Management of unresectable hilar bile duct cancer--preoperative diagnosis,treatment selection,and clinical outcome

BACKGROUND/AIMS: Hilar bile duct cancer progresses slowly but easily invades the nearby portal vein or hepatic artery. Thus, in some cases, curative resection is impossible, so we need to determine the best non-surgical treatments for this tumor. METHODOLOGY: We classified 98 patients with hilar bile duct cancer into 3 categories: a non-surgical group (34 cases), an exploratory laparotomy group (9 cases), and a surgical resection group (55 cases). Survival rates were examined in the light of clinical factors. RESULTS: In the non-surgical group, extensive vessel invasion was the most common reason for unresectability (13 cases), with broad biliary extension the second most common (11 cases). In the exploratory laparotomy group the most common reason for unresectability was severe vessel invasion (6 cases). Cumulative 1- and 2-year survival rates for patients with unresectable tumors without distant metastasis were 26.9% and 7.2%, respectively. One- and 2-year survival rates for patients with unresectable tumors and with total bilirubin of less than 2 mg/dL on discharge were 36.8% and 9.8%, respectively. The 1-year survival rate with placement of an expandable metallic stent was as high as 55.6%; without the stent it was 7.1% (P = 0.005). Radiation therapy gave a better prognosis than did no radiation (P = 0.01). CONCLUSIONS: Portal and arterial invasion were the principal reasons for unresectability. Use of an expandable metallic stent or radiation therapy, and a total bilirubin level of less than 2 mg/dL on discharge, were factors that enhanced survival in unresectable cases, but distant metastasis, dissemination, and poor general condition or liver function were negative factors for survival.     

Surgical anatomy of the inferior vena cava ligament

BACKGROUND/AIMS: The inferior vena cava ligament is a fibrous membrane located around the inferior vena cava. Few reports exist on the ligament's location, attachment to the liver, or the inferior vena cava. METHODOLOGY: We obtained 16 specimens of human liver and inferior vena cava from cadavers. The inferior vena cava ligament was photographed and then dissected for histological examination. Relationships among the ligament, inferior vena cava, and liver were examined microscopically. The numbers and diameters of veins, arteries, and lymph vessels at least 1 mm in diameter were recorded. RESULTS: The cranial margin of the inferior vena cava ligament was ended in a blind loop. The cranial portion above the mid-portion of the Spiegel lobe was thicker than the caudal portion. The ligament was attached to the right and left hepatic veins. The mean length of the right side of the inferior vena cava ligament was 37.0 mm and the mean width 15.6 mm. The inferior vena cava ligament had a mean thickness of 0.8 mm (thin end) and 2.5 mm (thick end). Although the inferior vena cava ligament was usually tightly continuous with the liver capsule, microscopically the attachment between the ligament and the inferior vena cava was loose. The mean number and diameter of veins in the inferior vena cava ligament was 1.0 and 1.4 mm, respectively. The mean number and diameter of arteries was 0.2 and 2.4 mm, respectively. The mean number and diameter of lymphatic vessels was 2.8 and 1.7 mm, respectively. CONCLUSIONS: After dissection of the inferior vena cava ligament, major hepatic veins can be dissected extrahepatically. Because the ligament is wider caudally, the forceps should be inserted caudocranially during separation. Since both the number and diameters of lymphatic vessels in the ligament are large, the ligament should be ligated and cut.     

Non-perforating pericardial rupture causing cardiac tamponade

A 51-year-old auto truck driver was transferred to our hospital after crashing. He had a severe pain on the left anterior chest wall with high central venous pressure of 30 cm H(2)O. Surveillance of the chest revealed cardiac tamponade and the right seventh rib fracture with left pleural effusion. Pericardiotomy through median sternotomy led to extrusive bloody pericardial effusion. Non-perforating pericardial laceration at the site of the adjoining muscular structure of the diaphragm was repaired with direct suture closure. His postoperative course was uneventful.     

Intraocular hemangiopericytoma. A case report

A 55-year-old man presented with a smoothly elevated solid choroidal mass with choroidal detachment in the temporal region of the left eye. Both fluorescein and indocyanine green angiography suggested a vascularized lesion such as an angioma. However, radiographic examination revealed a solid, circumscribed, dome-shaped mass. During a 3-month observation, the mass gradually enlarged and invaded the iris. The possibility of malignant melanoma could not be ruled out. Due to rapid and continued growth of the tumor, the eye was enucleated. Histopathologic examination revealed proliferation of spindle-shaped cells surrounding reticulin-positive vessels, which is characteristic of hemangiopericytoma. To our knowledge, this is only the fourth reported case of intraocular hemangiopericytoma and the first diagnosed in a male patient.     

Acquisition of english grammatical morphology by native mandarin-speaking children and adolescents: age-related differences.

PURPOSE: This 5-year longitudinal study investigated the acquisition of 6 English grammatical morphemes (i.e., regular and irregular past tense, 3rd person singular, progressive aspect -ing, copula BE, and auxiliary DO) by 10 native Mandarin-speaking children and adolescents in the United States (arrived in the United States between 5 and 16 years of age). The goals were to chart and compare the acquisition trajectories and levels of mastery across the morphemes, identify when age-related differences emerged and which forms they took. METHOD: Morphological proficiency was measured by the accuracy of these morphemes in obligatory contexts during spontaneous speech. RESULTS: The morphemes were mastered by different numbers of participants and showed different growth trajectories. Performance variance was partially predicted by age of arrival (AoAr) in the United States, with early arrivals achieving greater proficiency than late arrivals. However, such AoAr effects took several years to occur and only existed for 2 of the 6 morphemes (i.e., 3rd person singular and regular past tense). Growth curve analysis revealed that language environment was a stronger predictor of individual differences than AoAr. Results did not uncover age-related differences in the acquisition of tense versus non-tense-related morphemes, nor in regular versus irregular morphemes, nor in the error types. CONCLUSION: Findings support an Environmental account for age-related differences in 2nd language (L2) morphological acquisition. Results also indicate that the acquisition of some grammatical morphemes by school-aged immigrants takes several years to complete. As L2 learners exhibit some error types and difficulties similar to monolingual children with specific language impairment, caution needs to be taken when interpreting and using morphological errors as indicators of speech/language learning problems in this population.     

Effect of HER-2/neu overexpression on chemoresistance and prognosis in ovarian carcinoma

AIM: To investigate the effect of HER-2/neu protein overexpression on chemoresistance and prognosis in patients with epithelial ovarian carcinoma. METHODS: A total of 141 ovarian carcinoma tissues surgically resected between 1987 and 2003 were assessed by immunohistochemistry (IHC). The characteristic of the patients and immunohistochemical results were compared by chi2-test. Survival analysis was performed by the Kaplan-Meier method and the log-rank test. RESULTS: HER-2/neu overexpression was detected in 18 cases (12.8%). There were no significant differences in histopathological subtypes (P = 0.3550), FIGO stages (P = 0.8858), or residual tumor size at first surgery (P = 0.6607) between the cases with HER-2/neu overexpression and the cases without HER-2/neu overexpression. Among the 58 cases which responded to chemotherapy, only five cases (8.6%) showed HER-2/neu overexpression. However, among the 38 cases which did not respond to chemotherapy, eight cases (21.1%) showed HER-2/neu overexpression. Overexpression of HER-2/neu had a tendency to relate with chemoresistance of epithelial ovarian carcinoma, but there were no statistically significant differences (P = 0.0817). No association was observed between HER-2/neu overexpression and cumulative survival rate (P = 0.4970). CONCLUSIONS: The results of the current study show that although HER-2/neu overexpression has a tendency to be associated with chemoresistance, it can not be a prognostic factor for the patients with epithelial ovarian carcinoma.     

Three-year follow up of term and near-term infants treated with inhaled nitric oxide

BACKGROUND: The present study describes the outcome at 3 years in term and near-term infants treated with inhaled nitric oxide (iNO) for persistent pulmonary hypertension of the newborn (PPHN). METHODS: The study population consisted of 18 infants delivered at 34 weeks by best obstetric estimate who were admitted to the neonatal intensive care units with a diagnosis of PPHN. RESULTS: Eighteen infants (mean gestational age 38.5 +/- 2.6 weeks, mean birthweight 3015 +/- 587 g) were treated with iNO. The mean oxygenation index before iNO was 27.2 +/- 15.2. Responses to iNO were classified into three groups: (i) early response in eight infants; (ii) late response in two; and (iii) poor response in eight infants. Three infants died within seven postnatal days. Fifteen surviving infants were followed up to 3 years. The mean developmental scale was 98.4 +/- 9.0. One infant was diagnosed with severe neurodevelopmental disability due to cerebral palsy. Another infant was diagnosed with mild neurodevelopmental disability because of a low developmental scale. No infant showed significant hearing loss. Five infants had reactive airway disease (RAD) at 18 months, these infants required a significantly longer duration of mechanical ventilation in their neonatal period than non-RAD infants (P = 0.02). The frequency of survival with normal neurodevelopmental outcome was significantly higher in the early response group than the late or poor response groups (P = 0.03). CONCLUSION: In iNO-treated PPHN, mortality and neurodevelopmental outcome were associated with response to iNO, and pulmonary outcome was associated with duration of mechanical ventilation.     

P-glycoprotein plays a major role in the efflux of fexofenadine in the small intestine and blood-brain barrier, but only a limited role in its biliary excretion.

Fexofenadine is a selective, nonsedating H(1)-receptor antagonist approved for symptoms of allergic conditions, which is mainly excreted into feces via biliary excretion. The purpose of this study is to investigate its pharmacokinetics in mice and rats to determine the role of P-glycoprotein (P-gp) in its biliary excretion. In mice, biliary excretion clearance (17 ml/min/kg) accounted for almost 60% of the total body clearance (30 ml/min/kg). Comparing the pharmacokinetics after intravenous and oral administration indicated that the bioavailability of fexofenadine was at most 2% in mice. Knockout of Mdr1a/1b P-gp did not affect the biliary excretion clearance with regard to both plasma and liver concentrations, whereas the absence of P-gp caused a 6-fold increase in the plasma concentration after oral administration. In addition, the steady-state brain-to-plasma concentration ratio of fexofenadine was approximately 3-fold higher in Mdr1a/1b P-gp knockout mice than in wild-type mice. Together, these results show that P-glycoprotein plays an important role in efflux transport in the brain and small intestine but only a limited role in biliary excretion in mice. In addition, there was no difference in the biliary excretion between normal and hereditarily multidrug resistance-associated protein 2 (Mrp2)-deficient mutant rats (Eisai hyperbilirubinemic rats) and between wild-type and breast cancer resistance protein (Bcrp) knockout mice. These results suggest that the biliary excretion of fexofenadine is mediated by unknown transporters distinct from P-gp, Mrp2, and Bcrp.     

Differences in histological features and PD-L1 expression between sporadic microsatellite instability and Lynch-syndrome-associated disease in Japanese patients with colorectal cancer

Background

The field of immunotherapy has recently focused on cancers with microsatellite instability (MSI). These cancers include both Lynch-syndrome-associated tumors, which are caused by mismatch repair (MMR) germline mutations, and sporadic MSI tumors, which are mainly attributed to MLH1 promoter methylation. The present study aimed to clarify differences in the histological and PD-L1 expression profiles between these two types of MSI cancers in Japanese patients.

Methods

Among 908 cases of colorectal cancer treated via surgical resection from 2008 to 2014, we identified 64 MSI cancers, including 36 sporadic MSI and 28 Lynch-syndrome-associated cancers, using a BRAF V600E mutation analysis and MLH1 methylation analysis. Of the latter subgroup, 21 (75%) harbored MMR germline mutations.

Results

The following were more frequent with sporadic MSI than with Lynch syndrome associated cancers: poor differentiation (50.0 vs. 7.1%, P = 0.0002), especially solid type (30.6 vs. 3.6%, P = 0.0061); medullary morphology (19.4 and 0%, P = 0.015), Crohn-like lymphoid reaction (50.0 vs. 25.0%, P = 0.042), and PD-L1 expression (25.0 vs. 3.6%, P = 0.034). However, the groups did not differ in terms of the mean invasive front and intratumoral CD8-positive cell densities. In a logistic regression analysis, PD-L1 expression correlated with poor differentiation (odds ratio: 7.65, 95% confidence interval: 1.55–37.7, P = 0.012), but not with the difference between sporadic MSI cancer and Lynch-syndrome-associated cancer (odds ratio: 4.74, 95% confidence interval: 0.50–45.0, P = 0.176).

Conclusions

Therefore, compared with Lynch-syndrome-associated cancers, sporadic MSI cancers are more frequently solid, poorly differentiated medullary cancers that express PD-L1.