgeon’s career volume seems to be a determinant in improving outcomes for pancreatoduodenectomy (PD), the influence of individual surgeon experience within high-volume institutional settings remains undefined. Within such a framework, the present investigation analyzes the association of cumulative surgeon volume experience with risk-adjusted postoperative outcomes after PDs.

Methods:
A total of 8,189 PDs performed by 82 surgeons at 18 international institutions (median:140 PD/year) were accrued from 2003 to 2020. Surgeon’s cumulative PD volume was categorized in 4 quartiles (≤150, 151 to 285, 286 to 525 and ≥526 PDs). Associations of categorical and continuous variables were analyzed with appropriate univariate tests. Fistula Risk Score (FRS)-stratified performance comparisons of postoperative outcomes across each volume quartile were quantified through multivariable analyses. Next, the same methodology was implemented when considering the ten most impactful scenarios (previously defined as a combination of occurrence and severity) for the development of clinically relevant pancreatic fistula (CR-POPF; n = 2,830 patients).

Results:
Within the overall cohort, 18.7% patients suffered severe complications (Accordion≥3), 14% developed CR-POPF, 4.8% were reoperated upon, and 2.2% expired. Surgeons performed a median of 68.5 career PDs (IQR 21-136), with a median FRS of 4 (IQR 3-5). When compared with those with less experience, the top-quartile surgeons more often operated on intermediate/high FRS cases (73% vs 61%, p <0.001); yet, their performance was associated with significant declines in CR-POPF, severe complications, reoperations, and length of stay (8 vs 9 d), whereas mortality and failure-to-rescue were not affected (Figure). This same outcome profile was accentuated even more when considering the most frequent and impactful FRS scenarios that surgeon encounter. In the overall cohort, risk-adjusted models indicate male gender, increasing age, ASA class and FRS, but not surgeon experience, as predictors for severe complications, failure-to-rescue and mortality. Instead, in advanced fistula risk circumstances, upper-echelon experience demonstrates significant reductions in CR-POPF, reoperations and LOS (Table).

Conclusion:
At specialty institutions, mortality and failure-to-rescue depend primarily on baseline patient and systemic characteristics, while cumulative surgical experience independently impacts pancreatic fistula occurrence and its attendant effects - even more so for riskier PDs. These data suggest an extended learning curve exists for this operation and reinforce the notion that surgeon experience is a key contributor for outcome improvement.

Importance: Guidelines recommend surgical exploration in selected patients with locally advanced pancreatic cancer (LAPC) following induction chemotherapy. However, surgical exploration, has potential drawbacks related to surgical risks and treatment breaks, which apply in particular to patients undergoing exploration without resection (i.e. non-therapeutic laparotomy). Data regarding the impact of non-therapeutic laparotomy for LAPC treated with (m)FOLFIRINOX induction chemotherapy could guide aggresiveness of surgeons for this patient population.
Objective: To assess the incidence and oncologic impact of a non-therapeutic laparotomy for LAPC treated with (m)FOLFIRINOX induction chemotherapy.
Design: Retrospective cohort study
Setting: International multicenter study including patients from 5 referral centers in the USA and The Netherlands (2012-2019).
Participants: Patients diagnosed with pathology-proven LAPC treated with ≥1 cycle (m)FOLFIRINOX (± radiotherapy). Patients with metastatic disease on radiologic (re)staging or clinical deterioration during induction therapy were excluded. Patients undergoing non-therapeutic laparotomy (group A) were compared to those not explored (group B). Patients undergoing resection were assigned to group C.
Main outcomes and measures: 90-day mortality, palliative systemic treatment, and median OS from date of pathology-proven diagnosis.
Results: Overall, 663 patients with LAPC were included, of whom 78 (11.8%) subsequently received a second-line induction chemotherapy after (m)FOLFIRINOX and 413 (66.8%) received radiotherapy. In total, 67 patients (10.1%) were included in group A, 425 patients (64.1%) in group B, and 171 patients (25.8%) in group C. Resection was aborted in 28.2% (n=67/238) of all surgical explorations, commonly due to occult metastases (n=30/238, 12.6%). The 90-day mortality in group A was 3.0% (n=2/67). The proportion of patients receiving palliative therapy did not differ between groups A and B (65.9% vs. 73.1%; P=0.307). Median OS for groups A and B were 20.4 (95%CI; 15.9-27.3) and 20.2 (95%CI; 19.1-22.7) months respectively (P=0.752). Median OS in group C was 36.1 (95%CI; 30.5-41.2) months. Corresponding 3-year survival rates for all groups were 25.0%, 21.4% and 51.1%, respectively. Compared to unexplored patients, non-therapeutic laparotomy was not associated with reduced OS (HR=0.88 [95%CI 0.61-1.27]) in Cox regression analysis.
Conclusion and relevance: Even in experienced hands, about ¼ of surgically explored LAPC patient will remain unresectable. However, non-therapeutic laparotomy does not appear to substantially reduce short- and long-term outcomes compared to similar patients who are not explored.

Background

Long-term survival in patients with localized pancreatic adenocarcinoma (PDAC) or ampullary adenocarcinoma (AA) who undergo resection is rare, even in lymph node (LN)-negative disease. We aimed to assess the frequency of occult metastases (OM) in patients with resected PDAC or AA discovered with a detailed pathologic examination technique on LNs previously considered negative with conventional analysis. We also examined the association between OM and overall survival (OS).

Methods

Patients with LN-negative disease on conventional pathologic analysis following resection of PDAC or AA from 2010 to 2020 were identified from our institutional database, and those with available tissue for re-analysis were included. LNs were selected for re-examination based on proximity to the tumor and size. Original hematoxylin & eosin slides, three 4-micron-thick sections from deeper levels, and one pan-cytokeratin (AE1/AE3/PCK26) immunostain were examined for each block. The primary outcome was the frequency of OM. The secondary outcome was OS.

Results

A total of 598 LNs from 74 LN-negative patients (PDAC=71; AA=3) were re-examined in detail. A total of 49 patients (66.2%) underwent pancreatoduodenectomy, 17 (23.0%) underwent distal pancreatectomy/splenectomy, and 7 (10.8%) underwent total pancreatectomy. The median LN yield was 19. Sixteen patients (21.6%) had positive surgical margins, 18 (24.3%) had lymphovascular invasion, and 47 (63.5%) had perineural invasion. Twenty-six patients (35.1%) received neoadjuvant therapy and 35 (47.3%) received adjuvant chemotherapy.
On detailed LN analysis, 19 patients (25.7%) had OM. Of these, 9 OM (47.4%) were found only with immunohistochemistry but not on hematoxylin & eosin staining. The number of positive lymph nodes ranged from 1-3. On multivariable analysis, no clinicodemographic or pathologic factors were associated with OM.
The proportion of OM was 10.5% for patients with operative LN yields of <10 LNs, 42.0% for 10-19 LNs, 37.0% for 20-29 LNs, and 10.5% for ≥30 LNs. On conventional pathologic analysis, 3 patients (15.8%) had stage IA disease, 9 patients (26.5%) had stage IB disease, and 7 patients (36.8%) had stage IIA disease, all upstaged to stage IIB on detailed LN analysis.
On survival analysis, patients with OM had an associated decrease in OS as compared to those without OM (median OS: 22.3 vs. 50.5 months; HR=3.86, 95% CI: 1.53-9.78; Figure).

Conclusions

There is a high discordance rate between conventional and detailed LN pathologic analysis in resected PDAC and AA. The presence of OM is associated with worse OS. The high rate of occult nodal disease may in part explain poor survival outcomes in patients with node-negative disease.

Background. A wrong diagnosis of nature is common in pancreatic cystic neoplasms (PCNs). The aim of the current study is to reappraise the diagnostic errors for presumed PCNs undergoing surgery.
Methods. All pancreatic resections performed for presumed PCNs at the Verona Pancreas Institute between 2011 and 2020 were analyzed. “Misdiagnosis” was defined as the discrepancy between preoperative diagnosis of nature and final pathology. “Mismatch” was defined as the discrepancy between the preoperative suspect of malignancy (or its absence) and final pathology. Features considered suggestive for malignancy at preoperative work-up and at final pathology are described in Figure 1. Diagnostic errors considered “clinically relevant” implied a potential over- or under-treatment for the patient.
Results. A total of 601 patients were included. Endoscopic Ultrasound (EUS) was performed in 301 (50%) patients. Overall misdiagnosis and mismatch were 19% and 34%, respectively, with no significant benefit for those patients who underwent EUS. The highest rate of misdiagnosis was reached for cystic neuroendocrine tumors (61%) and the lowest for solid pseudopapillary tumors (6%). Several diagnostic errors had clinical relevance, including 7 (13%) presumed serous cystic neoplasms eventually found to be other malignant entities, 50 (24%) intraductal papillary mucinous neoplasms (IPMN) with high-risk stigmata (HRS) revealed to be non-malignant, and 38 (33%) IPMN without HRS revealed to be malignant at final pathology. A preoperative presumption of malignant mucinous cystic neoplasm was correct in only 20 (16%) patients (Table 1).
Conclusions. Despite not always clinically relevant, diagnostic errors are still common among resected PCNs when applying International Guidelines. New diagnostic tools beyond EUS are needed to refine diagnosis of those lesions at higher risk for unnecessary surgery or accidentally observed nevertheless being malignant.

Background: A standardized future liver remnant (sFLR) <30% and a kinetic growth rate (KGR) <2% are associated with increased risk of hepatic insufficiency and death from liver failure after hepatectomy. Here, we sought to identify clinicopathologic factors associated with inadequate sFLR and KGR to help predict which patients may not achieve sufficient hypertrophy with portal vein embolization (PVE) alone and inform selection for liver venous deprivation (LVD).

Methods: A prospectively maintained single institution database was evaluated for patients undergoing PVE between 1998 and 2020. Clinicopathologic variables, including age, sex, BMI, a known diagnosis of liver disease, diabetes, cycles of neoadjuvant chemotherapy, liver function tests, baseline sFLR, and extended PVE (segment 4 embolization) were evaluated for associations with sFLR and KGR.

Results: A total of 474 patients were identified who underwent right PVE and had both pre- and post-PVE volumetric assessments. Median patient age was 58 years (interquartile range [IQR] 49-66) and median BMI was 27kg/m² (IQR 25-30). The most common histology was metastatic colorectal cancer (66%) followed by hepatocellular carcinoma (12%) extrahepatic cholangiocarcinoma (7%), and intrahepatic cholangiocarcinoma (4%). Most patients (77%) received neoadjuvant chemotherapy prior to PVE (median 6 cycles [IQR 4-11]). Median baseline sFLR was 22% (IQR 16-29%). A sFLR >30% was achieved in 60% of patients following PVE, while KGR >2% was noted in 58%. 71% of patients ultimately underwent surgery, which involved right hepatectomy in 58% and extended right hepatectomy in 41%. Multiple logistic regression revealed that baseline sFLR (OR 1.39 [95% CI 1.30-1.50]) was predictive of post-PVE sFLR >30%. Extended PVE (OR 0.44 [95%CI 0.25-0.77]) and planned two-stage hepatectomy (OR 0.51 [95%CI 0.32-0.82]) were predictive of KGR <2%. ROC analysis revealed that a baseline sFLR ≥19 is 90% sensitive and 78% specific for sFLR >30% (AUC 0.92) (Figure).

Conclusions: Patients with a baseline sFLR <19% or those requiring extended hepatectomy may not achieve adequate hypertrophy with PVE alone. In this subset of patients, LVD should be considered to optimize hepatic regeneration.

Introduction. Microvascular invasion (MVI) is the main risk factor for overall mortality and recurrence after surgery for hepatocellular carcinoma (HCC). Its diagnosis can be made only postoperatively on the histological specimen. The aim of this preliminary study was to train machine-learning models to predict MVI on preoperative CT scan (fig.1).
Methods. Clinical data and 3-phases CT scans were retrospectively collected among 4 Italian centres. DICOM files were manually segmented to detect the liver and the tumor(s). An already available segmentation algorithm (Nnunet) was retrained to obtain automatic detection focused on HCC. An implementation was added to automatically extract radiomics features from the tumoral, peritumoral (among 5mm from the tumor margin) and healthy liver areas in each phase. Performance comparison between manual and algorithm segmentations was measured by intersection over union (Jaccard Index). Data obtained were explored and principal component analysis (PCA) was performed to reduce the dimensions of the dataset, keeping only the PC’s explaining 95% of the variability. After normalization, data were divided between training (70%) and test (30%) sets. Random-Forest (RF), fully connected MLP Artificial neural network (neuralnet) and extreme gradient boosting (XGB) models were fitted to predict MVI. Hyperparameters tuning was made per each model to reduce the out-of-bag error. Prediction accuracy was estimated in the test set and employed as the study end-point.
Results. Between 2008 and 2022, 218 consecutive preoperative CT scans of patients affected by HCC and submitted to surgery were collected with the relative clinical data. At the histological specimen, 72 (33.02%) patients had MVI. The Jaccard index between manual and algorithm segmentations was overall 90%. First and second order radiomics features were extracted, obtaining 672 variables per patient. After data exploration, PCA selected 58 dimensions explaining >95% of the variance. After standardization and normalization, RF, neuralnet and XGB were fitted to predict the presence of MVI. Tuning parameters were: 1) RF: n.tree=500, mtry=30; 2) Neuralnet: 2 hidden layer with 40 and 20 neurons, learning rate= 0.001, threshold for termination= 1%, activation function= sigmoid; 3) XGB: nrounds = 100, max_depth = 3, eta = 0.3. The models were then fitted in the testset to estimate prediction accuracy by confusion-matrix. RF was the best performer (Acc=98.4%, 95%CI: 0.91-0.99, Sens: 95.2%, Spec: 100%, PPV: 100% and NPV: 97.7%, fig.2).
Conclusion. Our model allowed an impressive prediction accuracy of the presence of MVI at the time of HCC diagnosis, never reached until now. This could lead to change the treatment allocation, the surgical extension and the follow-up strategy for those patients. The algorithm will be freely distributed online for medical purpose.

Introduction: There is a paucity of evidence supporting the use of adjuvant radiation therapy in resected biliary cancer. National guidelines recommend the consideration of use in patients with positive margins after resection, however, supporting evidence comes mainly from a phase II trial of 79 patients, SWOG S0809, which demonstrated that the use of adjuvant chemoradiation was well tolerated and resulted in an overall median survival of 35 months. We aimed to use a large national database to evaluate the use of adjuvant chemoradiation in resected extrahepatic bile duct and gallbladder cancer.

Methods: Using the National Cancer Database (NCDB), we selected patients from 2004-2017 with pT2-4, pN0-1, M0 extrahepatic bile duct or gallbladder adenocarcinoma with either R0 or R1 resection margins, and examined factors associated with overall survival using Cox proportional hazards model. We also examined overall survival in a subset of patients who received adjuvant chemo- and radiotherapy (CRT) using the Kaplan-Meier method and log rank test.

Results: Overall, 4,997 patients with gallbladder or extrahepatic adenocarcinoma with available survival information meeting the SWOG S0809 criteria were selected from the NCDB, 469 of whom received both adjuvant chemo- and radiotherapy. Of the CRT cohort, all patients received multi-agent chemotherapy, 211 (45.0%) had extrahepatic cholangiocarcinoma and 258 (55.0%) had gallbladder cancer, the majority were pT3 (n=281, 59.9%), pN1 (n=323, 68.9%), and had an R0 resection (n=387, 82.5%). Median overall survival in patients undergoing CRT was 36.9 months, and was not different between primary sites (p=0.841). Patients with a R1 margin had abbreviated overall survival compared to patients with an R0 resection (41.8 months vs 24.1 months, p<0.001). On multivariable cox regression analysis of all patients who underwent resection agnostic to adjuvant therapy, age, insurance status, Charlson-Deyo comorbidity index, T-stage, N-stage, lymphovascular invasion, margin status, chemo- and radiotherapy were all associated with overall survival. Adjuvant chemoradiation compared to chemotherapy alone showed an overall survival benefit for patients with either R0 (41.8 vs 30.8 months, p<0.001) or R1 (24.1 vs 20.2 months, p<0.001) resections.

Conclusion: Using a large national database, our data validates the findings of SWOG S0809 with a similar median overall survival in patients receiving chemoradiation. Patients receiving CRT had improved overall survival compared to patients receiving chemotherapy only after both R0 and R1 resections. These data further support the consideration of adjuvant multi-modal therapy in resected biliary cancers, regardless of margin status.

Background: Although enhanced recovery pathways (ERPs) have been established as safe and effective care strategies in hepatobiliary surgery, compliance with ERP components may or may not be correlated with outcomes such as length of stay (LOS).

Methods: Variables for a cohort of hepatectomy patients on our previously published risk-stratified post-hepatectomy pathways (RHPSPs) were prospectively collected (6/14/22 to 11/18/22). Compliance with pathway components, reasons for deviations, and 90-day postoperative outcomes were prospectively reviewed by one faculty and three advanced practice providers biweekly and compared with index hospitalization LOS.

Results: Among 103 patients, 11 (10.7%) were on the minimally invasive (MIS) pathway with median LOS 2 days (interquartile range, IQR 1-2), 39 (37.9%) were low-intermediate risk pathway with median LOS 3 days (IQR 3-4), 27 (26.2%) were high-risk pathway with median LOS 4 days (IQR 3-5), and 26 (25.2%) were combination operations with median LOS 5 days (4-6). The goal LOS was 2-3 days for low-intermediate risk patients and 3-4 days for high-risk patients. Pathway compliance was perfect for 56 patients (54%); the remaining 47 patients had at least one instance of pathway deviation (46%). By pathway, only 1 (9%) MIS patient, 16 (41%) low-intermediate risk patients, 13 (48%) high-risk patients and 17 (65%) combination surgery patients experienced a pathway deviation (p=0.015). Patients with at least one pathway deviation had an increased median LOS compared to those with perfect compliance (LOS 5 [IQR 4-6] vs. LOS 3 [IQR 2-3.5], p=0.018).

Linear regression demonstrated postoperative compliance factors associated with increasing LOS included postoperative days until advancement to solid food (coefficient 1.86, 95% confidence interval [CI] 1.1-2.6), p<0.001), days until solid food was tolerated for 24 hours (coefficent 1.6, 95% CI 0.7-2.6, p=0.002), and days to complete conversion to oral medications (coefficent 0.82, 95% CI 0.02-1.6, p=0.045). Other traditional compliance factors, including simply clear liquid diet tolerance, discontinuation of intravenous fluids (but not all intravenous medications), bladder catheter removal, and return of flatus, were not associated with reduced LOS (all p>0.30).

Conclusions: Despite imperfect compliance, median LOS for patients treated with risk-stratified post-hepatectomy pathways remains favorable for both low-intermediate and high-risk patients. Combination operations require further optimization and process improvements to identify barriers to pathway compliance and better outcomes. Focusing on the straightforward goals of solid food and oral medications may be associated with expedited discharge after hepatectomy.

Background
The timing to surgery for acute cholecystitis (AC) remains variable, ranging anywhere from early (<7 days) to delayed surgery (>7 days). Accelerated surgery for AC may result in better outcomes by reducing patient exposure to inflammatory, hypercoagulable, and stress states. We undertook a pilot trial to determine the feasibility of providing accelerated care (i.e., surgery within 6 hours of diagnosis) compared to standard care among patients with calculus AC.

Methods
Adult patients with AC requiring surgery were randomized to receive accelerated surgery or standard care. The primary feasibility outcome included recruitment of 1 patient per site per month, ≥95% follow-up at 90 days, and determining timelines of accelerated surgery. The secondary outcome was a composite of major perioperative complications (all-cause mortality, reinterventions and reoperations, various intra- and post-operative complications, cardiovascular events, venous thromboembolism, bleeding) within 90 days of randomization. Other outcomes included individual components of the composite, length of hospital stay, readmissions, surgery duration, and feasibility of drawing preoperative point-of-care N-terminal-pro hormone BNP (NT-proBNP) in ≥90% of patients. Analysis included descriptive statistics and cox proportional hazards models to calculate hazard ratios (HR) and 95% confidence interval (CI) for outcomes with time to event data.

Results
Sixty patients were randomly assigned to accelerated surgery (N=31) and standard care (N=29) across 4 Canadian hospitals. There was ≥1 patient recruited per site per month. All patients completed 90 day follow up. The median time and interquartile range (IQR) from diagnosis to surgery in the accelerated arm was 5.8 [4.4-11.1] hours versus 20.3 [6.8-26.8] hours in the standard care arm. A major perioperative complication occurred in 9/31 (29.0%) patients in the accelerated and 4/29 (13.8%) patients in the standard care arm (HR 2.42, 95% CI 0.74-7.91). The main contribution was from 5/31 (16.1%) versus 1/29 (3.4%) post-operative endoscopic retrograde cholangiopancreatography performed in the accelerated versus standard care arm, respectively (HR 5.11, 95% CI 0.60-43.9). Of note, 4/31 and 3/29 patients in the accelerated and standard care groups underwent intraoperative cholangiogram. Between both groups, there were no differences in surgery duration (mean (standard deviation): 86.8 (30.0) vs. 86.4(32.3) minutes), length of hospital stay (median [IQR]: 2.0 [1.0-3.0] vs. 2.0 [2.0-3.0] days), readmissions (2/31 vs. 4/29), or cardiovascular events (2/31 vs. 1/29). Preoperative NT-proBNP was drawn in 57/60 (95.0%) patients.

Conclusion
These results demonstrate the feasibility of a trial comparing accelerated and standard care among patients requiring surgery for AC and supports a definitive trial.

Background: For patients with synchronous liver metastases (LM) from rectal cancer, 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. Larger LM, BRAF mutation, and TP53 mutation were independently associated with worse overall survival (OS) (p = 0.001, 0.001 and 0.048, respectively). Although 35% of reverse-approach patients did not undergo primary tumor resection, OS did not differ between groups (Figure 1), and 82% of reverse-approach patients 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).
Conclusion: The reverse approach results in survival similar to that with the combined and classic approaches and may obviate primary rectal tumor resections and diversions that do not improve oncologic outcome but affect quality of life. RAS/TP53 co-mutation is associated with lower rate of completion of the reverse approach.

Introduction: The proportion of women surgeons is steadily increasing, although the number of women in surgical leadership and research has not. The Society for Surgery of the Alimentary Tract (SSAT), a global association of academic gastrointestinal surgeons, pledged its commitment to diversity and inclusion with the creation of a task force and diversity symposium in 2016. Our study sought to evaluate the temporal trend of gender representation in leadership and research presented at SSAT.
Methods: Publicly available SSAT meeting programs from 2010-2022 were reviewed to assess gender proportions within leadership positions (officers and committee chairs), invited speakerships moderators and speakers, clinical symposium moderators and speakers, committee panel session moderators and speakers, and contributions to scientific sessions (moderator, first author and senior author). Verified individual professional profiles (eg, LinkedIn, Doximity, affiliate institution websites) were analyzed to categorize gender as women, men, or not available. Identification of sex was deferred. Descriptive and trend analyses using linear regression and chi-squared testing were performed.
Results: A total of 5,493 individuals were reviewed, of which 1,182 (21.5%) were identified as women and 4,113 (74.7%) as men. 209 (3.8%) did not have an available gender profile. The trend in total women participation is demonstrated in Figure 1 with an increase of 1.04% per year (R²=0.81), comparable to published US trend on active women surgeons. There was a statistically significant difference in the total proportion of women engagement before and after the task force creation in 2016 (18.6% vs 27.1%, p<0.0001), although the increase was 1.93% per year (R²=0.96) prior to 2016 compared to 1.15% (R²=0.64) after. When analyzed by category, annual increases in the proportion of women were demonstrated in: leadership (2.22%, R²=0.50), invited speakerships (2.11%, R²=0.46), invited speakerships moderators (1.35%, R²=0.16 ), clinical symposium moderator (1.25%, R²=0.37), clinical symposium speaker (2.09%, R²=0.63), committee panel session moderator (2.81%, R²=0.25), scientific session moderators (1.06%, R²=0.25), There was no increase seen in committee panel session speakers (0.51%, R²=0.01). 1,595 abstracts were reviewed, with an increase in proportion of first author (1.18%, R²=0.42), but no change in the proportion of women senior author (0.02%, R²=0.00).
Conclusion: There has been an encouraging upward trajectory in women participation at SSAT over the past 13 years. However, if persistent at the current trend, gender parity will not be attained until 2044. Active promotion of gender diversity through creation of a task force or annual diversity symposium, as modeled by SSAT, is an effective tool to improve gender parity, but substantial opportunity for improvement remains.

Introduction
Toupet fundoplication (TF) has been shown to have fewer adverse effects compared to Nissen fundoplication (NF), however, it is unknown whether the advantages of TF persist when comparing outcomes by the distensibility of post-fundoplication lower esophageal sphincter (LES). Therefore, we aimed to compare quality of life (QOL) outcomes between NF and TF according to distensibility index (DI) measured by intraoperative endoluminal impedance planimetry.

Methods
This is a retrospective study of a prospectively maintained database of patients who underwent laparoscopic NF or TF, intraoperative EndoFLIP, and self-reported QOL outcomes postoperatively at 3-weeks, 6-months, 1-year, and 2-years using RSI, GERD-HQRL, and dysphagia surveys. Comparisons were made using chi-square and Wilcoxon rank-sum tests.

Results
From 2018 to 2021, 303 patients were analyzed (68% female) who underwent NF (n=80) and or TF (n= 223) for treatment of GERD, including paraesophageal hernia which represented 65% of cases. Of those who returned postoperative surveys, at 30mL fill-volumes, there were a total of 20 NF versus 25 TF with DI <2.0mm²/mmHg, 32 NF versus 71 TF with DI 2.0-3.5mm²/mmHg, and 13 NF versus 89 TF with DI>3.5 mm²/mmHg. At the optimal DI range of 2.0-3.5 mm²/mmHg at 30mL fill, no statistical differences were found on analysis at 3-weeks, 6-months, 1-year, and 2-year timepoints when evaluating RSI, GERD HQRL, gasbloat, and dysphagia scores. No statistical differences were found on QOL comparisons of NF versus TF within DI ranges <2.0mm²/mmHg or DI> 3.5mm²/mmHg at any timepoint (Table 1). At 40ml fill volume, there was a total of 20 NF versus 25 TF at DI < 2.0mm²/mmHg, 32 NF versus 71 TF with DI 2.0-3.5 mm²/mmHg, and 13 NF versus 89 TF at DI >3.5 mm²/mmHg. Analysis of postoperative surveys demonstrated no statistical differences when comparing RSI, GERD-HQRL, gasbloat and dysphagia scores of NF versus TF according to DI range <2.0mm²/mmHg, 2.0-3.5mm²/mmHg (Figure 1), or >3.5mm²/mmHg at any postoperative timepoint.

Conclusion
Impedance planimetry appears to be an objective measure of the physiology of the LES before, during, and after fundoplication. NF is comparable to TF when compared according to DI range, suggesting that QOL outcomes are dependent on post-fundoplication LES distensibility rather than type of fundoplication.

Introduction: Social risk factors impact the diagnosis, management and survival of patients with hepatocellular carcinoma (HCC). This is relevant as the incidence of HCC increases nationally, particularly among non-white, immigrant patients, yet receipt of treatment and overall outcomes for HCC continue to have disparities based on race, ethnicity, and socioeconomic status. We evaluated the relationship between social determinants of health and presentation, treatment and survival of patients with HCC at an urban, safety-net hospital.
Methods: A single institution retrospective chart review of patients with all stages of HCC from January 2009 through May 2019 was conducted. Demographic, disease, and treatment characteristics were obtained. Chi-square and Wilcoxon tests were used for categorical and continuous variables, respectively. Univariate analysis was used to evaluate stage at presentation, receipt of intervention (resection, ablation, TACE), receipt of systemic therapy and median overall survival. Survival between stage at diagnosis was compared using Kaplan-Meier methods.
Results: 388 patients with HCC were identified; median age was 61 years and 83.2% were male. Patients had an overall similar sociodemographic distribution for presentation of early versus late disease. However, commercial insurance status resulted in diagnosis at earlier stage (24.7% early stage vs 13.3% late stage; p=0.014) while safety-net/no insurance was a significant risk factor for advanced presentation at diagnosis (9.9% early stage vs 17.6% late stage; p=0.014). Higher level of education (high school and above) was associated with increased intervention for all stages of disease (70.1% vs no education/unknown 29.9%; p=0.048) as was origin of mainland USA (60.3% vs other countries/unknown 39.7%; p=0.018). No sociodemographic differences were seen for receipt of treatment, intervention or systemic therapy, for patients with early stage disease. Patients with late stage disease who had a higher level of education were more likely to receive intervention (73.0% vs no education/unknown 27.0%; p = 0.049). Receipt versus lack of systemic therapy was associated with employment status (unemployed/unknown 40.3% vs 17.5%; retired 40.3% vs 65.0%, employed 19.4% vs 17.5%; p=0.002). Median survival was not impacted by any examined sociodemographic factors.
Conclusion: Despite clear evidence of disparities in the diagnosis and care of patients with HCC in the literature, our data show that an urban academic safety net hospital is able to mitigate the impact of social determinants of health for these patients. Urban safety-net hospitals with a focus on vulnerable patient populations are able to provide outcomes on par with those seen on the national level and should serve as a care system model to address disparities in HCC care.

BACKGROUND:
Post-pancreatoduodenectomy patients at our institution are managed on risk-stratified pancreatectomy care pathways preoperatively determined by risk of clinically relevant postoperative pancreatic fistula (CR-POPF). We previously published cut-off ranges for drain fluid amylase on postoperative day (POD) 1 (DFA1) and POD 3 (DFA 3) to encourage timely drain removal. The aim of this study was to validate and recalibrate our cut-off values using a prospective cohort of patients managed immediately after implementing those DFA thresholds.

METHODS:
We performed a single-institution prospective cohort study of consecutive patients who underwent pancreatoduodenectomy from DFA1/DFA3 threshold implementation in February 2019 to April 2022. Ninety-day postoperative complications were prospectively graded and reported according to the ACCORDION system and International Study Group on Pancreatic Surgery definitions. Patient characteristics, perioperative details, and DFA1/DFA3 (measured in U/L) were compared between care pathways. Receiver Operating Characteristic (ROC) curve analysis was performed to determine optimal cut-off values based on preoperative risk stratification.

RESULTS:
In total, 267 patients underwent 228 (85%) open and 39 (15%) robotic procedures, with 173 (65%) patients stratified into low-risk and 94 (35%) into high-risk pathways. Seven (4%) low-risk patients and 21 (22%) high-risk patients developed CR-POPF. Of 147 patients with drains removed before/on POD3, only 1 (0.7%) developed CR-POPF in the prospective cohort recalibration. CR-POPF was excluded with 100% sensitivity if DFA1 <286 (area under curve, AUC=0.893, p=0.001) or DFA3 <97 (AUC=0.856, p=0.002) in low-risk patients. DFA1 <137 (AUC=0.786, p<0.001) or DFA3 <56 (AUC=0.819, p<0.001) were 100% sensitive in ruling out CR-POPF in high-risk patients. Our previous DFA1 cut-offs of 100 in low-risk patients and <26 in high-risk patients were 100% sensitive, while our DFA3 cut-offs of 300 (low-risk) and 200 (high-risk) had 57% and 91% sensitivity.

CONCLUSION:
Risk-stratified post-pancreatoduodenectomy DFA thresholds can effectively and safely guide early POD1/POD3 drain removal. Previously identified cut-off values appear overly restrictive for DFA1 and overly liberal for DFA3. As a learning health system, we further propose recalibrating our drain removal thresholds to DFA1 ≤300, DFA3 ≤100 in low-risk patients and DFA1 ≤100, DFA3 ≤50 in high-risk patients. This methodology can be implemented at other centers to develop institution-specific criteria for early drain removal.

Introduction:
Leaks of the gastrointestinal tract are a devastating complication that can occur after foregut operations. It has been suggested that the pathogenesis of foregut leaks is directly influenced by the gut microbiome. The purpose of this study was to evaluate the composition of the microbiome within and between patients with gastrointestinal leaks to better understand the pathogenesis of these leaks.

Methods:
Patients undergoing interventions for gastrointestinal leaks from October 2021 to October 2022 were included in this study. During endoscopic and surgical interventions for gastrointestinal leaks, both microbial and host samples were collected. Genomic DNA of microbial samples were extracted and amplified. PCR products were sequenced using Illumina Nextera protocol. Effective sequence of bacterial 16S-rRNA gene was clustered into OTUs for analysis.

Results:
A total of 196 samples were collected from 16 patients (13 females; 3 males) with 49 samples used for the 16S analysis. The majority (56.2%) of patients required multiple interventions for their leaks, while a smaller portion (43.8%) underwent a single intervention. 42/49 samples (85.7%) included in the 16S analysis were from patients requiring multiple interventions with a mean of 4.6 interventions performed per patient in this group. In the entire cohort, Firmicutes was consistently the most abundant bacteria present. For patients that required multiple interventions, the microorganism composition changed over the course of treatment. At the index procedure, Firmicutes and Actinobacteria were on average the most abundant phyla present. By the end of treatment, Firmicutes remained dominant. However, abundances of Bacteroidetes and Proteobacteria increased, and the abundance of Actinobacteria decreased. Notably, there was a significant reduction in the Firmicutes to Bacteroidetes ratio by the end of treatment. In one patient who was not progressing well clinically, they were noted to have an increase in their Firmicutes to Bacteroidetes ratio and a much higher abundance of Proteobacteria when compared to other patients.

Conclusions:
In conclusion, data from our study indicates that the Firmicutes to Bacteroidetes ratio of the gut microbiome significantly changed throughout the treatment of gastrointestinal leaks. A better understanding of this ratio and its role in gastrointestinal leaks could allow for more effective prevention and treatment strategies.

Introduction: Existing human studies have shown conflicting effects of bariatric surgery on colorectal cancer (CRC) risk[1] [2]. These equivocal findings are likely due in part to the heterogeneity of CRC. We have previously found that sleeve gastrectomy (SG) leads to increased colonic tumor growth in a mouse model of colitis-associated cancer, but the effect of SG on genetic CRC syndromes such as Familial Adenomatous Polyposis (FAP) remains unknown. In the murine analogue of FAP, mice with a mutated Adenomatous Polyposis Coli (APC) allele, known as APC^Min, develop gastrointestinal (GI) tumors predominantly in the small bowel. Here we examine the effects of SG on tumor formation in APC^Min mice.

Methods: Thirty 12-week-old C57BL/6J-APC^Min mice were randomized to SG (n=18) or sham (n=12) operation. Five days postoperatively, the mice were begun on a high-fat diet to promote tumor formation. Mice were weighed daily for the first postoperative week and then at three-to-four day intervals until sacrifice 25 days after surgery. At sacrifice, tumors were counted in the colon and proximal, mid, and distal small bowel, and tumor numbers in SG and sham mice were compared using t-tests. Small bowel samples were analyzed for mRNA expression of five cytokines: IL-1b, IL-6, IL-23, IL-33, and TNFa. Additionally, RNA sequencing (RNA-Seq) was performed on colonic tissue to identify transcriptional differences between SG and sham mice.

Results: SG mice developed significantly fewer GI tumors than sham mice (10.9 vs 21.3; p < 0.0001; Figure 1A) with fewer tumors in the mid small bowel (1.7 vs 5.5; p < 0.0001; Figure 1B) and distal small bowel (6.8 vs 12.8; p < 0.01; Figure 1B). TNFa expression was significantly lower in SG mice while IL-1b, IL-6, and IL-23 trended lower. RNA-Seq showed upregulation of 209 genes and downregulation of 107 genes in SG mice compared to sham mice, and transcriptional pathway analysis demonstrated decreased expression of major histocompatibility complex (MHC) class I associated genes in SG mice compared to sham mice.

Conclusions: SG protects against APC-related tumors. SG is associated with a reduction in intestinal inflammatory cytokines and MHC class I pathways, highlighting a potential role of cell-mediated immunity in tumor control after SG.




[1] Bailly L, Fabre R, Pradier C, Iannelli A. Colorectal Cancer Risk Following Bariatric Surgery in a Nationwide Study of French Individuals With Obesity. JAMA Surg. 2020;155(5):395–402. doi:10.1001/jamasurg.2020.0089

[2] Tao, W., Artama, M., von Euler-Chelpin, M., Hull, M., Ljung, R., Lynge, E., Ólafsdóttir, G.H., Pukkala, E., Romundstad, P., Talbäck, M., Tryggvadottir, L. and Lagergren, J. (2020), Colon and rectal cancer risk after bariatric surgery in a multicountry Nordic cohort study. Int. J. Cancer, 147: 728-735. https://doi.org/10.1002/ijc.32770