Effect of quercetin on apoptosis of PANC-1 cells / 대한외과학회지

PURPOSE: To investigate the chemotherapeutic effect of quercetin against cancer cells, signaling pathway of apoptosis was explored in human pancreatic cells. METHODS: Various anticancer drugs including adriamycin, cisplatin, 5-fluorouracil (5-FU) and gemcitabine were used. Cell viability was measured by 3-[4,5-dimethylthiazol-2-yl]-2,5-diphe-nyltetra zolium bromide assay. Apoptosis was determined by 4'-6-diamidino-2-phenylindole nuclei staining and flow cytometry in PANC-1 cells treated with 50 microg/mL quercetin for 24 hours. Expression of endoplas mic reticulum (ER) stress mediators including, Grp78/Bip, p-PERK, PERK, ATF4, ATF6 and GADD153/CHOP proteins were measured by Western blot analysis. Mitochondrial membrane potential was measured by fluorescence staining with JC-1, rhodamine 123. Quercetin induced the apoptosis of PANC-1, which was characterized as nucleic acid and genomic DNA fragmentation, chromatin condensation, and sub-G0/G1 fraction of cell cycle increase. But not adriamycin, cisplatin, gemcitabine, and 5-FU. PANC-1 cells were markedly sensitive to quercetin. RESULTS: Treatment with quercetin resulted in the increased accumulation of intracellular Ca2+ ion. Treatment with quercetin also increased the expression of Grp78/Bip and GADD153/CHOP protein and induced mitochondrial dysfunction. Quercetin exerted cytotoxicity against human pancreatic cancer cells via ER stress-mediated apoptotic signaling including reactive oxygen species production and mitochondrial dysfunction. CONCLUSION: These data suggest that quercetin may be an important modulator of chemosensitivity of cancer cells against anticancer chemotherapeutic agents.

Clinical results between single incision laparoscopic cholecystectomy and conventional 3-port laparoscopic cholecystectomy: prospective case-matched analysis in single institution / 대한외과학회지

PURPOSE: The aim of our study was to compare single incision laparoscopic cholecystectomy (SILC) and conventional laparoscopic cholecystectomy (CLC) with respect to clinical outcomes. METHODS: Patients with less than a 28 body mass index (BMI) and a benign gall bladder disease were enrolled in this study. From January 2011 to February 2012, 30 consecutive patients who underwent SILC were compared with 30 patients who underwent CLC during the same period. In this study, all operations were performed by one surgeon. In each group, patient characteristics and perioperative data were collected. RESULTS: There was no significant difference in the preoperative characteristics. There was no significant difference in the postoperative laboratory result (alanine aminotransferase, aspartate aminotransferase, and alanine aminotransferase), number of conversion and complication cases, and length of hospital stay. The operation time was significantly longer in the SILC group (78.5 +/- 17.8 minutes in SILC group vs. 34.9 +/- 5.75 minutes in CLC group, P < 0.0001). The total nonsteroidal antiinflammatory drug usage during perioperative period showed significantly higher in SILC groups (162 +/- 51 mg in the SILC group vs. 138 +/- 30 mg in the CLC group), but there was no statistically significant difference in opioid usage between two groups. The postoperative pain score was significantly higher in the SILC group at second, third, and tenth postoperative day. Satisfaction of postoperative wound showed superiority in SILC group. CONCLUSION: SILC seems to be an acceptable alternative to CLC with acceptable results. However, it is not enough to propose any real benefits of SILC when compared with CLC in terms of operation time and postoperative pain.

Successful percutaneous management of bronchobiliary fistula after radiofrequency ablation of metastatic cholangiocarcinoma in a patient who has a postoperative stricture of hepaticojejunostomy site

Bronchobiliary fistula (BBF) is a rare condition that is defined as an abnormal communication between the biliary system and bronchial tree. Furthermore, a BBF is an extremely rare complication of radiofrequency ablation (RFA). A 54 year-old man with a history of extrahepatic biliary cancer had been suffering with a benign stricture of hepaticojejunostomy site and was treated with RFA for metastatic cholangicarcinoma. In this report, we describe a patient with BBF complicated by an abscess which occurred after RFA. He was treated by placement of external drainage catheter into the liver abscess and percutaneous transhepatic biliary drainage (PTBD) into the right intrahepatic duct. After 6 weeks, a complete obliteration of the BBF was confirmed by a repeated follow-up of computed tomography scan and cholangiography through PTBD.

Huge subcapsular hematoma caused by intrahepatic sarcomatoid cholangiocarcinoma

Intrahepatic sarcomatoid cholangiocarcinomais is a very rare disease with a poor prognosis due to its biologically aggressive tumor behavior. We report a patient who presented with subcapsular hemorrhage and a rapidly growing liver mass. A 57 year-old man was admitted with severe abdominal pain. CT and MRI images showed the presence of a 10 cm-sized subcapsular hemorrhage connected with a multi-lobulated mass with hemorrhage and necrotic foci in the right liver. The patients underwent right hemihepatectomy with caudate lobectomy and lymphadenectomy. The operation findings revealed metastatic nodules to the diaphragm and omentum. Detailed histopathological analysis through immunohistochemistry confirmed the diagnosis of sarcomatoid cholangiocarcinoma with a poorly undifferentiated sarcomatous component. The patient underwent chemotherapy. To date, the patient is doing well for 8 months after initial diagnosis.

Preliminary Experience of Laparoscopic Hepatectomy for Hepatocellular Carcinoma

PURPOSE: Laparoscopic liver resection has gained much popularity in recent years, but relatively few centers have performed hepatectomies in hepatocellular carcinoma (HCC) patients due to the technical difficulties faced with underlying liver cirrhosis. We now present our early experience with laparoscopic liver resection in HCC performed in a single institution. METHODS: From October 2003 until March 2009, 39 laparoscopic liver resections were performed on HCC patients among whom 26 had underlying liver cirrhosis. RESULTS: The location of the tumor was in the left lateral section in 15, segment 5 or 6 in 20, segment 4 in 3 and caudate lobe in 1. Resection involving less than a monosegment was done in 26 and more than 2 segments in 13. Tumor size ranged from 0.8 cm to 6.6 cm (median 2.35) and the resection margin from 0.1 to 6 cm (median 1.5 cm). All patients were either stage I (29) or II (10). There was no difference between cirrhotic and non-cirrhotic patients in operation time (median 210 minutes, range 60~637), change of hematocrit value (4.8%, -1~19.6%), or hospital stay (8 days, 3~67 days). The median follow up duration was 15.1 months, and the 2-year recurrence free survival rate was 48.3%. CONCLUSION: Laparoscopic liver resection in HCC with or without underlying cirrhosis seems to be feasible with minimal morbidity, especially in well selected cases with early stage HCC.

Comparison of Clinical Result between Early Laparoscopic Cholecystectomy and Delayed Laparoscopic Cholecystectomy after Percutaneous Transhepatic Gallbladder Drainage (PTGBFD) in more than 70 Years Old Patients with Acute Cholecystitis

PURPOSE: Operative management of acute cholecystitis in aged patients has been shown to have relatively higher morbidity and mortality. The aim of this study was to determine appropriate management protocols for acute cholecystitis in those more than 70 years old. METHODS: From May 2003 to Dec 2009, we performed this study of patients over 70 years old that were diagnosed with acute cholecystitis (n=257). We excluded patients that had a hepatobilliary malignancy, a previous laparotomy history, secondary cholecystitis, or a high operative risk factor (n=78). Eligible participants were divided into two groups according to the first management of acute cholecystitis. One hundred two of the 179 (group A) had undergone a laparoscopic cholecystectomy (LC) or open cholecystectomy (OC) within 48 hr after arriving at the emergency room; 77 of the 179 (group 2) had PTGBD done as the first management protocol. We divided group 2 into group C (n=47) and D (n=30) according to cholecystectomy or not. We compared clinical outcomes of the two groups. RESULTS: The mean age of patients was 77.5 years old (102 for Group A and 77 for Group B. Univariant analysis of pre-operative clinical findings between groups A and B showed a significant difference only in age and in type of acute cholecystitis, However, the pre-operative co-morbidity of group B was significantly higher than that for group A. Comparing postoperative results between groups A and C, postoperative complications, open conversion rate, and mortality after cholecystectomy were not significantly different. CONCLUSION: PTGBD could be considered as appropriate management in aged patients with acute cholecystitis. Moreover, PTGBD can reduce unnecessary cholecytectomies.

Cardiac tamponade caused by tuberculosis pericarditis in renal transplant recipients / 대한외과학회지

A 50-year-old male, renal transplant recipient, was admitted with fever and chest discomfort. At admission, chest radiologic finding was negative and echocardiography showed minimal pericardial effusion. After 2 days of admission, chest pain worsened and blood pressure fell to 60/40 mmHg. Emergency echocardiography showed a large amount of pericardial effusion compressing the entire heart. Pericardiocentesis was performed immediately. Mycobacterium tuberculosis was isolated from pericardial fluid. Tuberculosis pericarditis should be considered as the cause of cardiac tamponade in renal transplant recipients, even with the absence of pericardial effusion in the initial study or suggestive history.

Partial gastric outlet obstruction caused by a huge submucosal tumor originating in the heterotopic pancreas

A 21-year-old woman presented gastrointestinal manifestation showing intermittent abdominal pain, nausea, and vomiting. An upper endoscopic examination showed round, elevated mucosa at the antrum of the stomach anterior wall. After CT scanning, a huge degenerated gastrointestinal stromal tumor was suspected. Subtotal gastrectomy with Billroth II anastomosis was performed. Histologically, pseudocystic degeneration of the heterotopic pancreas was confirmed. The patient showed eventful postoperative course except temporary dilated gastric emptying. The patient is doing well without any abnormal symptom at 8-month follow-up. This report is a rare case of gastric outlet obstruction caused by a pseudocyst originating from a heterotopic pancreas in the gastric antrum.

A Gastric Hemorrhage through the Fistula between Stomach and Pancreatic Pseudocyst with Ruptured Splenic Artery Pseudoaneurysm : A Case Report

Pancreatic pseudocysts are a common complication of both acute and chronic pancreatitis. But fistular formation or spontaneous perforation of a pancreatic pseudocyst through adjacent organs is rare. Even rarer is bleeding through the fistula between stomach and pancreatic pseudocyst with splenic artery pseudoaneurysm. Therapeutic modalities for ruptured splenic artery pseudoaneurysm with pancreatic pseudocyst include surgical correction and/or angiographic intervention likely splenic artery embolization. However, there seem to be a debate about which treatments are superior. We experienced a case of massive gastric bleeding through a gastrocystic fistula that was controlled surgically by distal pancreatectomy and gastric wedge resection. We report the case with a literature review.

Investigation of the Effective Dose of Agonistic 4-1BB Monoclonal Antibody in a Murine Colon Cancer Metastasis Model

PURPOSE: The aim of this study was to find the dose of agonistic 4-1BB monoclonal antibody (mAb) that results in optimal T cell activation. METHODS: Cancer was induced in mice by an intrahepatic parenchymal injection of 1x10(5) cells of CT26 cells. Cancer-carrying mice (n=84) were divided into seven groups and treated with either rat IgG or agonistic 4-1BB monoclonal antibody (mAb) (5microgram, 10microgram, 20microgram, 100microgram, 200microgram, or 300microgram). All treatments were administered intraperitoneally on days 7, 9, and 11. Mice from each group were sacrificed on days 14, 28, and 42. Harvested livers were weighed and the numbers of T cells in the splenocytes were analyzed with a FACS Vantage flow cytometer. RESULTS: Liver weights increased when 5microgram of agonistic 4-1BB mAb was administered, but showed no additional weight increase for doses greater than 10microgram. The absolute numbers of CD4+ and CD8+ T cells increased in groups treated with low doses of agonistic 4-1BB mAb (5microgram, 10microgram, or 20microgram), but did not increase in the groups treated with high doses of mAb (100microgram, 200microgram, or 300microgram). The levels of CD4/annexin V and CD8/annexin V increased as the dose increased, and the absolute cell numbers of CD4/annexin V were greater than those of CD8/annexin V. CONCLUSION: Liver weight, including the cancer mass, failed to increase at agonistic 4-1BB mAb doses greater than 10microgram. A high dose (> or =100microgram) of agonistic 4-1BB mAb resulted in lower counts of absolute T cells. This study suggests that a low dose (20microgram) of agonistic 4-1BB mAb can be used for optimal T cell activation in combination with other anti-cancer treatments.

A Case of Liver Metastasis of Gastrointestinal Stromal Tumor That Was Resected after Treatment with Imatinib Mesylate and Sunitinib

A 65-year old man underwent wedge resection for a gastrointestinal stromal tumor (GIST) of the gastric fundus in 1997. In 2003, the abdominal CT and sono-guided biopsy revealed he had a large GIST liver metastasis. He underwent treatment with 400 mg/day of imatinib mesylate. As a result, the liver metastasis markedly decreased in size. However, focal progression of the liver metastasis was observed on the follow up CT, so we increased the imatinib from 400 mg/day to 800 mg/day. We then performed extended left hepatectomy. We report here on a patient who presented with an isolated metastatic GIST to the liver, and the patient was successfully treated with imatinib therapy and hemihepatectomy.

The Risk Factors of Acute Cellular Rejection in Adult Living Donor Liver Transplantation:Doubting the Value of Positive Lymphocytotoxic Cross-match Results / 대한이식학회지

BACKGROUND: The influence of lymphocytotoxic cross-match results on acute cellular rejection in adult living donor liver transplantation (LDLT) has not been well examined. Therefore, in this study, we investigated the risk factors of acute rejection, including positive lymphocytotoxic cross-match results. METHODS: Patients inquired in this study are adults who underwent their first LDLT between June 1997 and June 2007 (n=382). We reviewed retrospectively the medical records of donors and recipients, including medical history, surgical procedures, and progress, then analyzed the risk factors of acute rejection using Cox's proportion hazard model. RESULTS: Among the total subjects of 382, 32 recipients had positive lymphocytotoxic cross-match results. Median follow-up duration was 28.0 months (range, 1~93). Fifty six recipients had suffered at least one or more acute rejection episodes. In univariate analysis, positive lymphocytotoxic cross-match results didn't turn out to be a significant risk factor of acute rejection (p=0.735), while recipient age (P=0.012), HCV-related (P=0.001), MELD score (P=0.042), gender mismatch (P=0.001) and no induction of anti-IL-2 receptor antibody (P=0.034) were revealed as risk factors for acute rejection. Recipient age (P=0.001, Hazard Ratio 0.937, 95% Confidence Interval 0.902~0.973), gender mismatch (P=0.001, Hazard Ratio 2.970, 95% Confidence Interval 1.524~5.788), HCV-related (P=0.001, Hazard Ratio 4.313, 95% Confidence Interval 1.786~10.417) were considered as significant risk factors in multivariate analysis. CONCLUSIONS: Positive lymphocytotoxic cross-match results may not be the risk factor for acute rejection. Therefore, it should not be considered as a determinant when matching donors with recipients in adult LDLT.

Report of 1,000 Kidney Transplants at the Sungkyunkwan University of Korea / 대한이식학회지

BACKGROUND: This study aims to report clinical outcome and long term graft and patient survival rate of one thousand kidney transplantation. We analyzed risk factors that impact on graft survival in the 1,000 case of kidney transplantation through this study. METHODS: We have performed 1,000 cases of kidney transplantation in Samsung Medical Center, Seoul, Korea from February 1995 to January 2008. We retrospectively reviewed medical record of recipients and donors. RESULTS: The mean follow up period was 69 months. Composition of type of donor was living donor, 653 cases and deceased donor, 347 cases. Type of donor source was mostly living-related type. 94 cases had graft failure. Major cause of graft failure was chronic allograft nephropathy. And major viral infection was cytomegalovirus infection. Major non-viral infection was urinary tract infection. 47 cases of immediate post operative complication was diagnosed as lymphocele. Overall 10-year graft survival rate was 83.9% respectively. 10-year patient survival rate was 95.7% respectively. 10-year graft survival and patient survival of recipient were significantly different between living donation group and deceased donation group. CONCLUSIONS: In this report, only two risk factor were statically significant difference.

Invasive Gastrointestinal and Cutaneous Mucormycosis in Deceased Donor Small Bowel Transplantation: Case Report and Review of Literature / 대한이식학회지

Fungal infection is an uncommon complication after small bowel transplantation. We present a rare form of mucormycosis found in the small bowel graft and in the skin of a recipient. We reviewed chart data and performed MEDLINE searches and found that this case was the first to report 2 kinds of mucormycosis to be found after organ transplantation. The patient was a 12 month old female baby who underwent small bowel transplantation due to short bowel syndrome. After 12 days she experienced acute cellular rejection which responded to steroid. 6 days later due to sustained fever, poor feeding and abdominal distention endoscopic biopsy was done which revealed mucormycosis. Antifungal treatment with lipo-amphotericin B was initiated, yet there was no improvement of clinical symptoms. On the 23 post operative day a black eschar developed on the incision site of the skin and biopsy was done which revealed cutaneous mucormycosis. Infected skin debridement and graftectomy was done but our patient expired because of septic shock.