Recurrence and tumor-related death after resection of hepatocellular carcinoma in patients with metabolic syndrome.

Background & Aims: Metabolic syndrome (MS) is a growing epidemic and a risk factor for the development of hepatocellular carcinoma (HCC). This study investigated the long-term outcomes of liver resection (LR) for HCC in patients with MS. Rates, timing, patterns, and treatment of recurrences were investigated, and cancer-specific survivals were assessed. Methods: Between 2001 and 2021, data from 24 clinical centers were collected. Overall survival (OS), recurrence-free survival (RFS), and cancer-specific survival were analyzed as well as recurrence patterns and treatment. The analysis was conducted using a competing-risk framework. The trajectory of the risk of recurrence over time was applied to a competing risk analysis. For post-recurrence survival, death resulting from tumor progression was the primary endpoint, whereas deaths with recurrence relating to other causes were considered as competing events. Results: In total, 813 patients were included in the study. Median OS was 81.4 months (range 28.1-157.0 months), and recurrence occurred in 48.3% of patients, with a median RFS of 39.8 months (range 15.7-174.7 months). Cause-specific hazard of recurrence showed a first peak 6 months (0.027), and a second peak 24 months (0.021) after surgery. The later the recurrence, the higher the chance of receiving curative intent approaches (p = 0.001). Size >5 cm, multiple tumors, microvascular invasion, and cirrhosis were independent predictors of recurrence showing a cause-specific hazard over time. RFS was associated with death for recurrence (hazard ratio: 0.985, 95% CI: 0.977-0.995; p = 0.002). Conclusions: Patients with MS undergoing LR for HCC have good long-term survival. Recurrence occurs in 48% of patients with a double-peak incidence and time-specific hazards depending on tumor-related factors and underlying disease. The timing of recurrence significantly impacts survival. Surveillance after resection should be adjusted over time depending on risk factors. Impact and implications: Metabolic syndrome (MS) is a growing epidemic and a significant risk factor for the development of hepatocellular carcinoma (HCC). The present study demonstrated that patients who undergo surgical resection for HCC on MS have a good long-term survival and that recurrence occurs in almost half of the cases with a double peak incidence and time-specific hazards depending on tumor-related factors and underlying liver disease. Also, the timing of recurrence significantly impacts survival. Clinicians should therefore adjust follow-up after surgery accordingly, considering timing of recurrence and specific risk factors. Also, the results of the present study might help design future trials on the use of adjuvant therapy following resection.

Pancreas preserving duodenectomy (PPrD).

BACKGROUND: Pancreaticoduodenectomy has been the standard of care for managing duodenal neoplasms, but recent studies show similar overall and disease-specific survival after pancreas-preserving duodenectomy (PPrD) with potentially less morbidity. METHODS: Retrospective cohort of all adult (age >18) patients who underwent PPrD with curative intent of a neoplasm in or invading into the duodenum at our institution from 2011 to 2022 (n â€‹= â€‹29), excluding tumors involving the Ampulla of Vater or the pancreas. Statistical analyses were performed using STATA. RESULTS: R0 resection was achieved in 93 â€‹% patients. Ten (34.4 â€‹%) experienced postoperative complications (13.7 â€‹% within Clavien-Dindo III-V). PPrD patients had lower rates of pancreatic leak, delayed gastric emptying, and deep surgical site infection. CONCLUSIONS: In this case series, we demonstrate PPrD is safe and effective, with a high rate of complete resection and lower complication rate than that seen in pancreaticoduodenectomy.

FOLFIRINOX or Gemcitabine-based Chemotherapy for Borderline Resectable and Locally Advanced Pancreatic Cancer: A Multi-institutional, Patient-Level, Meta-analysis and Systematic Review.

BACKGROUND: Pancreatic cancer often presents as locally advanced (LAPC) or borderline resectable (BRPC). Neoadjuvant systemic therapy is recommended as initial treatment. It is currently unclear what chemotherapy should be preferred for patients with BRPC or LAPC. METHODS: We performed a systematic review and multi-institutional meta-analysis of patient-level data regarding the use of initial systemic therapy for BRPC and LAPC. Outcomes were reported separately for tumor entity and by chemotherapy regimen including FOLFIRINOX (FIO) or gemcitabine-based. RESULTS: A total of 23 studies comprising 2930 patients were analyzed for overall survival (OS) calculated from the beginning of systemic treatment. OS for patients with BRPC was 22.0 months with FIO, 16.9 months with gemcitabine/nab-paclitaxel (Gem/nab), 21.6 months with gemcitabine/cisplatin or oxaliplatin or docetaxel or capecitabine (GemX), and 10 months with gemcitabine monotherapy (Gem-mono) (p < 0.0001). In patients with LAPC, OS also was higher with FIO (17.1 months) compared with Gem/nab (12.5 months), GemX (12.3 months), and Gem-mono (9.4 months; p < 0.0001). This difference was driven by the patients who did not undergo surgery, where FIO was superior to other regimens. The resection rates for patients with BRPC were 0.55 for gemcitabine-based chemotherapy and 0.53 with FIO. In patients with LAPC, resection rates were 0.19 with Gemcitabine and 0.28 with FIO. In resected patients, OS for patients with BRPC was 32.9 months with FIO and not different compared to Gem/nab, (28.6 months, p = 0.285), GemX (38.8 months, p = 0.1), or Gem-mono (23.1 months, p = 0.083). A similar trend was observed in resected patients converted from LAPC. CONCLUSIONS: In patients with BRPC or LAPC, primary treatment with FOLFIRINOX compared with Gemcitabine-based chemotherapy appears to provide a survival benefit for patients that are ultimately unresectable. For patients that undergo surgical resection, outcomes are similar between GEM+ and FOLFIRINOX when delivered in the neoadjuvant setting.

Minimally Invasive Versus Open Liver Resections for Hepatocellular Carcinoma in Patients With Metabolic Syndrome.

OBJECTIVE: To compare minimally invasive (MILR) and open liver resections (OLRs) for hepatocellular carcinoma (HCC) in patients with metabolic syndrome (MS). BACKGROUND: Liver resections for HCC on MS are associated with high perioperative morbidity and mortality. No data on the minimally invasive approach in this setting exist. MATERIAL AND METHODS: A multicenter study involving 24 institutions was conducted. Propensity scores were calculated, and inverse probability weighting was used to weight comparisons. Short-term and long-term outcomes were investigated. RESULTS: A total of 996 patients were included: 580 in OLR and 416 in MILR. After weighing, groups were well matched. Blood loss was similar between groups (OLR 275.9±3.1 vs MILR 226±4.0, P =0.146). There were no significant differences in 90-day morbidity (38.9% vs 31.9% OLRs and MILRs, P =0.08) and mortality (2.4% vs 2.2% OLRs and MILRs, P =0.84). MILRs were associated with lower rates of major complications (9.3% vs 15.3%, P =0.015), posthepatectomy liver failure (0.6% vs 4.3%, P =0.008), and bile leaks (2.2% vs 6.4%, P =0.003); ascites was significantly lower at postoperative day 1 (2.7% vs 8.1%, P =0.002) and day 3 (3.1% vs 11.4%, P <0.001); hospital stay was significantly shorter (5.8±1.9 vs 7.5±1.7, P <0.001). There was no significant difference in overall survival and disease-free survival. CONCLUSIONS: MILR for HCC on MS is associated with equivalent perioperative and oncological outcomes to OLRs. Fewer major complications, posthepatectomy liver failures, ascites, and bile leaks can be obtained, with a shorter hospital stay. The combination of lower short-term severe morbidity and equivalent oncologic outcomes favor MILR for MS when feasible.

Model to predict major complications following liver resection for HCC in patients with metabolic syndrome.

BACKGROUND: Metabolic syndrome (MS) is rapidly growing as risk factor for HCC. Liver resection for HCC in patients with MS is associated with increased postoperative risks. There are no data on factors associated with postoperative complications. AIMS: The aim was to identify risk factors and develop and validate a model for postoperative major morbidity after liver resection for HCC in patients with MS, using a large multicentric Western cohort. MATERIALS AND METHODS: The univariable logistic regression analysis was applied to select predictive factors for 90 days major morbidity. The model was built on the multivariable regression and presented as a nomogram. Performance was evaluated by internal validation through the bootstrap method. The predictive discrimination was assessed through the concordance index. RESULTS: A total of 1087 patients were gathered from 24 centers between 2001 and 2021. Four hundred and eighty-four patients (45.2%) were obese. Most liver resections were performed using an open approach (59.1%), and 743 (68.3%) underwent minor hepatectomies. Three hundred and seventy-six patients (34.6%) developed postoperative complications, with 13.8% major morbidity and 2.9% mortality rates. Seven hundred and thirteen patients had complete data and were included in the prediction model. The model identified obesity, diabetes, ischemic heart disease, portal hypertension, open approach, major hepatectomy, and changes in the nontumoral parenchyma as risk factors for major morbidity. The model demonstrated an AUC of 72.8% (95% CI: 67.2%-78.2%) ( https://childb.shinyapps.io/NomogramMajorMorbidity90days/ ). CONCLUSIONS: Patients undergoing liver resection for HCC and MS are at high risk of postoperative major complications and death. Careful patient selection, considering baseline characteristics, liver function, and type of surgery, is key to achieving optimal outcomes.

Gemcitabine-Based Neoadjuvant Treatment in Borderline Resectable Pancreatic Ductal Adenocarcinoma: A Meta-Analysis of Individual Patient Data.

Background: Non-randomized studies have investigated multi-agent gemcitabine-based neo-adjuvant therapies (GEM-NAT) in borderline resectable pancreatic ductal adenocarcinoma (BR-PDAC). Treatment sequencing and specific elements of neoadjuvant treatment are still under investigation. The present meta-analysis aims to assess the effectiveness of GEM-NAT on overall survival (OS) in BR-PDAC. Patients and Methods: A meta-analysis of individual participant data (IPD) on GEM-NAT for BR-PDAC were performed. The primary outcome was OS after treatment with GEM-based chemotherapy. In the Individual Patient Data analysis data were reappraised and confirmed as BR-PDAC on provided radiological data. Results: Six studies investigating GEM-NAT were included in the IPD metanalysis. The IPD metanalysis was conducted on 271 patients who received GEM-NAT. Pooled median patient-level OS was 22.2 months (95%CI 19.1-25.2). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Median OS was 27.8 months (95%CI 23.9-31.6) in the patients who received NAT-GEM followed by resection compared to 15.4 months (95%CI 12.3-18.4) for NAT-GEM without resection and 13.0 months (95%CI 7.4-18.5) in the group of patients who received upfront surgery (p < 0.0001). R0 rates ranged between 81 and 95% (I 2 = 0%, p = 0.64), respectively. Overall survival in the R0 group was 29.3 months (95% CI 24.3-34.2) vs. 16.2 months (95% CI 7·9-24.5) in the R1 group (p = 0·001). Conclusions: The present study is the first meta-analysis combining IPD from a number of international centers with BR-PDAC in a cohort that underwent multi-agent gemcitabine neoadjuvant therapy (GEM-NAT) before surgery. GEM-NAT followed by surgical resection improve survival and R0 resection in BR-PDAC. Also, GEM-NAT may result in a good palliative option in non-resected patients because of progressive disease after neoadjuvant treatment. Results from randomized controlled trials (RCTs) are awaited to validate these findings.

Current Imaging Standards for Nonmetastatic Benign and Malignant Liver Tumors.

The accurate diagnosis of a liver mass can usually be established with a thorough history, examination, laboratory inquiry, and imaging. The necessity of a liver biopsy to determine the nature of a liver mass is rarely necessary. Contrast-enhanced computed tomography and magnetic resonance are the standard of care for diagnosing liver lesions and high-quality imaging should be performed before performing a biopsy. This article discusses current consensus guidelines for imaging of liver masses, as well as masses found on surveillance imaging. The ability to accurately characterize lesions requires proper use and understanding of the technology and expert interpretation.

Significance of radiographic splenic vessel involvement in the pancreatic ductal adenocarcinoma of the body and tail of the gland.

BACKGROUND AND OBJECTIVES: Unlike pancreatic head tumors, little is known about the biological significance of radiographic vessel involvement with pancreatic body/tail adenocarcinoma. We hypothesized radiographic splenic vessel involvement may be an adverse prognostic factor. METHODS: All distal pancreatectomies performed for resectable pancreatic adenocarcinoma between 2000 and 2016 were reviewed and clinicopatholgic data were collected, retrospectively. Preoperative computed tomography imaging was re-reviewed and splenic vessel involvement was graded as none, abutment, encasement, or occlusion. RESULTS: Among a total of 71 patients, splenic artery or vein encasement/occlusion was present in 41% (29 of 71) of patients, each. There were no significant differences in tumor size or grade, margin positivity, and perineural or lymphovascular invasion. However, splenic artery encasement/occlusion (P = 0.001) and splenic vein encasement/occlusion (P = 0.038) both correlated with lymph node positivity. Splenic artery encasement was associated with a reduced median overall survival (20 vs 30 months, P = 0.033). Multivariate analysis also showed that splenic artery encasement was an independent risk factor of worse survival (hazard ratio, 2.246; 95% confidence interval, 1.118-4.513; P = 0.023). CONCLUSION: Patients with cancer of the body or tail of the pancreas presenting with radiographic encasement of the splenic artery, but not the splenic vein, have a poorer prognosis and perhaps should be considered for neoadjuvant therapy before an attempt at curative resection.

Role of fibroblast growth factor 23 and klotho cross talk in idiopathic pulmonary fibrosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial pneumonia that mainly affects the elderly. Several reports have demonstrated that aging is involved in the underlying pathogenic mechanisms of IPF. α-Klotho (KL) has been well characterized as an "age-suppressing" hormone and can provide protection against cellular senescence and oxidative stress. In this study, KL levels were assessed in human plasma and primary lung fibroblasts from patients with idiopathic pulmonary fibrosis (IPF-FB) and in lung tissue from mice exposed to bleomycin, which showed significant downregulation when compared with controls. Conversely, transgenic mice overexpressing KL were protected against bleomycin-induced lung fibrosis. Treatment of human lung fibroblasts with recombinant KL alone was not sufficient to inhibit transforming growth factor-ß (TGF-ß)-induced collagen deposition and inflammatory marker expression. Interestingly, fibroblast growth factor 23 (FGF23), a proinflammatory circulating protein for which KL is a coreceptor, was upregulated in IPF and bleomycin lungs. To our surprise, FGF23 and KL coadministration led to a significant reduction in fibrosis and inflammation in IPF-FB; FGF23 administration alone or in combination with KL stimulated KL upregulation. We conclude that in IPF downregulation of KL may contribute to fibrosis and inflammation and FGF23 may act as a compensatory antifibrotic and anti-inflammatory mediator via inhibition of TGF-ß signaling. Upon restoration of KL levels, the combination of FGF23 and KL leads to resolution of inflammation and fibrosis. Altogether, these data provide novel insight into the FGF23/KL axis and its antifibrotic/anti-inflammatory properties, which opens new avenues for potential therapies in aging-related diseases like IPF.

Initiation of adjuvant therapy following surgical resection of pancreatic ductal adenocarcinoma (PDAC): Are patients from rural, remote areas disadvantaged?

BACKGROUND AND OBJECTIVES: Although race and socioeconomic status have been shown to affect outcomes in pancreatic ductal adenocarcinoma (PDAC), the impact of rural residence on the delivery of adjuvant therapy (AT) has not been studied. METHODS: Patients with resected PDAC were identified using the National Cancer Database (NCDB). Individuals were classified as living in a metro area, urban/rural adjacent to a metro area (URA), and urban/rural remote (URR) area. Multivariate logistic regression was used to assess geographic inhabitance as a predictor of receiving AT. RESULTS: A total of 32 521 individuals who underwent pancreatectomy for PDAC were identified. Univariate analysis demonstrated individuals in URR areas were less likely to receive adjuvant chemotherapy (ACT) than those living in URA or metro areas (55.3% vs 55.6% vs 58.8%, P = 0.011). However on multivariate analysis URR inhabitance was no longer a predictor of ACT (OR = 0.911 P = 0.125) or ART (OR = 0.953 P = 0.462). Cox proportional hazard modeling demonstrated URR inhabitance remained independently associated with poor OS (HR 1.076; 95% CI [1.008, 1.149], P < 0.029). CONCLUSIONS: URR inhabitance does not impact access to AT, however it is independently associated with a decreased OS. Attention must be focused on optimizing oncologic care to patients with disparate access to healthcare.

Fibroblast growth factor 23 and Klotho contribute to airway inflammation.

Circulating levels of fibroblast growth factor (FGF)23 are associated with systemic inflammation and increased mortality in chronic kidney disease. α-Klotho, a co-receptor for FGF23, is downregulated in chronic obstructive pulmonary disease (COPD). However, whether FGF23 and Klotho-mediated FGF receptor (FGFR) activation delineates a pathophysiological mechanism in COPD remains unclear. We hypothesised that FGF23 can potentiate airway inflammation via Klotho-independent FGFR4 activation.FGF23 and its effect were studied using plasma and transbronchial biopsies from COPD and control patients, and primary human bronchial epithelial cells isolated from COPD patients as well as a murine COPD model.Plasma FGF23 levels were significantly elevated in COPD patients. Exposure of airway epithelial cells to cigarette smoke and FGF23 led to a significant increase in interleukin-1ß release via Klotho-independent FGFR4-mediated activation of phospholipase Cγ/nuclear factor of activated T-cells signalling. In addition, Klotho knockout mice developed COPD and showed airway inflammation and elevated FGFR4 expression in their lungs, whereas overexpression of Klotho led to an attenuation of airway inflammation.Cigarette smoke induces airway inflammation by downregulation of Klotho and activation of FGFR4 in the airway epithelium in COPD. Inhibition of FGF23 or FGFR4 might serve as a novel anti-inflammatory strategy in COPD.

Localized pancreatic cancer with positive peritoneal cytology as a sole manifestation of metastatic disease: a single-institution experience.

BACKGROUND: Pancreatic cancer patients with positive peritoneal cytology (PPC) as a sole metastatic site are poorly characterized. Whether they behave similarly to other stage IV patients is unknown. METHODS: Patients with stage IV disease at our institution between 2003 and 2013 were identified. Inclusion criteria for PPC cohort were PPC at laparoscopy and no laparoscopic and/or radiographic evidence of metastasis. Patients with gross metastasis had laparoscopic and/or radiographic evidence of metastasis. RESULTS: Among 308 patients, 43 patients had PPC and 265 had gross metastasis. PPC cohort: 3 (7%) resectable, 8 (19%) borderline resectable, and 32 (74%) unresectable tumor. Disease progression occurred in 37 (86%). Sixteen of 43 (37%) also received local therapy (1 surgery and 15 chemoradiation). PPC vs gross metastasis cohort differed as follows: baseline Ca 19-9 (440 vs 1,904 IU/mL, P < .0001); Eastern Cooperative Oncology Group (ECOG) score ≤1 (98 vs 88%, P = .04); median overall survival (13.9 vs 9.4 months, P = .0001). CONCLUSIONS: Patients with PPC failed to display long-term disease-free survival, although overall survival was superior compared with those with gross metastasis. Patients with PPC may need to be considered a specific subgroup for staging and survival analysis.

Survival and clinical outcome after endoscopic duodenal stent placement for malignant gastric outlet obstruction: comparison of pancreatic cancer and nonpancreatic cancer.

BACKGROUND: Data on endoscopic stenting of malignant gastric outlet obstruction (GOO) are based on studies predominantly involving patients with pancreatic adenocarcinoma. OBJECTIVE: To compare survival and clinical outcome after stent placement for GOO due to pancreatic cancer compared with nonpancreatic cancer. DESIGN: Retrospective study. SETTING: Single tertiary hospital. PATIENTS: A total of 292 patients with malignant GOO. INTERVENTION: Stent placement. MAIN OUTCOME MEASUREMENTS: Post-stent placement survival and clinical outcome. RESULTS: In 196 patients with pancreatic cancer and 96 with nonpancreatic cancer, median post-stent placement survival was similar (2.7 months in pancreatic cancer vs 2.4 months in nonpancreatic cancer). Overall survival was shorter in patients with pancreatic cancer (13.7 vs 17.1 months; P = .004). Clinical success rates at 2 months (71% vs 91%) and reintervention rates (30% vs 23%) were comparable. Post-stent placement chemotherapy and the absence of distant metastasis were associated with better post-stent placement survival in both groups (pancreatic cancer: chemotherapy vs no chemotherapy, 5.4 vs 1.5 months, P < .0001; metastasis vs no metastasis, 1.8 vs 4.6, P = .005; nonpancreatic cancer: chemotherapy vs no chemotherapy, 9.2 vs 1.8, P = .001; metastasis vs no metastasis, 2.1 vs 6.1, P = .009). LIMITATIONS: Retrospective study. CONCLUSIONS: In this large series of patients undergoing stent placement for malignant GOO in North America, we observed no difference in post-stent placement survival despite better overall survival in patients with nonpancreatic cancer. GOO is a marker for poor survival in malignancy, regardless of the type. Chemotherapy and the absence of distant metastasis were associated with better post-stent placement survival in both groups.

Nonsteroidal anti-inflammatory drugs and the risk for anastomotic failure: a report from Washington State's Surgical Care and Outcomes Assessment Program (SCOAP).

IMPORTANCE: Nonsteroidal anti-inflammatory drugs (NSAIDs) have many physiologic effects and are being used more commonly to treat postoperative pain, but recent small studies have suggested that NSAIDs may impair anastomotic healing in the gastrointestinal tract. OBJECTIVE: To evaluate the relationship between postoperative NSAID administration and anastomotic complications. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort study of 13,082 patients undergoing bariatric or colorectal surgery at 47 hospitals in Washington State from January 1, 2006, through December 31, 2010, using data from the Surgical Care and Outcomes Assessment Program linked to the Washington State Comprehensive Abstract Reporting System. EXPOSURE: NSAID administration beginning within 24 hours after surgery. MAIN OUTCOMES AND MEASURES: We used multivariate logistic regression modeling to assess the risk for anastomotic complications (reoperation, rescue stoma, revision of an anastomosis, and percutaneous drainage of an abscess) through 90 days after bariatric and colorectal surgery involving anastomoses. RESULTS: Of the 13,082 patients (mean [SD] age, 58.1 [15.8] years; 60.7% women), 3158 (24.1%) received NSAIDs. The overall 90-day rate of anastomotic leaks was 4.3% for all patients (151 patients [4.8%] in the NSAID group and 417 patients [4.2%] in the non-NSAID group; P=.16). After risk adjustment, NSAIDs were associated with a 24% increased risk for anastomotic leak (odds ratio, 1.24 [95% CI, 1.01-1.56]; P=.04). This association was isolated to nonelective colorectal surgery, for which the leak rate was 12.3% in the NSAID group and 8.3% in the non-NSAID group (odds ratio, 1.70 [95% CI, 1.11-2.68]; P=.01). CONCLUSIONS AND RELEVANCE: Postoperative NSAIDs were associated with a significantly increased risk for anastomotic complications among patients undergoing nonelective colorectal resection. To determine the role of NSAIDs in colorectal surgery, future evaluations should consider specific formulations, the dose effect, mechanism, and other relevant outcome domains, including pain control, cardiac complications, and overall recovery.

Patients' preferences and trade-offs for the treatment of early stage hepatocellular carcinoma.

BACKGROUND: Radio frequency ablation (RFA) and hepatic resection (HR) provide similar survival for early stage hepatocellular carcinoma (ES-HCC). Although RFA has a higher recurrence rate, HR is associated with an increased risk of complications and death. When multiple treatments are available, patients should be enabled to direct their preferred therapy. Yet there is lack of knowledge on patients' preferences for the treatment of ES-HCC. The objective of this study was to assess treatment preferences between HR and RFA for ES-HCC. METHODS: A cohort of 75 cirrhotic adults was educated about the natural history of HCC, treatment options, and the risks and the benefits of HR and RFA. Probability trade-off interviews were used to elicit participants' preferences between the two treatments and strength of their decisions. RESULTS: RFA was preferred by 70% of participants (P = 0.001) who identified the risk of perioperative morbidity and mortality of HR as the main reasons for their decision. Participants changed their minds if HR could provide better 5 (≥15%) and 3-y disease-free survival (≥10%) when compared with RFA. Their preference also changed when RFA had a median ≥8% risk for complications, ≥5% for mortality, ≥8% for nonradical therapy, and ≥5% for tumor seeding. CONCLUSIONS: Informed cirrhotic patients prefer RFA for the treatment of ES-HCC. Participants who preferred RFA were more concerned about the risks of perioperative morbidity and mortality of HR than long-term cancer outcomes. Patients' values and attitudes toward risks and benefits for the treatment of ES-HCC should be explicitly elicited and included in multidisciplinary treatment decisions.

Extended neoadjuvant chemotherapy for borderline resectable pancreatic cancer demonstrates promising postoperative outcomes and survival.

BACKGROUND: The optimum approach to neoadjuvant therapy for patients with borderline resectable pancreatic cancer is undefined. Herein we report the outcomes of an extended neoadjuvant chemotherapy regimen in patients presenting with borderline resectable adenocarcinoma of the pancreatic head. METHODS: Patients identified as having borderline resectable pancreatic head cancer by American Hepato-Pancreato-Biliary Association/Society of Surgical Oncology consensus criteria from 2008 to 2012 were tracked in a prospectively maintained registry. Included patients were initiated on a 24-week course of neoadjuvant chemotherapy. Medically fit patients who completed neoadjuvant treatment without radiographic progression were offered resection with curative intent. Clinicopathologic variables and surgical outcomes were collected retrospectively and analyzed. RESULTS: Sixty-four patients with borderline resectable pancreatic cancer started neoadjuvant therapy. Thirty-nine (61 %) met resection criteria and underwent operative exploration with curative intent, and 31 (48 %) were resected. Of the resected patients, 18 (58 %) had positive lymph nodes, 15 (48 %) required en-bloc venous resection, 27 (87 %) had a R0 resection, and 3 (10 %) had a complete pathologic response. There were no postoperative deaths at 90 days, 16 % of patients had a severe complication, and the 30-day readmission rate was 10 %. The median overall survival of all 64 patients was 23.6 months, whereas that of unresectable patients was 15.4 months. Twenty-five of the resected patients (81 %) are still alive at a median follow-up of 21.6 months. CONCLUSIONS: Extended neoadjuvant chemotherapy is well tolerated by patients with borderline resectable pancreatic head adenocarcinoma, selects a subset of patients for curative surgery with low perioperative morbidity, and is associated with favorable survival.

Posterior 'superior mesenteric artery first' approach for resection of locally advanced pancreatic cancer.

BACKGROUND: En bloc resection of the superior mesenteric vein (SMV), portal vein (PV), and/or splenic vein (SV) with concomitant venous reconstruction is required in 11-65 % of cases of locally advanced pancreatic cancer.1 Early retropancreatic dissection of the superior mesenteric artery (SMA) from behind the pancreatic head utilizing an 'artery first' approach has been reported to be an efficient and safe approach to pancreaticoduodenectomy when SMA involvement is suspected.2 Additionally, this technique has been shown to reduce blood loss and result in shorter PV clamp times.3 While there are multiple variations to 'artery first' resection,4 this video will illustrate the critical steps of using the 'posterior approach' in patients with locally advanced pancreatic cancer. This approach has the benefit of early identification of a replaced right hepatic artery, but may be difficult in obese patients or those with extensive peripancreatic inflammation. These difficulties may be overcome by utilizing an 'inferior supracolic (anterior) approach', but this necessitates early division of the pancreatic neck and stomach.5 METHODS: Select video clips were compiled from several pancreatoduodenectomies to demonstrate this technique. A variety of bipolar devices were utilized for dissection depending on surgeon preference. All patients were diagnosed with locally advanced pancreatic cancer by Americas Hepato-Pancreato-Biliary Association/Society of Surgical Oncology (AHPBA/SSO) consensus criteria, confirmed by biopsy, and completed neoadjuvant chemotherapy. Patients were restaged by pancreas protocol computed tomography scan at the end of chemotherapy and offered local resection if the tumor did not progress and they were medically fit. No Institutional Review Board approval was required. RESULTS: The operation begins by dividing the attachment of the transverse mesocolon to the right perinephric area and extending this down to the white line of Toldt, followed by a wide Kocher maneuver. The lateral attachments to the pancreatic head are then divided, thereby exposing the left renal vein. The lesser sac is entered directly over the uncinate, allowing for a full visceral rotation of the pancreatic head, and further facilitating exposure of the left renal vein. In the setting of malignancy, the SMA may now be palpated posterior to the pancreatic head and/or neck to confirm it is free of tumor. If tumor is invading the SMA, the pancreaticoduodenectomy is aborted prior to performing any gastrointestinal or pancreatic transections. If the SMA is free, the dissection is then carried on to the inferior aspect of the pancreatic neck. Here the SMV (jejunal and ileal branches), middle colic vein, and the gastroepiploic vein are identified and the latter is ligated and transected. Following this, dissection of the portal structures (hepatic arteries, gastroduodenal artery, common bile duct, and PV) is performed. The jejunum is then divided, the ligament of Treitz is taken down, and the jejunum is then mobilized to the patient's right side. This allows for clear visualization of the pancreatic head/uncinate/SMV relationship. At this point, proximal and distal control of the PV, SMV, and SV should be obtained using vessel loops or umbilical tape. The dissection then proceeds laterally along the SMA border (posterior to the pancreatic head). This is often facilitated by use of a bipolar sealing device due to a rich lymphovascular network. Once the lateral border of the SMA is clearly exposed, dissection along its longitudinal axis is performed utilizing the jejunum for traction. Following this dissection, larger vessels such as the inferior pancreaticoduodenal artery can be more readily identified and ligated to fully mobilize the pancreatic head. After the head is completely separated from the SMA, the neck is divided. This leaves the specimen attached solely by the PV and SMV, which greatly facilitates venous resection and reconstruction when necessary. CONCLUSION: The 'artery first' approach has been shown to be safe and feasible in pancreatic resections. This technique should be considered whenever tumor is thought to involve the SMV and/or PVs as a means to facilitate safe venous resection and reconstruction while preserving sound oncologic principles.

Use the duodenum, it's right there: a retrospective cohort study comparing biliary reconstruction using either the jejunum or the duodenum.

IMPORTANCE: This is the largest series to date comparing end-to-side biliary reconstruction for all indications performed using either the duodenum or jejunum and with at least 2-year follow-up. OBJECTIVE: To demonstrate that duodenal anastomoses for biliary reconstruction are at least as safe and effective as Roux-en-Y jejunal anastomoses, with the benefits of operative simplicity and ease of postoperative endoscopic evaluation. DESIGN, SETTING, AND PARTICIPANTS: Retrospective record review with telephone survey of patients undergoing nonpalliative biliary reconstruction in the hepatopancreatobiliary surgery division of a high-volume tertiary care facility. INTERVENTIONS: Biliary reconstruction via either end-to-side Roux-en-Y jejunal anastomosis or direct duodenal anastomosis. MAIN OUTCOMES AND MEASURES: The primary end points were anastomosis-related complications (leak, cholangitis, bile gastritis, or stricture), and the secondary end points were overall complications, endoscopic or radiologic interventions, readmissions, and death. RESULTS: Ninety-six nonpalliative biliary reconstructions were performed between February 1, 2000, and November 23, 2011 for bile duct injury, cholangiocarcinoma, choledochal cysts, or benign strictures; the procedures included 59 duodenal reconstructions and 37 Roux-en-Y jejunal reconstructions. The groups were similar with regard to demographics, operative indications, postoperative length of stay, and mortality rates. However, anastomosis-related complications (leaks, cholangitis, or strictures) were fewer in the duodenal than the jejunal cohort (7 patients [12%] vs 13 [35%]; P = .009). Of patients with stricture, 5 of 9 in the jejunal cohort required percutaneous transhepatic access for management compared with only 1 of 2 in the duodenal cohort. CONCLUSIONS AND RELEVANCE: Duodenal anastomosis is a safe, simple, and often preferable method for biliary reconstruction. This anastomosis can successfully be performed to all levels of the biliary tree with low rates of leak, stricture, cholangitis, and bile gastritis. When anastomotic complications do occur, there is less need for transhepatic intervention because of easier endoscopic access.