Current status in the treatment options for esophageal achalasia

Recent advances in the treatment of achalasia include the use of high-resolution manometry to predict the outcome of patients and the introduction of peroral endoscopic myotomy(POEM).The first multicenter randomized,controlled,2-year follow-up study conducted by the European Achalasia Trial group indicated that laparoscopic Heller myotomy(LHM)was not superior to pneumatic dilations(PD).Publications on the long-term success of laparoscopic surgery continue to emerge.In addition,laparoscopic single-site surgery is applicable to advanced laparoscopic operations such as LHM and anterior fundoplication.The optimal treatment option is an ongoing matter of debate.In this review,we provide an update of the current progress in the treatment of esophageal achalasia.Unless new conclusive data prove otherwise,LHM is considered the most durable treatment for achalasia at the expense of increased reflux-associated complications.However,PD is the first choice for non-surgical treatment and is more costeffective.Repeated PD according to anon-demandstrategy based on symptom recurrence can achieve long-term remission.Decision making should be based on clinical evidence that identifies a subcategory of patients who would benefit from specific treatment options.POEM has shown promise but its long-term efficacy and safety need to be assessed further.     

Hemorrhoidectomy with self-retaining retraction

Hemorrhoidectomy is one of the most effective treatments for significantly symptomatic hemorrhoids. By placing the patient in the Sims' position and appropriately using the Hill-Ferguson retractor and towel clip, the surgeon can get good exposure and perform a Ferguson closed hemorrhoidectomy without any assistance.     

Primary fallopian tube carcinoma: clinicopathological analysis of 12 cases

ObjectivePrimary fallopian tube carcinoma is one of the least common gynecological cancers and is difficult to diagnose preoperatively. We aimed to analyze the clinicopathological characteristics of this rare disease and to identify the prognostic factors predicting prognosis.Materials and MethodsTwelve cases of primary fallopian tube carcinoma that had been diagnosed and treated in Kaohsiung Chang Gung Memorial Hospital between July 1986 and December 2005 were retrospectively reviewed. Factors, including age, gravidity, parity, stage, surgical intervention, pathological findings, relapse, and survival, were analyzed.ResultsThe median age of the 12 cases was 54 years (range, 32–67 years), whereas the median follow-up time was 38 months. None of the 12 cases were diagnosed preoperatively. Preoperative diagnoses were adnexal mass of unknown nature in six (50%), tubo-ovarian abscess in three (25%), ovarian carcinoma in two (16.7%), and endometrioma in one (8.3%) cases. Two patients (16.7%) had experienced the typical symptom of watery vaginal discharge. Three patients (25%) were in Stage I, three (25%) in Stage II, four (33.3%) in Stage III, and two (16.7%) were unstaged. Nine patients had received postoperative platinum-based adjuvant chemotherapy. The 5-year disease-free survival rate was 64%. On evaluating the correlation between clinicopathological parameters and survival, only the Federation of Gynecology and Obstetrics stage (p = 0.017) was a significant prognostic factor.ConclusionAlthough preoperative diagnosis of fallopian tube carcinoma is difficult, still 16.7% of our patients experienced the typical symptom suggestive of tubal carcinoma. Prognostic factors associated with fallopian tube cancer were similar to those of epithelial ovarian cancer.     

Validation of clinical AJCC/UICC TNM staging system for hepatocellular carcinoma: analysis of 5,613 cases from a medical center in southern Taiwan

This study was aimed to validate the 5th and 6th editions of tumor-node-metastasis (TNM) system for patients with hepatocellular carcinoma (HCC), and attempted to improve prognostic stratification by modifying the 6th edition according to vascular invasion and tumor size. From 1986 to 2002, a total of 5,613 HCC cases from Kaohsiung Chang Gung Memorial Hospital in southern Taiwan were enrolled. The 6th edition was modified by dividing stage I into stages IA (single tumor, < or =2cm) and IB (single tumor, >2cm), and by dividing stage II into IIA (multiple tumors, none >5cm) and IIB (tumor with segmental macro vascular invasion). The Akaike information criteria (AIC), within a Cox proportional hazard regression model were used; lower AIC value indicated a better discriminatory ability for staging system. The 1-, 3-, 5-, and 7-year overall survival rates were 45.6, 25.9, 17.9, and 13.4%, respectively. Significant differences in survival curve existed in the 5th, 6th, and modified 6th edition TNM systems. For the modified 6th edition TNM, survival differed significantly between stages IA and IB, and between stage IIA and IIB. The AIC values of 5th (72,328), 6th (72,188), modified 6th (71,991) edition TNM system were decreasing. This investigation demonstrated better prognostic stratifications for the 6th edition than the 5th edition TNM staging system. Moreover, the modified 6th edition staging system demonstrated better prognostic prediction than the former two. Pretreatment staging and simple classification of current modified 6th edition TNM staging can be applied to all HCC patients and are clinically useful.     

Mutation analysis of the <Emphasis Type="Italic">APC</Emphasis> gene in Taiwanese FAP families: low incidence of <Emphasis Type="Italic">APC</Emphasis> germline mutation in a distinct subgroup of FAP families

Familial adenomatous polyposis (FAP) is an autosomal-dominant disease caused by germline mutations in the adenomatous polyposis coli (APC) gene. The affected individuals develop colorectal polyposis and show various extra-colonic manifestations. In this study, we aimed to investigate the genetic and clinical characteristics of FAP in Taiwanese families and analyze the genotype–phenotype correlations. Blood samples were obtained from 66 FAP patients registered in the hereditary colorectal cancer database. Then, germline mutations in the APC genes of these 66 polyposis patients from 47 unrelated FAP families were analyzed. The germline-mutation-negative cases were analyzed by performing multiplex ligation-dependent probe amplification (MLPA) and single-strand conformation polymorphism (SSCP) analysis of the MUTYH gene. Among the analyzed families, 79% (37/47) of the families showed 28 APC mutations, including 19 frameshift mutations, 4 nonsense mutations, 3 genomic deletion mutations, 1 missense mutation, and 1 splice-site mutation. In addition, we identified 15 novel mutations in 32% (15/47) of the families. The cases in which APC mutations were not identified showed significantly lower incidence of profuse polyposis (P = 0.034) and gastroduodenal polyps (P = 0.027). Furthermore, FAP families in which some affected individuals had less than 100 polyps showed significant association with low incidence of APC germline mutations (P = 0.002). We have added the APC germline-mutation data for Taiwanese FAP patients and indicated the presence of an FAP subgroup comprising affected individuals with nonadenomatous polyps or less than 100 adenomatous polyps; this form of FAP is less frequently caused by germline mutations of the APC gene.     

Hepatoma-derived growth factor is a novel prognostic factor for gastrointestinal stromal tumors

Proliferating activity as mitotic count is generally accepted as a major prognostic indicator for gastrointestinal stromal tumors (GISTs). Hepatoma-derived growth factor (HDGF) is a novel growth factor and elevated in several types of cancer. Our study was designed to elucidate the expression and prognostic role of HDGF in GISTs. A total 178 surgically resected CD117-positive GISTs specimens were collected for immunohistochemical analysis using antibodies against HDGF. The immunoreactivities were scored as labeling index (LI) and correlated with clinicopathologic parameters of GIST patients. The HDGF immunoreactivities were detected in both nucleus and cytoplasm of GISTs tissues. Besides, the nuclear and cytoplasmic HDGF was parallely upregulated in GISTs (p < 0.001). The nuclear HDGF LI were positively correlated with that of PCNA (p < 0.001) and Ki-67 (p < 0.001), tumor mitosis (p < 0.001), tumor sizes (p = 0.007) and NIH risk categories (p < 0.001). In addition, the cytoplasmic HDGF LI were also positively correlated with that of PCNA (p = 0.031) and Ki-67 (p = 0.038), tumor sizes (p = 0.003) and tumor mitosis (p = 0.015). Patients with higher HDGF levels had earlier tumor recurrence and unfavorable outcome (p < 0.05). In addition to standard prognostic factors (NIH risk categories), the nuclear HDGF LI is an independent prognostic factor for disease free and overall survivals of GIST patients after operation. We conclude that HDGF is a novel prognostic factor for GIST patients.     

Incidence of needle tract seeding and responses of soft tissue metastasis by hepatocellular carcinoma postradiotherapy.

AIM: To determine the incidence of needle tract seeding after fine needle aspiration (FNA) or percutaneous ethanol injection (PEI) and compare iatrogenic or spontaneous soft tissue metastasis (STM) by hepatocellular carcinoma (HCC) postradiotherapy (RT) in responses. METHODS: From November 1997 to January 2006, those who presented with STM by HCC after our invasive procedures or developed spontaneously were enrolled into this retrospective study. Metastatic lesions could be divided into procedure related (PR), which were located at the liver span and were related to invasive procedures, and non-procedure related (NPR), which were in extrahepatic areas. STM was treated with an electron or photon beam. RESULTS: A total of 39 HCC cases with developed STM were referred for RT, including 17 in the PR group and 22 in the NPR group. During the same period, a total of 18,227 person-times of FNA or PEI were performed on these HCC patients. The overall incidence of HCC with STM that was caused by invasive procedures was estimated at 0.13%. According to the Cox' regression model, the initial treatment modality influences the time duration after the initial diagnosis of HCC when STM has not occurred. None of these patients' soft tissue tumor increased in size during RT. The PR group had lower rates of bone metastasis (P=0.003) and coexisting extrahepatic metastasis (P=0.011) and a longer survival rate (P=0.003) than the NPR group. The estimated rates of 18-gauge and 22-gauge needle-induced HCC-related STM were 0.60% and 0.11%, respectively (P=0.064). CONCLUSION: The PR group bears a better prognosis than the NPR group post-RT.     

Changes in serum hepatitis B e antigen (HBeAg) levels associated with the emergence of YMDD mutants in HBeAg non-seroconverted patients during lamivudine therapy.

Background: To elucidate the associations between the changing patterns of hepatitis B e antigen (HBeAg) levels and the emergence of tyrosine–methionine–aspartate–aspartate (YMDD) mutants in HBeAg non‐seroconverted patients undergoing lamivudine therapy. Methods: This study analysed 76 HBeAg‐positive naïve chronic hepatitis B patients treated with lamivudine. The median duration of therapy was 52 weeks. The YMDD mutants were detected in 35 patients. The changing patterns of HBeAg levels were categorized into three groups: Descending, Descending–Ascending and Fluctuation. HBeAg breakthrough was defined as progressive HBeAg decreasing to <10% of pretreatment levels, followed by increases exceeding 50 S/Co [the ratio of the sample (S) to the cut‐off (Co)] above nadir levels. Results: Of 76 patients, the sensitivity and specificity for predicting YMDD mutants by the Descending–Ascending pattern were 66 and 100% respectively. Of 17 patients with YMDD mutants in the Descending–Ascending group, hepatitis B virus (HBV) DNA first increased, followed by increased HBeAg levels and finally by biochemical breakthrough. The median intervals between virological breakthrough and HBeAg breakthrough, between HBeAg breakthrough and biochemical breakthrough and between virological breakthrough and biochemical breakthrough were 4, 24 and 33 weeks respectively. Conclusions: Serial HBeAg levels are useful in predicting YMDD mutant emergence in HBeAg non‐seroconverted patients during lamivudine therapy.