Positive immunostaining of Sal-like protein 4 is associated with poor patient survival outcome in the large and undifferentiated Korean hepatocellular carcinoma.

PURPOSE: Previous studies have shown the role of Sal-like protein 4 (SALL4) as a biomarker in hepatocellular carcinoma (HCC), and some studies have shown the relationship between SALL4 and prognosis. Given the debates in study groups differences in terms of etiologic causes between Western and Asian HCC and detection methods, we attempted to verify the features of SALL4 immunoreactivity and its clinical correlation in Korean HCC patients. METHODS: Immunohistochemical staining of SALL4 of tissue microarrays (TMAs) consisting of 213 surgically resected HCC patients' tissue were scored in a semiquantitative scoring system with immunoreactive score and the results analyzed with clinical outcome, in addition to general demographics and clinical characteristics. RESULTS: SALL4 immunoreactivity was expressed in 50 cases. Relevance between SALL4 and α-FP correlated significantly (P = 0.002). Also, the SALL4-positive patients had considerably higher tumor grade (P < 0.001). The survival analysis showed negative correlation with SALL4 immunoreactivity in all HCC patient groups, but SALL4 immunoreactivity in T3 and T4 HCC correlated with poor prognosis. CONCLUSION: Here, we found that positive immunostaining of SALL4 is correlated with poor patient survival outcome in large and undifferentiated Korean HCC. SALL4 expression showed close relationship with clinical outcomes of HCCs in Korean patients.

One layer end-to-side pancreaticojejunostomy using reinforcing suture on the pancreatic stump.

BACKGROUND/AIMS: Pancreaticoduodenectomy is associated with a high incidence of postoperative morbidity, and pancreatic fistulas are the most important complication. We therefore designed a modified method of pancreaticojejunostomy using reinforcing suture on the pancreatic stump. METHODOLOGY: The procedure is performed as follow: first, insert a soft rubber catheter into the pancreatic duct, then make reinforcing sutures with 3-0 vicryl. These sutures are parallel to the cut edge of the pancreatic stump, and 5mm from the cut edge. The whole layer of jejunum is sewed to the pancreas including the reinforcing sutures. RESULTS: Between July 2002 and November 2011, 52 consecutive cases of pancreaticoduodenectomy were performed using this method. We used The International Study Group for Pancreatic Surgery (ISGPS) severity grading for postoperative pancreatic fistula (POPF) and delayed gastric emptying (DGE). There was 1 grade A fistula (1.9%), 16 grade B fistulas (30.8%), and 2 grade C fistulas (3.8%). CONCLUSIONS: This method of one layer anastomosis is straightforward and practicable; hence it saves operative time, and is not much affected by lack of familiarity with the surgical technique. Even if it does not actually prevent pancreatic fistula formation, it does prevent the life-threatening complete breakdown of the pancreaticojejunostomy.

What is the optimal time for laparoscopic cholecystectomy in gallbladder empyema?

PURPOSE: With the accumulating experience in laparoscopic surgery, early laparoscopic cholecystectomy (LC) is increasingly offered for acute cholecystitis. However, early LC without percutaneous transhepatic gallbladder drainage (PTGBD) for gallbladder empyema is still believed to be unsafe. The purpose of this study was to determine the optimal time for LC in gallbladder empyema. METHODS: A retrospective analysis was carried out of patients who underwent LC without PTGBD for gallbladder empyema between August 2007 and December 2010. All cases were confirmed by biopsy. The patients were divided into two groups on the basis of a cutoff of 72 h. RESULTS: LC for gallbladder empyema was performed without PTGBD in 61 patients during the study period. The overall conversion rate was 6.6 %. Based on the 72 h cutoff, there were 33 patients in the early group and 28 in the delayed group. There were no significant differences between early and late patients with respect to operation duration (75.5 vs. 71.4 min, p = 0.537), postoperative hospital stay (4.2 vs. 3.3 days, p = 0.109), conversion rate (12.1 vs. 0 %, p = 0.118), and complication rate (12.1 vs. 3.6 %, p = 0.363). However, the early group had a significantly shorter total hospital stay (5.3 vs. 8.7 days, p = 0.001). CONCLUSIONS: Early LC without PTGBD is safe and feasible for gallbladder empyema and is associated with a low conversion rate. Delayed LC for gallbladder empyema has no advantages and results in longer total hospital stays. LC should be performed as soon as possible within 72 h after admission to decrease length of hospital stay.

Inflammatory pseudotumor of the kidney mimicking malignancy on 18F-FDG PET/CT in a patient with diabetes and hepatocellular carcinoma.

Inflammatory pseudotumor (IPT) is a pseudoneoplastic lesion that most commonly involves lung. We report a case of IPT of kidney associated with hepatocellular carcinoma. CT and PET/CT showed the features of renal cell carcinoma. After radical nephrectomy, histologic examination demonstrated acute pyelonephritis associated with papillary necrosis, and IPT involving renal parenchyma and capsule. Although renal IPT is a very rare tumor, awareness of its existence in the differential diagnosis of a renal mass is critical to avoid misdiagnosis. Clinician should carefully consider differential diagnosis and complications associated with acute or chronic pyelonephritis and papillary necrosis in diabetic patients, particularly.

The applicability of laparoscopic gastrectomy in the surgical treatment of giant duodenal ulcer perforation.

PURPOSE: The present study aims to provide an applicability of laparoscopic gastrectomy used in the treatment of giant duodenal ulcer perforation. METHODS: Between July 2010 and April 2011, laparoscopic distal gastrectomy with ROUX-EN-Y gastrojejunostomy and truncal vagotomy was performed in consecutive 5 patients with giant duodenal ulcer perforation. RESULTS: There was no conversion to open surgery. There was no severe postoperative complication. The days of normalization of leukocytosis were 3, 1, 2, 2, and 5, respectively. The times to first flatus were postoperative days 2, 3, 5, 2, and 3. The days of commencement of a soft diet were postoperative days 5, 5, 6, 5, and 5. They were discharged on postoperative days 9, 11, 20, 10, and 11. CONCLUSIONS: We suggest that laparoscopic surgery may be a good surgical method to improve surgical outcomes and is worth a try in experts.

Hepatoid adenocarcinoma of the gallbladder with production of alpha-fetoprotein.

Hepatoid adenocarcinoma (HAC) is a tumor with aberrant hepatocellular differentiation that occurs in extrahepatic organs. HAC of the gallbladder is rare, and cases of alpha-fetoprotein production are extremely rare. A 61-year-old man was diagnosed with gallbladder adenocarcinoma after laparoscopic cholecystectomy. A radical operation including resection of liver bed and lymph node dissection was performed, and no tumor cell was found. However, at postoperative 19 months, he showed lymphadenopathy of the portocaval area and tumor thrombi in the right portal vein with high levels of serum alpha-fetoprotein. After right hemihepatectomy and portahepatis lymph node dissection was performed, he was diagnosed with metastatic HAC. On reviewing the gallbladder specimen, the tumor finally demonstrated HAC as the primary origin. Despite adjuvant therapy, the patient died from multiple liver metastasis 26 months after cholecystectomy. Although HAC of the gallbladder is a very rare malignancy, awareness of its existence is critical to avoid misdiagnosis.

Pattern analysis of lymph node metastasis and the prognostic importance of number of metastatic nodes in ampullary adenocarcinoma.

The aims of this study were to clarify the distribution and spread pattern of metastatic nodes and to evaluate the importance of the number, ratio, and location of positive nodes in ampullary adenocarcinoma. We analyzed the clinicopathologic data and survival of 52 patients who received curative pancreatoduodenectomy for ampullary adenocarcinoma between June 1994 and May 2009. Metastatic lymph nodes were found in 32 (61.5%) patients. The median number of evaluated nodes and positive nodes were 26 (range 10-60) and two (range 1-15), respectively. The most commonly involved nodes were the posterior pancreaticoduodenal nodes (26 patients) followed by the anterior pancreaticoduodenal nodes (11 patients). No positive hepatoduodenal and common hepatic artery nodes were found. In univariate analysis, number of positive nodes, and their ratio and location were significantly associated with survival. Only the factor of three or more metastatic nodes had the independent power in predicting a poor outcome in multivariate analysis (P < 0.001). Ampullary adenocarcinoma first spreads to the posterior pancreaticoduodenal nodes and then the anterior nodes. The number of positive lymph nodes, rather than their ratio and location, independently affects survival after curative resection in patients with ampullary carcinoma.

Bladder reconstruction using bovine pericardium in a case of enterovesical fistula.

The use of graft materials in bladder mucosa has been examined in animal models, but debate exists over which materials are effective. Intestine has been used as a substitute in augmentation cystoplasty for patients with neuropathic bladder, but serious adverse effects of the operation have occurred in some instances. We report a case of a successful repair of an enterovesical fistula by use of bovine pericardium. The patient has remained well for 2.5 years. We suggest that bovine pericardium may be a suitable option as a bladder substitute.

Carcinoid tumors of the extrahepatic biliary tract: report of four cases.

Carcinoid tumors located in the biliary tree are exceedingly rare, accounting for 0.2%-2% of all gastrointestinal carcinoids. This study describes four cases of carcinoid tumors of the extrahepatic biliary tract. Four carcinoid tumors arising in the common bile duct (Case 1, 59-year-old man), gallbladder (Case 2, 49-year-old man; Case 3, 65-year-old man), and ampulla of Vater (Case 4, 52-year-old woman) were studied. All of the cases were misdiagnosed before surgery as proximal bile duct cancer, stomach cancer with liver metastasis, gallbladder cancer, and adenocarcinoma of ampulla of Vater, respectively. The clinicopathological characteristics and clinical course were reviewed. Treatment depends on the location of the tumor and the extent of the disease. Aggressive surgical therapy with a curative intention therefore offers the only chance for cure and has to be considered whenever possible.

Significance analysis of histologic type and perineural invasion as prognostic factors after curative resection of ampulla of Vater carcinoma.

BACKGROUND/AIMS: Periampullary adenocarcinoma has either intestinal- or pancreatobiliary-type of differentiation. These types and perineural invasion have been shown to have prognostic relevance. The influences of histologic type and perineural invasion on recurrence and survival in ampullar of Vater carcinoma still need to be assessed. METHODOLOGY: We reviewed and analyzed the clinicopathologic data, surgical outcomes, recurrence and survival of 49 patients who received curative pancreatoduodenectomy for ampulla of Vater carcinoma at Hanyang University Hospital between July 1994 and June 2008. RESULTS: Twenty patients experienced recurrence, and the 5-year overall survival rates were 53.1%. Perineural invasion as well as tumor grade, T stage, lymph node metastasis, and lymphatic invasion were associated with survival (p < 0.05). The group positive for perineural invasion had a high recurrence rate (56.5% versus 28.0%) and a low 5-year survival (39.1% versus 68.0%) compared to those of the negative group. Pancreatobililary-type had a higher recurrence rate (58.3% versus 36.1%) and a lower 5-year survival rate (33.3% versus 61.1%) in comparison to intestinal-type. However, histologic type was not a statistically significant factor (p > 0.1). CONCLUSIONS: Perineural invasion is a significant factor for survival. Histologic type has no significance as a prognostic factor despite differences between the two subgroups.

Actinomycosis of the pancreas: a case report and review of the literature.

Actinomycosis is a chronic suppurative and granulomatous disease usually caused by Actinomyces israelii. The pathogen produces a characteristic granulomatous inflammatory fibrosis and mass lesion. Abdominal actinomycosis is often difficult to diagnose before operation because of its rarity and chronic disease progression without any characteristic clinical features. In particular, pancreas is very rare location of actinomycosis. The present paper is a report of a case of 55-year-old man with pancreatic actinomycosis presenting as symptoms of pancreatitis. The patient was confirmed by pancreatoduodenectomy for impression of pancreatolith and mass-like lesion of head portion of pancreas. Treatment with operation followed by additional oral penicillin therapy for 3 months was successful. We report a case of pancreatic actinomycosis with a brief review of literature.

[Acinar cell carcinoma of the pancreas in Korea--clinicopathologic analysis of 27 patients from korean literature and 2 cases from our hospital--].

BACKGROUND/AIMS: Acinar cell carcinoma (ACC) of the pancreas is a rare malignancy. ACC has been considered a cancer with poor prognosis due to frequent metastasis, a high recurrence rate, and low resectability. The aim of this study was to examine the clinical, radiologic and pathologic features of ACC in Korean patients, and surgical outcome was also investigated. METHODS: We reviewed the clinical records of two patients with ACC who had undergone operation in January 1996 and December 2005 at Hanyang University Medical Center. Through searching of medical journal from 1983 to 2009, 27 patients reported on literatures as Korean ACC patients were reviewed together. The clinical, pathohistologic, and radiologic features, treatment, and prognosis were investigated for all 29 patients. RESULTS: ACC was more common in male, and age at diagnosis ranged from 25 to 68 years (median 54). Symptoms were, mostly abdominal pain and mass. Liver was most common organ of metastasis at diagnosis and recurrence after operation. The mean tumor size was 7.0 cm, and most common location was tail. Of the 29 patients, 22 underwent surgical resection. Excluding 7 cases of not-reported survival, the median survival with operation was 22.4 months compared to 1.5 months with non-operation. CONCLUSIONS: In Korea, the clinical features of ACC include young age, large size, tail location, and nonspecific tumor markers. Surgery should be actively performed in the treatment of ACC regardless of size.

Biliary cystadenoma and cystadenocarcinoma of the liver: 10 cases of a single center experience.

BACKGROUND/AIMS: Biliary cystadenoma and cystadenocarcinoma constitute less than 5% of intrahepatic cysts originating from the bile duct. The aims of this study were to characterize the clinical and pathologic aspects of these lesions, and also to discuss the treatment and prognosis of them. METHODOLOGY: We reviewed the clinical records of six patients with intrahepatic biliary cystadenoma and four patients with cystadenocarcinoma who had undergone operation from January, 1990 to January, 2006 at Hanyang University Medical Center. RESULTS: Biliary cystadenoma mainly affected women compared to biliary cystadenocarcinoma. Both tumor have nonspecific symptom and were usually diagnosed by computed tomography and ultrasonography. These tumors were usually large, multilocular, and cystic in appearance. The pathologic findings revealed multiple cystic masses lined with cuboidal to columnar epithelium. The nature of cystic fluid was mostly mucous type. Of 10 patients in whom the lesions were completely excised, 8 patients are alive. CONCLUSIONS: Surgical resection of the tumor, including a margin of surrounding normal liver parenchyma, was the only curative method. Any therapy short of complete excision leads to local recurrence and risk of malignant transformation. Complete resection of a biliary cystadenoma and radical resection of a biliary cystadenocarcinoma seems to offer a chance for long-term survival.

Effect of human umbilical cord blood-derived mesenchymal stem cells in a cirrhotic rat model.

BACKGROUND/AIM: Cirrhosis is a long-term consequence of chronic hepatic injury and no effective therapy is currently available for this disease. Recent reports have shown that the mesenchymal stem cells (MSCs) have the capacity to differentiate into hepatocytes, and umbilical cord blood is a rich source of MSCs. Hence, we investigated the effect of infusing of human umbilical cord blood-derived MSCs (HMSCs) in carbon tetrachloride (CCl4)-induced cirrhosis in a rat model. METHODS: The effect of HMSCs on cirrhosis was evaluated using haematoxylin and eosin and Masson's trichrome staining. To evaluate cirrhosis-related factors, we measured protein and mRNA expression of transforming growth factor beta1 (TGF-beta1), collagen type I and alpha-smooth muscle actin (alpha-SMA). RESULTS: Histological findings showed that liver fibrosis in rats was alleviated by HMSCs infusion. Interestingly, CM-DiI-labelled HMSCs expressed the hepatocyte-specific markers, human albumin and alpha-fetoprotein. Infusion of HMSCs significantly inhibited TGF-beta1, collagen type I and alpha-SMA expressions in CCl4-induced cirrhotic rats. CONCLUSION: Our results showed that HMSCs infusion could improve liver fibrosis in rats with CCl4-induced cirrhosis, raising the possibility for clinical use of HMSCs in the treatment of cirrhosis.

Successful stem cell therapy using umbilical cord blood-derived multipotent stem cells for Buerger's disease and ischemic limb disease animal model.

Buerger's disease, also known as thromboangiitis obliterans, is a nonatherosclerotic, inflammatory, vasoocclusive disease. It is characterized pathologically as a panangiitis of medium and small blood vessels, including both arteries and adjacent veins, especially the distal extremities (the feet and the hands). There is no curative medication or surgery for this disease. In the present study, we transplanted human leukocyte antigen-matched human umbilical cord blood (UCB)-derived mesenchymal stem cells (MSCs) into four men with Buerger's disease who had already received medical treatment and surgical therapies. After the stem cell transplantation, ischemic rest pain suddenly disappeared from their affected extremities. The necrotic skin lesions were healed within 4 weeks. In the follow-up angiography, digital capillaries were increased in number and size. In addition, vascular resistance in the affected extremities, compared with the preoperative examination, was markedly decreased due to improvement of the peripheral circulation. Because an animal model of Buerger's disease is absent and also to understand human results, we transplanted human UCB-derived MSCs to athymic nude mice with hind limb ischemia by femoral artery ligation. Up to 60% of the hind limbs were salvaged in the femoral artery-ligated animals. By in situ hybridization, the human UCB-derived MSCs were detected in the arterial walls of the ischemic hind limb in the treated group. Therefore, it is suggested that human UCB-derived MSC transplantation may be a new and useful therapeutic armament for Buerger's disease and similar ischemic diseases.

A new alloantigen-independent control for chronic allograft nephropathy rat models.

BACKGROUND: Isografts are used as controls in many transplant experiments. Our laboratory and others have noticed histological changes in control isograft groups of rats similar to allograft groups, suggesting alloantigen-independent factors contributing to chronic allograft nephropathy. However, the isograft model as a nonalloantigen control is flawed because of the potential of unrecognized minor antigen differences between rats. We designed a study using autografts to isolate alloantigen-independent factors in the rat renal transplant allograft model. MATERIALS AND METHODS: Male Lewis rats weighing 150-250 g underwent a procedure designed to mimic the injury of renal transplant, in which the left kidney was perfused with cold University of Wisconsin solution and subjected to similar cold and warm ischemic times as Lewis isograft rats undergoing renal transplanation. RESULTS: Six autograft rats were compared to five isograft and three single nephrectomy rats. Autograft rats showed normal kidney function according to serum BUN, Cr, and urinary protein. At 360 days, four of six autografts displayed normal renal parenchymal histology, whereas the remaining two autografts displayed histological changes scored as Banff acute rejection 1a and 1b. At sacrifice time, four of five isografts showed histological changes scored as Banff chronic rejection 1 and the single nephrectomy group showed normal histology in the remaining native kidney. CONCLUSIONS: Our data demonstrate that the chronic nephropathy observed in the isograft cannot be completely freed from suspicion of immunological origin. We propose that the autograft model for rat renal transplant research is a better nonimmunologic control than the isograft model for chronic allograft nephropathy.

In vitro differentiation of human umbilical cord blood-derived mesenchymal stem cells into hepatocyte-like cells.

In addition to long-term self-renewal capability, human mesenchymal stem cells (MSCs) possess versatile differentiation potential ranging from mesenchyme-related multipotency to neuroectodermal and endodermal competency. Of particular concern is hepatogenic potential that can be used for liver-directed stem cell therapy and transplantation. In this study, we have investigated whether human umbilical cord blood (UCB)-derived MSCs are also able to differentiate into hepatocyte-like cells. MSCs isolated from UCB were cultured under the pro-hepatogenic condition similar to that for bone marrow (BM)-derived MSCs. Expression of a variety of hepatic lineage markers was analyzed by flow cytometry, RT-PCR, Western blot, and immunofluorescence. The functionality of differentiated cells was assessed by their ability to incorporate DiI-acetylated low-density lipoprotein (DiI-Ac-LDL). As the cells were morphologically transformed into hepatocyte-like cells, they expressed Thy-1, c-Kit, and Flt-3 at the cell surface, as well as albumin, alpha-fetoprotein, and cytokeratin-18 and 19 in the interior. Moreover, about a half of the cells were found to acquire the capability to transport DiI-Ac-LDL. Based on these observations, and taking into account immense advantages of UCB over other stem cell sources, we conclude that UCB-derived MSCs retain hepatogenic potential suitable for cell therapy and transplantation against intractable liver diseases.

Flavin-containing monooxygenase activity can be inhibited by nitric oxide-mediated S-nitrosylation.

Nitric oxide (NO) modifies the functions of a variety of proteins containing cysteine thiols or transition-metal centers, particularly by S-nitrosylation. In inflamed liver, NO is overproduced and hepatic drug-metabolizing enzymes, the flavin-containing monooxygenases (FMOs) and cytochrome P450s (CYPs), are suppressed. However, the NO-related mechanisms underlying the loss of these activities are not well understood, particularly for FMOs. In this study, we suggest that FMO3, the major FMO in human liver, is modified post-translationally by NO. This hypothesis is based on the imbalance observed between the decrease in FMO3 expression (40.7% of controls) and FMO3-specific ranitidine N-oxidation activity (15.1%), and on the partial or complete reversibility of FMO inhibition by sulfhydryl-reducing regents such as DTT (effective on both S-S and S-NO adducts) and ascorbate (effective on S-NO only). Furthermore, NO donors (SNP, SNAP, and Sin-1), including the pure NO donor DEA/NO, directly suppressed in vitro FMO activity (N- or S-oxidation of ranitidine, trimethylamine, and thiobenzamide) in human liver microsomal proteins and recombinant human FMO3. These activities were restored completely after treatment with DTT or ascorbate. These results suggest that NO-mediated S-nitrosylation is involved in the rigorous inhibition of FMO activity in vitro and in vivo, resulting in the suppression of FMO-based drug metabolism or detoxification.