Thomas Hui

Enhanced proliferation and differentiation of rat hepatocytes cultured with bone marrow stromal cells.

Liver transplantation is the only clinically effective method of treating acute liver failure. However, wider application of this therapeutic modality is restricted primarily by shortage of donor organs. In the search for alternative methods of liver replacement therapy, investigators have focused on transplantation of normal allogeneic hepatocytes and on the development of liver support systems utilizing isolated hepatocytes. Since all human livers suitable for cell harvest are being used for transplantation, hepatocyte therapy using human tissue would require growing of cells in vitro. Unfortunately, although hepatocytes have tremendous capacity to proliferate in vivo, their ability to grow in culture is severely limited. Stromal cells from bone marrow and other blood‐forming organs have been found to support hematopoiesis. In this paper, we show that bone marrow‐derived stromal cells (BMSCs) enhance proliferation and support differentiation of rat hepatocytes in culture. Further, we demonstrate that in hepatocyte/BMSC co‐cultures, clonal expansion of small hepatocytes (SH) is increased. Using semipermeable membrane cultures, we established that direct cell–cell contact is necessary for stimulation of cell proliferation. We also show that BMSCs which are in direct contact with hepatocytes and SH colonies express Jagged1. This suggests a potential role for Notch signaling in the observed effects. Finally, we present evidence that the expression and activity of liver specific transcirption factors, CCAAT/enhancer binding proteins and liver specific key enzymes such as tryptophan 2,3‐dioxygenase, are improved in hepatocyte/BMSC co‐cultures. In conclusion, results of this study indicate that BMSCs could facilitate proliferation and differentiation of primary rat hepatocytes and their progenitors (SH) in vitro.

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.

Serologic Responses in Indeterminate Colitis Patients Before Ileal Pouch-Anal Anastomosis May Determine Those at Risk for Continuous Pouch Inflammation

PURPOSEAlthough acute pouchitis after ileal pouch-anal anastomosis is common and easily treated, continuous pouch inflammation seen clinically as chronic, antibiotic-dependent pouchitis, and/or Crohn’s disease remains a difficult management problem. Compared with ulcerative colitis, indeterminate colitis patients undergoing ileal pouch-anal anastomosis have a higher incidence of continuous pouch inflammation, which may represent persistent immune reactivity to microbial antigens. Antibody responses to three microbial antigens (oligomannan anti-Saccharomyces cerevisiae, outer membrane porin C of Escherichia coli, and an antigen (I2) from Pseudomonas flourescens) are more commonly seen in Crohn’s disease, whereas antibodies to a cross-reactive antigen (perinuclear antineutrophil cytoplasmic antibodies) is more suggestive of ulcerative colitis. We examined whether preoperative serologic responses to these antigens were associated with Crohn’s disease in indeterminate colitis patients after ileal pouch-anal anastomosis.METHODSTwenty-eight indeterminate colitis patients undergoing ileal pouch-anal anastomosis were prospectively assessed for the development of pouchitis or Crohn’s disease. Serologic responses were determined by enzyme-linked immunosorbent assay and immunofluorescence. Patients were classified based on four predominant profiles of antibody expression. Antibody profiles were determined before knowledge of clinical outcome.RESULTSMedian follow-up was 38 (range, 3–75) months. Of 16 patients (61 percent) who developed pouch inflammation, 4 (25 percent) had acute pouchitis and 12 (75 percent) had continuous pouch inflammation (9 had chronic pouchitis, 3 had Crohn’s disease). No preoperative clinical factor predicted the development of these pouch complications. Overall, 16 patients (57 percent) had a positive antibody reactivity profile. Serologic expression of any marker alone did not predict the development of continuous pouch inflammation. However, continuous pouch inflammation developed in 10 of 16 patients (63 percent) who had a positive antibody reactivity profile compared with only 2 of 12 patients (17 percent) who had a negative antibody reactivity profile (P = 0.015).CONCLUSIONSIndeterminate colitis patients who have a positive antibody reactivity profile before ileal pouch-anal anastomosis have a significantly higher incidence of continuous pouch inflammation after surgery than those with a negative profile.

Laparoscopic Diaphragmatic Hernia Repair

BackgroundAdult-congenital diaphragmatic hernias and chronic traumatic diaphragmatic hernias are uncommon entities that are often technically challenging to repair. There is growing experience with a minimal access approach to these defects.MethodsWe reviewed the English-language literature using a MEDLINE search for “diaphragmatic hernia” and “laparoscopy”.ResultsWe found 19 case reports of laparoscopic adult-congenital diaphragmatic hernia repair. Reported complications included two enterotomies, one of which required conversion to laparotomy. We also found 11 case reports of laparoscopic chronic traumatic diaphragmatic hernia repair, with no reported complications or recurrences. Average operative time was 98 min, and average length of stay was 4.5 days. All reports claimed that there was less postoperative pain and an earlier return to full activity with the laparoscopic approach. Herein we discuss anatomy, pathophysiology, diagnosis, method of repair, and recurrence.ConclusionAdult-congenital diaphragmatic hernia and chronic traumatic diaphragmatic hernia are amenable to laparoscopic repair. Although experience is still limited, laparoscopic repair appears safe and is associated with a shorter hospital stay.

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 99mTc-galactosyl serum albumin scintigraphy, 99mTc-mebrofenin hepatobiliary scintigraphy and transient elastography are also available, but future studies are needed to validate their clinical efficacy.

The effect of antioxidants and a caspase inhibitor on cryopreserved rat hepatocytes.

Hepatocyte transplantation and use of bioartificial liver support systems have been suggested as potential therapies for fulminant hepatic failure. Cryopreservation in liquid nitrogen is presently the major method of long-term storage of isolated hepatocytes. However, cryopreservation can result in low cell recovery and reduction in differentiated function. Several possible mechanisms of cell death during cryopreservation have been proposed. The most important mechanisms appear to be oxidative stress and apoptosis. In this study, we isolated fresh rat hepatocytes and cryopreserved them in three media: University of Wisconsin (UW) solution, an antioxidant-containing medium, and medium containing a caspase inhibitor. Viability and function of hepatocytes cryopreserved in these media were examined. Cryopreservation conditions had no effect on hepatocyte viability after thawing. However, after culture we found significant improvements in viability and function in both antioxidant- and caspase inhibitor-treated hepatocytes at 6 and 24 h.

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.

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.

Single-incision laparoscopic splenectomy in children

PURPOSE Single-incision laparoscopic surgery is being incorporated into the practices of many pediatric surgeons. Its superior cosmetic outcomes have resulted in increased patient- and parent-driven demand for the approach. This article describes a series of single-incision laparoscopic splenectomies (SSs) in children and compares outcomes with a historical series of standard laparoscopic splenectomies (LS). METHODS The medical records of patients who underwent standard splenectomy and SS at our institution between 2007 and 2010 were reviewed. Perioperative data were recorded. Descriptive comparisons were made between the SS and LS groups. RESULTS Seven patients underwent SS, and 4 underwent LS during the study period. Operative times for the SS group decreased as experience with the procedure accumulated and ultimately approached LS operative times. No conversions to a standard laparoscopic or open approach were required. No complications occurred. Length of stay and postoperative pain were similar in both groups. single-incision laparoscopic splenectomy provided excellent cosmetic outcomes. CONCLUSIONS Single-incision laparoscopic splenectomy is feasible in children. Its main benefit is improved cosmesis. It can be performed without detrimental increases in operative times or patient discomfort. Given an increased demand for the approach, it remains a viable option in children.

Laparoscopically assisted repair of inguinal hernia through a micro-incision and extra-peritoneal division and ligation of the hernia sac

IntroductionHigh ligation and division of the hernia sac are the two important steps in open pediatric indirect inguinal hernia repair. We describe a laparoscopically assisted method of delivering the hernia sac through a 5-mm micro-incision with complete division and high ligation of the hernia sac similar to the open repair method.MethodA new laparoscopic technique of pediatric inguinal hernia repair which allows high ligation, complete division and removal of the indirect inguinal hernia sac is described.ResultsTwenty-six patients (15 boys, 11 girls) underwent laparoscopic inguinal hernia repair. The mean age was 40 months. 13 patients had bilateral inguinal hernia repair. There were no intra-operative complications and at mean follow-up of 6 months, there was 1 recurrence. No other complications (wound infection, suture granuloma formation, hydrocele) were seen post-operatively.ConclusionThis new laparoscopically assisted inguinal hernia repair technique combines the advantages of standard open method and laparoscopy. The efficacy of this repair will need confirmation with a longer follow-up and a larger patient series. The effect of traction on cord structure will need to be monitored.