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Background Limited data from small series have suggested that brain metastases from biliary tract cancers (BrM-BTC) affect ≤2% of patients with BTC. We sought to review our experience with patients with BrM-BTC and to identify associations of tumor-related molecular alterations with outcomes. Materials and Methods A retrospective review of patients with BTC seen at a tertiary referral center from 2005 to 2021 was performed; patients with BrM-BTC were identified, and clinical and molecular data were collected. Results Twenty-one of 823 patients with BTC (2.6%) developed BrM. For patients with BrM-BTC, median follow-up time was 27.9 months after primary BTC diagnosis and 3.1 months after BrM diagnosis. Median time from primary diagnosis to diagnosis of BrM was 14.4 [range, 1.1-66.0] months. Median overall survival (OS) from primary diagnosis was 31.5 [2.9-99.8] months and median OS from BrM diagnosis was 4.2 [0.2-33.8] months. Patients who underwent BrM-directed therapy trended toward longer OS following BrM diagnosis than patients receiving supportive care only (median 6.5 vs 0.8 months, P = .060). The BrM-BTC cohort was enriched for BRAF (30%), PIK3CA (25%), and GNAS (20%) mutations. patients with BrM-BTC with BRAF mutations trended toward longer OS following BrM diagnosis (median 13.1 vs 4.2 months, P = .131). Conclusion This is the largest series of patients with BrM-BTC to date and provides molecular characterization of this rare subgroup of patients with BTC. Patients with BrM-BTC may be more likely to have BRAF mutations. With advances in targeted therapy for patients with BTC with actionable mutations, continued examination of shifting patterns of failure, with emphasis on BrM, is warranted.

Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) colorectal cancer, increased TGFβ signaling results in exclusion of antitumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGFβRII receptor (“TGFβ trap”) and anti-PD-L1 antibody. Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1,200 mg of BA intravenously every 14 days for six doses. The primary endpoint was ctDNA clearance. Radiographic characteristics at recurrence were compared using independent t tests to historical data from a similar cohort of patients with liver-limited mCRC who underwent observation. Only 4 of 15 planned patients received BA before the study was stopped early for loss of equipoise. There was no grade ≥3 adverse event. None of the patients cleared ctDNA. All patients developed radiographic recurrence by the first planned restaging. Although not detectable at prior to treatment, TGFβ3 was found in circulation in all patients at cycle 2 day 1. Compared with a historical cohort, patients administered BA developed more metastases (15 vs. 2, P = 0.005) and greater tumor volumes (9 cm vs. 2 cm, P = 0.05). Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific complexity of dual TGFβ and PD-L1 inhibition. Significance: Use of ctDNA to identify patients with micrometastatic disease for therapeutic intervention is feasible. Treatment with BA in patients with liver-limited mCRC and with detectable ctDNA after resection generated rapid progression. Approaches targeting TGFβ signaling must consider its pathway complexity in future immunotherapy combination strategies.

Neoadjuvant therapy (NAT) is increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). Patients with PDAC often show heterogenous responses to NAT with variable clinical outcomes, and the clinicopathologic parameters associated with these variable outcomes remain unclear. In this study, we systematically examined the clinicopathologic characteristics of 60 short-term survivors (overall survival < 15 months) and 149 long-term survivors (overall survival > 60 months) and compared them to 352 intermediate-term survivors (overall survival: 15–60 months) of PDAC who received NAT and pancreatoduodenectomy. We found that the short-term survivor group was associated with male gender (p = 0.03), tumor resectability prior to NAT (p = 0.04), poorly differentiated tumor histology (p = 0.006), more positive lymph nodes (p = 0.04), higher ypN stage (p = 0.002), and higher positive lymph node ratio (p = 0.03). The long-term survivor group had smaller tumor size (p = 0.001), lower ypT stage (p = 0.001), fewer positive lymph nodes (p < 0.001), lower ypN stage (p < 0.001), lower positive lymph node ratio (p < 0.001), lower rate of lymphovascular invasion (p = 0.001) and perineural invasion (p < 0.001), better tumor response grading (p < 0.001), and less frequent recurrence/metastasis (p < 0.001). The ypN stage is an independent predictor of both short-term and long-term survivors by multivariate logistic regression analyses. In addition, tumor differentiation was also an independent predictor for short-term survivors, and tumor response grading and perineural invasion were independent predictors for long-term survivors. Our results may help to plan and select post-operative adjuvant therapy for patients with PDAC who received NAT and pancreatoduodenectomy based on the pathologic data.

OBJECTIVES: 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 (OME) were reviewed for pancreatectomy patients treated with IV-PCA at a single institution before and after (3/2016–8/2017 vs. 3/2019–11/2020) implementation of a standardized initial IV-PCA dosing regimen (initial limit 0.1mg hydromorphone, or 1mg OME, every 10 min as needed). IV-PCA OME in the first 24 hours and total inpatient OME were compared between cohorts. RESULTS: Of 220 total patients, 132 were in the pre-standardization historical cohort. First-24-hour IV-PCA use was different (pre-standardization median 95mg vs. post-standardization 15mg, p

Supplemental Figure S1

Supplemental Table S4

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC.Significance:To improve the efficacy of immunotherapy in PDAC, there is a great need to understand the PDAC TIL landscape. This study represents a reference of PDAC TIL subpopulations and their relationships and provides a foundation upon which to base future immunotherapeutic efforts.This article is highlighted in the In This Issue feature, p. 2221

Identification of circulating tumor DNA (ctDNA) following curative intent therapies is a surrogate for microscopic residual disease for patients with metastatic colorectal cancer (mCRC). Preclinically, in micrometastatic microsatellite stable (MSS) colorectal cancer, increased TGFβ signaling results in exclusion of antitumor cytotoxic T cells from the tumor microenvironment. Bintrafusp alfa (BA) is a bifunctional fusion protein composed of the extracellular domain of the TGFβRII receptor (“TGFβ trap”) and anti-PD-L1 antibody. Patients with liver-limited, MSS mCRC and with detected ctDNA after complete resection of all known tumors and standard-of-care therapy were treated with 1,200 mg of BA intravenously every 14 days for six doses. The primary endpoint was ctDNA clearance. Radiographic characteristics at recurrence were compared using independent t tests to historical data from a similar cohort of patients with liver-limited mCRC who underwent observation. Only 4 of 15 planned patients received BA before the study was stopped early for loss of equipoise. There was no grade ≥3 adverse event. None of the patients cleared ctDNA. All patients developed radiographic recurrence by the first planned restaging. Although not detectable at prior to treatment, TGFβ3 was found in circulation in all patients at cycle 2 day 1. Compared with a historical cohort, patients administered BA developed more metastases (15 vs. 2, P = 0.005) and greater tumor volumes (9 cm vs. 2 cm, P = 0.05). Treatment with BA in patients with ctDNA-detected, liver-limited mCRC did not clear ctDNA and was associated with large-volume recurrence, highlighting the potential context-specific complexity of dual TGFβ and PD-L1 inhibition.Significance:Use of ctDNA to identify patients with micrometastatic disease for therapeutic intervention is feasible. Treatment with BA in patients with liver-limited mCRC and with detectable ctDNA after resection generated rapid progression. Approaches targeting TGFβ signaling must consider its pathway complexity in future immunotherapy combination strategies.

Supplementary Table from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer

Supplementary Figure from Single-Cell Sequencing Reveals Trajectory of Tumor-Infiltrating Lymphocyte States in Pancreatic Cancer

Purpose:Somatic gene mutations have been increasingly recognized to impact prognosis following resection of colorectal liver metastases (CLM). We aimed to determine the impact of combinations of somatic mutations on survival in patients undergoing CLM resection.Experimental Design:We identified patients who underwent initial CLM resection during 2007–2017 and had genetic sequencing data available. Risk factors for overall survival (OS) and recurrence-free survival (RFS) were determined using Cox proportional hazards models.Results:Of 1460 patients who underwent CLM resection during the study period, 507 met the inclusion criteria. Multigene testing revealed mutation rates greater than 10% for TP53 (mutated in 70.8% of patients), APC (53.5%), RAS (50.7%), PIK3CA (15.8%), and SMAD4 (11.0%). BRAF was mutated in 2.0% of patients. BRAF, RAS, TP53, and SMAD4 mutations were significantly associated with OS, and RAS, TP53, and SMAD4 mutations were significantly associated with RFS. Coexisting mutations in RAS, TP53, and SMAD4 were associated with significantly worse OS and RFS than coexisting mutations in any 2 of these genes and mutations in 1 or none of these genes. Coexisting mutations in 2 genes conferred significantly worse OS and RFS than single mutation or no mutations. OS and RFS did not differ significantly between patients with RAS mutation and wild-type TP53 and SMAD4 and patients with wild-type RAS (P = 0.858 and 0.729, respectively).Conclusions:RAS mutation status alone is not sufficient for precisely predicting prognosis after CLM resection.

Supplementary Figure 3. Overall survival (OS) and recurrence-free survival (RFS) by RAS mutation status.

Supplementary Figure description

Supplementary Figure 1. Patient selection

Supplementary Figure 4. Overall survival (OS) by RAS, TP53, and SMAD4 mutation status in 313 patients with unresectable colorectal metastases.

Supplementary Table 1. Genes and codon tested for adequate amplicons Supplementary Table 2. Multivariable hazard ratios (HRs) for OS and RFS by RAS mutation status in 507 patients Supplementary Table 3. Demographic and clinicopathologic characteristics of 313 patients with unresectable colorectal metastases.

Recent studies defined a potentially important role of the microbiome in modulating pancreatic ductal adenocarcinoma (PDAC) and responses to therapies. We hypothesized that antibiotic usage may predict outcomes in patients with PDAC. We retrospectively analyzed clinical data of patients with resectable or metastatic PDAC seen at MD Anderson Cancer from 2003 to 2017. Demographic, chemotherapy regimen and antibiotic use, duration, type, and reason for indication were recorded. A total of 580 patients with PDAC were studied, 342 resected and 238 metastatic patients, selected retrospectively from our database. Antibiotic use, for longer than 48 hrs, was detected in 209 resected patients (61%) and 195 metastatic ones (62%). On resectable patients, we did not find differences in overall survival (OS) or progression‐free survival (PFS), based on antibiotic intake. However, in the metastatic cohort, antibiotic consumption was associated with a significantly longer OS (13.3 months vs. 9.0 months, HR 0.48, 95% CI 0.34–0.7, p = 0.0001) and PFS (4.4 months vs. 2 months, HR 0.48, 95% CI 0.34–0.68, p =, We have analyzed the effect of antibiotics’ intake on two cohorts of patients with pancreatic adenocarcinoma, resectable, and metastatic. We have found that on the metastatic cohort, antibiotics use was significantly associated with better outcomes, particularly, on patients that received gemcitabine based‐chemotherapy as the first line.

Pancreatic ductal adenocarcinoma (PDAC) has few effective treatments. Immunotherapy, an attractive alternative strategy, remains challenging with the lack of knowledge on the tumor-infiltrating lymphocyte (TIL) landscape in PDAC. To generate a reference of T-cell subpopulations, we profiled 80,000 T cells from 57 PDAC samples, 22 uninvolved/normal samples, and cultured TIL using single-cell transcriptomic and T-cell receptor analysis. These data revealed 20 cell states and heterogeneous distributions of TIL populations. The CD8+ TIL contained a putative transitional GZMK+ population based on T-cell receptor clonotype sharing, and cell-state trajectory analysis showed similarity to a GZMB+PRF1+ cytotoxic and a CXCL13+ dysfunctional population. Statistical analysis suggested that certain TIL states, such as dysfunctional and inhibitory populations, often occurred together. Finally, analysis of cultured TIL revealed that high-frequency clones from effector populations were preferentially expanded. These data provide a framework for understanding the PDAC TIL landscape for future TIL use in immunotherapy for PDAC. Significance: To improve the efficacy of immunotherapy in PDAC, there is a great need to understand the PDAC TIL landscape. This study represents a reference of PDAC TIL subpopulations and their relationships and provides a foundation upon which to base future immunotherapeutic efforts. This article is highlighted in the In This Issue feature, p. 2221

Neoadjuvant FOLFIRINOX and gemcitabine/nab-paclitaxel (GemNP) therapies are increasingly used to treat patients with pancreatic ductal adenocarcinoma (PDAC). However, limited data are available on their clinicopathologic prognosticators. We examined the clinicopathologic factors and survival of 213 PDAC patients who received FOLFIRINOX with 71 patients who received GemNP. The FOLFIRINOX group was younger (p < 0.01) and had a higher rate of radiation (p = 0.049), higher rate of borderline resectable and locally advanced disease (p < 0.001), higher rate of Group 1 response (p = 0.045) and lower ypN stage (p = 0.03) than the GemNP group. Within FOLFIRINOX group, radiation was associated with decreased lymph node metastasis (p = 0.01) and lower ypN stage (p = 0.01). The tumor response group, ypT, ypN, LVI and PNI, correlated significantly with both DFS and OS (p < 0.05). Patients with the ypT0/T1a/T1b tumor had better DFS (p = 0.04) and OS (p = 0.03) than those with ypT1c tumor. In multivariate analysis, the tumor response group and ypN were independently prognostic factors for DFS and OS (p < 0.05). Our study demonstrated that the FOLFIRINOX group was younger and had a better pathologic response than the GemNP group and that the tumor response group, ypN, ypT, LVI and PNI, are significant prognostic factors for survival in these patients. Our results also suggest that the tumor size of 1.0 cm is a better cut off for ypT2. Our study highlights the importance of systemic pathologic examination and the reporting of post-treatment pancreatectomies.

ObjectivesTumor size measurement is critical for accurate tumor staging in patients with pancreatic ductal adenocarcinoma (PDAC). However, accurate tumor size measurement is challenging in patients who received neoadjuvant therapy before resection, due to treatment-induced fibrosis and tumor invasion beyond the grossly identified tumor area. In this study, we evaluated the correlation between the tumor size and tumor volume measured on post-therapy computed tomography (CT) scans and the pathological measurement. Also, we investigated the correlation between these measurements and clinicopathological parameters and survival.Materials and methodsRetrospectively, we evaluated 343 patients with PDAC who received neoadjuvant therapy, followed by pancreaticoduodenectomy and had pre-operative pancreatic protocol CT imaging. We measured the longest tumor diameter (RadL) and the radiological tumor volume (RadV) on the post-therapy CT scan, then we categorized RadL into four radiologic tumor stages (RTS) based on the current AJCC staging (8th edition) protocol and RadV based on the median. Pearson correlation or Spearman's coefficient (δ), T-test and ANOVA was used to test the correlation between the radiological and pathological measurement. Chi-square analysis was used to test the correlation with the tumor pathological response, lymph-node metastasis and margin status and Kaplan-Meier and Cox-proportional hazard for survival analysis. P-value < 0.05 was considered significant.ResultsAs a continuous variable, RadL showed a positive linear correlation with the post-therapy pathologic tumor size in the overall patient population (Pearson correlation coefficient: 0.72, P&nbsp

In the midst of the coronavirus disease 2019 (COVID-19) pandemic, governmental agencies, state medical boards, and healthcare organizations have called for restricting “elective” operations to mitigate the risk of transmission of the virus amongst patients and healthcare providers and to preserve essential resources for potential regional surges of COVID patients. While the fear of delaying surgical care for many of our patients is deeply challenging for us as cancer care providers, we must balance our personal commitment to providing timely and appropriate oncologic care to our cancer patients with our societal responsibility to protect our patients (including those on whom we are operating), co-workers, trainees, families, and community, from undue risks of contracting and propagating COVID-19. Herein, we present guidelines for surgical decision-making and case prioritization developed among all adult disease specialties in the MD Anderson Cancer Center Departments of Surgical Oncology and Breast Surgical Oncology in Houston, Texas.

Background The objective of this study was to assess current perceptions surrounding opioid prescribing in surgical oncology to inform perioperative quality improvement initiatives. Methods After the Society of Surgical Oncology (SSO) approval, a survey was distributed to its membership. Five sample procedures were used to assess provider perceptions and prescribing habits. Data were summarized and compared by self-reported demographics. Results One hundred and seventy-five participants completed the survey: 149 (85%) faculty, 24 (14%) trainees, and 2 (1%) advanced practice providers. Most participants (76%) practiced in academic programs and 21% practiced in non-US locations. Few differences were identified based on clinical role, academic rank, or practice years. Compared with non-US providers, US providers expected higher pain scores at discharge, recommended greater opioid prescriptions, and estimated more days of opioid use for almost every procedure. More non-US providers believed discharge opioids should not be distributed to patients who are opioid-free in their last 24 inpatient hours (80% vs 50%, P = .001). All providers ranked education as "very important" for reducing opioid prescriptions. Conclusions Compared with their international counterparts, US surgical oncology providers expected greater opioid needs and recommended higher prescription numbers. Educating providers on multimodal opioid-sparing bundles, accelerated weaning protocols, and standardized discharge prescribing habits could have a positive impact the US opioid epidemic.

Introduction Short-term outcomes after distal pancreatectomy (DP) for retroperitoneal (RP) tumors are unknown. We sought to identify rates of postoperative pancreatic fistula (POPF) and morbidity after en bloc DP with RP tumor resection. Methods A retrospective review of 43 patients who underwent DP with RP tumor resection (1/2011–12/2017) was performed. Results Seventeen patients had RP sarcoma, 12 renal cell carcinoma, 11 gastrointestinal stromal tumor, and 3 adrenocortical carcinoma. Grade III-IV complications occurred in 7 patients. Grade B POPF occurred in 14 patients, grade C POPF in none, and biochemical leak in 6. Of 22 patients who developed radiographically evident peri-pancreatic fluid collections, 7 required percutaneous drainage. The 90-day readmission rate was 33%. Conclusions DP with RP tumor resection is associated with high rates of clinically relevant POPF compared to historical results for DP for primary pancreatic tumors. Multi-center studies to identify targetable predictors and risk mitigation strategies for POPF in this rare high-risk population are needed.

BACKGROUND: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide but with an approximate 5-year survival of greater than 50% in patients after surgical resection. Survival estimates have limited utility for patients who have survived several years after initial treatment. We analyzed how conditional survival (CS) after curative-intent surgery for HCC predicts survival estimates over time. METHODS: NCDB(2004–2014) was queried for patients undergoing definitive surgical resection for HCC. Cumulative overall survival (OS) was calculated using the Kaplan-Meier method, and conditional survival (CS) at x years after diagnosis was calculated as CS(1) = OS ((X+5)) / OS ((X)). RESULTS: Final analysis encompassed 11,357 patients. Age, negative margin status, grade severity and radiation prior to surgery were statistically significant predictors of cumulative overall conditional survival (p≤0.0001). Overall unconditional 5-year survival was 65.7%, but CS estimates were higher. A patient who has already survived 3 years has an additional 2-year, or 5-year CS, estimate of 86.96%. CONCLUSION: Survival estimates following hepatic resection in HCC patients change according to survival time accrued since surgery. CS estimates are improved relative to unconditional OS. The impact of different variables influencing OS is likewise non-linear over the course of time after surgery.

Objective To summarize the multi-specialty strategy and initial guidelines of a Case Review Committee in triaging oncologic surgery procedures in a large Comprehensive Cancer Center and to outline current steps moving forward after the initial wave. Summary of background data The impetus for strategic rescheduling of operations is multifactorial and includes our societal responsibility to minimize COVID-19 exposure risk and propagation among patients, the healthcare workforce, and our community at large. Strategic rescheduling is also driven by the need to preserve limited resources. As many states have already or are considering to re-open and relax stay-at-home orders, there remains a continued need for careful surgical scheduling because we must face the reality that we will need to co-exist with COVID-19 for months, if not years. Methods The quality officers, chairs, and leadership of the 9 surgical departments in our Division of Surgery provide specialty-specific approaches to appropriately triage patients. Results We present the strategic approach for surgical rescheduling during and immediately after the COVID-19 first wave for the 9 departments in the Division of Surgery at The University of Texas MD Anderson Cancer Center in Houston, Texas. Conclusions Cancer surgeons should continue to use their oncologic knowledge to determine the window of opportunity for each surgical procedure, based on tumor biology, preoperative treatment sequencing, and response to systemic therapy, to safely guide patients through this cautious recovery phase.

First postoperative day drain fluid amylase (DFA1)5000 U/L is commonly used for early drain removal. We manage patients with risk-stratified pancreatectomy care pathways determined preoperatively by risk for postoperative pancreatic fistula. We hypothesized that preoperative risk stratification would yield unique DFA1/DFA3 cutoffs for safe early drain removal.Patients with DFA1/DFA3 values after pancreaticoduodenectomy or distal pancreatectomy were identified. Patients were risk stratified as "low-risk pancreaticoduodenectomy," "high-risk pancreaticoduodenectomy," or "distal pancreatectomy." Receiver operator characteristic analyses yielded clinically relevant sensitivity thresholds for International Study Group on Pancreatic Surgery grade B/C postoperative pancreatic fistulas.From October 2016 to April 2018, 174 patients were preoperatively stratified as low-risk pancreaticoduodenectomy (n = 78, 45%), high-risk pancreaticoduodenectomy (n = 51, 29%), and distal pancreatectomy (n = 45, 26%). B/C postoperative pancreatic fistulas developed in 3% (n = 2) of low-risk pancreaticoduodenectomies, 37% (n = 19) of high-risk pancreaticoduodenectomies, and 24% (n = 11) of distal pancreatectomies (low- vs high-risk pancreaticoduodenectomy P.001, low-risk pancreaticoduodenectomy versus distal pancreatectomy P = .004, high-risk pancreaticoduodenectomy versus distal pancreatectomy P = .25). B/C postoperative pancreatic fistulas occurred in 16% (n = 21) pancreaticoduodenectomy patients (high- + low-risk pancreaticoduodenectomy), and B/C postoperative pancreatic fistulas were excluded in pancreaticoduodenectomy with 100% sensitivity if DFA1 ≤ 136 or DFA3 ≤ 93. DFA15000 excluded B/C postoperative pancreatic fistulas with only 57% sensitivity after pancreaticoduodenectomy. Exclusion of B/C postoperative pancreatic fistulas occurred with 100% sensitivity if DFA1 ≤ 661 or DFA3 ≤ 141 in low-risk pancreaticoduodenectomy patients, DFA1 ≤ 136 or DFA3 ≤ 93 in high-risk pancreaticoduodenectomy patients, and DFA149 or DFA326 in distal pancreatectomy patients.Preoperative risk stratification results in unique DFA1/DFA3 thresholds to exclude B/C postoperative pancreatic fistulas, thus allowing for safe drain removal and potential for accelerated discharge. Rather than applying generic DFA cutoffs based on national databases, we propose institution-specific DFA1 and DFA3 values tailored to 3 replicable postoperative pancreatic fistula-risk pathways.

Single-institution studies have shown the oncologic benefit of ablative liver radiotherapy (A-RT) for patients with unresectable intrahepatic cholangiocarcinoma (ICC). However, adoption of A-RT across the United States and its associated outcomes are unknown.We queried the National Cancer Data Base for nonsurgically managed patients with ICC diagnosed between 2004 and 2018. Patients were labeled A-RT for receipt of biologically effective doses (BEDOf 27,571 patients, the most common treatments were chemotherapy without liver RT (45%), no chemotherapy or liver RT (42%), and liver RT ± chemotherapy (13%). Use of liver RT remained constant over time. Of 1112 patients receiving liver RT with known doses, RT was 73% Conv-RT (median BEDAlthough A-RT has been increasingly used, use of liver RT as a whole in the United States remained constant despite growing evidence supporting its use, suggesting continued unmet need. A-RT is associated with longer survival versus Conv-RT.Bile duct cancer is a rare, deadly disease that often presents at advanced stages. Single-institution retrospective studies have demonstrated that use of high-dose radiotherapy may be associated with longer survival, but larger studies have not been conducted. We used a large, national cancer registry of patients diagnosed between 2004 and 2018 to show that liver radiotherapy use remains low in the United States, despite growing evidence that patients who receive it live longer. Furthermore, we showed that patients who received high-dose radiotherapy lived longer than those who received lower doses. Greater awareness of the benefits of liver radiotherapy is needed to improve patient outcomes.

We have previously shown that ablative radiotherapy (A-RT) with a biologically effective dose (BED10) ≥ 80.5 Gy for patients with unresectable intrahepatic cholangiocarcinoma (ICC) is associated with longer survival. Despite recent large-scale sequencing efforts in ICC, outcomes following RT based on genetic alterations have not been described. We reviewed records of 156 consecutive patients treated with A-RT for unresectable ICC from 2008 to 2020. For 114 patients (73%), next-generation sequencing provided molecular profiles. The overall survival (OS), local control (LC), and distant metastasis-free survival (DMFS) were estimated using the Kaplan–Meier method. Univariate and multivariable Cox analyses were used to determine the associations with the outcomes. The median tumor size was 7.3 (range: 2.2–18.2) cm. The portal vein thrombus (PVT) was present in 10%. The RT median BED10 was 98 Gy (range: 81–144 Gy). The median (95% confidence interval) follow-up was 58 (42–104) months from diagnosis and 39 (33–74) months from RT. The median OS was 32 (29–35) months after diagnosis and 20 (16–24) months after RT. The one-year OS, LC, and intrahepatic DMFS were 73% (65–80%), 81% (73–87%), and 34% (26–42%). The most common mutations were in IDH1 (25%), TP53 (22%), ARID1A (19%), and FGFR2 (13%). Upon multivariable analysis, the factors associated with death included worse performance status, larger tumor, metastatic disease, higher CA 19-9, PVT, satellitosis, and IDH1 and PIK3CA mutations. TP53 mutation was associated with local failure. Further investigation into the prognostic value of individual mutations and combinations thereof is warranted.

BACKGROUND AND OBJECTIVES: Opioids are commonly prescribed following surgery and can lead to persistent opioid use. We assessed changes in prescribing practices following an opioid education initiative for patients undergoing lymphadenectomy for cutaneous malignancy. METHODS: A single-institution retrospective study of all eligible patients (3/2016–3/2020) was performed. RESULTS: Indications for lymphadenectomy in 328 patients were metastatic melanoma (84%), squamous cell carcinoma (10%), and Merkel cell carcinoma (5%). At discharge, non-opioid analgesics were increasingly utilized over the 4-year study period, with dramatic increases after education initiatives (32%, 42%, 59%, and 79% of pts, respectively each year; p

In the pandemic of severe acute respiratory syndrome due to coronavirus-2 (SARS-CoV-2), United States (U.S.) also experienced the spread of coronavirus disease 2019 (COVID-19). Here, we report the current status of Houston, Texas and the response to COVID-19 at MD Anderson Cancer Center (MDACC) and in the Department of Surgical Oncology. MDACC has taken the institutional measures in order to prevent its employees and patients from COVID-19. Furthermore, surgeons have also responded aggressively in the outpatient setting, operating room and inpatient care. The predicted peak in Texas is on April 29 and our mitigation measures appear to be effective at the time of writing, however there still remain a lot of unknowns about SARS-CoV-2 and the performance of cancer operations remains an ongoing and delicate issue. In order to minimize the risks to patients, our healthcare system, and our community, MDACC has navigated the countering pressures through honest and open communication with patients, judicious use of alternative treatment strategies, and thoughtful selection of surgical cases.

In the United States, hepatocellular carcinoma (HCC) incidence rates were approximately three times higher in over 30 years. To investigate the long-term outcomes of patients who underwent resection, ablation, and trans-arterial chemoembolization (TACE) of HCC, we analyzed the National Cancer Data Base (NCDB), which is a nationwide oncology outcomes database and covers approximately 70% of new cancer cases in the United States. A total of 56,512 patients with HCC in the NCDB during 2004-2013 were retrospectively analyzed. Results showed that liver resection (48.5%) and ablation (57.0%) were performed more frequently than TACE (31.5%) in patients with AJCC stage I HCC. The 5-year overall survival (OS) was significantly higher in patients undergoing resection (52.4%) than in patients undergoing ablation (40.5%; P < 0.001) and patients undergoing TACE (36.1%; P < 0.001). For patients with AJCC stage I, the 5-year OS of patients undergoing resection (51.6%; P < 0.001) and patients undergoing ablation (51.1%, P = 0.005) remains significantly better than patients undergoing TACE (40.0%). However, the 5-year OS did not differ significantly between patients undergoing resection and patients undergoing ablation (P = 0.486). Additionally, the findings of our study confirm that the sub-stratification of T1 category by HCC diameter in the AJCC staging eighth edition (i.e., T1a, HCC diameter ≤ 2 cm and T1b, HCC diameter > 2 cm) is valid, with a 5-year OS of 54.1% and 50.4%, respectively (P = 0.031).

OBJECTIVES: Neoadjuvant therapy (NT) is used for advanced pancreatic ductal adenocarcinoma (PDAC). No clear guidelines exist for switching therapies when patients do not respond to initial NT. We sought to characterize patients who underwent early switch from FOLFIRINOX to gemcitabine/nab-paclitaxel (GA) as NT for PDAC. METHODS: We identified patients at a single institution switched from FFX to GA within the first 4 months of NT for PDAC during 2012–2017. We compared clinicopathologic data and oncologic outcomes. RESULTS: Of 25 patients who met criteria, 21 showed a serologic or radiographic response to GA; 11 (52%) reached resection. Responders had decreased carbohydrate antigen (CA) 19-9 levels from pre-treatment to post-GA (P = 0.036). Resected responders had significantly decreased CA 19-9 comparing pre-switch to post-GA (P = 0.048). The only predictor of GA response was pre-chemotherapy CA 19-9

Background With the increasing use of biliary stents for neoadjuvant therapy (NT) for pancreatic adenocarcinoma (PDAC), the risk of post-pancreaticoduodenectomy (PD) infection remains relevant. This study documents the contemporary incidence of stent-related complications (SRC) during NT and to analyze their impact on surgical infections. Methods Consecutive patients from a single institution (2011–15) with resected PDAC treated with biliary decompression, NT, and PD were analyzed. Stent-related complications (SRC) were compared among patients with/without prospectively documented composite pre- and post-operative infections (surgical site infection [SSI], organ space infection [OSI], and cholangitis). Results Of 114 total patients, (median 164 days, initial stent to surgery), 95% had initial endoscopic (vs. percutaneous) stenting. Initial stents were often plastic (80/114, 70%), with 43/114 (38%) undergoing routine exchange to metal stent before NT. Fifteen (13%) patients had stent cholangitis during NT requiring antibiotics and/or stent exchange. There were 33/114 (29%) patients with SRC, requiring 66 exchanges. Post-PD rates of SSI, OSI, and cholangitis were 23%, 5%, and 4%, respectively [composite rate 30%]. On multivariate analysis, SRC were not associated with composite surgical infections (p > 0.05). Conclusions Although SRC occurred in almost one-third of PDAC patients during NT, with appropriate intervention, there was no association with increased surgical infections.

OBJECTIVE: To assess the impact of somatic gene mutations on survival among patients undergoing resection of colorectal liver metastases (CLM). SUMMARY BACKGROUND DATA: Patients undergoing CLM resection have heterogeneous outcomes, and accurate risk stratification is necessary to optimize patient selection for surgery. METHODS: Next-generation sequencing of 50 cancer-related genes was performed from primary tumors and/or liver metastases in 401 patients undergoing CLM resection. Missense TP53 mutations were classified by the Evolutionary Action Score (EAp53), a novel approach that dichotomizes mutations as low or high risk. RESULTS: The most frequent somatic gene mutations were TP53 (65.6%), followed by KRAS (48.1%) and APC (47.4%). Double mutation in RAS/TP53, identified in 31.4% of patients, was correlated with primary tumor location in the right colon (P = 0.006). On multivariable analysis, RAS/TP53 double mutation was an independent predictor of shorter overall survival (hazard ratio, 2.62; 95% confidence interval 1.41 to 4.87; P = 0.002). In patients with co-mutated RAS, EAp53 high risk mutations were associated with shorter 5-year overall survival of 12.2%, compared with 55.7% for TP53 wild-type (P < 0.001). The negative prognostic effects of RAS and TP53 mutations were limited to tumors harboring mutations in both genes. CONCLUSIONS: Concomitant RAS and TP53 mutations are associated with decreased survival after CLM resection. A high EAp53 predicts a subset of patients with worse prognosis. These preliminary analyses suggest that surgical resection of liver metastases should be carefully considered in this subset of patients.

BACKGROUNDPancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies, with unpredictable responses to chemotherapy. Approaches to assay patient tumors before treatment and identify effective treatment regimens based on tumor sensitivities are lacking. We developed an organoid-based platform (OBP) to visually quantify patient-derived organoid (PDO) responses to drug treatments and associated tumor-stroma modulation for personalized PDAC therapy.METHODSWe retrospectively quantified apoptotic responses and tumor-stroma cell proportions in PDOs via 3D immunofluorescence imaging through annexin A5, α-smooth muscle actin (α-SMA), and cytokeratin 19 (CK-19) levels. Simultaneously, an ex vivo organoid drug sensitivity assay (ODSA) was used to measure responses to standard-of-care regimens. Differences between ODSA results and patient tumor responses were assessed by exact McNemar's test.RESULTSImmunofluorescence signals, organoid growth curves, and Ki-67 levels were measured and authenticated through the OBP for up to 14 days. ODSA drug responses were not different from patient tumor responses, as reflected by CA19-9 reductions following neoadjuvant chemotherapy (P = 0.99). PDOs demonstrated unique apoptotic and tumor-stroma modulation profiles (P0.0001). α-SMA/CK-19 ratio levels of more than 1.0 were associated with improved outcomes (P = 0.0179) and longer parental patient survival by Kaplan-Meier analysis (P = 0.0046).CONCLUSIONHeterogenous apoptotic drug responses and tumor-stroma modulation are present in PDOs after standard-of-care chemotherapy. Ratios of α-SMA and CK-19 levels in PDOs are associated with patient survival, and the OBP could aid in the selection of personalized therapies to improve the efficacy of systemic therapy in patients with PDAC.FUNDINGNIH/National Cancer Institute grants (K08CA218690, P01 CA117969, R50 CA243707-01A1, U54CA224065), the Skip Viragh Foundation, the Bettie Willerson Driver Cancer Research Fund, and a Cancer Center Support Grant for the Flow Cytometry and Cellular Imaging Core Facility (P30CA16672).

Over the past few decades, robotic surgery techniques required to resect gastric and pancreatic malignancies have evolved remarkably; however, the safety and generalizability of robotic pancreatoduodenectomy remain unknown. At our cancer center, gastrectomies and pancreatectomies are performed in a combined foregut minimally-invasive surgery program; this effectively increases the composite case volume and shortens the learning curve for any individual surgeon. In this video, we demonstrate the shared steps in pancreatoduodenectomy and gastrectomy and explain how the skills gained through robotic gastrectomy can be used during robotic pancreatoduodenectomy. During the initial 2-year period of our robotic foregut surgery program, we performed 120 pancreatic and gastric operations, including 22 pancreatoduodenectomies and 37 gastrectomies. Our first robotic pancreatoduodenectomy was performed following successful completion of 45 other robotic foregut operations. Of those 22 patients who underwent robotic pancreatoduodenectomy, the median hospital stay was 4 days (range 3-17 days) and the readmission rate was 14% (3/22). The rate of grade B/C pancreatic fistula was 9% (2/22) and there was no 90-day mortality. In conclusion, the presented video showing the shared steps in robotic pancreatoduodenectomy and gastrectomy demonstrates the potential for a combined robotic surgery program to increase composite case volumes and to shorten the learning curve. At our cancer center, implementation of this approach has been helpful in accelerating the development of our new robotic pancreatectomy program, especially in honing the skills necessary to perform robotic pancreatoduodenectomy.