Inflammatory Bowel Disease Serological Immune Markers Anti-Saccharomyces cerevisiae Mannan Antibodies and Outer Membrane Porin C are Potential Biomarkers for Hirschsprung-associated Enterocolitis.

OBJECTIVE: Hirschsprung-associated enterocolitis (HAEC) is the most frequent complication in Hirschsprung disease (HSCR) patients. Currently HAEC is diagnosed clinically, leaving uncertainty in the diagnosis thereby potentially leading to over- or undertreatment of patients. The aim of this study was to identify immune biomarkers to aid in the diagnosis of HAEC. METHODS: From 2012 to 2017, 43 children with HSCR enrolled in a multicenter study, underwent retrospective evaluation of their medical records, and questionnaire-directed parent interviews. HAEC status was determined using HAEC score with cutoff ≥4. Plasma was collected and analyzed by ELISA for the inflammatory bowel disease-associated antibodies: anti-Saccharomyces cerevisiae mannan antibodies (ASCA), outer membrane porin C (OmpC), CBir1, antineutrophil cytoplasmic antibodies. Data were analyzed using t test, univariate, multivariable, and binomial regression models. RESULTS: Eighteen patients had at least 1 episode of HAEC, 25 had no history of HAEC. The HAEC and NO HAEC groups had similar median ages (3 years) and family histories of HSCR. The HAEC group showed markedly elevated ASCA IgA and OmpC antibody levels compared with the NO HAEC group, whereas CBir1 and antineutrophil cytoplasmic antibodies were similar between the groups. Both univariate and multivariable analysis revealed higher OmpC antibody levels associated with HAEC (odds ratio 1.39, confidence interval 1-1.92, P = 0.048), whereas univariate analysis identified a trend toward elevated IgA and immunoglobulin G ASCA levels with HAEC. CONCLUSIONS: We identified elevated OmpC and ASCA serum antibody levels in HAEC patients, and that increased OmpC antibody levels correlated with HAEC occurrence, suggesting HAEC and Crohn disease share gut microbial-host immune responses. These antibodies may serve as potential biomarkers for HAEC, although prospective study with larger sample size is needed.

Preoperative liver function assessments to estimate the prognosis and safety of liver resections.

Liver function assessment is important to ensure safe surgical procedures in patients with hepatocellular disease. Because the liver influences a wide variety of functions, including protein synthesis and metabolic, immune and storage functions, no single parameter is sufficient to adequately address all of these functions. We reviewed the relevant literature concerning the scoring systems, functional tests, plasma parameters and imaging modalities currently used to evaluate the liver function in an attempt to determine which parameters provide the most comprehensive and useful results. While the Child-Pugh scoring system is the gold standard for liver disease assessment, the liver damage grading system recommended by the Liver Cancer Study Group of Japan is also useful. Various models for end-stage liver disease scoring are used for organ allocation. While the indocyanine green clearance test is widely accepted throughout the world, other assessments have not been used routinely for clinical evaluations. The levels of plasma proteins, including albumin, prealbumin, retinol binding protein, apolipoprotein, coagulation factors and antithrombin III, represent the liver productivity. Liver fibrotic markers also correlate with liver function. Imaging modalities such as (99m)Tc-galactosyl serum albumin scintigraphy, (99m)Tc-mebrofenin hepatobiliary scintigraphy and transient elastography are also available, but future studies are needed to validate their clinical efficacy.

Prognosis and predictors of surgical complications in hepatocellular carcinoma patients with or without cirrhosis after hepatectomy.

BACKGROUND: Although poor liver function is associated with a high morbidity rate and poor prognosis in hepatocellular carcinoma (HCC) patients, the exact effects of liver pathology on the surgical outcomes of HCC patients are poorly understood. The purpose of this study was to assess how the liver pathology of HCC patients affects their prognosis and complications rate after liver resection. METHODS: Between January 2006 and November 2010, 149 consecutive hepatocellular carcinoma patients, including 79 noncirrhosis patients and 70 cirrhosis patients, were enrolled in this study. RESULTS: Among the noncirrhotic patients, operative time, fresh frozen plasma (FFP) transfusion requirement, tumor size, and serum retinol binding protein (RBP) levels were significantly higher in the complications group than in the complications-free groups. On the other hand, in the cirrhotic patients the prothrombin time (PT) and indocyanine green retention value at 15 min (ICGR15) of the complications group were significantly lower and higher, respectively, than those of the complications-free group. In the noncirrhotic patients, recurrence-free survival and overall survival did not differ between the complications and complications-free groups. On the other hand, in the cirrhotic patients, the recurrence-free survival and overall survival of the complications-free group were significantly longer than those of the complications group. CONCLUSIONS: In the noncirrhotic patients, surgical complications had no prognostic effect, whereas they had a significant survival impact in the cirrhotic patients. The surgical strategy for HCC should be based on the patient's pathological background.

Current standard values of health utility scores for evaluating cost-effectiveness in liver disease: A meta-analysis.

BACKGROUND: Health utility assessments have been developed for various conditions, including chronic liver disease. Health utility scores are required for socio-economic evaluations, which can aid the distribution of national budgets. However, the standard health utility assessment scores for specific health conditions are largely unknown. AIM: To summarize the health utility scores, including the EuroQOL 5-dimensions 5-levels (EQ-5D-5L), EuroQol-visual analogue scale, short from-36 (SF-36), RAND-36, and Health Utilities Index (HUI)-Mark2/Mark3 scores, for the normal population and chronic liver disease patients. METHODS: A systematic literature search of PubMed and MEDLINE, including the Cochrane Library, was performed. Meta-analysis was performed using the RevMan software. Multiple means and standard deviations were combined using the StatsToDo online web program. RESULTS: The EQ-5D-5L and SF-36 can be used for health utility evaluations during antiviral therapy for hepatitis C. HUI-Mark2/Mark3 indicated that the health utility scores of hepatitis B patients are roughly 30% better than those of hepatitis C patients. CONCLUSION: The EQ-5D-5L is the most popular questionnaire for health utility assessments. Health assessments that allow free registration would be useful for evaluating health utility in patients with liver disease.

Experience with a new 3-mm laparoscope in complex neonatal minimally invasive surgery: a preliminary report.

Neonatal minimally invasive surgery requires small, light-weight instruments and excellent image quality to be performed safely and efficiently. We performed laboratory studies comparing the image quality of a new 3-mm 14-cm telescope with a 5-mm 25-cm telescope with identical viewing angles and found they were very similar. We employed the new 3-mm telescope exclusively in endosurgical procedures on 5 infants weighing less than 4 kg and found the image quality and light intensity to be more than adequate. In addition, we found the shorter length and lighter weight easier to maneuver in the limited working space of the neonatal abdomen or hemithorax. Our experience with the new 3-mm telescope is superb for the demands of complex neonatal endosurgical procedures.

Critical evaluation of the Hirschsprung-associated enterocolitis (HAEC) score: A multicenter study of 116 children with Hirschsprung disease.

OBJECTIVE: To identify the optimal clinical criteria to diagnose Hirschsprung-associated enterocolitis (HAEC) in children with Hirschsprung disease (HSCR). BACKGROUND: HAEC is the most common life-threatening complication in HSCR patients, yet the diagnostic criteria for HAEC remain unclear. The consensus-based HAEC scoring system was not validated using patient data, thereby making its diagnostic accuracy uncertain. METHODS: From 2009 to 2015, consecutive children with HSCR underwent retrospective evaluation of their medical records, and questionnaire-directed parent interviews to identify treatment of suspected HAEC episodes and the 16 clinical criteria in the HAEC score. Logistic regression modeling was employed to identify criteria predicting suspected HAEC episodes. RESULTS: One hundred sixteen HSCR patients met inclusion criteria, 43 patients (37.1%) were treated for at least one suspected HAEC episode. An HAEC score of 4 maximized the sum of sensitivity (83.7%) and specificity (98.6%) while the previously established cut-off score of 10 showed lower sensitivity (41.9%) with perfect specificity. Multivariable analysis identified four criteria utilized to create a new HAEC Risk score with performance characteristics similar to the HAEC score cutoff of 4. CONCLUSION: When using the HAEC score, a cutoff of 4 should be used rather than 10, which under-diagnosed patients with HAEC. Alternatively, the new HAEC Risk score could be employed. LEVEL OF EVIDENCE: Diagnostic Study, Level 3.

Altered fecal short chain fatty acid composition in children with a history of Hirschsprung-associated enterocolitis.

PURPOSE: Children with Hirschsprung disease (HD) who have a history of enterocolitis (HAEC) have a shift in colonic microbiota, many of which are necessary for short chain fatty acid (SCFA) production. As SCFAs play a critical role in colonic mucosal preservation, we hypothesized that fecal SCFA composition is altered in children with HAEC. METHODS: A multicenter study enrolled 18 HD children, abstracting for history of feeding, antibiotic/probiotic use, and enterocolitis symptoms. HAEC status was determined per Pastor et al. criteria (12). Fresh feces were collected for microbial community analysis via 16S sequencing as well as SCFA analysis by gas chromatography-mass spectrometry. RESULTS: Nine patients had a history of HAEC, and nine had never had HAEC. Fecal samples from HAEC children showed a 4-fold decline in total SCFA concentration vs. non-HAEC HD patients. We then compared the relative composition of individual SCFAs and found reduced acetate and increased butyrate in HAEC children. Finally, we measured relative abundance of SCFA-producing fecal microbiota. Interestingly, 10 of 12 butyrate-producing genera as well as 3 of 4 acetate-producing genera demonstrated multi-fold expansion. CONCLUSION: Children with HAEC history have reduced fecal SCFAs and altered SCFA profile. These findings suggest a complex interplay between the colonic metabolome and changes in microbiota, which may influence the pathogenesis of HAEC.

New technique of extracorporeal hepatic inflow control for pure laparoscopic liver resection.

We have developed a new technique of the Pringle maneuver by clamping outside the abdominal wall for pure laparoscopic liver resection (pure Lap). Our technique successfully controls bleeding and enables pure Lap to be completed without any events, even for a large tumor. Between 2008 and 2010, we compared consecutive patients who received pure Lap with (n=11) and without (n=7) this Pringle maneuver. Although tumor size in the Pringle group was significantly larger than in the no-Pringle group (3.35±1.64 vs. 1.11±0.29 cm, respectively), intraoperative bleeding was not significantly different (165.5±188.5 vs. 177.9±364.4 mL, respectively). In contrast, operation time in the Pringle group was significantly longer than in the no-Pringle group (343.1±99.5 vs. 199.6±63.2 min, respectively). Pure Lap for large tumors is feasible when employing a new Pringle maneuver outside the abdominal wall.

Characterization of Bacterial and Fungal Microbiome in Children with Hirschsprung Disease with and without a History of Enterocolitis: A Multicenter Study.

Development of potentially life-threatening enterocolitis is the most frequent complication in children with Hirschsprung disease (HSCR), even after definitive corrective surgery. Intestinal microbiota likely contribute to the etiology of enterocolitis, so the aim of this study was to compare the fecal bacterial and fungal communities of children who developed Hirschsprung-associated enterocolitis (HAEC) with HSCR patients who had never had enterocolitis. Eighteen Hirschsprung patients who had completed definitive surgery were enrolled: 9 had a history of HAEC and 9 did not. Fecal DNA was isolated and 16S and ITS-1 regions sequenced using Next Generation Sequencing and data analysis for species identification. The HAEC group bacterial composition showed a modest reduction in Firmicutes and Verrucomicrobia with increased Bacteroidetes and Proteobacteria compared with the HSCR group. In contrast, the fecal fungi composition of the HAEC group showed marked reduction in diversity with increased Candida sp., and reduced Malassezia and Saccharomyces sp. compared with the HSCR group. The most striking finding within the HAEC group is that the Candida genus segregated into "high burden" patients with 97.8% C. albicans and 2.2% C. tropicalis compared with "low burden" patients 26.8% C. albicans and 73% C. tropicalis. Interestingly even the low burden HAEC group had altered Candida community structure with just two species compared to more diverse Candida populations in the HSCR patients. This is the first study to identify Candida sp. as potentially playing a role in HAEC either as expanded commensal species as a consequence of enterocolitis (or treatment), or possibly as pathobioants contributing to the pathogenesis of HAEC. These findings suggest a dysbiosis in the gut microbial ecosystem of HAEC patients, such that there may be dominance of fungi and bacteria predisposing patients to development of HAEC.

Outcome of elderly patients with appendicitis: effect of computed tomography and laparoscopy.

HYPOTHESIS: Elderly patients who have appendicitis have a greater morbidity and mortality rate when compared with younger patients. We hypothesized that recent changes in the diagnosis and management of appendicitis in elderly patients might affect the outcome. DESIGN: Retrospective review. SETTING: Large metropolitan teaching hospital. PATIENTS: All patients aged 70 years and older who underwent appendectomy for appendicitis between January 1, 1991, and December 31, 2000, were divided into groups 1 (those treated from January 1, 1991, through December 31, 1995) and 2 (those treated from January 1, 1996, through December 31, 2000). MAIN OUTCOME MEASURES: Age, sex, preoperative evaluation, operative duration and findings, postoperative course, duration of hospital stay, and mortality rate. Continuous and categorical variables were analyzed using t and chi(2) tests, respectively. RESULTS: Ninety-five patients met inclusionary criteria. The mean age (78 years), sex, preoperative suggestion of appendicitis (group 1, 39 [83%] of 47 patients; group 2, 45 [94%] of 48 patients), and duration of the preoperative hospitalization over 24 hours (group 1, 11 patients [23%]; group 2, 9 patients [19%]) were similar in both groups. There was an increasing use of diagnostic computed tomography (group 1, 13 patients [28%]; group 2, 32 patients [67%]; P<.001) and laparoscopy (group 1, 14 patients [30%]; group 2, 23 patients [48%]; P =.02) between the 2 study periods associated with no significant difference in the duration of hospitalization, frequency of appendiceal perforation or abscess, occurrence of complications, or mortality. The length of operating time increased in the second period (ie, January 1, 1996, through December 31, 2000). CONCLUSIONS: Appendicitis in elderly patients continues to be a challenging surgical problem. While computed tomography may represent a useful diagnostic tool and laparoscopic appendectomy may be appropriate therapy for selected patients, neither has affected outcome when measured for morbidity and mortality rates. Overall results might improve with earlier consideration of the diagnosis in elderly patients with abdominal pain, followed by prompt surgical consultation and operation.

Octreotide in the treatment of lymphorrhea after axillary node dissection: a prospective randomized controlled trial.

BACKGROUND: Axillary lymph node dissection for staging and local control of nodal disease is an integral part of breast cancer therapy. Lymphorrea is a serious and disabling complication of axillary lymphadenectomy, but no effective therapy is currently available. Octreotide is a hormone with general antisecretory effects that has been used to control lymphorrhea in thoracic duct injury and after radical neck dissection. The aim of the study we describe in this article was to determine whether octreotide has a role in the treatment of post axillary lymphadenectomy lymphorrhea. STUDY DESIGN: This is a prospective randomized controlled trial. Two hundred sixty-one consecutive patients with various stages of breast cancer who underwent axillary lymph node dissection were randomized and followed for 7 years. The treatment group received 0.1 mg octreotide subcutaneously three times a day for 5 days, starting on the first postoperative day, while the control group received no treatment. Of the 261 patients undergoing axillary node dissection, 136 were assigned to the control group and 125 composed the treatment group. The control group and the treatment group were evaluated for amount and duration of lymphorrhea as well as inflammatory and infectious complications. RESULTS: In the control group, the mean quantity (+/- standard deviation) of lymphorrhea was 94.6 +/- 19 cc per day and the average duration was 16.7 +/- 3.0 days. In comparison, the mean quantity of lymphorrhea in the treatment group was 65.4 +/- 21.1 cc (p < 0.0001) per day and the average duration was 7.1 +/- 2.9 days (p < 0.0001). We did not find an important difference in the number of infectious complication or hematomas formation between the study groups. CONCLUSIONS: Octreotide can be used successfully for the treatment of post-axillary dissection lymphorrea, and potentially, in the prevention of post-axillary lymph node dissection lymphosarcoma, since the amount and duration of lymphorrhea in this setting are known to be important risk factors for its development. Potentially, octreotide might be used in similar situations where lymphorrhea is detrimental, such as peripheral vascular surgery and regional lymph node dissection for melanoma.

Laparoscopic antireflux surgery and its effect on cough in patients with gastroesophageal reflux disease.

In addition to heartburn and regurgitation, cough is a frequent nonspecific complaint of patients with gastroesophageal reflux disease. The incidence of alternative etiologies for patients with chronic cough who are undergoing antireflux surgery is not known. To determine this, and the response of chronic cough to fundoplication, we performed a retrospective review of 129 patients with proven gastroesophageal reflux referred for surgical therapy. Chronic cough was present in 37 (29%) preoperatively. No differences were found in age, sex, or preoperative manometric findings between those with and without chronic cough. Patients with cough had a higher number of lower esophageal reflux events on preoperative 24-hour pH testing, and were more likely to have persistent dysphagia after surgery. Fifty-nine percent of patients with cough had an alternative etiology for cough, compared to 36% of those without cough. Of the common alternative etiologies, only a history of postnasal drip occurred more frequently in those with cough. Complete resolution of cough occurred in 24 patients (64%), with another 10 (27%) reporting significant improvement. The average cough score improved significantly regardless of which coexisting etiology the patients may have had. Additionally, heartburn and regurgitation were improved in 94% of all patients.

Immediate early genes and p21 regulation in liver of rats with acute hepatic failure.

It has been observed that liver regeneration in acute hepatic failure (AHF) is suppressed [Eguchi et al. Hepatology 1996;24(6):1452-9]. The molecular mechanism regulating this inhibition is not known. We previously reported that in AHF rats, hepatocyte proliferation was significantly impaired with elevation in serum IL-6, TGF-beta1, and HGF [Kamohara et al. Biochem Biophys Res Commun 2000;273(1):129-35]. Following either 70% partial hepatectomy (PH) or liver injury, quiescent mature hepatocytes are "primed" to re-enter the cell cycle. The process of "priming" appears to be triggered by extracellular cytokines (IL-6 and TNF-alpha) and is characterized by expression of immediate early genes. Under the stimulation of growth factors such as HGF, "primed" hepatocytes exit the G1 phase of the cell cycle. G1-associated cyclins and their inhibitors play a pivotal role in G1/S cell cycle transition. Here, we demonstrate that immediate early gene (i.e. c-myc, c-fos) expression and AP-1 activity are preserved in AHF rat livers despite absence of hepatocyte proliferation. In contrast, p21 mRNA and protein are both over-expressed in AHF livers compared to livers from rats undergoing PH; this elevation leads to inhibition in Cdk2 activity, resulting in G1 cell cycle arrest and inhibition of regeneration.

Propensity score analysis demonstrated the prognostic advantage of anatomical liver resection in hepatocellular carcinoma.

AIM: To compare the prognoses of hepatocellular carcinoma (HCC) patients that underwent anatomic liver resection (AR) or non-anatomic liver resection (NAR) using propensity score-matched populations. METHODS: Between January 2002 and December 2010, 268 consecutive HCC patients, including 110 and 158 patients that underwent AR and NAR, respectively, were retrospectively enrolled in this study. Forty-four patients from each group were selected and matched using logistic multivariate analysis followed by propensity score analysis. RESULTS: In the whole analysis set, the histological background of the liver, liver function, and tumor marker levels differed significantly among the groups. Although the overall survival (OS) and recurrence-free survival rates of the two groups did not differ significantly in the whole analysis set, the OS of the AR group was significantly longer than that of the NAR group after propensity matching (76.2 ± 6.3 mo vs 58.9 ± 6.3 mo; P = 0.0039). Although AR (HR = 0.456, P = 0.039) was found to be a prognostic factor in the univariate analysis, only vascular invasion (HR = 0.228, P = 0.002) and the hepatocyte growth factor level (HR = 52.366, P = 0.035) were subsequently found to be independent prognostic factors. CONCLUSION: AR conveys a survival advantage over NAR in specific subpopulations of HCC patients with tumors of less than 5 cm in diameter, single tumor, and good liver function.