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1.  Efficacy of hepatic arterial infusion chemotherapy in advanced hepatocellular carcinoma 
AIM: To investigate the efficacy of hepatic arterial infusion chemotherapy (HAIC) using floxuridine (FUDR) in patients with advanced hepatocellular carcinoma (HCC) confined to the liver.
METHODS: Thirty-four patients who had advanced HCC with unresectability or unsuccessful previous therapy in the absence of extrahepatic metastasis were treated with intra-arterial FUDR chemotherapy at our hospital between March 2005 and May 2008. Among the 34 patients, 9 patients were classified as Child class C, and 18 patients had portal vein tumor thrombus (PVTT). One course of chemotherapy consisted of continuous infusion of FUDR (0.3 mg/kg during day 1-14) and dexamethasone (10 mg on day 1, 4, 7 and 11), and this treatment was repeated every 28 d.
RESULTS: Two patients (5.9%) displayed a complete response, and 12 patients (35.3%) had a partial response. The tumor control rate was 61.8%. The median overall survival times were 15.3 mo, 12.4 mo and 4.3 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0392). The progression-free survival was 12.9 mo, 7.7 mo and 2.6 mo for the patients who were classified as Child class A, Child class B and Child class C, respectively (P = 0.0443). The cumulative survival differed significantly according to the Child-Pugh classification and the presence of PVTT. In addition to hepatic reserve capacity and PVTT, the extent of HCC was an independent factor in determining a poor prognosis. The most common adverse reactions to HAIC were mucositis, diarrhea and peptic ulcer disease, but most of these complications were improved by medical treatment and/or a delay of HAIC.
CONCLUSION: The present study demonstrates that intra-arterial FUDR chemotherapy is a safe and effective treatment for advanced HCC that is recalcitrant to other therapeutic modalities, even in patients with advanced cirrhosis.
PMCID: PMC3396196  PMID: 22807613
Hepatic arterial infusion chemotherapy; Floxuridine; Advanced hepatocellular carcinoma; Child-Pugh classification; Portal vein tumor thrombus
2.  Management of giant hepatic cysts in the laparoscopic era 
We sought to evaluate the feasibility and outcomes of laparoscopic resection of giant hepatic cysts and surgical success, focusing on cyst recurrence.
From February 2004 to August 2011, 37 consecutive patients with symptomatic hepatic cysts were evaluated and treated at Dong-A University Hospital. Indications were simple cysts (n = 20), multiple cysts (n = 6), polycystic disease (n = 2), and cystadenoma (n = 9).
The median patient age was 64 years, with a mean lesion diameter of 11.4 cm. The coincidence between preoperative imaging and final pathologic diagnosis was 54% and half (n = 19) of the cysts were located in segments VII and VIII. Twenty-two patients had American Society of Anesthesiologists (ASA) classification I and II, and nine had ASA classification III. Surgical treatment of hepatic cysts were open liver resection (n = 3), laparoscopic deroofing (n = 24), laparoscopic cyst excision (n = 4), laparoscopic left lateral sectionectomy (n = 2), hand assisted laparoscopic procedure (n = 2), and single port laparoscopic deroofing (n = 2). The mean fellow-up was 21 months, and six patients (16%) experienced radiographic-apparent recurrence. Reoperation due to recurrence was performed in two patients. Among the factors predicting recurrence, multivariate analysis revealed that interventional radiological procedures and pathologic diagnosis were statistically significant.
Laparoscopic resection of giant hepatic cysts is a simple and effective method to relieve symptoms with minimal surgical trauma. Moreover, the recurrence is dependent on the type of pathology involved, and the sclerotherapy undertaken.
PMCID: PMC3764362  PMID: 24020020
Liver; Hepatic cyst; Laparoscopy
3.  Prognostic factors for gallbladder cancer in the laparoscopy era 
Hepatobiliary surgery has changed dramatically in recent decades with the advent of laparoscopic techniques. The aim of this retrospective study was to compare survival rates according to stages, adjusting for important prognostic factors.
A retrospective study of a 17-year period from January 1994 to April 2011 was carried out. The cases studied were divided into two time period cohorts, those treated in the first 9-years (n = 109) and those treated in the last 7-years (n = 109).
An operation with curative intent was performed on 218 patients. The 5-year survival rates according to the depth of invasion were 86% (T1), 56% (T2), 45% (T3), and 5% (T4). The number of cases of incidental gallbladder cancer found during 3,919 laparoscopic cholecystectomies was 96 (2.4%). Incidental gallbladder cancer revealed a better survival rate (P = 0.003). Iatrogenic bile spillage was found in 20 perforations of the gallbladder during laparoscopic cholecystectomies, 16 preoperative percutaneous transhepatic gallbladder drainages and 16 percutaneous transhepatic biliary drainages; only percutaneous transhepatic biliary drainage patients showed a significantly lower survival rate than patients without iatrogenic bile spillage (P < 0.034). Chemoradiation appeared to improve overall survival (P < 0.001). Multivariate analysis also revealed that time period, type of surgery, surgical margin, lymphovascular invasion, lymph node involvement, and chemoradiation therapy had significant effects.
This study found that the prognosis of gallbladder cancer is still determined by the stage at presentation due to the aggressive biology of this tumor. Early diagnosis, radical resection and appropriate adjuvant therapy can increase overall survival.
PMCID: PMC3467389  PMID: 23091795
Gallbladder cancer; Laparoscopy; Prognosis
4.  Review of 100 cases of single port laparoscopic cholecystectomy 
Single port laparoscopic cholecystectomy (SPLC) is a new advanced technique in laparoscopic surgery. Many laparoscopic surgeons seek to gain skill in this new technique. However, little data has been accumulated and published formally yet. This article reports the achievement of 100 cases of SPLC with the hopes it will encourage laparoscopic surgery centers in the early adoption of SPLC.
A retrospective review of 100 prospectively selected cases of SPLC was carried out. All patients had received elective SPLC by a single surgeon in our center from May 2009 to December 2010. Our review suggests patients' character, perioperative data and postoperative outcomes.
Forty-two men and 58 women with an average age of 45.8 years had received SPLC. Their mean body mass index (BMI) was 23.85 kg/m2. The mean operating time took 76.75 minutes. However, operating time was decreased according to the increase of experience of SPLC cases. Twenty-one cases were converted to multi-port surgery. BMI, age, previous low abdominal surgical history did not seem to affect conversion to multi-port surgery. No cases were converted to open surgery. Mean duration of hospital stay was 2.18 days. Six patients had experienced complications from which they had recovered after conservative treatment.
SPLC is a safe and practicable technique. The operating time is moderate and can be reduced with the surgeon's experience. At first, strict criteria was indicated for SPLC, however, with surgical experience, the criteria and area of SPLC can be broadened. SPLC is occupying a greater domain of conventional laparoscopic cholecystectomy.
PMCID: PMC3294112  PMID: 22403752
Single port surgery; Laparoscopic cholecystectomy
5.  Lessons learned from 100 initial cases of laparoscopic liver surgery 
Laparoscopic liver resection (LLR) is now widely accepted and is being increasingly performed. The present study describes our experience with LLR at a single center over an eight-year period.
This retrospective study enrolled 100 patients between October 2002 and February 2010. Forty-six benign lesions and 54 malignant lesions were included. The LLR performed included 58 pure laparoscopy procedures, 18 hand-assisted laparoscopy procedures and 24 hybrid technique procedures.
The mean age of the patients was 57 years; among these patients, 31 were over 65 years of age. The mean operation time was 220 minutes. The overall morbidity was 11% and the mortality was zero. Among the 20 patients with simple hepatic cysts, 50% unexpectedly recurred. Among the 41 patients with hepatocellular carcinoma, 21 patients (51%) underwent preoperative radiofrequency ablation therapy or transarterial chemoembolization. During parenchymal-transection, 11 received blood transfusion. The width of the resection margins was under 0.5 cm in 11 cases (27%); 0.5 to 1 cm in 22 cases (54%) and over 1 cm in eight cases (12%). There was no port site seeding, but argon beam coagulation-induced tumor dissemination was observed in two cases. The overall two-year survival rate was 75%.
This study suggests that the applications for LLR can be gradually expanded when assuring that the safety and curability of LLR are equivalent to that of open liver resection.
PMCID: PMC3204701  PMID: 22066057
Laparoscopic liver resection; Hepatic cyst; Hapatocellular carcinoma; Resection margin
6.  Prognostic significance of thymidylate synthase, thymidine phosphorylase and dihydropyrimidine dehydrogenase expression in biliary tract cancer patients receiving adjuvant 5-fluorouracil-based chemotherapy 
Molecular and Clinical Oncology  2013;1(6):987-994.
Biliary tract cancer (BTC) is a relatively uncommon type of cancer, accounting for ∼4% of the malignant neoplasms of the gastrointestinal tract. The aim of this study was to determine whether the expression of thymidylate synthase (TS), thymidine phosphorylase (TP) and dihydropyrimidine dehydrogenase (DPD) predict clinical outcome in BTC patients treated with adjuvant 5-fluorouracil (5-FU)-based chemotherapy. TS and TP expression were found to be significantly correlated with cancer location (P=0.044 and 0.031, respectively). The multivariate analysis revealed that age [hazard ratio (HR)=2.157, P=0.008], stage (HR=2.234, P<0.001), resection margin status (HR=2.748, P=0.004) and TP expression (HR=2.014, P=0.039) were independently associated with overall survival (OS).
PMCID: PMC3915652  PMID: 24649282
biliary tract cancer; 5-fluorouracil; thymidine phosphorylase
7.  Comparison of Outcomes After Single-Port Laparoscopic Cholecystectomy in Relation to Patient Body Mass Index 
Background and Objectives:
Single-port laparoscopic cholecystectomy may contribute to a paradigm shift in the field of laparoscopic cholecystectomy surgery by providing patients with benefits beyond those observed after other surgical procedures. This study was designed to evaluate clinically meaningful differences in operative outcomes between obese and nonobese patients after single-port laparoscopic cholecystectomy.
Data were collected retrospectively from 172 patients who had undergone single-port laparoscopic cholecystectomy performed by the same surgeon at a single medical center between January and December 2011. For the outcome analysis, patients were divided into nonobese and obese patient groups according to their body mass index (<25 kg/m2 vs ≥25 kg/m2).
Demographic and clinical data did not differ significantly between obese patients (n = 65) and nonobese patients (n = 107). In addition, statistically significant differences pertaining to most measured surgical outcomes including postoperative hospital stay, bile spillage, additional port use, and open conversion were not detected between the groups. However, the two groups differed significantly regarding operative time such that nonobese patients had shorter operative times than obese patients (P < .05).
The results of this study showed that operative time for single-port laparoscopic cholecystectomy was the only difference between obese and nonobese patients. Given this result, body mass index may not be as relevant a factor in patient selection for single-port laparoscopic cholecystectomy as previously thought.
PMCID: PMC4266224  PMID: 25516701
Laparoscopic cholecystectomy; Single port; Body mass index (BMI)
8.  Early experience of the compression anastomosis ring (CARTM 27) in left-sided colon resection 
AIM: To evaluate clinical validity of the compression anastomosis ring (CAR™ 27) anastomosis in left-sided colonic resection.
METHODS: A non-randomized prospective data collection was performed for patients undergoing an elective left-sided colon resection, followed by an anastomosis using the CAR™ 27 between November 2009 and January 2011. Eligibility criteria of the use of the CAR™ 27 were anastomoses between the colon and at or above the intraperitoneal rectum. The primary short-term clinical endpoint, rate of anastomotic leakage, and other clinical outcomes, including intra- and postoperative complications, length of operation time and hospital stay, and the ring elimination time were evaluated.
RESULTS: A total of 79 patients (male, 43; median age, 64 years) underwent an elective left-sided colon resection, followed by an anastomosis using the CAR™ 27. Colectomy was performed laparoscopically in 70 patients, in whom two patients converted to open procedure (2.9%). There was no surgical mortality. As an intraoperative complication, total disruption of the anastomosis occurred by premature enforced tension on the proximal segment of the anastomosis in one patient. The ring was removed and another new CAR™ 27 anastomosis was constructed. One patient with sigmoid colon cancer showed postoperative anastomotic leakage after 6 d postoperatively and temporary diverting ileostomy was performed. Exact date of expulsion of the ring could not be recorded because most patients were not aware that the ring had been expelled. No patients manifested clinical symptoms of anastomotic stricture.
CONCLUSION: Short-term evaluation of the CAR™ 27 anastomosis in elective left colectomy suggested it to be a safe and efficacious alternative to the standard hand-sewn or stapling technique.
PMCID: PMC3229627  PMID: 22147979
Compression anastomosis; Colon; Anastomotic leakage; CAR™ 27
9.  Collision tumor of the rectum: A case report of metastatic gastric adenocarcinoma plus primary rectal adenocarcinoma 
Collision tumors are thought to arise from the accidental meeting and interpenetration of two independent tumors. We report here a highly unusual case of a 61-year old man who had a unique tumor that was composed of a metastatic adenocarcinoma from the stomach to the rectum, which harbored a collision tumor of primary rectal adenocarcinoma. The clonalities of the two histologically distinct lesions of the rectal mass were confirmed by immunohistochemical and molecular analysis. Although histologic examination is the cornerstone in pathology, immunohistochemical and molecular analysis can provide evidence regarding whether tumors originate from the same clone or different clones. To the best of our knowledge, this is the first reported case of such an occurrence.
PMCID: PMC4088248  PMID: 17007003
Collision tumor; Rectum; Clonality
10.  Composite RNAi-Microsponges Form through Self-Assembly of the Organic and Inorganic Products of Transcription 
Inorganic nanostructures have been used extensively to package nucleic acids into forms useful for therapeutic applications. Here we report that the two products of transcription, RNA and inorganic pyrophosphate, can self-assemble to form composite microsponge structures composed of nanocrystalline magnesium pyrophosphate sheets (Mg2P2O7·3.5H2O) with RNA adsorbed to their surfaces. The microsponge particles contain high loadings of RNA (15–21 wt.%) that are protected from degradation and can be obtained through a rolling circle mechanism as large concatemers capable of mediating RNAi. The morphology of the RNAi microsponges is influenced by the time-course of the transcription reaction and interactions between RNA and the inorganic phase. Previous work demonstrated that polycations can be used to condense RNAi microsponges into nanoparticles capable of efficient transfection with low toxicity. Our new findings suggest that the formation of these nanoparticles is mediated by the gradual dissolution of magnesium pyrophosphate that occurs in the presence of polycations. The simple one-pot approach for assembling RNAi microsponges along with their unique properties could make them useful for RNA-based therapeutics.
PMCID: PMC4031615  PMID: 24851252
RNAi; self-assembly; nanocomposites; rolling circle transcription; microsponges
11.  Extramedullary Plasmacytoma of the Pancreas Diagnosed Using Endoscopic Ultrasonography-Guided Fine Needle Aspiration 
Clinical Endoscopy  2014;47(1):115-118.
Extramedullary plasmacytoma involves organs outside the bone marrow; however, involvement of the pancreas is rare. We recently experienced a case of extramedullary plasmacytoma of the pancreas that was diagnosed by endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA). EUS-FNA, which has a high diagnostic accuracy and an excellent safety profile, is the modality of choice for establishing tissue diagnosis. We report a case of extramedullary plasmacytoma of the pancreas diagnosed using EUS-FNA.
PMCID: PMC3928484  PMID: 24570894
Extramedullary plasmacytoma; Pancreas; Endosonography; Biopsy, fine-needle
12.  A Case of Hepatic Angiomyolipoma Which Was Misdiagnosed as Hepatocellular Carcinoma in a Hepatitis B Carrier 
Case Reports in Hepatology  2012;2012:606108.
We report a rare case of resected hepatic AML, which was misdiagnosed as hepatocellular carcinoma in a chronic hepatitis B carrier. A 45-year-old woman who was a carrier of hepatitis B virus infection presented with a hepatic tumor. Her serum alpha-fetoprotein level was normal. Ultrasonography revealed a round and well-circumscribed echogenic hepatic tumor measuring 2.5 cm in the segment VI. On contrast-enhanced computed tomography, a hypervascular tumor was observed in the arterial phase and washing-out of the contrast medium in the portal phase and delayed phase. On MR T1-weighted in-phase images, the mass showed low signal intensity, and on out-of-phase images, the mass showed signal drop and dark signal intensity. On MR T2-weighted images, the mass showed high signal intensity. The mass demonstrated high signal intensity on arterial phase after contrast injection, suggestive of hepatocellular carcinoma. The patient underwent hepatic wedge resection and histopathological diagnosis was a hepatic angiomyolipoma.
PMCID: PMC4208446  PMID: 25374707
13.  Isolated primary schwannoma arising on the colon: report of two cases and review of the literature 
Primary schwannoma of the large intestine is an extremely rare neoplasm. Here, we report two cases of colonic schwannoma confirmed pathologically after laparoscopic resection. A 52-year-old female and a 59-year-old female were referred by their general practitioners to our coloproctologic clinic for further evaluation and management of colonic submucosal masses. Colonoscopies performed in our institution revealed round submucosal tumors with a smooth and intact mucosa in the mid-ascending and descending colon, respectively. Computed tomography (CT) scans showed an enhancing soft tissue mass measuring 2 × 2 cm in the right colon and well-defined soft tissue nodule measuring 1.5 × 1.7 cm in the proximal descending colon, respectively. We performed laparoscopic right hemicolectomy and segmental left colectomy under the preoperative impression of gastrointestinal stromal tumors. Two cases were both diagnosed to be benign schwannoma of the colon after immunohistochemical stains (S-100 (+), smooth muscle actin (-), CD117 (-), and CD34 (-)).
PMCID: PMC3204696  PMID: 22066062
Schwannoma; Colon; Immunohistochemical stain
14.  Prognostic implication of metastatic lymph node ratio in node-positive rectal cancer 
The aim of this study was to evaluate the prognostic significance of the ratio between metastatic and examined lymph nodes (LNs) in patients with stage III rectal cancer.
A review was made of 175 (male, 98) patients with stage III rectal cancer of R0 resection. LN disease was stratified both by the American Joint Committee on Cancer/International Union Against Cancer nodal classification (pN) and by quartiles of the lymph node ratio (LNR). Disease-free survivals (DFS) were made using Kaplan-Meier curves and assessed by the log rank test and multivariate analysis was performed using the Cox proportional hazards model.
Patients ranged in age from 29 to 83 (median, 60) years with median follow-up of 47 months (range, 13 to 181 months). months. There was a significant correlation between the number of metastatic LNs and the LNR (r = 0.8681, P < 0.0001). Cut-off points of LNR quartiles best to separate patients with regard to 5-year DFS were between quartile 2 and 3, and between 3 and 4 (LNR1, 2, and 3); the 5-year DFS according to such stratification was 89.6%, 55.8%, and 18.2% in LNR1, 2, and 3, respectively (P < 0.0001). Cox model identified the LNR as the most significant independent prognostic covariate; LNR2 showed 3.6 times (95% confidence interval [CI], 1.682 to 7.584; P = 0.0009) and LNR3, 18.7 times (95% CI, 6.872 to 50.664; P < 0.0001) more risky than LNR1.
This study suggests that ratio-based LN staging, which reflects the number of LNs examined and the quality of LN dissection, is a simple and reliable system for prognostic LN stratification in patients with stage III rectal cancer.
PMCID: PMC3204678  PMID: 22066045
Rectal cancer; Metastatic lymph node ratio; Prognostic factor
15.  Intensity of Tumor Budding as an Index for the Malignant Potential in Invasive Rectal Carcinoma 
The aim of this study was to quantitatively assess the intensity of tumor budding in rectal carcinoma and to determine how it correlates with the malignant potential.
Materials and Methods
Intensities of the tumor budding at the invasive front of the surgical specimens from 90 patients (male, 51) with well- or moderately-differentiated rectal carcinoma were investigated. Differences in the budding intensity among pathologic variables were compared, and recurrences and survivals were analyzed in accordance with degree of the budding intensity. The patients ranged in age from 33 to 75 years (mean, 55.4) with the median follow-up being 43 months (range, 12~108).
Tumor budding was identified in 89 patients (98.9%) with a mean intensity of 7.5±5.3. The budding intensity was significantly higher in tumors with lymphatic invasion (p=0.0081), blood vessel invasion (p<0.0001), and perineural invasion (p=0.0013) than in those tumor without these findings. It became significantly higher with the increase in nodal stage (p<0.0001). The intensity of tumor budding in patients with relapse (29 patients) was significantly higher than that in patients without relapse (6.2±5.0 vs. 10.2±4.9; p=0.0005), but this difference in the intensity was observed only for the node-positive patients (8.0±3.4 vs. 11.9±5.1; p=0.0064). When the patients were stratified into two groups on either side of the mean of the intensity, the higher intensity group showed a significantly less favorable disease-free (DFS) and overall survival (OS) (p=0.0026 and 0.0205, respectively). Based on the multivariate analysis, the nodal stage and the intensity of budding proved to be the independent variables associated with DFS (p=0.023 and 0.03, respectively).
Tumor budding at the invasive margin is a reliable pathologic index that indicates a higher malignant potential and a less favorable prognosis for patients with advanced rectal carcinoma.
PMCID: PMC2785407  PMID: 19956500
Rectal carcinoma; Tumor budding; Malignant potential

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