Ming-Chin Yu

Recurrence and Poor Prognosis Following Resection of Small Hepatitis B-Related Hepatocellular Carcinoma Lesions Are Associated with Aberrant Tumor Expression Profiles of Glypican 3 and Osteopontin

BackgroundEarly detection and following appropriate treatments of hepatocellular carcinoma (HCC) is still the gold standard for favored outcome of HCC patients; nevertheless, a small portion of hepatitis B virus (HBV)-related small HCC (<5xa0cm) patients got poor prognosis. Furthermore, the study for small HBV–HCC was limited. Therefore, the aim of this study was to explore the potential genetic signature for HBV-related small HCC as novel prognostic factors.MethodsWe examined expression profiles of HBV-related small HCC using an Affymetrix U133A GeneChip, evaluated differential gene expression by quantitative real-time polymerase chain reaction (qRT-PCR), and finally validated these expression patterns by immunohistochemistry (IHC).Results:A total of 57 genes were differentially expressed between tumor and normal parts (nxa0=xa020 pairs) using Affymetrix U133A chip, and 16 genes were further evaluated by qRT-PCR. The result was compatible with the finding of oligonucleotide microarray (Pearson’s correlation, rxa0=xa00.87). Furthermore, the expression pattern in HCC tissue by IHC in another group of small HBV–HCC (nxa0=xa0100) showed overexpression of either osteopontin (OPN) or glypican 3 (GPC3) is an independent prognostic factor for disease-free survival (DFS) in HBV-positive small HCC (Pxa0<xa00.01 and 0.03, respectively). Long-term DFS and overall survival (OS) for small HBV–HCC patients with high risk (both elevated GPC3+/OPN+) were DFS 0%, OS 0%, respectively; on the other hand, DFS and OS in patients with moderate (only 1 gene elevated) or low (OPN−/GPC3−) risk were 35.0 and 46.5%, respectively.ConclusionsElevation of both OPN and GPC3 may act as an adverse indicator for HBV-related small HCC patients after curative resection.

Alkaline Phosphatase: Does it have a Role in Predicting Hepatocellular Carcinoma Recurrence?

BackgroundsSurgical resection remains the first line of treatment for earlier stages of hepatocellular carcinoma (HCC), and it offers the best prognosis for long-term survival. Nevertheless, the recurrence rates after resection are still high in reports. Therefore, it is still essential to explore any potential prognostic factors to attain relatively longer-term survival of HCC patients.Materials and MethodsIn the period from 1983 to 2005, 1,685 patients who underwent hepatectomy at Chang Gung Memorial hospital were enrolled in the study, and their clinicopathological data were retrospectively reviewed for survival analysis.ResultsThe 1-, 3-, 5-, and 10-year disease-free survival (DFS) rates in this series were 60.3%, 39.7%, 31.3%, and 24.0%, respectively, whereas the 1-, 3-, 5-, and 10-year overall survival (OS) rates were 80.1%, 59.1%, 46.6%, and 27.7%, respectively. Gross vascular invasion, tumor status, lymph node involvement, satellite lesion, positive surgical margin, alkaline phosphatase (ALP), albumin, presence of cirrhosis, and Child grade B or C were independent prognostic factors for prediction of DFS; while α-fetoprotein, ALP, surgical factors, including complications, blood transfusion, positive resection margin, and tumor characters including tumor status, vascular invasion, and lack of tumor encapsulation were found to be independent predicting factors for OS, as determined by Cox regression analysis. Interestingly, we found that preoperative level of ALP was one of the most important independent predictors of recurrence, even more important that α-fetoprotein (AFP) as we noticed that elevation of ALP above (82xa0U/L) predicted poor prognosis in patients where AFP levels was less than 66xa0ng/ml. It is worth to mention that ALP was statistically related to other liver function tests, but not tumor characters by hierarchical clustering; which means that we were able to correlate ALP with prognosis statistically, but not with pathological criteria of the tumor; to elucidate these finding, further basic science research is required.ConclusionALP among liver function tests, in addition to other tumor characters were independent factors for DFS and OS; our results suggest that preoperative ALP levels could be utilized to monitor and predict recurrence in high risk HCC patients.

Hepatic Resection for Hepatocellular Carcinoma With Lymph Node Metastasis: Clinicopathological Analysis and Survival Outcome

OBJECTIVEnLymph node metastasis (LNM) rarely occurs in hepatocellular carcinoma (HCC). Few studies have reported the potential risk factors of LNM and the influence of LNM on the progression and prognosis of HCC. The purposes of this study were to explore the clinicopathological characteristics of operable HCC with LNM and to demonstrate the effects of LNM on HCC prognosis.nnnMETHODSnA retrospective review of 2,034 HCC patients undergoing surgery from 1982 to 2005 was performed. The influence of LNM was assessed by clinicopathological factors, tumour recurrence, and overall survival. A total of 66 randomly selected patients matched for clinicopathological variables were used to analyse the difference in survival.nnnRESULTSnA total of 25 patients (1.23%) were reported to have LNM. Higher preoperative carcinoembryonic antigen levels (> 10 ng/mL) were significantly associated with a higher incidence of LNM than were low preoperative carcinoembryonic antigen levels (≤ = 10 ng/mL) (15.38%vs. 3.79%, p = 0.042). Furthermore, HCC with LNM (N1 disease) was larger in size (mean, 9.44 vs. 5.85 cm, p = 0.016) and significantly associated with vascular invasion, worse histological grade, and nonencapsulation (p = 0.002, < 0.001, and < 0.001, respectively). Finally, patients with HCC accompanied by LNM had shorter mean disease-free survival and overall survival (p = 0.001 and < 0.001, respectively).nnnCONCLUSIONnThis study identified the worst prognosis of HCC in a population with LNM. HCC with LNM tends to be the infiltrating type with larger tumour size (> 5 cm), presence of microvascular invasion, and worse histological grade. Liver resection with lymphadenectomy is possibly beneficial for patients with HCC accompanied by LNM.

Gallbladder carcinoma with biliary invasion: clinical analysis of the differences from nonbiliary invasion.

Gallbladder carcinoma is the most common malignancy of the biliary tract. Because of a lack of specific presentations, this condition frequently is diagnosed only at an advanced stage. The clinical difference between gallbladder carcinoma with and without biliary involvement remains uncertain. This study recruited all patients with gallbladder carcinoma treated at Chang Gung Memorial Hospital (Taoyuan, Taiwan) from 1987 to 2002. The sample included 120 patients aged 28 to 91 years (mean 65.5 ± 12.3 years) (39 men, 81 women), whose medical records were reviewed retrospectively. Based on the 2002 newly revised TNM classification, 25, 38, 28, and 29 patients had stage I, II, III, and IV disease, respectively. After we excluded patients with stage I, the other patients were classified into two groups as follows: group I, gallbladder carcinoma with biliary invasion (n = 41); group II, carcinoma without biliary involvement (n = 54). The clinical presentations, laboratory data, operative methods, and outcome of these two groups were compared. The two groups did not differ in terms of age, sex distribution, cholelithiasis, and most clinical presentations. Chemistry laboratory data also identified patients in group I with significantly elevated liver function tests. Group II had a borderline tendency toward better curative resectability than group I (p = 0.09). Survival was significantly better for group I patients who underwent curative resection (n = 5) via cholecystectomy, partial hepatectomy, and bile duct resection than for those with noncurative resection (p < 0.05). However, long-term survival demonstrated that gallbladder carcinoma had the same poor prognosis in the two groups. In conclusion, gallbladder carcinoma with biliary invasion has been found to a more overt clinical presentation and abnormal laboratory data, which might alert clinicians to consider gallbladder carcinoma at an advanced stage or biliary invasion and examine the underlying disease. Generally, the outcome of gallbladder carcinoma is dismal, and radical curative resection the combined with cholecystectomy, partial hepatectomy, and bile duct resection perhaps may offer good benefits for advanced gallbladder carcinoma. Furthermore, surgical resection should be performed whenever possible in patients with gallbladder carcinoma to increase life expectancy.

Prognostic Impact of Fas Ligand on Hepatocellular Carcinoma after Hepatectomy

The expression of Fas ligand on tumor cells may counterattack the host’s immunity and worsen the prognosis. Knowledge of the prognostic impact of Fas ligand on patients with hepatocellular carcinoma (HCC) after hepatectomy is still limited. Fas ligand expression in HCCs was examined in 59 patients who underwent hepatectomy for HCC. The prognosis was analyzed and correlated to the expression of Fas ligand. Expression of Fas ligand was detected by immunohistochemical staining in 27 of the 59 HCCs (45.8%). The Fas ligand was expressed in only a small number of cancer cells. However, even though only a few cancer cells expressed it, the prognosis for patients whose HCCs showed Fas ligand expression was worse than that for patients with an HCC without Fas ligand expression. The mean disease-free survival was only 10.83 ± 1.90 months when HCCs expressed Fas ligand compared with 43.51 ± 7.02 months for those without Fas ligand expression (p = 0.0007). The overall patient survival was 28.34 ± 4.08 months when the HCC expressed Fas ligand compared with 55.31 ± 5.37 months for HCC without Fas ligand expression (p = 0.0003). The expression of Fas ligand did not correlate with the presentation of other prognostic factors. Fas ligand expression is thus an independent prognostic factor for HCC. Thus the HCC expressing Fas ligand has a worse prognosis than the HCC without Fas ligand expression.

The expression of cytokeratin 19 in lymph nodes was a poor prognostic factor for hepatocellular carcinoma after hepatic resection

BackgroundThe expression of CK19 in primary hepatocellular carcinoma (HCC) is associated with a poor outcome. However, few studies have investigated the expression profile of CK19 in regional lymph nodes (LNs) of HCC after hepatic resection. The purpose of this study was to evaluate the expression of CK19 in primary liver tumor and regional LNs of HCC with and without lymph node metastasis (LNM).MethodsThe expression of CK19 in patients with (nu2009=u200916) and without LNM (nu2009=u200926) was examined using immunohistochemical staining. Both the primary tumor and LN specimen were studied for their CK19 expression. Clinico-pathological variables and prognostic significance were analyzed.ResultsImmunopositivity of CK19 in primary liver tumor was significantly correlated with LNM (Pu2009=u20090.005) and tumor non-encapsulation (P <0.005). Univariate analysis showed that CK19 expression in primary liver tumor, CK19 expression in regional LN, vascular invasion, daughter nodules, positive resection margin and American Joint Committee on Cancer (AJCC) tumor stage significantly decreased overall survival. Multivariate analysis demonstrated that daughter nodules (Pu2009=u20090.001) and CK19 expression in regional LN (Pu2009=u20090.002) were independent prognostic factors for overall survival.ConclusionsThis study showed that CK19 expression in regional LN of HCC was associated with LNM and an extremely poor outcome after operation. It is of clinical significance to identify these patients at risk for more aggressive HCC, and multi-modality treatment could be helpful to improve their dismal outcome.

Intrahepatic biliary mucinous cystic neoplasms: clinicoradiological characteristics and surgical results

BackgroundIntrahepatic biliary mucinous cystic neoplasms are rare hepatic tumors and account for less than 5% of intrahepatic cystic lesions. Accurate preoperative diagnosis is difficult and the outcome differs among various treatment modalities.The aim of this study is to investigate the clinico-radiological characteristics of intrahepatic biliary mucinous cystic neoplasms and to establish eligible diagnostic and treatment suggestions.MethodsNineteen patients with intrahepatic biliary cystadenomas and two patients with biliary cystadenocarcinomas were retrospectively reviewed. Their clinico-radiological variables and survival outcome were analyzed.ResultsOf the 19 patients with biliary cystadenoma, 16 (84.2xa0%) were female. 11 (57.9xa0%) patients had symptoms before operation with the most common presenting symptom being abdominal pain. Among the patients with available data, serum and cystic fluid CA 19–9 levels were invariably elevated and the CA 19–9 level in the cystic fluid was significantly higher than that in the serum. Loculations (84.2xa0%) and septations (63.2xa0%) were the most common radiologic findings. For treatment, 11 (57.9xa0%) patients received radical resection by either enucleation or hepatic resection, while the remaining 8 (42.1xa0%) patients underwent only fenestration of liver cysts. Radical resection provided a significantly better clinical outcome than fenestration in terms of tumor recurrence (pu2009=u20090.018). The only two male patients with biliary cystadenocarcinoma received radical hepatic resection and achieved a disease-free survival of 16.5xa0months and 33xa0months, respectively.ConclusionIntrahepatic biliary mucinous cystic neoplasms are rare and preoperative diagnosis is difficult. Internal septations and loculations on radiologic examinations should raise some suspicion of this diagnosis. Complete tumor excision is the standard treatment that may provide patients with better long term results after the operation.

Patient outcomes following surgical management of multinodular goiter: Does multinodularity increase the risk of thyroid malignancy?

Background: the difference in the risk of thyroid malignancy for patients with multinodular goiter (MNG) and solitary nodular goiter (SNG) remains controversial. Although total thyroidectomy (TT) is the current preferred surgical option for MNG, permanent hypothyroidism in these patients may be a concern. Therefore, we discuss whether nontotal thyroidectomy is a reasonable alternative surgical option. Methods: A retrospective cohort study was performed for 1598 consecutive patients who underwent thyroid surgery for nodular goiter between January 2007 and December 2012. Numerous clinical parameters were collected and analyzed. Results: We reviewed 795 patients with MNG and 803 patients with SNG. The prevalence of malignancy on final pathology was significantly higher in the patients with MNG than in the patients with SNG (15.6% vs 10.1%, P = 0.001). However, a multivariate analysis revealed that this difference was insignificant (P = 0.50). Papillary carcinoma was the predominant type in both groups, but papillary microcarcinoma was more frequently found (41.1%) in the patients with MNG. The only multifocal cancers were of the papillary carcinoma histologic type, and the incidence of multifocal papillary carcinoma was significantly higher in the patients with MNG (23.4% vs 7.4%, P = 0.005). Reoperation was not required for the patients who underwent TT for goiter recurrence or incidental carcinoma. The overall rate of recurrence following nontotal thyroidectomy was 12.2%. Among the patients who underwent reoperation for goiter recurrence, 2 (20.0%) were complicated with permanent hypoparathyroidism. Among the patients who underwent a nontotal bilateral thyroidectomy, an average of 56.5% had permanent hypothyroidism. Conclusions: Multinodularity does not increase the risk of thyroid malignancy. However, patients with MNG who develop papillary carcinoma are at an increased risk of cancer multifocality. If a patient can tolerate lifelong thyroid hormone replacement, TT is the preferred surgical option because it helps avoid reoperation and the associated complications. Nontotal bilateral thyroidectomy does not ensure the preservation of thyroid hormone function.

Surgical management of substernal goitres at a tertiary referral centre: A retrospective cohort study of 2,104 patients

BACKGROUNDnWhen to use a thoracic approach to treat substernal goitres has often been discussed in the literature. But there are few published reports describing surgical outcomes and associated complications for patients with right-sided vs. left-sided substernal goitres.nnnOBJECTIVEnThis study evaluated the characteristics and clinical outcomes of patients who underwent surgical management of substernal goitres, presenting factors indicating the use of a thoracic approach and differences between right- and left-sided goitre extensions.nnnDESIGNnRetrospective cohort study.nnnSETTINGnTertiary referral centre.nnnMETHODSnBetween January 2007 and December 2012, 2104 patients underwent thyroidectomy at Chang Gung Memorial Hospital and 140 (6.7%) were diagnosed with substernal goitres. Patient medical records were retrospectively reviewed, and data were analysed to assess surgical outcomes.nnnRESULTSnSeven (5.0%) patients required a thoracic approach for goitre removal. Goitre malignancy was verified in 17 (12.1%) patients. The most common postoperative complication was transient hypoparathyroidism (15.0%). Permanent RLN injury occurred in 4.3% of patients and was significantly more frequent using the thoracic approach. Unilateral extension of a substernal goitre was more common than bilateral extension. Right- and left-sided extensions occurred with equal frequency. The rate of postoperative complications was similar between groups and there were no patient deaths.nnnCONCLUSIONnChest radiography and thyroid sonography may provide initial radiologic evidence of goitre extension into the superior mediastinum. Computed tomography evaluation of the depth of goitre extension to the tracheal bifurcation was the strongest predictor of the need to use a thoracic approach. There were no significant differences in the clinical features and outcomes of patients with right- and left-sided substernal goitres. The right recurrent laryngeal nerve shows increased susceptibility to damage during thyroid surgery for substernal goitres. The incidence of malignant substernal goitres is similar to that of malignant cervical goitres.

Comparison study of gastrinomas between gastric and non-gastric origins

BackgroundGastrinomas are one of the neuroendocrine tumors with potential distant metastasis. Most gastrinomas are originated from pancreas and duodenum, but those of gastric origin have been much less reported. The aim of the study is to compare gastrinomas of gastric and non-gastric origins.MethodsFour hundred twenty-four patients with neuroendocrine tumor by histological proof in Chang Gung Memorial Hospital, Linkou branch in the past 10xa0years were included. A total of 109 (25.7xa0%) cases were identified of upper gastrointestinal origins, of which 20 (18.3xa0%) were proven gastrinomas. The clinical characteristics were collected and analyzed retrospectively.ResultsIn our study, 21 tumors of the 20 cases were identified by pathologic proof, 11 (55xa0%) had resection or endoscopic mucosa resection, 9 of gastric origins, 9 of duodenal origins, 2 of pancreatic origins, and 1 of hepatic origins. One case had multiple lesions. Patients with gastric gastrinomas had older age, higher levels of gastrin, seemingly smaller tumor size (pu2009=u20090.024, 0.030, and 0.065, respectively), and usually lower grade in differentiation (pu2009=u20090.035). Though gastric gastrinomas had a high recurrent rate (80xa0%), the lymph node and liver involvement was less common. Gastrinomas with liver involvement/metastasis had a high mortality rate where 80xa0% died of liver dysfunction.ConclusionsGastrinomas originating from stomach had higher gastrin level and lower tumor grading and presented at older age. The long-term outcome was probably better than non-gastric origin because of lower grading and less lymph node and liver involvement.