Explore the vast range of titles available.

Background Patients with colorectal liver metastases (CLM) are increasingly treated with preoperative chemotherapy. Chemotherapy associated liver injury is associated with postoperative hepatic insufficiency (PHI) and mortality. The adequate minimum future liver remnant (FLR) volume in patients treated with extensive chemotherapy remains unknown. Methods All patients with standardized FLR > 20 %, who underwent extended right hepatectomy for CLM from 1993-2011, were divided into three cohorts by chemotherapy duration: no chemotherapy (NC, n  = 30), short duration (SD, ≤12 weeks, n  = 78), long duration (LD, >12 weeks, n  = 86). PHI and mortality were compared by using uni-/multivariate analyses. Optimal FLR for LD chemotherapy was determined using a minimum p -value approach. Results A total of 194 patients met inclusion criteria. LD chemotherapy was significantly associated with PHI (NC + SD 3.7 vs. LD 16.3%, p  = 0.006). Ninety-day mortality rates were 0 % in NC, 1.3 % in SD, and 2.3% in LD patients, respectively ( p  = 0.95). In patients with FLR > 30 %, PHI occurred in only two patients (both LD, 2/20, 10 %), but all patients with FLR > 30 % survived. The best cutoff of FLR for preventing PHI after chemotherapy >12 weeks was estimated as >30 %. Both LD chemotherapy (odds ratio [OR] 5.4, p  = 0.004) and FLR ≤ 30 % (OR 6.3, p  = 0.019) were independent predictors of PHI. Conclusions Preoperative chemotherapy >12 weeks increases the risk of PHI after extended right hepatectomy. In patients treated with long-duration chemotherapy, FLR > 30 % reduces the rate of PHI and may provide enough functional reserve for clinical rescue if PHI develops.

BackgroundMargin-negative (R0) resection is the strongest positive prognostic factor in perihilar cholangiocarcinoma (PHC). Due to its anatomic location, the caudate lobe is frequently involved in PHC. This review aimed to examine the impact of caudate lobe resection (CLR) in addition to hepatectomy and bile duct resection for patients with PHC. MethodsThe MEDLINE, EMBASE, and Cochrane databases were systematically reviewed from inception to October 2021 to identify studies comparing patients undergoing surgical resection with hepatectomy and bile duct resection with or without CLR for treatment of PHC. Outcomes included the proportion of patients achieving R0 resection, overall survival (OS), and perioperative morbidity. ResultsAltogether, 949 studies were screened. The review included eight observational studies reporting on 1137 patients. The patients who underwent CLR had a higher likelihood of R0 resection (odds ratio [OR], 5.85; 95% confidence interval [CI], 2.64–12.95) and a better OS (hazard ratio [HR], 0.65; 95% CI, 0.54–0.79) than those who did not. The use of CLR did not increase the risk of perioperative morbidity (OR, 1.03; 95% CI, 0.65–1.63). ConclusionsGiven the higher likelihood of R0 resection, improved OS, and no apparent increase in perioperative morbidity, this review supports routine caudate lobectomy in the surgical management of PHC. These results should be interpreted with caution given the lack of high-quality prospective data and the high probability of selection bias.

BackgroundPerihilar cholangiocarcinoma (PHC) is a rare malignancy that arises at the biliary confluence. Achieving a margin-negative resection (R0) is challenging given the anatomic location of tumors and remains the most important prognostic indicator of long-term survival. The objective of this study is to review the impact of intraoperative revision of positive biliary margins in PHC on oncologic outcomes.Patients and MethodsElectronic databases were searched from inception to October 2021. Studies comparing three types of patients undergoing resection of PHC with intraoperative frozen section of the proximal and/or distal bile ducts were identified: those who were margin-negative (R0), those with an initially positive margin who had revised negative margins (R1R0), and those with a persistently positive margin with or without revision of a positive margin (R1). The primary outcome was overall survival (OS). Secondary outcomes included risk of postoperative complication.ResultsA total of 449 studies were screened. Ten retrospective observational studies reporting on 1955 patients were included. Patients undergoing successful revision of a positive proximal and/or distal bile duct margin (R1R0) had similar OS to those with a primary margin-negative resection (R0) [hazard ratio (HR) 0.93, 95% confidence interval (CI) 0.72–1.19, p = 0.56, I2 = 84%], and significantly better OS than patients with a positive final bile duct margin (R1) (HR 0.52, 95% CI 0.34–0.79, p = 0.002, I2 = 0%). There was no increase in the risk of postoperative complications associated with additional resection, although postoperative morbidity was inconsistently reported.ConclusionsThis review supports routine intraoperative biliary margin evaluation during resection of PHC with revision if technically feasible.

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 = <0.0001). In multivariate analysis, the impact of ATB remained significant for PFS (HR 0.59, p = 0.005) and borderline statistically significant for OS (HR 0.69, p = 0.06). When we analyzed by chemotherapy regimen, we found that patients who received gemcitabine‐based chemotherapy as first‐line therapy (n = 118) had significantly prolonged OS (HR 0.4, p 0.0013) and PFS (HR 0.55, p 0.02) if they received antibiotics, while those receiving 5FU‐based chemotherapy (n = 98) had only prolonged PFS (HR 0.54, p = 0.03). Antibiotics‐associated modulation of the microbiome is associated with better outcomes in patients with metastatic PDAC. 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.

Introduction Previous studies have suggested that the use of regional anesthesia can reduce recurrence risk after oncologic surgery. The purpose of this study was to assess the effect of epidural anesthesia on recurrence-free (RFS) and overall survival (OS) after hepatic resection for colorectal liver metastases (CLM). Methods After approval of the institutional review board, the records of all adult patients who underwent elective hepatic resection between January 2006 and October 2011 were retrospectively reviewed. Patients were categorized according to use of perioperative epidural analgesia versus intravenous analgesia. Univariate and multivariate analyses were performed to identify factors influencing RFS and OS. Results Of 510 total patients, 390 received epidural analgesia (EA group) and 120 patients received intravenous analgesia (IVA group). Compared with the IVA group, more patients in the EA group underwent associated surgical procedures with consequently longer operative times ( p  < 0.001). In addition, the EA group received more intraoperative fluids and had higher urine output volumes ( p  ≤ 0.001). Five-year RFS was longer in the EA group (34.7 %) compared with the IVA group (21.1 %). On multivariate analysis, the receipt of epidural analgesia was an independent predictor of improved RFS ( p  = 0.036, hazard ratio [HR] 0.74; 95 % confidence interval [CI] 0.56–0.95), but not OS ( p  = 0.102, HR 0.72; 95 % CI 0.49–1.07). Conclusions This study suggests an association between epidural analgesia and improved RFS, but not OS, after CLM resection. These results warrant further prospective, randomized studies on the benefits of regional anesthesia on oncologic outcomes after hepatic resection for CLM.

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).

Background We evaluated the associations of surgical margin status and somatic mutations with the incidence of local recurrence (LR) and oncologic outcomes in patients undergoing R0-intent (microscopically negative margin) resection of colorectal liver metastases (CLM). Methods Patients with CLM who underwent initial R0-intent resection and analysis of tumor tissue using next-generation sequencing during 2001–2018 were analyzed. Recurrences were classified as LR (at the resection margin), other intrahepatic recurrence, or extrahepatic recurrence. Predictors and survival effect of LR were evaluated using univariate and multivariate analysis. Results Of 552 patients analyzed, 415 (75%) had R0 resection (margin width ≥ 1.0 mm), and 38 (7%) had LR. LR incidence was not affected by surgical margin width. RAS / TP53 co-mutation was associated with increased risk of intrahepatic recurrence (67% vs. 49%; p  < 0.001) and overall recurrence ( p  < 0.001). However, incidence of LR did not differ significantly by RAS / TP53 , BRAF , SMAD4 , or FBXW7 mutation. Extrahepatic disease (hazard ratio [HR], 1.47; p  = 0.034), > 8 cycles of preoperative chemotherapy (HR, 1.98; p  = 0.033), tumor viability ≥ 50% (HR, 1.55; p  = 0.007), RAS / TP53 co-mutation (HR, 1.69; p  = 0.001), and SMAD4 mutation (HR, 2.44; p  < 0.001) were independently associated with poor overall survival, but surgical margin status was not. Conclusions Although somatic mutations were associated with overall recurrence, neither surgical margin width nor somatic mutations affected LR risk after R0-intent hepatectomy for CLM. LR and prognosis were likely driven by individual tumor biology rather than surgical margins.

BackgroundLaparoscopic resection (LLR) of colorectal liver metastases (CRLM) located in the posterosuperior liver (segments 4a, 7, and 8) is challenging but has become more practical recently due to progress in operative techniques. We aimed to compare tumor-specific, perioperative, and short-term oncological outcomes after LLR and open liver resection (OLR) for CRLM.MethodsPatients who underwent curative resection of CRLM with at least 1 tumor in the posterosuperior liver during 2012–2015 were analyzed. Tumor-specific factors associated with the adoption of LLR were analyzed by logistic regression model. One-to-one propensity score matching was used to match baseline characteristics between patients with LLR and OLR.ResultsThe original cohort included 30 patients with LLR and 239 with OLR. Median follow-up time was 23.8 months. Logistic regression analysis showed that multiple, diameter ≥30 mm, deep location, and closeness to major vessels were associated with OLR. None of the 24 patients with none or one of these factors were converted from LLR to OLR. After matching, 29 patients with LLR and 29 with OLR were analyzed. The 2 groups had similar preoperative factors. The LLR and OLR groups did not differ with respect to operative time, intraoperative bleeding, incidence of blood transfusion, surgical margin positivity, incidence of postoperative complications, and unplanned readmission within 45 days. Median length of postoperative hospital stay was significantly shorter for LLR versus OLR (4 days [1–12] vs. 5 days [4–18]; p = 0.0003). Median recurrence-free survival was similar for patients who underwent LLR versus OLR (10.6 months for LLR vs. 13.4 months for OLR; p = 0.87).ConclusionsCompared to OLR, LLR of posterosuperior CRLM is associated with significantly shorter postoperative hospital stay but otherwise similar perioperative and short-term oncological outcomes. Tumor-specific factors associated with safe and routine LLR approach despite challenging location are superficial, solitary, and small (<30 mm) CRLM not associated with major vessels.

Barriers to multimodality therapy (MMT) completion among patients with resectable pancreatic adenocarcinoma include early cancer progression and postoperative major complications (PMC). We sought to evaluate the influence of these factors on MMT completion rates of patients treated with neoadjuvant therapy (NT) and surgery-first (SF) approaches. We evaluated all operable patients treated for clinically resectable pancreatic head adenocarcinoma at our institution from 2002 to 2007. Rates of MMT completion, 90-day PMC, and overall survival (OS) were evaluated. Ninety-five of 115 (83 %) NT and 29/50 (58 %) SF patients completed MMT. Patients who completed MMT lived longer than those who did not (36 vs. 11 months, p  < 0.001). The most common reason that NT (11 %) and SF (26 %) patients failed to complete MMT was early disease progression. The rates of PMC among NT and SF patients were similar. Among SF patients, 69 % with no PMC completed MMT versus 29 % after PMC ( p  = 0.040). PMC were associated with decreased OS in SF patients but not in NT patients. The impact of early cancer progression and PMC upon completion of MMT is reduced by delivery of nonoperative therapies prior to pancreaticoduodenectomy. NT sequencing is a practical treatment strategy, particularly for patients at high biological or perioperative risk.

While risk-stratified post-hepatectomy pathways (RSPHPs) reduce length-of-stay, can they stratify hepatectomy patients by risk of early postoperative events. 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. 1354 patients were included: MIS/n= ​119 (9 ​%); low-intermediate risk/n= ​443 (33 ​%); high-risk/n= ​328 (24 ​%); Combination/n= ​464 (34 ​%). There was no difference in readmission (pre: 13 ​% vs. post:11.5 ​%, p ​= ​0.398). There were fewer readmissions in post-pathway patients amongst MIS, low-intermediate risk, and Combination patients (all p ​> ​0.1). 114 (8.4 ​%) 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 ​< ​0.001). RSPHPs can reliably stratify patients by risks of readmission or need for an IR procedure by predicting the most frequent period for these events. •RSPHPs stratify patients by risk of readmission or need for IR procedure by predicting the frequency of these events.•Knowledge of hepatectomy complexity and risk of complications informs intensity of postoperative follow-up after hepatectomy.•Utilization of telehealth for lower risk patients may minimize loss of time and money while maintaining excellent outcomes.