Postoperative Global Period Cost Reduction Using 3 Successive Risk-Stratified Pancreatectomy Clinical Pathways.

BACKGROUND: We hypothesized that iterative revisions of our original 2016 risk-stratified pancreatectomy clinical pathways would be associated with decreased 90-day perioperative costs. STUDY DESIGN: From a single-institution retrospective cohort study of consecutive patients with 3 iterations: "version 1" (V1) (October 2016 to January 2019), V2 (February 2019 to October 2020), and V3 (November 2020 to February 2022), institutional data were aggregated using revenue codes and adjusted to constant 2022-dollar value. Grand total perioperative costs (primary endpoint) were the sum of pancreatectomy, inpatient care, readmission, and 90-day global outpatient care. Proprietary hospital-based costs were converted to ratios using the mean cost of all hospital operations as the denominator. RESULTS: Of 814 patients, pathway V1 included 363, V2 229, and V3 222 patients. Accordion Grade 3+ complications decreased with each iteration (V1: 28.4%, V2: 22.7%, and V3: 15.3%). Median length of stay decreased (V1: 6 days, interquartile range [IQR] 5 to 8; V2: 5 [IQR 4 to 6]; and V3: 5 [IQR 4 to 6]) without an increase in readmissions. Ninety-day global perioperative costs decreased by 32% (V1 cost ratio 12.6, V2 10.9, and V3 8.6). Reduction of the index hospitalization cost was associated with the greatest savings (-31%: 9.4, 8.3, and 6.5). Outpatient care costs decreased consistently (1.58, 1.41, and 1.04). When combining readmission and all outpatient costs, total "postdischarge" costs decreased (3.17, 2.59, and 2.13). Component costs of the index hospitalization that were associated with the greatest savings were room or board costs (-55%: 1.74, 1.14, and 0.79) and pharmacy costs (-61%: 2.20, 1.61, and 0.87; all p < 0.001). CONCLUSIONS: Three iterative risk-stratified pancreatectomy clinical pathway refinements were associated with a 32% global period cost savings, driven by reduced index hospitalization costs. This successful learning health system model could be externally validated at other institutions performing abdominal cancer surgery.

Utilizing risk-stratified pathways to personalize post-hepatectomy discharge planning: A contemporary analysis of 1,354 patients.

BACKGROUND: While risk-stratified post-hepatectomy pathways (RSPHPs) reduce length-of-stay, can they stratify hepatectomy patients by risk of early postoperative events. METHODS: 90-day outcomes from consecutive hepatectomies were analyzed (1/1/2017-12/31/2021). Pre/post-pathway analysis was performed for pathways: minimally invasive surgery ("MIS"); non-anatomic resection/left hepatectomy ("low-intermediate risk"); right/extended hepatectomy ("high-risk"); "Combination" operations. Time-to-event (TTE) analyses for readmission and interventional radiology procedures (IRPs) was performed. RESULTS: 1354 patients were included: MIS/n= â€‹119 (9 â€‹%); low-intermediate risk/n= â€‹443 (33 â€‹%); high-risk/n= â€‹328 (24 â€‹%); Combination/n= â€‹464 (34 â€‹%). There was no difference in readmission (pre: 13 â€‹% vs. post:11.5 â€‹%, p â€‹= â€‹0.398). There were fewer readmissions in post-pathway patients amongst MIS, low-intermediate risk, and Combination patients (all p â€‹> â€‹0.1). 114 (8.4 â€‹%) patients required IRPs. Time-to-readmission and time-to-IR-procedure plots demonstrated lower plateaus and flatter slopes for MIS/low-intermediate-risk pathways post-pathway implementation (p â€‹< â€‹0.001). CONCLUSION: RSPHPs can reliably stratify patients by risks of readmission or need for an IR procedure by predicting the most frequent period for these events.

Prognostic significance of trophoblastic cell surface antigen 2 expression and pathologic parameters in patients with ampullary adenocarcinoma.

Trophoblastic cell surface antigen 2 (TROP2) has been reported to be up-regulated in several types of carcinomas and is associated with aggressive behavior and poor survival. However, TROP2 expression and its clinical significance in ampullary adenocarcinoma (AA) have not been investigated. We examined TROP2 expression by immunohistochemistry in 112 patients with AAs. The associations of TROP2 expression with clinicopathologic characteristics were evaluated by χ2 analyses or Fisher's exact tests. The associations of TROP2 expression and pathologic parameters with survival were evaluated by the Kaplan-Meier method and univariate and multivariate Cox regression analyses. Eighty-six AAs (76.8%) were positive for TROP2, which showed a membranous and cytoplasmic staining. TROP2 expression was associated with higher frequency (P = .04) and higher number (P = .03) of lymph node metastasis, higher pN stage (P = .03), less frequent adenoma (P = .04), and higher frequency of recurrence/metastasis (P = .004). TROP2 expression was associated with shorter disease-free survival (P = .02) and overall survival (P = .03). TROP2 expression was an independent prognostic factor for disease-free survival (P = .04). We demonstrated that TROP2 was expressed in 76.8% of AAs. TROP2 expression was associated with higher frequency and high number of lymph node metastasis and higher pN stage. More importantly, TROP2 expression was associated with higher frequency of recurrence/metastasis, shorter disease-free and overall survival and was an independent prognostic factor for disease-free survival. Our results suggest that TROP2 may be used both as a prognostic marker and as a therapeutic target for patients with AAs.

Setting the Standard for Cutaneous Melanoma Wide Local Excision: An Overview of the American College of Surgeons Commission on Cancer Standard 5.5.

The purpose of this article is to review the objectives of the American College of Surgeons Commission on Cancer Operative Standards with a specific focus on Standard 5.5, which pertains to curative intent wide local excision of primary cutaneous melanoma lesions. We review the details and rationale of the standard itself, including its requirement to include specific elements and responses in synoptic format in operative reports.

3D imaging analysis on an organoid-based platform guides personalized treatment in pancreatic ductal adenocarcinoma.

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 (P < 0.0001). 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).

Nab-Paclitaxel, Capecitabine, and Radiation Therapy After Induction Chemotherapy in Treating Patients With Locally Advanced and Borderline Resectable Pancreatic Cancer: Phase 1 Trial and Imaging-based Biomarker Validation.

PURPOSE: Effective consolidative chemoradiation (CRT) regimens are lacking. In this phase 1 trial, we evaluated the safety and efficacy of nab-paclitaxel, capecitabine, and radiation therapy after induction chemotherapy in patients with locally advanced and borderline-resectable pancreatic cancer (LAPC and BRPC). Also, we evaluated a computed tomography (CT)-based biomarker of response. METHODS AND MATERIALS: Eligible patients had pathologically confirmed pancreatic ductal adenocarcinoma, underwent computed tomography-imaging, received a diagnosis of LAPC or BRPC, and received induction chemotherapy. Standard 3 + 3 study design was used, with 3 escalating nab-paclitaxel dose levels (50, 75, and 100 mg/m2) with concurrent capecitabine and RT in cohort sizes of 3 starting at the lowest dose. Dose limiting toxicity was defined as grade 3 or higher toxicity. Patients were restaged 4 to 6 weeks post-CRT completion, and surgical resection was offered to those with stable/responsive disease. We scored the tumor interface response (IR) postchemotherapy and post-CRT into type I (remained/became more defined) and type II (became less defined). Overall survival (OS) and progression-free survival (PFS) from time of CRT were estimated using Kaplan-Meier method. P ≤ .05 was considered significant. RESULTS: Twenty-three patients started and finished on protocol (LAPC = 14, BRPC = 9). No grade 3 and 4 toxicities were reported in level 1 (n = 3) or level 2 (n = 3) initial groups. Two patients in the initial level 3 group developed dose limiting toxicity, establishing level 2 dose as the maximal tolerated dose. Level 2 group was expanded for additional 15 patients (for a total of 23 on trial), 5 of whom developed grade 3 toxicities. Seven patients underwent surgical resection. Median OS and PFS were 21.2 and 8.1 months, respectively. Type I IR was associated with better OS (P = .004) and PFS (P = .03) compared with type II IR. CONCLUSIONS: We established the maximum tolerated dose for nab-paclitaxel in a consolidative CRT regimen for pancreatic ductal adenocarcinoma. Preliminary efficacy results warrant phase 2 trial evaluation. IR may be used for personalized treatment.

GRP78 expression and prognostic significance in patients with pancreatic ductal adenocarcinoma treated with neoadjuvant therapy versus surgery first.

BACKGROUND: Glucose-regulated protein 78 (GRP78) plays an essential role in protein folding, transportation, and degradation, thus regulates ER homeostasis and promotes cell survival, proliferation and invasion. GRP78 expression in PDAC patients who received neoadjuvant therapy has not been reported. METHODS: This retrospective study of resected PDAC patients included 125 patients treated with neoadjuvant therapy (NAT) and 140 patients treated with surgery first (SF). The expression of GRP78 was evaluated by immunohistochemistry on tissue microarrays and the results were correlated with clinicopathologic parameters and survival. RESULTS: GRP78 expression was higher in SF patients compared to NAT patients (P < 0.001). In SF cohort, the median disease-free survival (DFS) and overall survival (OS) for patients with GRP78-positive tumors were 11.2 months and 25.0 months, respectively, compared to DFS of 52.1 months (P = 0.008) and OS of 69.5 months (P = 0.02) for those with GRP78-negative tumors. GRP78 expression correlated with higher frequency of recurrent/metastasis (P = 0.045). In NAT cohort, GRP78 expression correlated with shorter OS (P = 0.03), but not DFS (P = 0.08). GRP78 expression was an independent prognosticator for both DFS (P = 0.02) and OS (P = 0.049) in SF cohort and was an independent prognosticator for OS (P = 0.03), but not for DFS (P = 0.06) in NAT cohort by multivariate analysis. CONCLUSIONS: Our study showed that GRP78 expression in NAT cohort is lower than that in SF cohort. GRP78 expression correlated with shorter survival in both SF and NAT patients. Our findings suggest that targeting GRP78 may help to improve the prognosis in PDAC patients.

Early postoperative drain fluid amylase in risk-stratified patients promotes tailored post-pancreatectomy drain management and potential for accelerated discharge.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. DFA1 < 5000 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 DFA1 < 49 or DFA3 < 26 in distal pancreatectomy patients. CONCLUSION: 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.

Multidisciplinary management of resectable adenocarcinoma of the pancreatic head.

Although surgery is considered the only treatment to offer patients with localized pancreatic adenocarcinoma a chance of cure, resection alone is rarely sufficient for long-term survival. High rates of postoperative recurrence and subsequent disease-related mortality have, over the past two decades, encouraged the study and use of multimodality strategies that include adjuvant systemic chemotherapy and radiation. These modalities have been utilized both preoperatively and postoperatively with encouraging results. Moreover, their use has led increasingly to the development of institutional multidisciplinary groups with a focused interest in the care of patients with pancreatic malignancy, which have become responsible for the diagnosis, staging, treatment, follow-up and study of these patients. We review the rationale for the use of and the outcomes that may be achieved through the use of a multidisciplinary approach to patients with resectable adenocarcinoma of the pancreatic head.