Administration of interferon for two or more years decreases early stage hepatocellular carcinoma recurrence rate after radical ablation: A retrospective study of hepatitis C virus‐related liver cancer

Background: Since hepatocellular carcinoma often recurs after surgical resection or radiofrequency ablation, we analyzed a retrospective large cohort of patients with small hepatocellular carcinoma caused by hepatitis C virus (HCV). Methods: Among 379 patients with HCV RNA‐positive small hepatocellular carcinoma (multiple up to three nodules, 3 cm or less each), 77 received interferon‐alpha injection and 302 received no anti‐viral therapy. Results: Four patients (5.2%) attained sustained virological response (SVR). Cumulative recurrence rates in the treated and untreated groups were 41.1% and 57.5% at the end of the third year, and 63.0% and 74.5% at the fifth year, respectively (P = 0.013). Fifth year‐recurrence rates in treated group were 25.0% in SVR, 85.7% in biochemical response, 71.1% in no response, and 46.7% in patients with continuous administration. When four patients with SVR were excluded, recurrence rates in short‐term interferon therapy (<2 years) and long‐term therapy (≥2 years) were 46.2% and 39.3% at the third year, and 66.2% and 57.4% at the fifth year, respectively (P = 0.012). Multivariate analysis showed that long‐term interferon therapy significantly decreased recurrence rate (hazard ratio for interferon <2 years 0.80, interferon ≥2 years 0.60, P = 0.044), after adjustment with background covariates including indocyanine green retention rate (P = 0.018), alpha‐fetoprotein (P = 0.051), and tumor treatment (P = 0.066). Conclusion: A long‐term administration of low‐dose interferon significantly decreased recurrence of hepatocellular carcinoma after surgical resection or radiofrequency ablation.     

Change in cross‐sectional area of esophageal muscle does not correlate with the outcome of achalasia after pneumatic balloon dilatation

Background and Aim: Patients with achalasia have a thicker muscularis propria compared to normal patients. Because pneumatic balloon dilatation (PD) is an effective treatment for achalasia, the changes in the esophageal muscles after PD may predict treatment outcomes, if muscular change is of primary importance. In the present study, we aimed to observe the changes in esophageal muscle thickness following PD and assessed whether symptom relapse can be predicted on the basis of the esophageal muscle cross‐sectional area (CSA), as measured by high‐frequency intraluminal ultrasound (HFIUS). Methods: Fifteen patients treated by PD were studied and followed up for a median of 3.6 years. An HFIUS was done before PD and 6 months after PD. The esophageal muscle CSA measured at the lower esophageal sphincter (LES), and 3 and 6 cm above the LES, was used to see whether any association was present between symptom recurrence and the esophageal muscle CSA. Results: A single PD resulted in a 2‐year remission rate of 66%. A significance variance in change (?65%–248%) was noticed in the muscle CSA after PD. The predilation muscle CSA, post‐dilation muscle CSA, and change in the muscle CSA after PD was not associated with symptom recurrence. Conclusion: Our findings suggest that measuring the muscle CSA does not help to predict treatment outcome. Muscular changes in achalasia might be just reactive changes.     

Percutaneous radiofrequency ablation as first‐line treatment for small hepatocellular carcinoma: Results and prognostic factors on long‐term follow up

Background and Aims: We evaluated the prognosis and associated factors in patients with small hepatocellular carcinoma (HCC; up to 3 nodules, each up to 3cm in diameter) treated with percutaneous radiofrequency ablation (RFA) as first‐line treatment. Methods: Eighty‐eight consecutive patients who underwent percutaneous RFA as first‐line treatment were enrolled, among whom 70 who had hypervascular HCC nodules which were treated by a combination of transcatheter arterial chemoembolization and RFA. RFA was repeated until an ablative margin was obtained. Results: The rate of local tumor progression at 1 and 3 years was 4.8% and 4.8%, respectively. The rate of overall survival at 3 and 5 years was 83.0% and 70.0%, and the rate of disease‐free survival at 3 and 5 years was 34.0% and 24.0%, respectively. On multivariate analysis, age (< 70 years; hazard ratio [HR] = 2.341, 95% confidence interval [CI] = 1.101–4.977, P = 0.027) and indocyanine green retention rate at 15 min (< 15%; HR = 3.621, 95% CI = 1.086–12.079, P = 0.036) were statistically significant determinants of overall survival, while tumor number (solitary, HR = 2.465, 95% CI = 1.170–5.191, P = 0.018) was identified for disease‐free survival. Overall survival of patients with early recurrence after RFA was significantly worse than that of patients with late recurrence. Tumor size was the only independent risk factor of early recurrence after RFA of HCC (tumor size > 2 cm; risk ratio [RR] = 4.629, 95% CI = 1.241–17.241, P = 0.023). Conclusion: Percutaneous RFA under the protocol reported here has the potential to provide local tumor control for small HCC. In addition to host factors, time interval from RFA to recurrence was an important determinant of prognosis.     

Multicentric evaluation of a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas

Objective: To develop a clinical and prognostic scoring system predictive of survival after resection of intrahepatic cholangiocarcinomas (ICC). Patients: Two hundred and one consecutive ICC patients (83 from Essen, Germany, 54 from New York, USA and 64 from Chiba, Japan). The scoring systems were developed utilizing the data set from Essen University and then applied to the data sets from Mount Sinai Medical Center and Chiba University for validation. Eighteen potential prognostic factors were evaluated. Statistical analysis included multivariable regression analyses with the Cox proportional hazard model, power analysis, internal validation with structural equation modelling bootstrapping and external validation. The prognostic scoring model was based mainly in pathological and demographical variables, whereas the clinical scoring model was based mainly in radiological and demographical variables. Results: Gender (P=0.0086), UICC stage (P=0.0140) and R‐class (P=0.0016) were predictive of survival for the prognostic scoring model, while gender (P=0.0023), CA 19‐9 levels (P=0.0153) and macrovascular invasion (P=0.0067) were predictive of survival for the clinical scoring model. Prognostic points were assigned as follows: female:male=1:2 points, UICC (I–II):UICC (III–IV)=1:2 points and R0:R1=1:2 points. Clinical points were allocated as follows: female:male=1:2 points, CA 19‐9 (<100 U/ml):CA 19‐9 (≥100 U/ml)=1:2 points and no macrovascular invasion:macrovascular invasion=1:2 points. Prognostic groups with 3–4, 5 and 6 points (P=0.000001) and clinical groups with 3–4 and 5–6 points (P=0.0103) achieved statistically significant difference. Conclusions: We propose a clinical and prognostic scoring system predictive of long‐term survival after surgical resections for ICC.     

Diffuse intrahepatic recurrence after percutaneous radiofrequency ablation for solitary and small hepatocellular carcinoma

Two patients developed segmental, diffuse intrahepatic recurrence after percutaneous radiofrequency ablation (RFA) to treat a primary, solitary, and small (2.5 cm) hepatocellular carcinoma (HCC). Despite the size of the HCC, levels of the tumor markers (α-fetoprotein, α-fetoprotein-L3%, and des-γ-carboxyprothrombin) were all elevated before RFA, and tumors in both patients were contiguous with a major branch of the portal vein. Tumor biopsies of both patients revealed moderately differentiated HCC but diagnostic imaging showed an area of reduced tumor blood flow, suggesting a poorly differentiated component. Since early detection of post-RFA malignancies by standard ultrasonography and contrast-enhanced computed tomography was difficult, the most sensitive indicator of recurrence in these two patients was the elevated tumor markers. The diffuse intrahepatic recurrence was thought to be caused by increased intratumoral pressure during RFA, resulting in the dissemination of cancer cells through the contiguous portal vein. The clinical course of these tumors indicate that the choice of RFA should be carefully considered when treating specific subtype of HCC that is adjacent to main portal vein branch and involves a possible poorly differentiated component and that surgical resection or combinations of RFA with other treatment modalities such as transcatheter arterial chemoembolization should be considered as alternative treatment strategies.     

Gallstone recurrence after direct contact dissolution with methyltert-butyl ether

To determine the rate and characteristics of gallstone recurrence after direct contact dissolution with methyltert-butyl ether, 60 consecutive patients were followed for up to 4.5 years (median 2.2 years) after complete disappearance of all stone residues and debris and cessation of adjuvant bile acid therapy. Initial gallstones had been multiple in all but four patients. Twenty-eight of the 60 patients developed recurrent gallstones. The cumulative risk of gallstone recurrence (actuarial analysis) was 23±6%, 34±7%, 55±8%, and 70±9% at one, two, three, and four years, respectively. The recurrent stones were usually multiple and small (6±4 mm). Gallstone recurrence was associated with recurrent biliary pain in two patients, one of whom developed acute cholecystitis. Recurrent stones were cleared completely by bile acid medication with or without shock-wave lithotripsy in 61±15% of patients at one year (actuarial analysis). In conclusion, gallstone recurrence after successful contact dissolution of multiple stones with methyltert-butyl ether has to be expected in a high percentage of patients. Most patients, however, remain free of biliary pain during long-term follow-up.     

G-CSF in Peg-IFN induced neutropenia in liver transplanted patients with HCV recurrence

AIM: To evaluate the efficacy of granulocyte colony stimulating factors (G-CSF) in liver transplanted patients with hepatitis C (HCV) recurrence and Pegylated-IFN α-2b induced neutropenia, and to evaluate the impact of G-CSF administration on virological response.METHODS: Sixty-eight patients undergoing antiviral treatment for post-liver transplantation (OLT) HCV recurrence were enrolled.All patients developing neutropenia received G-CSF.RESULTS: Twenty three (34%) received G-CSF.Mean neutrophil count at the onset of neutropenia was 700/mmc (range 400-750/mmc); after 1 mo of G-CSF it increased to 1210/mmc (range 300-5590/mmc) ( P < 0.0001).Three patients did not respond to G-CSF.Treatment duration was similar in neutropenic and non-neutropenic patients.No differences in the rate of discontinuation, infections or virological response were observed between the two groups.G-CSF was protective for the onset of de novo autoimmune hepatitis ( P < 0.003).CONCLUSION: G-CSF administration is effective in the case of Peg-IFN induced neutropenia increasing neutrophil count, prolonging treatment and leading to sustained virological response (SVR) rates comparable to non-neutropenic patients.It prevents the occurrence of de novo autoimmune hepatitis.     

Stereotactic body radiotherapy for isolated paraaortic lymph node recurrence from colorectal cancer

AIM: To evaluate the efficacy and complications of stereotactic body radiotherapy in localized paraaortic lymph node recurrence from colorectal cancer. METHODS: From 2003 to 2009, 7 patients with paraaortic lymph node recurrence (1-3 lesions) from colorectal cancer were treated with stereotactic body radiotherapy. Total gross tumor volumes ranged from 4 to 40 mL. The doses were escalated from 36 Gy/patient to 51 Gy/patient and were delivered in 3 fractions. RESULTS: One and 3 year overall survival rates were 100% and 71.4%, respectively, and median survival was 37 mo. Grade Ⅳ intestinal obstruction was reported in 1 of 7 patients. This patient received 48 Gy in 3 fractions with a maximum point dose to the intestine of 53 Gy and V_(45Gy) = 3.6 mL. However, 6 patients received an intestinal maximum point dose of < 51 Gy and V_(45Gy) of < 1 mL, and did not develop any severe complications. CONCLUSION: This pilot study suggests selected paraaortic lymph node recurrence (1-3 closed lesions) that failed to respond to chemotherapy can be potentially salvaged by stereotactic body radiotherapy.     

尖锐湿疣患者HPV型别及DNA载量与复发的关系

目的研究天津地区尖锐湿疣（CA）患者人乳头瘤病毒（HPV）6/11、16/18型及DNA载量与复发的关系。方法采用实时荧光定量聚合酶链反应（FQ-PCR）检测CA患者皮损中HPV型别及DNA载量,并随访至少3个月观察有无复发。结果83例CA标本中,HPV阳性80例（96.4%）,其中单纯HPV6/11型63例,单纯HPV16/18型4例,HPV6/11型和HPV16/18型混合感染13例,不同型别复发率比较无统计学差异（P〉0.05）。HPV6/11阳性标本中,复发组与未复发组DNA载量比较有统计学差异（P〈0.05）。结论CA患者的HPV感染以HPV6/11型为主,患者疣体中HPV DNA载量与复发有关。