Prognosis and feasibility of en-bloc vascular resection in stage Ⅱ pancreatic adenocarcinoma

AIM:To establish the prognosis and feasibility of en-bloc vascular resection of stage pancreatic adenocarcinoma of the head and uncinate process.METHODS:We retrospectively analyzed 87 patients with stage pancreatic adenocarcinoma,who were subjected to pancreaticoduodenectomy (PD) and pylo-rus-preserving PD (PPPD) between 1996 and 2006 in Chang Gung Memorial Hospital,Taiwan. Twelve and 75 patients underwent PD/PPPD with and without resection of portal vein/superior mesenteric vein (PV/SMV),respectively.RESULTS:The overall 1-and 3-year survival rates of patients undergoing PD/PPPD with and without vas-cular resection were 50.0% and 16.7%,and 44.4% and 12.2%,respectively. Morbidity and mortality rates in the PV/SMV resection vs non-resection group were 50.0% and 0.0%,and 40.0% and 2.7%,respectively. In multivariate analysis,serum bilirubin,histological differentiation and adjuvant chemotherapy were independent prognostic factors that influenced survival.CONCLUSION:In stage adenocarcinoma of the pancreatic head and uncinate process,serum bilirubin,histological differentiation and adjuvant chemotherapy were independent prognostic factors,and en-bloc vascular resection is a feasible option in carefully selected patients.

Clinicopathological study of solid and pseudopapillary tumor of pancreas: Emphasis on magnetic resonance imaging findings

AIM: To report the clinicopathological features and magnetic resonance imaging (MRI) findings of solid and pseudopapillary tumor (SPT) of pancreas.METHODS: From 1981 to 2005, 26 surgically treated cases of SPT were retrospectively reviewed. MRI findings of the latest 11 consecutive SPT cases were investigated.RESULTS: There were 25 women and one man having SPT (median age: 23 year) with a median tumor size of 7.5 cm. Among them, nine patients developed solid pseudopapillary carcinoma. During the median follow-up period of 66 mo, the 5-year survival rate of the 26 SPT patients was 96.2%. Three MRI features were proposed including Type 1 image, displaying SPT with completely solid part. All SPT patients with type 1 image were detected incidentally. Type 2 image displays of SPT with solid mass hemorrhage and type 3 image with massive hemorrhage. All the eight SPT patients with type 2 and 3 images suffered abdominal pain due to hemorrhage from SPT.CONCLUSION: SPT had a favorable survival rate irrespective of surgical procedures, malignancy, and MRI findings, however, MRI could reliably correlate with its clinicopathological features.

Local anesthesia with ropivacaine for patients undergoing laparoscopic cholecystectomy

AIM:To investigate the effect of pain relief after infu-sion of ropivacaine at port sites at the end of surgery.METHODS:From October 2006 to September 2007,72 patients undergoing laparoscopic cholecystectomy(LC) were randomized into two groups of 36 patients.One group received ropivacaine infusion at the port sites at the end of LC and the other received normal saline.A visual analog scale was used to assess postoperative pain when the patient awakened in the operating room,6 and 24 h after surgery,and before discharge.The amount of analgesics use was also recorded.The demographics,laboratory data,hospital stay,and perioperative complications were compared between the two groups.RESULTS:There was no difference between the two groups preoperatively in terms of demographic and lab-oratory data.After surgery,similar operation time,blood loss,and no postoperative morbidity and mortality were observed in the two groups.However,a significantly lower pain score was observed in the patients undergo-ing LC with local anesthesia infusion at 1 h after LC and at discharge.Regarding analgesic use,the amount of meperidine used 1 h after LC and the total used during admission were lower in patients undergoing LC with local anesthesia infusion.This group also had a shorter hospital stay.CONCLUSION:Local anesthesia with ropivacaine at the port site in LC patients signif icantly decreased post-operative pain immediately.This explains the lower meperidine use and earlier discharge for these patients.

Prognostic analysis of surgical treatment of peripheral cholangiocarcinoma: Two decades of experience at Chang Gung Memorial Hospital

AIM: To analyze the prognostic factors influencing the overall survival of peripheral cholangiocarcinoma (PCC) patients undergoing surgical treatment during 25 years at a single institution. METHODS: This study retrospectively reviewed prospectively collecting data about 373 patients with historically proven PCC who underwent surgical treatment between 1977 and 2001. RESULTS: Three hundred and seventy-three PCC patients (159 men and 214 women) underwent surgical treatment from 1977 to 2001. Among them, 187 PCC patients underwent hepatectomy and 135 had curative resection (curative resectability rate: 36.2%). The follow-up duration ranged from 1.05 to 167.6 mo (mean/median = 14.1/7.2 mo). Overall cumulative survival rates at 1, 3, and 5 years were 32.5%, 9.2%, and 4.1%, respectively. Univariate log-rank analysis identified the following as adverse influences on overall survival: presence of symptoms, absence of mucobilia, elevated CEA and CA 19-9 levels, non-papillary tumor type, receiving non-hepatectomy, advanced tumor staging, lack of post-operative chemotherapy, and radiotherapy. Meanwhile, multivariate Cox's proportional hazard analysis demonstrated that absence of mucobilia, non-papillary tumor type, advanced tumor staging, non-hepatectomy, and lack of post-operative chemotherapy were the five independent prognostic factors that adversely affected overall survival. CONCLUSION: Favorable overall survival of PCC patients undergoing surgical treatment depends on early tumor stage, presence of mucobilia, papillary tumor type, hepatic resection, and post-operative chemotherapy.

Sunitinib for Taiwan Residents patients with gastrointestinal stromal tumor after imatinib treatment failure or intolerance

AIM:To report preliminary results of the efficacy and safety of sunitinib in the management of Taiwan Residents gastrointestinal stromal tumors (GIST) patients facing imatinib mesylate (IM) intolerance or failure.METHODS:Between 2001 and May 2010,199 Taiwan Residents patients with metastatic GIST were treated at Chang Gung Memorial Hospital.Among them,23 (11.6%) patients receiving sunitinib were investigated.RESULTS:Sixteen male and 7 female patients with a median age of 59 years (range:24-83 years) received sunitinib.Twenty-two GIST patients changed to sunitinib because of IM failure and 1 because of intolerance.The median duration of sunitinib administration was 6.0 mo (range:2-29 mo).The clinical benefit was 65.2% [2 complete response (CR),4 partial response (PR),and 9 stationary disease (SD);15/23].In 12 patients harboring mutations of the kit gene at exon 11,the clinical benefit rate (CR,PR,and SD) was 75.0% and 6 patients with tumors containing kit exon 9 mutations had a clinical benefit of 50.0% (not significant,P=0.344).The progression free survival (PFS) and overall survival (OS) did not differ between patients whose GISTs had wild type,KIT exon 9,or KIT exon 11 mutations.Hand-foot syndrome was the most common cause of grade Ⅲ adverse effect (26.1%),followed by anemia (17.4%),and neutropenia (13.0%).During the median 7.5-mo follow-up after sunitinib use,the median PFS and OS of these 23 GIST patients after sunitinib treatment were 8.4 and 14.1 mo,respectively.CONCLUSION:Sunitinib appears to be an effective treatment for Taiwan Residents with IM-resistant/intolerant GISTs and induced a sustained clinical benefit in more than 50% of Taiwan Residents advanced GIST patients.

Timing of mortality in severe acute pancreatitis:Experience from 643 patients

AIM: To determine the timing of mortality after onset of severe acute pancreatitis (SAP) and the course of the disease in a large series of patients. METHODS: From July 1996 to June 2005, all patients diagnosed with acute pancreatitis at Chang Gung Memorial Hospital, Taipei, Taiwan were retrospectively studied. Three thousand two hundred and fifty episodes of acute pancreatitis were recorded in 2248 patients (1431 males and 817 females; median age, 55.6 years; range, 18-97 years). Mortality was divided into two groups: early death (≤ 14 d after admission), and late death (> 14 d after admission). The clinical features of patients in these two groups were compared. RESULTS: Although the overall mortality rate of acute pancreatitis was 3.8% (123/3250), mortality rate of SAP was as high as 16.3% (105/643). Of those 105 SAP mortalities, 44 (41.9%) deaths occurred within the first 14 d after admission and 61 (58.1%) occurred after14 d. Incidence of early death did not significantly differ from that of late death. The co-morbidities did not contribute to the timing of death. Early deaths mainly resulted from multiple organ failure. Late deaths were mainly caused by secondary complication of infected necrosis. Intra- abdominal bleeding significantly caused higher mortality in late death. CONCLUSION: Approximately half (42%) of SAP deaths occur within 14 d and most were due to multiple organ failure. The late deaths of SAP were mostly due to infected necrosis.

Successful laparoscopic management for cholecystoenteric fistula

AIM： Since 1987, laparoscopic cholecystectomy （LC） has been widely used as the favored treatment for gallbladder lesions. Cholecystoenteric fistula （CF） is an uncommon complication of the gallbladder disease, which has been one of the reasons for the conversion from LC to open cholecystectomy. Here, we have reported four cases of CF managed successfully by laparoscopic approach without conversion to open cholecystectomy. METHODS： During the 4-year period from 2000 to 2004, the medical records of the four patients with CF treated successfully with laparoscopic management at the Chang Gung Memorial HospitaI-Taipei were retrospectively reviewed. RESULTS： The study comprised two male and two female patients with ages ranging from 36 to 74 years （median： 53.5 years）. All the four patients had right upper quadrant pain. Two of the four patients were detected with pneumobilia by abdominal ultrasonography. One patient was diagnosed with cholecystocolic fistula preoperatively correctly by endoscopic retrograde cholangiopancreatography and the other one was diagnosed as cholecystoduodenal fistula by magnetic resonance cholangiopancreatography. Correct preoperative diagnosis of CF was made in two of the four patients with 50% preoperative diagnostic rate. All the four patients underwent LC and closure of the fistula was carried out by using Endo-GIA successfully with uneventful postoperative courses. The hospital stay of the four patients ranged from 7 to 10 d （median, 8 d）. CONCLUSION： CF is a known complication of chronic gallbladder disease that is traditionally considered as a contraindication to LC. Correct preoperative diagnosis of CF demands high index of suspicion and determines the success of laparoscopic management for the subset of patients. The difficult laparoscopic repair is safe and effective in the experienced hands of laparoscopic surgeons.

Prognostic analysis of patients with pancreatic head adenocarcinoma less than 2cm undergoing resection

AIM:To investigate the differences in clinicopathological features between patients with pancreatic cancer greater or less than 2 cm situated over the pancreatic head and the prognostic factors for survival of patients with pancreatic cancer<2 cm over the pancreatic head. METHODS:From 1983 to 2006,159 patients with histologically proven pancreatic adenocarcinoma(PAC) at the pancreatic head undergoing curative resection at the Department of Surgery,Chang Gung Memorial Hospital,Taipei,Taiwan were reviewed,comprising 123 cases of large(L)-PAC(tumor>2 cm)and 36 cases of small(S)-PAC(tumor≤2 cm).We compared the clinicopathological characteristics and prognosis of L-PAC and S-PAC patients.The clinicopathological characteristics of S-PAC were investigated to clarify the prognosis predictive factors of S-PAC. RESULTS:One hundred and fifty-nine PAC patients, aged 16-93 years(median,59.0 years)with a tumor at the pancreatic head undergoing intentional curative resection were investigated.The S-PAC and L-PAC patients had similar demographic data,clinical features,and tumor markers(a similar positive rate of carcinoembryonic antigen and carbohy- drate antigen 19-9).There were also similar rates of lymph node metastasis,portal vein invasion,stage distribution,tumor differentiation,positive resection margin,surgical morbidity and mortality observedbetween the two groups.During a follow-up period ranging from 1.0 to 122.7 mo(median,10.9 mo), S-PAC and L-PAC patients had a similar prognosis after resection(P=0.4805).Among the S-PAC patients group,patients with higher albumin level(>3.5 g/dL) had more favorable survival than those with lower albumin levels,which was the only favorable predictive prognostic factor.Meanwhile,early-staged(stageⅠ,Ⅱ) S-PAC patients tended to have a more favorable outcome than late-stage(stageⅢ,Ⅳ)S-PAC patients, but this was not statistically significant. CONCLUSION:S-PAC patients should not be regarded as early PAC.Only higher albumin level(>3.5 g/dL) and early stage disease(stageⅠ,Ⅱ)were the favorable prognosis factors for S-PAC patients.

Treatment of patients with advanced gastrointestinal stromal tumor of small bowel: Implications of imatinib mesylate

AIM： To examine the impact of imatinib mesylate （Glivec） on patient survival and response and its safety, and the correlation of the response rate with the kit gene mutation status. METHODS： Thirty-three of 74 （44.6%） small bowel gastrointestinal stromal tumor （GIST） patients who developed recurrence after curative resection and not treated with Glivec were classified as group A patients. Twenty-two advanced small bowel GIST patients treated with Glivec were classified as group B patients. Clinicopathological features, post-recurrence and overall survival rates were compared. Each tumor in group B patients was investigated for mutations of kit or plateletderived growth factor alpha （PDGFRA）. The mutation type was correlated with clinical outcomes. The antitumor effect and safety of Glivec in group B patients were also assessed. RESULTS： Advanced small bowel GIST patients treated with Glivec had substatntially longer post-recurrence survival and higher overall survival rates than those not treated with Glivec. A total of 15 patients had a partial response （PR） （67.8%）. Activated mutations of c-kit were found in 16 of 19 tested patients and no PDGFRA mutant was identified. In 13 patients with GISTs harboring exon 11 kit mutations, the partial response rate （PR） was 69.3%, whereas two of three patients with tumors containing an exon 9 kit mutation had an overall response rate （ORR） of 66.7% （not significant）. CONCLUSION： Glivec significantly prolongs the postrecurrence and overall survival of Asian patients with advanced GISTs. Glivec induces a sustained objective response in more than half of Asian patients withadvanced small bowel GISTs. Activated mutations of kit exon 11 are detectable in the vast majority of GISTs. There is no difference in the PR rate for patients whose GISTs have kit exon 9 and exon 11 mutations.

Correct diagnosis and successful treatment for pericardial effusion due to toothpick injury: A case report and literature review

We reported a 55-year-old man who suffered from chest pain and dyspnea on exertion for two weeks associated with night sweating, general malaise, poor appetite, and body weight loss. Physical examination revealed friction rub with distant heart sound, bilateral clear breathing sound, no abdomen tenderness, and normal bowel sound. Subsequent chest X-ray revealed cardiomegaly and cardiac echo showed massive pericardial and pleural effusion with normal left ventricular function. Constrictive pericarditis was diagnosed based on clinical information. Tuberculosis (TB), malignancy, autoimmune disease, infection, hypothyroidism, and idiopathic could be the causes but excluded by further study. High-resolution lung CT scan after reconstruction revealed a moderate amount pericardial effusion with possible superimposed infection. Thickness of pericardium and left lobe liver abscess were found. A straight tubular structure about 6 cm in length transverses the lateral segment of liver to pericardial space and unknown foreign body was suspected. Laparotomy was performed, 6.5 cm toothpick was found through the liver into pericardium. Post-operative course was uneventful and he discharged one week later. The patient could not remember swallowing the toothpick before. He had no chest pain and dyspnea on exertion during a 6-mo follow-up period.

Predicting cholecystocholedochal fistulas in patients with Mirizzi syndrome undergoing endoscopic retrograde cholangiopancreatography

BACKGROUND Mirizzi syndrome(MS) is defined as an extrinsic compression of the extrahepatic biliary system by an impacted stone in the gallbladder or the cystic duct leading to obstructive jaundice. Endoscopic retrograde cholangiopancreatography(ERCP) could serve diagnostic and therapeutic purposes in patients with MS in addition to revealing the relationships between the cystic duct, the gallbladder, and the common bile duct(CBD). Cholecystectomy is a challenging procedure for a laparoscopic surgeon in patients with MS, and the presence of a cholecystocholedochal fistula renders preoperative diagnosis important during ERCP.AIM To evaluate cholecystocholedochal fistulas in patients with MS during ERCP before cholecystectomy.METHODS From 2004 to 2018, all patients diagnosed with MS during ERCP were enrolled in this study. Patients with associated malignancy or those who had already undergone cholecystectomy before ERCP were excluded. In total, 117 patients with MS diagnosed by ERCP were enrolled in this study. Among them, 21 patients with MS had cholecystocholedochal fistulas. MS was further confirmed during cholecystectomy to check if cholecystocholedochal fistulas were present. The clinical data, cholangiography, and endoscopic findings during ERCP were recorded and analyzed.RESULTS Gallbladder opacification on cholangiography is more frequent in patients with MS complicated by cholecystocholedochal fistulas(P < 0.001). Pus in the CBD and stricture length of the CBD longer than 2 cm were two additional independent factors associated with MS, as demonstrated by multivariate analysis(odds ratio 5.82, P = 0.002;0.12, P = 0.008, respectively).CONCLUSION Gall bladder opacification is commonly seen in patients with MS with cholecystocholedochal fistulas during pre-operative ERCP. Additional findings such as pus in the CBD and stricture length of the CBD longer than 2 cm may aid the diagnosis of MS with cholecystocholedochal fistulas.

Primary squamous cell carcinoma of the liver:A successful surgically treated case

Primary squamous cell carcinoma (SCC) of the liveris rare. Totally nine such cases have been reportedin the literature. Primary SCC of the liver has beenreported to be associated with hepatic teratoma,hepatic cyst, or hepatolithiasis. Complete remission ofpoorly differentiated SCC of the liver could be achievedby systemic chemotherapy followed by surgery orremarkably respond to hepatic arterial injection of lowdose chemotherapeutic drugs. Here we report the fi rstcase of primary SCC of the liver presenting as a solidtumor and receiving successful hepatic resection with9-mo disease free survival.

Neurosurgical procedures in patients with liver cirrhosis: A review

Liver cirrhosis, a devastating liver fibrosis caused by hepatitis/inflammation or tumors, is a major comorbid factor in known surgery fields, such as cardiovascular and abdominal surgeries. It is important to review possible comorbid results in neurosurgical procedures in cirrhotic patients. In the reviewed literature, ChildPugh and model for end-stage liver disease scores are commonly used in the assessment of surgical risks for cirrhotic patients undergoing abdominal, cardiovascular or neurosurgical procedures. The major categories of neurosurgery are traumatic brain injury(TBI), spontaneous intracranial hemorrhage(SICH), brain tumors, and spinal instrumentation procedures. TBI was reported with surgical mortality as high as 34.5% and a complication rate of 87.2%. For SICH, mortality ranged from 22.7% to 47.0%, while complications were reported to be 43.2%. Less is discussed in brain tumor patients; still the postoperative hemorrhage rate approached 26.7%. In spinal fusion instrumentation procedures, the complication rate was as high as 41.0%. Preoperative assessment and correction could possibly decrease complications such as hemorrhage, wound infection and other cirrhosis-related complications(renal, pulmonary, ascites and encephalopathy). In this study, we reviewed the neurosurgical-related literature with regard to liver cirrhosis as a prognostic factor influencing neurosurgical outcomes.

Advanced gastrointestinal stromal tumor patients with complete response after treatment with imatinib mesylate

AIM： Most gastrointestinal stromal tumors （GISTs） express constitutively activated mutant isoforms of kit kinase or platelet-derived growth factor receptor alpha （PDGFRA）, which are potential therapeutic targets for imatinib mesylate （Glivec）. Partial response occurred in almost two thirds of GIST patients treated with Glivec. However, complete response （CR） after Glivec therapy was sporadically reported. Here we illustrated advanced GIST patients with CR after Glivec treatment. METHODS： Between January 2001 and June 2005, 42 advanced GIST patients were treated with Glivec. Patients were administered 400 mg of Glivec in 100-mg capsules, taken orally daily with food. The response of the tumor to Glivec was evaluated after one month, three months, and every three months thereafter or whenever medical need was indicated. Each tumor of patients was investigated for mutations of kit or PDGFRA. RESULTS： The median follow-up time of the 42 ad-vanced GIST patients treated with Glivec was 16.9 months （range, 1.0- 47.0 months）. Overall, 3 patients had complete response CR （7.1%）, 26 partial response （67.8%）, 5 stationary disease （11.9%）, and 3 progressive disease （11.9%）. The median duration of Glivec administration for the three patients was 36 months （range, 23-36 months）. The median time to CR after Glivec treatment was 20 months （range, 9-26 months）. Deletion and insertion mutations of c-kit exon 11 and insertion mutation of c-kit exon 9 were found in two cases and one case, respectively. CONCLUSION： Complete response （CR） can be achieved in selected advanced GIST patients treated with Glivec. The median time to CR after Glivec treatment was 20 months. Deletion and insertion mutations of kit exon 11 and insertion mutation of kit exon 9 contribute to the genetic features in these selected cases.

Multifocal intraductal papillary mucinous neoplasm of the pancreas-A case report

Cystic neoplasms of the pancreas are relatively rare, comprising 10 percent of pancreatic cysts and only 1 percent of pancreatic cancers. Cystic neoplasms include mucinous cystic neoplasms, serous cystadenomas, papillary cystic tumors, cystic islet cell tumors and intraductal papillary mucinous neoplasms of the pancreas (IPMNs). IPMN was first described in 1982. It has been most commonly described in 60 to 70 years old males, and represents a relatively ''new'' but increasingly recognized disease. The improvement and widespread use of modern imaging equipments and heightened awareness of physicians contribute to the increasing incidence of IPMN. The majority of IPMNs are located in the pancreatic head (75%) while the rest involves the body/tail regions. Multifocal IPMNs have been hypothesized, but the true presence of multifocality is unknown. Here we present a 72-yearold male diagnosed with IPMN (carcinoma in situ ) in the pancreatic head and a branch duct type IPMN (duct atypia) in the pancreatic body and tail. The patient underwent a Whipple intervention and a distal pancreatectomy. A three-year disease-free survival has been observed so far.

Hepatic resection for hepatocellular carcinoma in end-stage renal disease patients: Two decades of experience at Chang Gung Memorial Hospital

AIM: Hepatocellular carcinoma (HCC) is a common disease in Taiwan. The prevalence of viral hepatitis infection and the subsequent development of HCC are well known to be higher in patients with end-stage renal disease (ESRD) requiring hemodialysis (HD) or peritoneal dialysis (PD) than among the general population. However, information on hepatic resection for ESRD-HCC patients is limited. METHODS: The clinical features of 26 ESRD-HCC patients who underwent hepatic resection from 1982 to 2001 were retrospectively reviewed. Meanwhile, the clinicopathological features and the outcome of 1 198 HCC patients without ESRD undergoing hepatic resection were used for comparison. RESULTS: Of 1 224 surgically resected HCC patients, 26 (4.2%) were ESRD-HCC. Univariate analysis revealed more associated disease, more physical signs of anemia and postoperative complications, lower hemoglobin, platelet, α-fetoprotein, elevated blood urea nitrogen (BUN) and creatinine levels, smaller tumors, lower HBsAg positivity, higher HCV positivity, and longer hospital stays in the ESRDHCC group compared with the HCC group. Furthermore, multivariate stepwise logistic regression analysis revealed that elevated BUN and creatinine levels were the only two independently significant factors in the patients in the ESRD-HCC group. Overall and disease-free survival rates were similar between the ESRD-HCC and HCC groups.CONCLUSION: Elevated BUN and creatinine were the only two main independent factors differentiating ESRD-HCC from HCC patients. ESRD should not be a contraindication of hepatic resection in HCC patients; however, careful operative techniques and perioperative care are crucial to achieving lower morbidity and mortality. Comparable overall survival and disease-free survival can be achieved in selected ESRD-HCC patients undergoing hepatic resection when compared with conventional HCC patients.

Intractable bleeding from solitary mandibular metastasis of hepatocellular carcinoma

Hepatocellular carcinoma （HCC） metastasizes to the mandible is infrequently seen. Solitary bony metastasis to the mandible is rarer. The intractable bleeding caused by rupture of the metastatic HCC is challenging to clinicians. We present a case of a 74-year-old woman with HCC under control without progression for 3 years. Left facial swelling and episodes of bleeding developed recently and biopsy revealed a metastatic HCC. Computer tomography showed a large tumor in parapharyngeal space with evident mandibular ramus destruction. Bleeding occurred from the metastatic tumor but could not be controlled by electrocauterization, SurgicelTM, tissue glue, and bone wax and angiographic embolization. Palliative radiotherapy （2400 cGy in 6 fractions） was tried and the intractable bleeding was successfully stopped after the radiotherapy. Because of the hypervascular and osteolytic nature of the solitary mandibular metastatic lesion, the bleeding was troublesome. Radiotherapy provided successful control of intractable bleeding from the metastatic tumor.

Characterization of a novel rat cholangiocarcinoma cell culture model-CGCCA

AIM： TO characterize a culture model of rat CCA cells, which were derived from a transplantable TTA-induced CCA and designated as Chang Gung CCA （CGCCA）. METHODS： The CGCCA cells were cultured at in vitro passage 12 times on a culture dish in DMEM medium. To measure the doubling time, 103 cells were plated in a 96-well plate containing the growth medium. The cells were harvested 4 to 10 d after seeding, and a standard MTT assay was used to measure the growth. The phenotype of CACCA cell and xenograft was determined by immunohistochemical study. We also determine the chromosomal alterations of CGCCA, G-banding and spectral karyotyping studies were performed. The CGCCA cell line was transplanted into the nude mice for examining its tumorigenicity. 2-Deoxy-2-（18F）fluoro-D- glucose （FDG） autoradiography was also performed to evaluate the FDG uptake of the tumor xenograft. RESULTS： The doubling time for the CGCCA cell line was 32 h. After transplantation into nude mice, FDG autoradiography showed that the tumors formed at the cell transplantation site had a latency period of 4-6 wk with high FDG uptake excluding necrosis tissue. Moreover, immunohistochemical staining revealed prominent cytoplasmic expression of c-erb-B2, CK19, c-Met, COX-n, EGFR, MUC4, and a negative expression of K-ras. All data confirmed the phenotypic features of the CGCCA cell line coincide with the xenograft mice tumors, indicating cells containing the tumorigenicity of CCA originated from CCA. In addition, karyotypic band- ing analysis showed that the diploid （2n） cell status combines with ring and giant rod marker chromosomes in these clones; either both types simultaneously appeared or only one type of marker chromosome in a pair appeared in a cell. The major materials contained in the marker chromosome were primarily identified from chromosome 4. CONCLUSION： The current CGCCA cell line may be used as a non-K-ras effect CCA model and to obtain information and reveal novel pathways for CCA. Further applications regarding tumor markers or therapeutic targeting of CCA should be addressed accordingly.

Hepatoma with cardiac metastasis: An advanced cancer requiring advanced treatment

AIM: To investigate the clinical and pathologic fi ndings, and to discuss the pathophysiology of hepatocellular carcinoma with cardiac metastasis. METHODS: Eight hepatoma patients with cardiac metastasis, who were treated by surgical excision from 1993 to 2006, were retrospectively studied. Detailed clinical parameters were analyzed. RESULTS: Of those eight patients, two (25%) were women and six (75%) were men, with the mean age of 50 years (range, 40-70 years). The presentations included: asymptomatic (75%), heart failure (25%), and pulmonary embolism (12.5%). All lesions involved the right atrium, and extended to the lung (12.5%), inferior vena cava (25%), and left atrium (12.5%). The level of tumor marker, alpha-fetal protein, was not correlated with the severity of metastasis or disease prognosis. Moreover, the availably estimated doubling time was less than 3 mo. The pathological fi ndings included variablehemorrhage and necrosis. The survival time following surgery also varied from one month to more than 30 mo. CONCLUSION: Hepatoma metastasis to the heart was detected in all eight patients. This study demonstrates that surgery might help the outcome in such cases.

Sporadic somatic mutation of c-kit gene in a family with gastrointestinal stromal tumors without cutaneous hyperpigmentation

We described two members in a family with gastrointestinal stromal tumors （GISTs） without cutaneous hyperpigmentation. The patients were father and son who did not have cutaneous hyperpigmentation. Histological examination showed that these tumors were GISTs expressing CD34 and CD117. Tumor DNA extracted from paraffin-embedded specimens revealed somatic mutation with a deletion mutation at different codons in exon 11 of c-kit gene after direct sequencing analysis. No germline mutation was detected in DNA extracted from peripheral leukocytes obtained from the father and son. We propose that GISTs could be caused by sporadic somatic mutation in a family without germline mutation and hyperpigmentation.