Rapidly Growing Acinar Cell Carcinoma of the Pancreatic Head: A Case Report and Literature Review / 대한췌담도학회지

Pancreatic acinar cell carcinoma (ACC) is a rare neoplasm accounting less than 1% of malignant pancreatic tumors. A 47-year-old male patient visited the emergency room with epigastric pain. Computed tomography or magnetic resonance imaging revealed a 4.7-cm heterogeneously enhanced solid and cystic mass with internal necrosis located in the head of the pancreas. Radiological diagnosis was borderline malignancy such as neuroendocrine tumor or solid pseudopapillary neoplasm. Two months later, the necrotic mass in the pancreas head had grown up to 11 cm, compressing the duodenum, superior mesenteric vein, and proximal transverse colon. Pylorus preserving pancreatoduodenectomy with segmental resection of transverse colon was performed. Histopathological examination revealed that the tumor was pancreatic ACC. The patient recovered without any complication and was doing well without recurrence for 12 months after surgery.

Postcholecystectomy syndrome: symptom clusters after laparoscopic cholecystectomy

PURPOSE: Postcholecystectomy syndrome (PCS) is characterized by abdominal symptoms following gallbladder removal. However, there is no consensus for the definition or treatment for PCS. The purpose of this study was to define PCS among various symptoms after laparoscopic cholecystectomy, and to identify risk factors affecting PCS. METHODS: This study was conducted at Dongguk University Ilsan Hospital and Chung-Ang University Hospital (2012–2013). Outcomes were assessed using European Organization for Research and Treatment of Cancer QLQ–C30 questionnaire. Symptom cluster for determining PCS was made by factor analysis. Cluster analysis evaluating risk factors of PCS was made by Ward methods and Dentogram. RESULTS: Factor analysis revealed three distinct symptom clusters, those are ‘insomnia and financial difficulties (eigenvalue, 1.707; Cronbach α, 0.190),’‘appetite loss and constipation (eigenvalue, 1.413; Cronbach α, 0.480),’ and ‘right upper quadrant (RUQ) pain and diarrhea (eigenvalue, 1.245; Cronbach α, 0.315).’ Among these symptom clusters, the cluster of ‘RUQ pain and diarrhea’ was determined as PCS. However, we could not find any risk factors between high symptomatic group and low symptomatic group. CONCLUSION: PCS could consist of RUQ pain and diarrhea. Well-designed prospective trials are needed to determine risk factors of PCS.

Predictors of Micrometastases in Patients with Barcelona Clinic Liver Cancer Classification B Hepatocellular Carcinoma

PURPOSE: Transarterial chemoembolization (TACE) is indicated for Barcelona Clinic Liver Cancer (BCLC) B hepatocellular carcinoma (HCC). Whether TACE provides any long-term survival benefits remains unclear. We aimed to investigate micrometastases predictors with which to identify patients who would benefit from surgical resection (SR). MATERIALS AND METHODS: First, we analyzed risk factors of micrometastases, microvascular invasion, and poor histologic grade in 38 patients with newly diagnosed resectable BCLC stage B HCC limited to one or two segments with well-preserved liver function and who underwent SR between January 2006 and December 2013. Second, we validated identified risk factors in 54 newly diagnosed resectable BCLC B HCC patients with well-preserved liver function who underwent TACE during the same period to determine their influence on survival. RESULTS: Risk factors of micrometastases in SR patients were α-fetoprotein (AFP) ≥110 [hazard ratio (HR)=5.166; 95% confidence interval (CI), 1.031–25.897; p=0.046] and prothrombin induced by vitamin K absence-II (PIVKA-II) ≥800 (HR=5.166; 95% CI, 1.031–25.897; p=0.046). The cumulative probability of tumor recurrence (p=0.009) after SR differed according to levels of AFP and PIVKA-II. After validation of these risk factors in the TACE group, patients with SR and AFP <110 and PIVKA-II <800 had superior survival outcomes than other patients (HR=0.116; 95% CI, 0.027–0.497; p=0.004). CONCLUSION: AFP and PIVKA-II levels predict micrometastases and survival. Therefore, they should be considered when selecting SR for BCLC B HCC.

Prevalence and Risk Factors of Gallbladder Polypoid Lesions in a Healthy Population

PURPOSE: To determine the prevalence of and investigate the risk factors for gallbladder (GB) polypoid lesions in a healthy population. MATERIALS AND METHODS: A total of 23827 subjects who underwent abdominal ultrasonography in conjunction with health screening examinations were retrospectively analyzed. The prevalence of risk factors for GB polypoid lesions were evaluated. In addition, risk factors according to the number of polypoid lesions and the presence of stones with polypoid lesions were investigated. To analyze these risk factors, a control group was established with a 1:2 ratio matched for age and sex. RESULTS: The prevalence of GB polypoid lesions was identified as 9.96%. On multivariate analysis, chronic hepatitis B infection (CHB) and the presence of metabolic syndrome (MS) were risk factors for GB polypoid lesions. CHB and MS were also significant independent risk factors for multiple GB polypoid lesions when compared with solitary GB polypoid lesions. In addition, gastric Helicobacter pylori infection and MS were significant risk factors for GB polypoid lesions with stones when compared with GB polypoid lesions without stones. CONCLUSION: The prevalence of GB polypoid lesions in a healthy Korean population was 9.96%. Patients with CHB and MS need to be carefully examined for such lesions.

Bilateral ovarian metastasis from distal common bile duct carcinoma developing after choledochal cyst excision

Ovarian metastases represent about 3-5% of all ovarian malignancies. Most of these tumors originate in the digestive tract and cholangiocarcinoma rarely involves the ovary. A 60-year-old woman was admitted for the investigation of abdominal distension that had lasted 1 week. One and a half years prior, the patient had undergone choledochal cyst excision, Roux-en Y hepaticojejunostomy and cholecystectomy. Computed tomography scans of the abdomen revealed a papillary mass in the remnant distal common bile duct and enlargement of both ovaries with a huge amount of ascites. An explorative laparotomy disclosed no peritoneal seeding with resectable cholangiocarcinoma and bilateral ovarian mass. Pylorus-preserving pancreatoduodenectomy and bilateral salphingo-oophorectomy with hysterectomy were performed. Histologically, it was a well-differentiated adenocarcinoma and all surgical margins were free of tumor. Both ovarian masses were consistent with metastatic adenocarcinoma from the common bile duct. The patient received six cycles of postoperative adjuvant systemic chemotherapy, dying after 10 months due to pulmonary embolism.

Pancreaticoduodenectomy performed in a patient with situs ambiguous accompanied with isolated levocardia, malrotation, and normal spleen

We report a case of common bile duct (CBD) cancer, successfully managed with pancreaticoduodenectomy, in a patient with isolated levocardia, malrotation, and situs ambiguous (without splenic anomalies). A 59-year-old male patient was referred to Chung-Ang University Hospital with epigastric pain and jaundice. CT and MRI revealed distal CBD cancer without significant lymphadenopathy. Multiple abdominal anatomic anomalies were identified preoperatively, whereas no anatomic anomalies were detected within the chest. The patient had a right-sided stomach and spleen, liver at the midline, several vascular variations around the celiac axis, and intestinal malrotation, but the inferior vena cava and portal vein were normal. A pancreaticoduodenectomy was performed to treat the cancer. The postoperative course was favorable, and the patient was started on combined chemotherapy and radiotherapy 15 days after the surgery. In this case study, we report that pylorus preserving pancreaticoduodenectomy was successful for distal CBD cancer in a patient with rare situs anomalies.

Single port laparoscopic appendectomy in children using glove port and conventional rigid instruments

PURPOSE: To further improve the advantages of minimally invasive surgery, single port laparoscopic techniques continue to be developed. We report our initial experience with single port laparoscopic appendectomy (SPLA) in children and compare its outcomes to those of conventional laparoscopic appendectomy (CLA). METHODS: Clinical data were prospectively collected for SPLA cases performed at Chung-Ang University Hospital by a single surgeon between March 2011 and December 2011, including operative time, perioperative complications, conversion rate, and length of hospital stay. Each case of SPLA was performed using conventional laparoscopic instruments through Glove port placed into the single umbilical incision. To compare outcomes, a retrospective review was performed for those patients who underwent CLA between March 2010 and December 2010. RESULTS: Thirty-one patients underwent SPLA and 114 patients underwent CLA. Mean age (10.5 years vs. 11.1 years, P = 0.43), weight (48.2 kg vs. 42.9 kg, P = 0.27), and operation time (41.8 minutes vs. 37.9 minutes, P = 0.190) were comparable between both groups. Mean hospital stay was longer for CLA group (2.6 days vs. 3.7 days, P = 0.013). There was no conversion to conventional laparoscopic surgery in SPLA group. In CLA group, there were nine complications (7.9%) with 3 cases of postoperative ileuses and 6 cases wound problems. There was one complication (3.2%) of umbilical surgical site infection in SPLA group (P = 0.325). CONCLUSION: The results of this study demonstrated that SPLA using conventional laparoscopic instruments is technically feasible and safe in children. SPLA using conventional laparoscopic instruments might be popularized by eliminating the need for specially designed instruments.

Left paraduodenal hernia combined with acute cholecystitis

Paraduodenal hernia is a rare congenital malformation. Management consists of reduction of the herniated intestine and repair of the defect. A 74-year-old woman presented to the Emergency Department with persistent right upper quadrant pain that began 3 hours ago. Physical examination revealed tenderness at right upper quadrant of abdomen. Computed tomography revealed multiple gallstones with gallbladder wall thickening, marked dilatation of stomach and duodenum and a sac-like mass of small bowel loops to left of ligament of Treitz suggesting acute cholecystitis and left paraduodenal hernia. Laparoscopic exploration of abdomen was performed and cholecystectomy, bowel reduction, and closure of defect with intracorporeal interrupted suturing were performed. For left paraduodenal hernia without bowel necrosis, laparoscopic reduction of incarcerated bowel and closure of hernial orifice are technically feasible and may be the surgical method of choice because of its minimal invasiveness and aesthetic advantage.

Left paraduodenal hernia combined with acute cholecystitis

Paraduodenal hernia is a rare congenital malformation. Management consists of reduction of the herniated intestine and repair of the defect. A 74-year-old woman presented to the Emergency Department with persistent right upper quadrant pain that began 3 hours ago. Physical examination revealed tenderness at right upper quadrant of abdomen. Computed tomography revealed multiple gallstones with gallbladder wall thickening, marked dilatation of stomach and duodenum and a sac-like mass of small bowel loops to left of ligament of Treitz suggesting acute cholecystitis and left paraduodenal hernia. Laparoscopic exploration of abdomen was performed and cholecystectomy, bowel reduction, and closure of defect with intracorporeal interrupted suturing were performed. For left paraduodenal hernia without bowel necrosis, laparoscopic reduction of incarcerated bowel and closure of hernial orifice are technically feasible and may be the surgical method of choice because of its minimal invasiveness and aesthetic advantage.

Initial Experience of Laparoscopic Hepatectomy for Intrahepatic Duct (IHD) Stones: Comparison with Open Hepatectomy

PURPOSE: The aim of this study is to analyze our initial experiences with laparoscopic hepatectomy for treatment of intrahepatic duct (IHD) stones and to compare the outcomes of laparoscopic hepatectomy and open hepatectomy. METHODS: From March 2010 to December 2012, for treatment of IHD stones we performed laparoscopic hepatectomy in seven cases (LH group), which consisted of four cases of left lateral sectionectomy and three cases of left hepatectomy, and open hepatectomy was performed in nine cases (OH group), which consisted of seven cases of left lateral sectionectomy and two cases of left hepatectomy. Because there was no case of right hepatectomy in the LH group, we excluded a case of right hepatectomy in the OH group. Retrospective analysis of the clinical outcomes was performed with exclusion of one case of right hepatectomy. RESULTS: There was no significant difference in male to female ratio, mean age, and mean operation time. The mean postoperative hospital stay of the LH group was significantly shorter than that of the OH group (10.9+/-4.7 vs. 22.0+/-9.0 days, p=0.007). There were two cases of intra-abdominal fluid collection in the OH group, but no case in the LH group. Remnant stones were detected in one patient of the LH group and two patients of the OH group. The initial success rate of stone clearance was 85.7% in the LH group and 77.8% in the OH group. During a mean follow-up period of 13 months (range, four to 25 months), recurrent stone was detected in one case of the OH group. CONCLUSION: Laparoscopic surgery could be an effective treatment modality for management of IHD stones in select patients.

Torsion of the gallbladder in pregnancy / 대한외과학회지

Torsion of the gallbladder is a rare condition that is difficult to diagnose preoperatively, but prompt surgical intervention is necessary to avoid possible sepsis and death. A 36-year-old pregnant woman presented to Emergency Department with a constant epigastric pain at 17 weeks of gestation. Abdominal ultrasonography and magnetic resonance imaging demonstrated a distended gallbladder that contained no stones but had mild wall thickening. Laparoscopic cholecystectomy using three ports was performed under the impression of an acalculous cholecystitis. The gallbladder was found to be rotated 180 degrees clockwise on gallbladder mesentery and to be gangrenous. The postoperative course was uneventful and the patient was discharged on the 4th day after surgery. It is important to keep in mind gallbladder torsion in the differential diagnosis from acute cholecystitis when the patient has an acute onset of abdominal pain and a severely distended gallbldder. Prompt cholecystectomy via a laparoscopic approach should be performed.

Learning Curve and Clinicopathologic Analysis in Transperitoneal Laparoscopic Adrenalectomy; Performed by a Single Young Surgeon with No Experience of Open Adrenalectomy / 대한내분비외과학회지

PURPOSE: Adrenalectomy is a very rare operation and its associated learning curve has not yet been studied. The objective of this study was to determine whether the operation time decreases with experience and to evaluate the safety and feasibility of laparoscopic adrenalectomy performed by a surgeon who is new to laparoscopic and open-surgical adrenalectomy. METHODS: This study is a retrospective analysis of laparoscopic adrenalectomies performed between April 2007 and September 2012. All surgeries were performed by a single young surgeon who had no experience in performance of open or laparoscopic adrenalectomy. All surgeries were performed using the transperitoneal approach. RESULTS: In total, 42 cases were included. The average tumor size was 4.7 cm. The mean operating time was 125 min. Mean duration of hospital stay was 8.7 days. None of the cases showed conversion to open surgery or perioperative mortality. The operator achieved mastery after performance of left laparoscopic adrenalectomy in 12 cases and right laparoscopic adrenalectomy in 11 cases. CONCLUSIONS: A new surgeon can perform laparoscopic transperitoneal adrenalectomy successfully, independently, and safely after having performed the surgery in 12 cases.

Laparoscopic Approach to a Case of Appendicular Schwannoma

Appendicular schwannoma is a rare tumor originating from Schwann's cells in the Auerbach plexus. The preoperative diagnosis is difficult because the clinical features are nonspecific, and it is mostly found accidentally via a radiologic image as a tumor, mimicking malignancy. We report a case of an appendicular schwannoma coexisting with an adenocarcinoma in the lung. A laparoscopic appendectomy was done with a clear resection margin, and the immunohistochemical staining showed positive S-100 protein, which confirmed the schwannoma. The patient also underwent a left upper lobectomy of the lung. The patient has been free of recurrence for the 6 months since the operation. The laparoscopic approach could be available for treatment of an appendicular schwannoma, thus avoiding an unnecessary laparotomy.

Risk Factors for Complications Following Resection of Gastric Cancer

PURPOSE: Operative morbidity and mortality from gastric cancer have decreased in recent years, but many studies have demonstrated that its prevalence is still high. Therefore, we investigated the risk factors for morbidity and mortality considering the type of complication in patients with gastric cancer. MATERIALS AND METHODS: A total of 259 gastrectomies between 2004 and 2008 were retrospectively reviewed. RESULTS: Overall morbidity and mortality rates were 26.6% and 1.9%, respectively. A major risk factor for morbidity was combined resection (especially more than two organs) (P=0.005). The risk factors for major complications in which a re-operation or intervention were required were type of gastrectomy, upper location of lesion, combined resection, and respiratory comorbidity (P=0.042, P=0.002, P=0.031). Mortality was associated with preexisting neurologic disease such as cerebral stroke (P=0.016). In the analysis of different complication's risk factors, a wound complication was not associated with any risk factor, but combined resection was associated with bleeding (P=0.007). Combined resection was an independent risk factor for a major complication, surgical complication, and anastomotic leakage (P=0.01, P=0.003, P=0.011, respectively). Palliative resection was an independent risk factor for major complications and a previous surgery for malignant disease was significantly related to anastomosis site leakage (P=0.033, P=0.007, respectively). CONCLUSIONS: The risk factors for gastrectomy complications of gastric cancer were combined resection, palliative resection, and a previous surgery for a malignant disease. To decrease post-gastrectomy complications, we should make an effort to minimize the range of combined resection, if a palliative gastrectomy is needed for advanced gastric cancer.

Effects of Three Different Types of Anti-adhesive Agents in a Rat Abdominal Wall Defect Model

PURPOSE: Postsurgical adhesion formation is a significant clinical problem within every surgical specialty. Several adhesion barriers have been developed in the form of solution, membrane or film in an attempt to solve these problems. The purpose of the present study is to compare the efficacy of antiadhesive agents in the prevention of postsurgical adhesion formation in a standardized rat adhesion model. METHODS: We examined forty Sprague-Dawley rats, which is a cecal abrasion with partial peritonectomy model. Three treatment groups (Group I: Film-type Surgiwrap(R), Group II: Solution-type Guardix-sol(R), Group III: Membrane-type Interceed(R)), each consists of 10 rats, and a control group of 10 rats were used by saline. Ten days after surgery, the rats were killed, and the levels of adhesion were graded. Immunohistochemical staining for microvessel density (CD34, MVD) and macrophage (ED1) were performed in adhesion tissue. RESULTS: The peritoneum adhesion mean scores are as follows: control group: 2.2+/-0.78, Group I: 1.0+/-1.06, Group II: 0.9+/-0.99, Group III: 0.6+/-0.84. All treatment groups showed significantly less peritoneum adhesion (P=0.006), while there was no significant difference in each group. The intraperitoneal organs adhesion mean scores are as follows: control group: 2.8+/-0.91, Group I: 2.6+/-1.06, Group II: 1.4+/-0.84, Group III: 1.0+/-0.81. Group I had no significant difference about intraperitoneal organs adhesion with control group, but Group II and Group III showed less intraperitoneal organs adhesion. The mean numbers of microvessel density are as follows: control group: 42.5+/-4.83, Group I: 40.8+/-6.53, Group II: 30.9+/-6.15, Group III: 15.60+/-4.37, from which there was a significant difference between Group II and Group III with control group (P<0.001). The mean numbers of macrophage are as follows: control group: 223.3+/-33.12, Group I: 211.25+/-10.96, Group II: 171.60+/-23.96, Group III: 147.0+/-12.22, from which there was a significant difference between Group II and Group III with control group (P<0.001). CONCLUSION: In our animal model, three different types of antiadhesive agents (Surgiwrap(R), Guardix-sol(R), Interceed(R)) were effective in adhesion prevention, but Surgiwrap(R) had less antiadhesive effect for intraperitoneal organs adhesion. Membrane-type Interceed(R) had a better effect for microvessel density (MVD) and macrophage than solution-type Guardix-sol(R).

Effects of Extremely Low Frequency Elecromagnetic Fields on Thyroid Carcinogenesis Induced by N-bis(2-hydroxypropyl)nitrosamine and Sulfadimethoxine

PURPOSE: Long-term exposure to extremely low-frequency (60 Hz) electromagnetic fields (ELF-EMF) raises the questions of the induction of biological effects including tumorigenesis. One mechanism through which ELF-MFS could influence neoplastic development is the imbalance of cellular proliferation and cell apoptosis. The present study investigated the effect of ELF-EMF on chemically-induced thyroid carcinogenesis in a rat. METHODS: We examined cellular proliferation index measured by anti-Ki-67 antigen, apoptosis, apoptosis related proteins such as caspase 3 and p53, and cell cycle-related proteins (cyclin D1 and p21(WAF1/Cip1)). Forty Male F344 rats received a subcutaneous N-bis(2-hydroxypropyl)nitrosamine (DHPN, 2,800 mg/kg) injection, and 1 week later were allowed free access to drinking water containing sulfadimethoxine (0.1%) for 12 weeks. Twenty rats were exposed by ELF-EMF. During the carcinogenesis, sequential histological changes from hyperplasia, adenoma, and ultimately to overt carcinomas were noted. RESULTS: The exposure group of ELF-EMF, significantly increases the number size of carcinomas. Also, the proliferative and apoptotic indices were significantly increased in the ELF-EMF exposure group than in the control group. The caspase 3 protein expression did not show any significant changes between ELF-EMF group and control group. The p53 protein was not detected in both ELF-EMF exposure and control group. Among the cell cycle related proteins, cyclin D1, not p21(WAF1/Cip1), was significantly increased in adenomas and carcinomas in ELF-EMF exposure group compared with the control group. CONCLUSION: Exposure of ELF-EMF effects on chemically-induced rat thyroid carcinogenesis as results of altered increase of cellular proliferation, apoptosis, and cyclin D1 expression.

The Initial Experience with a Single Incision Laparoscopic Appendectomy

PURPOSE: A laparoscopic appendectomy (LA) is becoming popular for the treatment of acute and perforated appendicitis. Since it was first described, the LA has been modified many times. We present the result for a new technique of LA, in which the LA is conducted through a single umbilical incision without exteriorizing the appendix to perform the operation. METHODS: A single incision laparoscopic appendectomy was attempted in 25 patients (17 men, 8 women). Under general anesthesia, a wound retractor was inserted through the umbilicus. The appendix was grasped and dissected from surrounding tissues with a single flexible dissector or grasper. After mesenteric dissection with ultrasonic shear, the base of the appendix was ligated with an Endoloop. The appendix was withdrawn into the wound protector and extracted from the abdomen. RESULTS: A single incision laparoscopic appendectomy was completed in 25 patients. No major intraoperative or postoperative complications were encountered. The average duration of the procedure was 50.3+/-21.3 min. The average hospital stay was 4.1+/-2.4 days. CONCLUSION: This new technique, a single incision laparoscopic appendectomy, further improves the minimal invasiveness of a LA because a single incision is used. This procedure is a safe, very minimally invasive procedure with excellent cosmetic results.

Case of Small Bowel Perforation due to Enteropathy-Type T-Cell Lymphoma

Enteropathy-type T-cell lymphoma (ETTL) is a rare disease with a poor prognosis. According to the World Health Organization (WHO) classification, it is a subtype of the peripheral T-cell lymphomas. This disease is associated with gluten-sensitive enteropathy, has a high risk of intestinal perforation and obstruction, and is refractory to chemotherapeutic treatment. We report the case of a 73-year-old woman who was diagnosed with enteropathy-type T-cell lymphoma of the small intestine, which was positive for the markers of cytotoxic T cells, CD3, CD8, and CD56, on immunohistochemical staining after resection of the perforated terminal ileum.

Significance of Expression of Cell Cycle Related Proteins and Apoptosis Related Proteins in Follicular Adenoma and Follicular Carcinoma of Thyroid

PURPOSE: To explore the role of cell cycle regulators and apoptosis regulators in carcinogenesis of thyroid, the expression of cell cycle related proteins (cyclin D1, Ki-67) and apoptosis related proteins (survivin, caspase 3, bcl-2, p53) were investigated in follicular adenoma and follicular carcinoma of thyroid. METHODS: The following formalin-fixed paraffin embedded surgical specimens were immunohistochemically stained by avidin-biotin complex method for cyclin D1, Ki-67, survivin, caspase 3, bcl-2, p53; 15 cases of follicular adenoma (FA), 31 cases of minimally invasive follicular carcinoma (MIFC) and 12 cases of widely invasive follicular carcinoma (WIFC). RESULTS: The overexpression of six gene products in follicular neoplasms of thyroid was noted in varying frequency. Among them, increased Ki-67, caspase 3 index and overexpression of bcl-2 were noted in statistically significant, widely invasive follicular carcinoma than that of follicular adenoma and minimally invasive follicular carcinoma. CONCLUSION: These results suggest that the overexpression of Ki-67, caspase 3, bcl-2 appear to play an important role during follicular carcinogenesis of thyroid. In addition, the overexpression of these proteins is related to the differentiation of MIFC and WIFC. However, further molecular genetic studies are required to determine the interrelationships between the expression of cell cycle related proteins and apoptosis related proteins.

Expression of Proteins Related Cell Cycle and Apoptosis during Diethylnitrosamine (DEN)-induced Hepatocarcinogenesis in Rats

PURPOSE: To explore the role of cell cycle and apoptosis regulators during hepatocarcinogenesis, the expression of cell cycle-related proteins (cyclin D1 and p27kip1) and apoptosis-related proteins (p53, survivin, caspase 3). METHODS: Sprague-Dawley rats were given 120 ppm diethylnitrosamine (DEN) as a carcinogen and sequentially sacrificed. The expression of cell cycle and apoptotic related proteins were examined by light microscopy and immunohistochemistry. RESULTS: During the DEN-induced hepatocarcinogenesis, sequential histologic changes from preneoplastic lesions (altered hepatic cellular foci, hyperplastic nodules, and hepatocellular adenomas) and ultimately overt hepatocellular carcinomas and metastatic lesions were noted. The cyclin D1 were progressively increased from preneoplastic lesions to hepatocellular carcinomas. However, the p27kip1 and the survivine proteins did not show any other difference with the increasing degree of carcinogenesis. The p53 and caspase 3 proteins were more significantly increased in hepatocellular carcinomas than preneoplastic lesions. The cyclin D1 protein expression did not show any correlation with the expression of p27Kip1 protein, but the p53 expression was related to the expression of survivin and caspase 3. CONCLUSION: From the above results, over-expression of cyclin D1 plays a role in the early and late stages of hepatocarcinogenesis. In addition p53 and caspase 3 might be useful markers for evaluating the risk of malignant transformation.