Nomograms predicting extra- and early intrahepatic recurrence after hepatic resection of hepatocellular carcinoma

BackgroundExtrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection are indicative of poor prognoses. We aimed to develop nomograms to predict extrahepatic recurrence and early intrahepatic recurrence after hepatic resection.MethodsThe participants of this study were 1,206 patients who underwent initial and curative hepatic resection for hepatocellular carcinoma. Multivariate logistic regression analyses using the Akaike information criterion were used to construct nomograms to predict extrahepatic recurrence and early intrahepatic recurrence (within 1 year of surgery) at the first recurrence sites after hepatic resection. Performance of each nomogram was evaluated by calibration plots with bootstrapping.ResultsExtrahepatic recurrence was identified in 95 patients (7.9%) and early intrahepatic recurrence in 296 patients (24.5%). Three predictive factors, α-fetoprotein >200 ng/mL, tumor size (3–5 cm or >5 cm vs ≤3 cm), and image-diagnosed venous invasion by computed tomography, were adopted in the final model of the extrahepatic recurrence nomogram with a concordance index of 0.75. Tumor size and 2 additional predictors (ie, multiple tumors and image-diagnosed portal invasion) were adopted in the final model of the early intrahepatic recurrence nomogram with a concordance index of 0.67. The calibration plots showed good agreement between the nomogram predictions of extrahepatic recurrence and early intrahepatic recurrence and the actual observations of extrahepatic recurrence and early intrahepatic recurrence, respectively.ConclusionWe have developed reliable nomograms to predict extrahepatic recurrence and early intrahepatic recurrence of hepatocellular carcinoma after hepatic resection. These are useful for the diagnostic prediction of extrahepatic recurrence and early intrahepatic recurrence and could guide the surgeon’s selection of treatment strategies for hepatocellular carcinoma patients.     

Accumulation of L-[2-(F-18)]fluorophenylalanine in peri-infarct area in a patient with acute cerebral infarction

We studied the brain uptake of amino acid in a patient with acute cerebral infarction with L-[2-(F-18)] fluorophenylalanine and positron emission tomography. The increased accumulation of the ligand was specifically found in the peri-infarct area where oxygen metabolism was still maintained but decreased later in the 72-day follow-up period. The kinetic analysis revealed that increased accumulation was not due to increased transport from the blood to the brain but to delayed washout from the brain to the blood. Although the mechanism is still unknown, abnormally high accumulation of L-[F-18]fluorophenylalanine may predict delayed neuronal changes after ischemic insults of the brain.     

Induction of tumor regression by passive transfer of antibody from mice vaccinated with anti-idiotype antibodies resembling a human renal cell carcinoma-associated antigen

We have shown that six different internal image antiidiotype antibodies (Ab2) raised against the combining site of the murine monoclonal antibody G250 (MAbG250; Abl), which specifically reacts with a human renal cell carcinoma (RCC)-associated antigen, induce antigen specific humoral and cellular responses in mice. These six Ab2 can be divided into four mutually exclusive groups: (1) NUH31 and NUH51, (2) NUH44 and NUH82, (3) NUH71, and (4) NUH91. Immunization with NUH82 or NUH91 resulted in Ab3 sera that gave complete protection against tumor challenge. In this study, we tested the antitumor efficacy of NUH82- and NUH91-induced mouse sera (Ab3 sera; Ab3-82 and Ab3-91) in mice with established subcutaneous human RCC xenografts. Mice were treated 3 times per week by intraperitoneal injection of Ab3 sera (0.2 ml) or MAbG250 (250 μg) for 6 weeks. Treatment of NU12 human RCC xenografts of approximately 20 mm(3) expressed as tumor size index (TSI) with NUH-Ab3 sera or MAbG250 resulted in significant tumor growth inhibition compared with tumors treated with Ab3 sera from mice immunized with control immunoglobulin (Ab3-MOPC). In all Ab3-NUH treated mice, tumors stabilized or disappeared completely. In contrast, Ab3-MOPC treatment did not result in any antitumor effects. Tumor remnants in Ab3-NUH treated animals contained viable tumor cells surrounded by infiltrating mouse cells, whereas no infiltration was observed in control tumors. These findings demonstrate that Ab3 sera obtained from NUH82- or NUH91-immunized mice are very effective in eradicating established RCC [i.e., Ab2 vaccination may be able to eradicate (minimal) residual disease in RCC patients].     

Pupillary responses in normal subjects following auditory stimulation

To clarify pupillary responses of humans following auditory stimuli, we studied both eyes of 61 normal subjects using a computed pupillograph. Unilateral auditory stimulation elicited pupillary dilatation in all cases. Pupillary responses were classified according to duration as being either “long” or “short”. The duration of dilatation was 1530±320 ms (mean±SD) in the longlasting group (n=45) and 850±250 ms in the short-lasting group (n=16). The latency time for dilatation was 460±80 ms. Both eyes of each subject showed the same response. Two drops of 10% guanethidine, a sympathetic blocking agent, were applied to one eye of 3 subjects. Although the early phase of dilatation was barely affected, the late phase was inhibited, as seen in long-lasting dilatation. The short-lasting response was unaffected. We conclude that the long-lasting response consists of an early pupillary dilatation due to inhibition of parasympathetic nervous activity and a late dilatation due to excitation of sympathetic activity. The short-lasting response is produced only by inhibition of the parasympathetic component.     

Post-traumatic pituitary apoplexy--two case reports

A 60-year-old female and a 66-year-old male presented with post-traumatic pituitary apoplexy associated with clinically asymptomatic pituitary macroadenoma manifesting as severe visual disturbance that had not developed immediately after the head injury. Skull radiography showed a unilateral linear occipital fracture. Magnetic resonance imaging revealed pituitary tumor with dumbbell-shaped suprasellar extension and fresh intratumoral hemorrhage. Transsphenoidal surgery was performed in the first patient, and the visual disturbance subsided. Decompressive craniectomy was performed in the second patient to treat brain contusion and part of the tumor was removed to decompress the optic nerves. The mechanism of post-traumatic pituitary apoplexy may occur as follows. The intrasellar part of the tumor is fixed by the bony structure forming the sella, and the suprasellar part is free to move, so a rotational force acting on the occipital region on one side will create a shearing strain between the intra- and suprasellar part of the tumor, resulting in pituitary apoplexy. Recovery of visual function, no matter how severely impaired, can be expected if an emergency operation is performed to decompress the optic nerves. Transsphenoidal surgery is the most advantageous procedure, as even partial removal of the tumor may be adequate to decompress the optic nerves in the acute stage. Staged transsphenoidal surgery is indicated to achieve total removal later.     

Simultaneous determination of grepafloxacin, ciprofloxacin, and theophylline in human plasma and urine by HPLC.

A specific and sensitive reversed-phase high-performance liquid chromatographic (HPLC) method has been developed and validated for the simultaneous determination of grepafloxacin, ciprofloxacin, and theophylline in human plasma and urine. This assay allows these drugs to elute and be resolved in a single chromatogram at 280 nm, using a linear gradient. The procedure involves liquid-liquid extraction. Separation was achieved on a C18 reversed-phase column. The quantification limits were 0.05 mg/L in plasma and 0.5 mg/L in urine for grepafloxacin and ciprofloxacin and 0.5 mg/L in plasma and urine for theophylline. Standard curves were linear (correlation coefficients >0.999) over the ranges 0.05 to 5 mg/L for grepafloxacin and ciprofloxacin in plasma, from 0.5 to 20 mg/L for theophylline in plasma, and from 0.5 to 500 mg/L for the three drugs in urine. The coefficients of variation for the three drugs were less than 10% for within- and between-day analyses. The recoveries averaged 94.5% for theophylline, 93% for ciprofloxacin, 93.7% for grepafloxacin, and 95.1% for the internal standard (IS). The assay can be used for pharmacokinetic studies of these drugs, to investigate the interaction of grepafloxacin and ciprofloxacin with theophylline, or for routine simultaneous monitoring of theophylline, grepafloxacin, and ciprofloxacin.     

Lectin bindings in non-neoplastic esophageal epithelium and esophageal carcinomas

Lectin binding was examined histochemically in 22 cases of primary esophageal carcinomas (10 well differentiated, 8 moderately differentiated and 3 poorly differentiated squamous cell carcinomas, and 1 undifferentiated carcinoma) and was compared with the adjacent non-neoplastic epithelium by means of a panel of 10 different lectins (RCA-I, WGA, Con A, LCA, SEA, UEA-I, HPA, PNA, DBA and GS-I) on formalin-fixed paraffin-embedded sections. In the non-neoplastic epithelium, RCA-I and WGA showed basal/parabasal binding, Con A, LCA, SEA, UEA-I, HPA and PNA revealed prickle cell binding, while DBA and GS-I only stained the surface cells of the squamous cell layer. In squamous cell carcinomas, no clear difference was evident regarding the grade of differentiation. However, basal/parabasal specific lectins were expressed in all the cases, the prickle cell-specific lectins were expressed less frequently, whereas lectins expressed at the surface cells of the squamous cell layer were only infrequently expressed. Therefore, basal/parabasal cell specific lectins were widely preserved in squamous cell carcinomas. One case of undifferentiated cancer tested was devoid of all the lectins.     

Nitric oxide and aneurysm formation in Kawasaki disease

The objective of this study is to show that nitric oxide plays a role in the development of coronary artery abnormalities in Kawasaki disease. We examined nitrite + nitrate, biopterin and neopterin in 316 urine samples of 34 patients with Kawasaki disease, those of 24 patients with other diseases, and those of 25 healthy children acting as a control group, because urinary nitrite + nitrate are reportedly useful as markers of nitric oxide generation in vivo , and pathways for neopterin-biopterin synthesis and nitric oxide generation are tightly coupled. In our study, the children with Kawasaki disease excreted more urinary nitrite + nitrate and neopterin than did the healthy control group children and excreted abnormally high quantities more often than did the patients with other diseases. Good relationships were found between the urinary nitrite + nitrate levels and the urinary biopterin levels, and between these biopterin levels and the urinary neopterin levels. Nitric oxide is therefore thought to be generated in abnormally high quantities, and to be closely related to the pathology of Kawasaki disease and to the development of coronary artery abnormalities. The role of nitric oxide in Kawasaki disease should be further studied to elucidate the pathophysiology of the disease and to aid in the development of new treatments.     

Subependymoma of the septum pellucidum: Characterization by PET

We report the evaluation of a subependymoma of the septum pellucidum by positron emission tomography (PET) with analysis of ₁₈F-fluorodeoxyglucose (FDG)kinetics. The tumor showed exceedingly low rates of glucose metabolism (rCMRG1) and kinetic constants (K1, K2, and K3). This hypometabolism indicates low cellular density and slow growth.