Evaluation of the ACS NSQIP Surgical Risk Calculator in Elderly Patients Undergoing Hepatectomy for Hepatocellular Carcinoma

Background: The American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP) surgical risk calculator (SRC) aims to help predict patient-specific risk for morbidity and mortality. The performance of the SRC among an elderly population undergoing curative-intent hepatectomy for hepatocellular carcinoma (HCC) remains unknown. Methods: Patients > 70 years of age who underwent hepatectomy for HCC between 1998 and 2017 were identified using a multi-institutional international database. To estimate the performance of SRC, 12 observed postoperative outcomes were compared with median SRC-predicted risk, and C-statistics and Brier scores were calculated. Results: Among 500 patients, median age was 75 years (IQR 72-78). Most patients (n = 324, 64.8%) underwent a minor hepatectomy, while 35.2% underwent a major hepatectomy. The observed incidence of venous thromboembolism (VTE) (3.2%) and renal failure (RF) (4.4%) exceeded the median predicted risk (VTE, 1.8%; IQR 1.5-3.1 and RF, 1.0%; IQR 0.5-2.0). In contrast, the observed incidence of 30-day readmission (7.0%) and non-home discharge (2.5%) was lower than median-predicted risk (30-day readmission, 9.4%; IQR 7.4-12.8 and non-home discharge, 5.7%; IQR 3.3-11.7). Only 57.8% and 71.2% of patients who experienced readmission (C-statistic, 0.578; 95%CI 0.468-0.688) or mortality (C-statistic, 0.712; 95%CI 0.508-0.917) were correctly identified by the model. Conclusion: Among elderly patients undergoing hepatectomy for HCC, the SRC underestimated the risk of complications such as VTE and RF, while being no better than chance in estimating the risk of readmission. The ACS SRC has limited clinical applicability in estimating perioperative risk among elderly patients being considered for hepatic resection of HCC.info:eu-repo/semantics/publishedVersio

Impact of Body Mass Index on Tumor Recurrence Among Patients Undergoing Curative - Intent Resection of Intrahepatic Cholangiocarcinoma - a Multi-institutional International Analysis

Background: The association between body mass index (BMI) and long-term outcomes of patients with ICC has not been well defined. We sought to define the presentation and oncologic outcomes of patients with ICC undergoing curative-intent resection, according to their BMI category. Methods: Patients who underwent resection of ICC were identified in a multi-institutional database. Patients were categorized as normal weight (BMI 18.5-24.9 kg/m2), overweight (BMI 25.0-29.9 kg/m2) and obese (BMI≥30 kg/m2) according to the World Health Organization (WHO) definition. Impact of clinico-pathological factors on recurrence-free survival (RFS) was assessed using Cox proportional hazards model among patients in the three BMI categories. Results: Among a total of 790 patients undergoing curative-intent resection of ICC in the analytic cohort, 399 (50.5%) had normal weight, 274 (34.7%) were overweight and 117 (14.8%) were obese. Caucasian patients were more likely to be obese (66.7%, n = 78) and overweight (47.1%, n = 129) compared with Asian (obese: 18.8%, n = 22; overweight: 46%, n = 126) and other races (obese: 14.5%, n = 17; overweight: 6.9%, n = 19)(p 0.05). On multivariable analysis, increased BMI was an independent risk factor for tumor recurrence (OR 1.16, 95% CI 1.02-1.32, for every 5 unit increase). Conclusion: Increasing BMI was associated with incremental increases in the risk of recurrence following curative-intent resection of ICC. Future studies should aim to achieve a better understanding of BMI-related factors relative to prognosis of patients with ICC.info:eu-repo/semantics/publishedVersio

Association of TMTC2 with human nonsyndromic sensorineural hearing loss

IMPORTANCE: Sensorineural hearing loss (SNHL) is commonly caused by conditions that affect cochlear structures or the auditory nerve, and the genes identified as causing SNHL to date only explain a fraction of the overall genetic risk for this debilitating disorder. It is likely that other genes and mutations also cause SNHL. OBJECTIVE: To identify a candidate gene that causes bilateral, symmetric, progressive SNHL in a large multigeneration family of Northern European descent. DESIGN, SETTING, AND PARTICIPANTS: In this prospective genotype and phenotype study performed from January 1, 2006, through April 1, 2016, a 6-generation family of Northern European descent with 19 individuals having reported early-onset hearing loss suggestive of an autosomal dominant inheritance were studied at a tertiary academic medical center. In addition, 179 unrelated adult individuals with SNHL and 186 adult individuals reporting nondeafness were examined. MAIN OUTCOMES AND MEASURES: Sensorineural hearing loss. RESULTS: Nine family members (5 women [55.6%]) provided clinical audiometric and medical records that documented hearing loss. The hearing loss is characterized as bilateral, symmetric, progressive SNHL that reached severe to profound loss in childhood. Audiometric configurations demonstrated a characteristic dip at 1000 to 2000 Hz. All affected family members wear hearing aids or have undergone cochlear implantation. Exome sequencing and linkage and association analyses identified a fully penetrant sequence variant (rs35725509) on chromosome 12q21 (logarithm of odds, 3.3) in the TMTC2 gene region that segregates with SNHL in this family. This gene explains the SNHL occurrence in this family. The variant is also associated with SNHL in a cohort of 363 unrelated individuals (179 patients with confirmed SNHL and 184 controls, P = 7 x 10-4). CONCLUSIONS AND RELEVANCE: A previously uncharacterized gene, TMTC2, has been identified as a candidate for causing progressive SNHL in humans. This finding identifies a novel locus that causes autosomal dominant SNHL and therefore a more detailed understanding of the genetic basis of SNHL. Because TMTC2 has not been previously reported to regulate auditory function, the discovery reveals a potentially new, uncharacterized mechanism of hearing loss

Effect of Surgical Margin Width on Patterns of Recurrence among Patients Undergoing R0 Hepatectomy for T1 Hepatocellular Carcinoma: an International Multi-Institutional Analysis

Introduction: Although a positive surgical margin is a known prognostic factor for recurrence, the optimal surgical margin width in the context of an R0 resection for early-stage hepatocellular carcinoma (HCC) is still debated. The aim of the current study was to examine the impact of wide (> 1 cm) versus narrow (< 1 cm) surgical margin status on the incidence and recurrence patterns among patients with T1 HCC undergoing an R0 hepatectomy. Methods: Between 1998 and 2017, patients with T1 HCC who underwent R0 hepatectomy for stage T1 HCC were identified using an international multi-institutional database. Recurrence-free survival (RFS) was estimated, and recurrence patterns were examined based on whether patients had a wide versus narrow resection margins. Results: Among 404 patients, median patient age was 66 years (IQR: 58-73). Most patients (n = 326, 80.7%) had surgical margin 1 cm margin. The majority of patients had early recurrences ( 1 cm: 85.7%, p = 0.141); recurrence site was mostly intrahepatic ( 1 cm: 61.9%, p = 0.169). The 1-, 3-, and 5-year RFS among patients with margin 1 cm, respectively (p = 0.02). Among patients undergoing anatomic resection, resection margin did not impact RFS (3-year RFS: 1 cm: 58.9%, p = 0.169), whereas in the non-anatomic resection group, margin width > 1 cm was associated with a better 3-year RFS compared to margin 1 cm remained protective against recurrence (HR = 0.50, 95%CI 0.28-0.89), whereas Child-Pugh B (HR = 2.13, 95%CI 1.09-4.15), AFP > 20 ng/mL (HR = 1.71, 95%CI 1.18-2.48), and presence of microscopic lymphovascular invasion (HR = 1.48, 95%CI 1.01-2.18) were associated with a higher hazard of recurrence. Conclusion: Resection margins > 1 cm predicted better RFS among patients undergoing R0 hepatectomy for T1 HCC, especially small (< 5 cm) HCC. Although resection margin width did not influence outcomes after anatomic resection, wider margins were more important among patients undergoing non-anatomic liver resections.info:eu-repo/semantics/publishedVersio

Safety and oncologic outcomes of robotic liver resections: A systematic review

The robotic system has emerged as a new minimally invasive technology with promising results. We sought to systematically review the available literature on the safety and the oncologic outcomes of robotic liver surgery. A systematic review was conducted using Medline (PubMed), Embase and Cochrane library through November 12th, 2017. A robotic approach may be a safe and feasible surgical option for minor and major liver resections. © 2018 Wiley Periodicals, Inc

KRAS Mutation Status Dictates Optimal Surgical Margin Width in Patients Undergoing Resection of Colorectal Liver Metastases

Background: The optimal tumor-free margin width remains controversial and may be inappropriate to investigate without considering differences in the underlying tumor biology. Methods: R1 resection was defined as margin clearance less than 1 mm. R0 resection was further divided into 3 groups: 1–4, 5–9, and ≥10 mm. The impact of margin width on overall survival (OS) relative to KRAS status [wild type (wtKRAS) vs. mutated (mutKRAS)] was assessed. Results: A total of 411 patients met inclusion criteria. Median patient age was 58 years (interquartile range, 49.7–66.7); most patients were male (n = 250; 60.8 %). With a median follow-up of 28.3 months, median and 5-year OS were 69.8 months and 55.1 %. Among patients with wtKRAS tumors, although margin clearance of 1–4 mm or more was associated with improved OS compared to R1 (all P &lt; 0.05), no difference in OS was observed when comparing margin clearance of 1–4 mm to the 5–9 mm and the ≥10 mm groups (all P &gt; 0.05). In contrast, among patients with mutKRAS tumors, all three groups of margin clearance (1–4, 5–9, and ≥10 mm) fared no better in terms of 5-year survival compared to R1 resection (all P &gt; 0.05). Conclusions: While a 1–4 mm margin clearance in patients with wtKRAS tumors was associated with improved survival, wider resection width did not confer an additional survival benefit. In contrast, margin status—including a 1 cm margin—did not improve survival among patients with mutKRAS tumors. © 2016, Society of Surgical Oncology

Perioperative Hyperglycemia and Postoperative Outcomes in Patients Undergoing Resection of Colorectal Liver Metastases

Introduction: There is limited evidence characterizing the impact of glycemic alterations on short-term outcomes among patients undergoing resection of colorectal liver metastases (CRLM). Methods: Hyperglycemia was defined as a glucose value &gt;125 mg/dl according to WHO definition. The impact of early postoperative hyperglycemia on short-term postoperative outcomes was assessed. Results: The mean postoperative glucose value was 128 mg/dl; 30 (9.8 %) patients had normal fasting glucose (&lt;100 mg/dl), 106 patients had glucose intolerance (100–125 mg/dl), and 170 (55.5 %) patients had hyperglycemia (&gt;125 mg/dl). A postoperative complication occurred in 101 patients (morbidity, 33.1 %); among patients who experienced a complication, an infectious complication was most common (38.6 %). After controlling for clinical factors, patients with hyperglycemia had an increased risk of overall complications [odds ratio (OR) 4.11; 95 % confidence interval (CI) 1.96–8.62, P &lt; 0.001]. This was the case for both patients with and without diabetes (P &lt; 0.05). Patients with hyperglycemia on the day of surgery were also at an increased risk of infections [OR 9.17; 95 % CI 2.26–37.13, P = 0.002] and had a longer hospital stay (normal glucose, 4 days vs. glucose 100–125 mg/dl, 4 days vs. glucose &gt;125 mg/dl, 5 days, P &lt; 0.001). Conclusions: Early postoperative hyperglycemia was associated with adverse outcomes in patients with and without diabetes who underwent resection of CRLM. Perioperative glucose evaluation may be an important quality target. © 2016, The Society for Surgery of the Alimentary Tract

Laparoscopic synchronous resection of colorectal cancer and liver metastases: A systematic review

While colorectal and hepatic resections are commonly performed through a laparoscopic approach, the safety and feasibility of total laparoscopic synchronous resections (LSR) of colorectal liver metastasis (CRLM) have not been established. In this systematic review, short- and long-term outcomes were comparable for patients undergoing LSR and open synchronous resection. LSR was safe and feasible for patients with synchronous CRLM and should be considered in well-selected patients. © 2018 Wiley Periodicals, Inc