Radiofrequency ablation of hepatocellular carcinoma: long-term outcome and prognostic factors.

PURPOSE: To investigate the efficacy of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), and the prognostic factors for post-RFA survival rate. METHODS: From 1999 to 2006, 266 patients with 392 HCCs underwent ultrasound guided RFA treatment. They were 216 males and 50 females, average age 59.4+/-15.4 years (24-87 years). The HCC were 1.2-6.7 cm in diameters (average 3.9+1.3 cm). There were 158 patients with single tumor, and the rest had multiple (2-5) tumors. Univariate and multivariate analysis with 19 potential variables were examined to identify prognostic factors for post-RFA survival rate. RESULTS: The overall post-RFA survival rates at 1st, 3rd, and 5th year were 82.9%, 57.9% and 42.9%, respectively. In the 60 patients with stage I HCC (AJCC staging), the 1-, 3-, 5-year survival rate were 94.8%, 76.4% and 71.6%, significantly higher than the 148 patients with stage II-IV tumors (81.8%, 57.6% and 41.2%, P=0.006). For the 58 patients with post-surgery recurrent HCC, the survival rates were 73.2%, 41.9% and 38.2% at the 1st, 3rd, and 5th year, which were significantly lower than those of stage I HCC (P=0.005). Nine potential factors were found with significant effects on survival rate, and they were number of tumors, location of tumors, pre-RFA liver function enzymes, Child-Pugh classification, AJCC staging, primary or recurrent HCC, tumor pathological grading, using mathematical protocol in RFA procedure and tumor necrosis 1 month after RFA. After multivariate analysis, three factors were identified as independent prognostic factors for survival rate, and they were Child-Pugh classification, AJCC staging and using mathematical protocol. CONCLUSION: Identifying prognostic factors provides important information for HCC patient management before, during and after RFA. This long-term follow-up study on a large group of HCC patients confirmed that RFA could not only achieve favorable outcome on stage I HCC, but also be an effective therapy for stage II-IV or recurrent HCC.

[Clinical analysis of curative resection with hemihepatectomy for advanced hilar cholangiocarcinoma].

OBJECTIVE: To investigate the superiority of curative resection with hemihepatectomy in treatment of hilar cholangiocarcinoma and the strategy to lower the incidence of complications and mortality. METHODS: The clinical data of 50 patients with hilar cholangiocarcinoma who underwent surgical procedures in Peking University School of Oncology from January 1998 to May 2006 were retrospectively analyzed. RESULTS: Forty-one patients (56.9%) underwent surgical resection. Twenty-two (53.6%) received a radical operation (RO). Thirty patients underwent preoperative percutaneous transhepatic cholangio-drainage (PTCD) to reduce the jaundice. Curative resection with hemihepatectomy was performed on 19 cases including 14 cases undergoing RO. Two patients who had undergone hemihepatectomy died of liver failure. The postoperative morbidity rate was 62% in all 50 cases, 78% in the hemihepatectomy group. The 1- and 2-year survival rates of the hemihepatectomy group were 57.1% and 27.3% respectively. CONCLUSION: Curative resection with hemihepatectomy is a safe and effective option for hilar cholangiocarcinoma, especially for Bismuth III or IV type. Preoperative biliary drainage is necessary before a major hepatic resection.

[Spleen-preserving distal pancreatectomy in treatment of solid-pseudopapillary neoplasm].

OBJECTIVE: To investigate the feasibility and safety of spleen-preserving distal pancreatectomy with conservation of the splenic arteries and veins in treatment of benign neoplasms of distal pancreas. METHODS: Four patients with solid-pseudopapillary neoplasm, 1 males and 3 females, aged 30 (17 - 37), underwent laparotomy. The distal pancreas with tumor was cut. The perforating branches between the splenic artery and vein and the distal pancreas were isolated, ligated, and cut. The splenic artery and vein and the short and left gastric vessels were all preserved. The spleen remained intact. RESULTS: The mean operation time was 208 minutes +/- 52 minutes, and the mean blood loss was 475 ml +/- 96 ml. Blood transfusion was not necessary. The mean post-operative hospital stay was 18 days +/- 13 days. No post-operative complications were found except for pancreatic leakage occurring in one patient that was cured by conservative treatment. No metastasis and recurrence was found. CONCLUSION: Safe and feasible, spleen-preserving distal pancreatectomy with conservation of the splenic arteries and veins is one of the best choices for treatment of benign and borderline tumors of pancreas.

[Clinicopathological features of solid pseudopapillary tumor of the pancreas].

OBJECTIVE: To elucidate the clinicopathological features of solid pseudopapillary tumor (SPT) of the pancreas. METHODS: Eight patients with SPT of the pancreas admitted from August 1996 to March 2005 were retrospectively analyzed. RESULTS: All the 8 patients were female with an average age of 25.3 (13-41) years. The primary clinical manifestations included abdominal mass (n = 3), vague abdominal pain (n = 3), and duodenal obstruction (n = 1). SPT was occasionally found in one patient during physical examination. Six tumors located at the head and the other two in the body and tail of the pancreas. Pancreaticoduodenectomies were performed in 4 patients, tumor enucleations in 2, distal pancreatectomies in 1, and palliative internal drainage with a cystoenterotomy in the other one with an unresectable huge cystic lesion. All patients were alive on an average follow-up of 37.8 (8-103) months. CONCLUSION: SPT occurs mainly in adolescent and young females, and satisfactory outcome may be achieved with active and appropriate surgeries.

Stomach-interposed cholecystogastrojejunostomy: a palliative approach for periampullary carcinoma.

AIM: For patients of periampullary carcinoma found to be unresectable at the time of laparotomy, surgical palliation is the primary choice of treatment. Satisfactory palliation to maximize the quality of life with low morbidity and mortality is the gold standard for a good procedure. Our aim is to explore such a procedure as an alternative to the traditional ones. METHODS: A modified double-bypass procedure is performed by, in addition to the usual gastrojejunostomy, implanting a mushroom catheter from the gall bladder into the jejunum through the interposed stomach as an internal drainage. A retrospective review was performed including 22 patients with incurable periampullary carcinomas who underwent this surgery. RESULTS: Both jaundice and impaired liver function improved significantly after surgery. No postoperative deaths, cholangitis, gastrojejunal, biliary anastomotic leaks, recurrent jaundice or late gastric outlet obstruction occurred. Delayed gastric emptying occurred in two patients. The total surgical time was 150+/-26 min. The estimated blood loss was 160+/-25 mL. The mean length of hospital stay after surgery was 22+/-6 d. The mean survival was 8 mo (range 1.5-18 mo). CONCLUSION: In patients of unresectable periampullary malignancies, stomach-interposed cholecystogastrojejunostomy is a safe, simple and efficient technique for palliation.

Preliminary study on proteomics of gastric carcinoma and its clinical significance.

AIM: To explore the preliminary identification of serum protein pattern models that may be novel potential biomarkers in the detection of gastric cancer. METHODS: A total of 130 serum samples, including 70 from patients with gastric cancer and 60 from healthy adults, were detected by surface-enhanced laser desorption and ionization time-of-flight mass spectrometry (SELDI-TOF-MS). The data of spectra were analyzed by Biomarker Patterns Software (BPS). Thirty serum samples of gastric cancer patients and 30 serum samples of healthy adults were grouped into the training group to build models, and the other 70 samples were used to test and evaluate the models. The samples of the test group were judged only with their peaks' height and were separated into cancer group or healthy control group by BPS automatically and the judgments were checked with the histopathologic diagnosis of the samples. RESULTS: Sixteen mass peaks were found to be potential biomarkers with a significant level of P< 0.01. Among them, nine mass peaks showed increased expression in patients with gastric cancer. Analyzed by BPS, two peaks were chosen to build the model for gastric cancer detection. The sensitivity, specificity, and accuracy of the model were 90%, 36/40, 86.7%, 26/30, and 88.6%, 62/70, respectively, which were greatly higher than those of clinically used serum biomarkers CEA (carcinoembryonic antigen), CA19-9 and CA72-4. Stage I/II gastric cancer samples of the test group were all judged correctly. CONCLUSION: The novel biomarkers in serum and the established model could be potentially used in the detection of gastric cancer. However, large-scale studies should be carried on to further explore the clinical impact on the model.

[Long term (5 years) outcome of radiofrequency ablation for hepatocellular carcinoma in 256 cases].

A total of 267 patients with hepatocellular carcinoma underwent ultrasound-guided radiofrequency ablation (RFA) in Peking University School of Oncology between 1999 and 2005 (421 RFA sessions). Among them, 254 patients were candidates for RFA treatment and the selective criteria were: (1) the greatest diameter of tumor 5 cm, respectively. According to tumor size, shape and location, we adopted a defined treatment strategy, which consisted of a mathematical protocol, an individualized protocol and adjunctive measures. And several methods were also used to prevent and deal with complications in tumors with different features. In this series the tumor complete necrosis rate (CR)was 95.2% (356/374 tumors). It was higher in 3.5 cm tumors with a CR of 91.3% (156/171 tumors). CR were 95.6% (44/46 tumors) for tumors near the gallbladder, 92.9%(79/85 tumors) for tumors near the diaphragm, 90.9%(40/44 tumors) for tumors near the gastrointestinal tract, 91.2% (31/34 tumors) for tumors near large vessel. In a follow-up period of 2-69 months, the local recurrence rates were 11.7% for HCC and 12.5% for recurrent HCC. The incidence of complications was 2.4% (10/409 sessions), including intraperitoneal hemorrhage (n=2), biliary duct stricture (n=1), hemothorax (n=1), bowel perforation (n=1) and needle tract seeding (n=5). Of these cases, only 3 required operation and the mortality related to RFA was zero in this series. We used Kaplain-Meier method and log-rank test to estimate and compare the survival rate. The 1-, 3-, and 5-year survival rates after RFA were 83.3%, 66.9%, 41.2%, respectively for all HCC patients and 74.6%, 41.3%, 33.6%, respectively for recurrent HCC. Survivals based on TNM stage, Child-Pugh grade, tumor number and tumor size are shown in Table 1. In conclusion, RFA with standard protocol has evolved as a minimally invasive local treatment that could achieve satisfactory outcomes for small liver tumors, and has become an effective and relatively safe alternative for the treatment of advanced tumors and recurrent tumors, which are not suitable for traditional therapy. RFA has broaded the treatment threshold for hepatic malignancies and might become one of the regular treatment methods in focal liver tumor and find wide application.

[Efficacy of radiofrequency ablation of 343 patients with hepatic tumor and the relevant complications].

OBJECTIVE: To investigate the treatment efficacy of radiofrequency ablation (RFA) of hepatic tumors and the relevant complications. METHODS: A total of 343 patients with 778 hepatic tumors underwent ultrasound-guided RFA (582 procedures). There were 212 cases of hepatic cellular carcinoma (HCC) with 448 tumors, and the average largest diameter was 4.0 cm. Of all the patients, 63 (29.7%) were in the stage of I-II (UICC Systems) and 149 (70.3%) in stage of III-IV (including 43 patients with tumor recurrence after surgical resection). There were 131 cases of metastatic liver carcinoma (MLC), with 330 metastases in the liver, the average diameter was 3.9 cm, and the liver metastases of 91 patients (69.5%) came from gastrointestinal tract. The patients were treated using the relatively standard protocol. Crucial attention must be paid to monitoring the abnormal changes in ultrasound images as well as the vital signs of the patients to find the possible hemorrhage and peripheral structure injury in time. The tumors were considered ablated successfully if no viability was found on enhanced CT within 24 hours or 1 month after RFA. The patients were followed up for 2-62 months. RESULTS: The ablation success rate for HCC was 95.5% (428/448 tumors), and the rate for MLC was 96.4% (318/330 tumors). The local tumor recurrence rates for HCC and MLC were 8.5% (38/448 tumors) and 11.8% (39/330 tumors), respectively. A total of 138 patients (40.2%) underwent repeated ablations for 2-11 times because of tumor recurrence or metastasis. The first, second and third years survival rates were 87.7%, 67.4% and 56.8% for HCC patients, 81.6%, 50.8% and 27.2% for MLC patients, respectively. The survival rate from 63 early-stage HCC patients were 92.9%, 82.8% and 74.5%, respectively. The major complication rate in this study was 2.4% (14 of 582 procedures). The complications which consisted of mechanical and thermal injuries usually occurred during or shortly after the RFA treatment. There were 5 hemorrhages, 1 colon perforation, 5 injuries of adjacent structures, 2 bile leakages and 1 skin burn. CONCLUSION: RFA, as a minimally invasive local treatment, has become an effective and relatively safety alternative for the patients of hepatic tumors, even of advanced live tumor, tumor recurrence, liver metastases which are unresectable or difficult to treat with traditional therapies. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.

[Abnormal expression of Thy-1 as a novel tumor marker in lung cancer and its prognostic significance].

OBJECTIVE: The purpose of this study was to investigate the expression of Thy-1 immunohistochemically in different lung tumors and its prognostic significance in non-small cell lung cancer (NSCLC) cases. We also evaluate relationship between Thy-1 and p53 expression status so as to find any clue about the mechanism. METHODS: In this study, we used anti-Thy-1/CD90 antibody to detect the expression pattern of Thy-1 in different lung tumor sections, which were embedded in paraffin blocks. The expressions of Thy-1 in 175 lung tissue cases, including different pathological types, were analyzed as tissue array form. We also detect expression status in 91 NSCLC among these cases and analyze the relationship between Thy-1 and p53. The relationship between Thy-1 expression and patients' survival was studied. RESULTS: We first found that anti-Thy-1 antibody can strongly stain a nuclear molecule in different type of lung cancer cells. Among lung cancer cases, 89 (56.7%) cases showed strong nuclear staining for Thy-1 specially. In univariate and multivariate analysis for 91 NSCLC patients we found TNM staging, lymph node status and Thy-1 overexpression in nuclei were independent factors to affect the prognosis of NSCLC patients. In lymph node non metastasis subgroup cases, Thy-1 negative patients had significant longer survival than Thy-1 positive cases (mean survival: 46.42 mons vs 38.56 mons, P = 0.0207). There was a significant association between Thy-1 and p53 expression (P < 0.0001). CONCLUSION: There is a significant overexpressed Thy-1 located in lung cancer cell nucleus as compared to the normal tissue or benign tumor cells of lung, and it is one of the factors effected on the prognosis of NSCLC patients. This finding suggests that Thy-1 maybe a novel latent malignant marker in the lung cancer pathology. The association between Thy-1 and p53 expression in nucleus suggests that p53 protein and Thy-1 may have some interaction.

[Standard treatment of liver malignancies with radiofrequency ablation].

OBJECTIVE: To investigate the role of standard treatment with ultrasound-guided radiofrequency ablation (RFA) in improving the treatment level of liver malignancies. METHODS: 302 patients with 476 liver malignancies were treated with established protocol and adjuvant measures and subjected to efficiency analysis. In the 302 patients, 181 had 282 hepatocellular carcinomas (HCC) with a mean diameter of 4.2 cm, and 121 had 194 metastatic liver carcinomas (MLC) with a mean diameter of 3.9 cm. According to UICC-TNM system 50 patients (27.6%) were in stage I/II and 131 (72.4%) in stage III/IV (including 39 patients with recurrent HCC after surgical resection). A standard protocol and an individualized protocol were used to treat the tumors based on their size, shape and special location such as the distance from diaphragm, gallbladder and gastrointestinal tract. Needle placement method and operation skill for the tumor region adjacent to important structures were described. Some adjuvant measures such as supplementary fine needle localization, local saline injection and feeding vessel ablation were used to improve RFA efficacy in tumors with different features. Local ablation of bleeding site and haemostatic administration systemically were adopted to deal with bleeding. For the patients with tumor adjacent to gastrointestinal tract, prolonged fasting after the RFA procedure was required. the patients were followed up regularly to assess the treatment efficiency, and the tumor was considered complete necrosed if no viability was found on enhanced CT or enhanced US one month after RFA. RESULTS: The tumor necrosis rate was 95.7% (270/282 tumors) for HCC, 94.8% (184/194 tumors) for MLC, 91.1% (51/56 tumors) for tumor near gastrointestinal tract, 88.5% (69/78 tumors) for tumors near diaphragm, and 94.3% (49/52 tumors) for tumor near gallbladder. The local recurrence rate was 10.3% (29/282 tumors) for HCC and 14.4% (28/194 tumors) for MLC. The 1, 2 and 3 year overall survival rates were 87.6%, 67.4% and 58.6% in the HCC patients, and 87.4%, 48.2%, 25.3% in the MLC patients respectively. The 1, 2 and 3 year survival rates of 50 HCC patients in early (I-II) stages were 90.7%, 85.9% and 73.7%, respectively. The incidence of complications was 2.2% (13/583 sessions), including 5 cases of hemorrhage, 1 case colon perforation, 8 cases of injury of adjacent structures. CONCLUSION: Application of proper protocol and adjuvant measures plays an important role in improving tumor ablation rate. Knowledge about possible complications and their control may increase the treatment efficacy and help to promote the use of RFA technique.

[Radiofrequency ablation of recurrent hepatocellular carcinoma after hepatectomy].

OBJECTIVE: To assess the efficiency and safety of radiofrequency ablation (RFA) of recurrent hepatocellular carcinoma (RHCC) after hepatectomy and to investigate efficacy of RFA for patients with early and late phase recurrence, separately, setting 1 year as the cut-off between the early and late phases. METHODS: A total of 42 patients with 77 RHCC and a history of hepatic resection for hepatocellular carcinoma (HCC) underwent ultrasound-guided percutaneous radiofrequency ablation in our department and entered this study (RHCC group). The average diameter of RHCC was (3.8 +/- 1.4) cm (range, 1.5-6.6 cm). 21 of the 42 RHCC patients had Child-Pugh class A cirrhosis 19, class B and two, class C cirrhosis. The average interval between initial surgery and the diagnosis of recurrence was 22.8 months (range, 1-96 month). 42 RHCC patients were divided into two groups as early recurrence group including 20 patients with 40 RHCC, and late recurrence group including the other 22 patients with 37 RHCC according to the recurrence interval. During the same period 148 patients with 217 primary HCC were also treated by RF ablation and regarded as primary HCC group. The average diameter of primary HCC was (4.0 +/- 1.4) cm (range, 1.2-7.0 cm). Regular follow-up with enhanced CT was performed to evaluate the treatment results. Ablation was considered a success if no contrast enhancement was detected in the treated area on 1 month CT scans. RESULTS: The ablation success rate, local recurrence rate, new tumor incidence and mean survival in RHCC group were 90.5%, 14.3%, 38.1% and (28.0 +/- 3.5) months, respectively, which were similar to the corresponding results of 87.2%, 16.2%, 37.8% and (39.0 +/- 2.1) month in primary HCC group. However, when further comparison was performed between early recurrence group, late recurrence group and primary HCC group, there were some significant differences. The incidence of new tumors in early recurrence group was significantly higher than that in late recurrent group (60.0% vs. 18.2%, P = 0.005); early recurrence group survived shorter than primary HCC group [(15.4 +/- 2.3) vs. (39.0 +/- 2.1) months, P < 0.005]. The survival time was similar between late recurrence group and primary HCC group. One case was found haemorrhage after RFA and recovered with conservative treatment. No major complications occurred in the remaining 41 patients. CONCLUSIONS: RF ablation is generally effective and safe in treating RHCC. And it's more effective in late recurrence than in early recurrence.

Clinical features, diagnosis, treatment and prognosis of multiple primary colorectal carcinoma.

AIM: To investigate the clinical features, diagnosis, treatment and prognosis of multiple primary colorectal carcinomas (MPCC). METHODS: A retrospective analysis of 37 patients with MPCC from 1974 to 1998 was carried out. RESULTS: The incidence of MPCC was 2.74%(37/1 348) in patients with primary colorectal carcinomas, 15 cases of them were patients with synchronous carcinomas (SC) and 22 cases were diagnosed as metachronous carcinomas (MC). Most tumors were located in the right colon and rectum. Fifty-five percent (12/22) of MC were diagnosed within 3 years after tumor resection and 41%(9/22) of MC occurred after 8 years. Radical resections were performed in all patients except for 1 case. The 5-year survival rate of SC was 72.7%(8/11) and that of MC after the first cancer and second cancer was 71.4%(15/21) and 38.9%(7/18), respectively. CONCLUSION: The results indicate the importance of complete preoperative examination, careful intraoperative exploration and periodic postoperative surveillance. Early diagnosis and radical resection can increase survival rate of MPCC.

[Expression of wild type and variant estrogen receptors in human hepatocellular carcinoma].

OBJECTIVE: To investigate the expression of wild type estrogen receptor (wER) and the exon-5 deleted ER (variant ER, vER) in human hepatocellular carcinoma (HCC) samples, and thereafter analyze the possibility of HCC treatment by endocrine therapy. METHODS: The mRNA expressions of wER and vER were analysed from 28 cases of HCC by RT-PCR. The expression of ER at the protein level was detected by immunohistochemistry (IHC). RESULTS: IHC results showed that 39.3% of the HCC specimens expressed ER. The mRNA of wER was detected in 89.3% (25/28) of the HCC specimens while that of vER was detected in 96.4%(27/28). Twenty four out of 28 HCC cases (85.7 %) expressed both wER and vER. One out of 28 patients (3.5%) expressed only wER whereas 3 patients out of 28 (10.7%) expressed vER only. CONCLUSION: Ninety six percent(27/28) of the HCC patients expressed vER,which suggests that the expression of vER is an important event in the development of HCC.

[Mathematical protocol for radiofrequency ablation of liver tumors and its clinical application].

OBJECTIVE: To develop a preoperative protocol for ultrasonography-guided percutaneous radiofrequency ablation (RFA) on liver tumors larger than 3.5 cm in diameter based on mathematical models and clinical experience, and to evaluate its ablated effect compared to the previous non-math method. METHODS: One hundred and twenty-five patients with 80 primary and 55 secondary liver tumors (4.7 +/- 0.9 cm in diameter, ranged from 3.6 - 7.0 cm) were enrolled in this study, of which the first 22 patients (23 tumors) had been treated empirically before the mathematical model was set up and were referred as the non-math group. The rest 103 patients (112 tumors) were treated based on the mathematical model and referred as the math group. Based on principle of overlapping spheres, a mathematical analysis was performed to investigate how multiple ablation spheres could overlap and cover larger tumors most efficiently. Some mathematical models such as regular prism and regular polyhedron model were chosen to estimate the mathematical protocol which included least ablation (sphere) number and optimal overlapping mode required to adequately ablate a large and spherical target lesion. The target volume consisted of the tumor plus a 0.5 - 1 cm tumor-free margin. The operation method for electrode placement was also described. RESULTS: The procedure success rate for the math group was 88.4% (99/112), local recurrence rate and estimated mean time until local recurrence were 25.9% (29/112) and 17.5 months, respectively. While for the non-math group the results were 52.2% (12/23) (P < 0.01), 56.5% (13/23) (P < 0.05) and 11.9 months (P < 0.05), respectively. The therapy results in the math group were much better than in the non-math group. CONCLUSION: This study provides theoretic basis and clinical guidance for RFA therapy for liver tumors larger than 3.5 cm. These results could be used to reduce local recurrence rate and improve treatment response.

Solid pseudopapillary tumor of the pancreas: report of 8 cases in a single institution and review of the Chinese literature.

BACKGROUND: Solid pseudopapillary tumor of the pancreas (SPTP) is a rare disease with a low-grade malignant potential. In recent years, the incidence has been increasing. No consensus has been reached regarding diagnostic or therapeutic strategies. METHODS: Eight cases of SPTP, admitted from 1996 to March 2005, were analyzed retrospectively, and all the literature concerning SPTP published in Chinese medical journals from January 1994 to March 2005 were analyzed. RESULTS: A total of 186 cases have been reported since 1995, among which 162 were females (87.1%), with a male to female ratio of 1:6.8. A histogram of the ages at onset illustrated an approximately smooth skewed distribution with a single peak, which was located between 10 and 19 years. The number of diseases located at the pancreatic head is similar to that located at the body and the tail. Malignancy was pathologically diagnosed in 22 cases (11.6%). Major clinical presentations included abdominal pain of varying degree (43.5%) and palpable abdominal masses (37.1%). Treatment strategies include different types of resection, ranging from tumor enucleation to multiple organ resection, and the prognosis is generally good. CONCLUSIONS: SPTP occurs predominantly in adolescent and young females, and a satisfactory effect could be achieved with active and appropriate surgeries.