Benign hilar bile duct strictures resected as perihilar cholangiocarcinoma.

BACKGROUND: Differentiation between perihilar cholangiocarcinoma (PHCC) and benign strictures is frequently difficult. The aim of this study was to investigate the incidence and long-term outcome of patients with tumours resected because of suspicion of PHCC, which ultimately turned out to be benign (malignancy masquerade). METHODS: Patients who underwent surgical resection with a diagnosis of PHCC between 2001 and 2016 were reviewed retrospectively. RESULTS: Among 707 consecutive patients, 685 had PHCC and the remaining 22 (3·1 per cent) had benign biliary stricture. All patients with benign disease underwent major hepatectomy, with no deaths. Preoperative histological assessment using bile duct biopsy or aspiration cytology had a high specificity (90 per cent), low sensitivity (62 per cent) and unsatisfactory accuracy (63 per cent). Despite the increasing use of histological assessment, the incidence of benign strictures resected did not decrease over time, being 0·9 per cent in 2001-2004, 4·0 per cent in 2005-2008, 3·8 per cent in 2009-2012 and 2·9 per cent in 2013-2016. The final pathology of benign strictures included IgG4-related sclerosing cholangitis (9 patients), hepatolithiasis (4), granulomatous cholangitis (3), non-specific chronic cholangitis (3), benign strictures after cholecystectomy (2), and a benign stricture possibly caused by parasitic infection (1). The 10-year overall survival rate for the 22 patients with benign stricture was 87 per cent, without recurrence of biliary stricture. CONCLUSION: The incidence of benign strictures resected as PHCC as a proportion of all resections was relatively low, at 3·1 per cent. Currently, unnecessary surgery for suspected PHCC is unavoidable.

ANTECEDENTES: La diferenciación entre colangiocarcinoma perihilar (perihilar colangiocarcinoma, PHCC) y estenosis benignas es con frecuencia difícil. El objetivo de este estudio fue investigar la incidencia y el resultado a largo plazo de los tumores resecados con sospecha diagnóstica de PHCC, que finalmente resultaron ser benignos (malignidad enmascarada). MÉTODOS: Se revisaron retrospectivamente los pacientes con diagnóstico de PHCC que se sometieron a resección quirúrgica entre 2001 y 2016. RESULTADOS: Entre 707 pacientes consecutivos, 685 pacientes presentaban PHCC y los 22 restantes (3,1%) tenían una estenosis biliar benigna. Todos los pacientes con patología benigna se sometieron a una hepatectomía mayor, sin mortalidad. La evaluación histológica preoperatoria mediante biopsia de conducto biliar o citología por aspiración tuvo una alta especificidad (90%), una baja sensibilidad (62%) y una exactitud diagnóstica insatisfactoria (63%). A pesar del uso creciente de la evaluación histológica, la incidencia de estenosis benignas resecadas no disminuyó con el tiempo, con un 0,9% en 2001-2004, un 4,0% en 2005-2008, un 3,8% en 2009-2012 y un 2,9% en 2013-2016. La patología final de las estenosis benignas incluyó colangitis esclerosante relacionada con IgG4 (n = 9), hepatolitiasis (n = 4), colangitis granulomatosa (n = 3), colangitis crónica no específica (n = 3), estenosis benignas tras una colecistectomía (n = 2) y una estenosis benigna posiblemente causada por una infección parasitaria (n = 1). Los resultados a largo plazo de los 22 pacientes con estenosis benigna fueron mejores (tasa de supervivencia a 10 años; 87,4%) sin recidiva de la estenosis biliar. CONCLUSIÓN: La incidencia de pacientes con estenosis benignas resecadas como PHCC en comparación con todas las resecciones fue relativamente baja, del 3,1%. Actualmente, la cirugía "innecesaria" por sospecha de PHCC es inevitable.

Major hepatectomy with or without pancreatoduodenectomy for advanced gallbladder cancer.

BACKGROUND: The indications for major hepatectomy for gallbladder cancer either with or without pancreatoduodenectomy remain controversial. The clinical value of these extended procedures was evaluated in this study. METHODS: Patients who underwent major hepatectomy for gallbladder cancer between 1996 and 2016 were identified from a prospectively compiled database. Postoperative outcomes and overall survival were compared between patients undergoing major hepatectomy alone or combined with pancreatoduodenectomy (HPD). RESULTS: Seventy-nine patients underwent major hepatectomy alone and 38 patients had HPD. The patients who underwent HPD were more likely to have T4 disease (P < 0·001), nodal metastasis (P = 0·015) and periaortic nodal metastasis (P = 0·006), but were less likely to receive adjuvant therapy (P = 0·006). HPD was associated with a high incidence of grade III or higher complications (P = 0·002) and death (P = 0·037). Overall survival was longer in patients who underwent major hepatectomy alone than in patients who underwent HPD (median survival time 32 versus 10 months; P < 0·001). In multivariable analysis, surgery in the early period (1996-2006) (P = 0·002), pathological T4 disease (P = 0·005) and distant metastasis (P < 0·001) were associated with shorter overall survival, and cystic duct tumour (P = 0·002) with longer overall survival. CONCLUSION: Major hepatectomy alone for gallbladder cancer contributes to favourable overall survival with low morbidity and mortality, whereas HPD is associated with poor overall survival and high morbidity and mortality rates. HPD may eradicate locally spreading gallbladder cancer; however, the indication for the procedure is questioned from an oncological viewpoint.

Ethanol ablation for refractory bile leakage after complex hepatectomy.

BACKGROUND: Only a few reports exist on the use of ethanol ablation for posthepatectomy bile leakage. The aim of this study was to assess the value of ethanol ablation in refractory bile leakage. METHODS: Medical records of consecutive patients who underwent a first hepatobiliary resection with bilioenteric anastomosis between 2007 and 2016 were reviewed retrospectively, with special attention to bile leakage and ethanol ablation therapy. Bile leakage was graded as A/B1/B2 according to the International Study Group of Liver Surgery definition. Absolute ethanol was injected into the target bile duct during fistulography. RESULTS: Of the 609 study patients, 237 (38·9 per cent) had bile leakage, including grade A in 33, grade B1 in 18 and grade B2 in 186. Left trisectionectomy was more often associated with grade B2 bile leakage than other types of hepatectomy (P < 0·001). Of 186 patients with grade B2 bile leakage, 31 underwent ethanol ablation therapy. Ethanol ablation was started a median of 34 (range 15-122) days after hepatectomy. The median number of treatments was 3 (1-7), and the total amount of ethanol used was 15 (3-71) ml. Complications related to ethanol ablation included transient fever (27 patients) and mild pain (13). Following ethanol ablation, bile leakage resolved in all patients and drains were removed. The median interval between the first ablation and drain removal was 28 (1-154) days. CONCLUSION: Ethanol ablation is safe and effective, and may be a treatment option for refractory bile leakage.

Effects of a membrane-bound trypsin-like proteinase and seminal proteinase inhibitors on the bicarbonate-sensitive adenylate cyclase in porcine sperm plasma membranes.

Plasma membranes were purified from flagella of porcine cauda epididymal sperm and proteolytic regulation of bicarbonate-sensitive adenylate cyclase was studied. It was found that the epididymal sperm plasma membrane contained a trypsin-like proteinase which inactivated adenylate cyclase. Bicarbonate activates adenylate cyclase as reported previously, but, at the same time, the anions enhance the inactivation of the enzyme by the membrane-bound trypsin-like proteinase. This phenomenon is not due to the direct activation of the proteinase, but closely related to the activation of adenylate cyclase by bicarbonate. It was also found that seminal proteinase inhibitors blocked the inactivation of adenylate cyclase and maintained the bicarbonate activation of the enzyme at high level. Actually, bicarbonate keeps adenylate cyclase fully active in ejaculated sperm, because membrane-bound proteinase is completely inhibited by the seminal proteinase inhibitors. These results suggest that the interactions between membrane-bound proteinase and seminal proteinase inhibitor are involved in the regulation of the bicarbonate-sensitive adenylate cyclase system.

Changes in glucose level affect rod function more than cone function in the isolated, perfused cat eye.

The glucose concentration (gl) in mammalian serum incorporates a normal range of variation of several millimoles. We studied the effects of such variations on light-evoked electrical signals in the in vitro arterially perfused cat eye, avoiding extraocular regulatory mechanisms that might confound data interpretation. Changes in gl from the nominal control value of 5 mmol/l were maintained for 5-40 min. Stimuli of near rod threshold intensity were presented in full dark adaptation, and stimuli of higher intensity were presented in the presence of a white background for cone responses. We recorded the dc-electroretinogram (ERG), the scotopic threshold response (STR), the optic nerve response (ONR), and the transretinal slow P-III and transepithelial retinal pigment epithelium c-wave from the subretinal space. The ocular standing potential changed by up to +/- 2 mV in parallel with an increase and decrease in gl, independent of the adaptation condition. Our results show that the rod-ERG, STR, and rod-driven optic nerve response (ONR) have a marked sensitivity to small changes in gl (+/- 1 to 3 mmol/l). The field potentials increased and decreased in parallel with changes in gl. The cone ERG and cone ONR, in contrast, failed to respond consistently to increases in gl and revealed decreases in amplitudes only with an extreme decrease in gl. Decrease in gl, down to 2 mmol/l and less, is known to induce drastic behavioral and electrophysiologic phenomena in the central nervous system. Our results imply that the "normal" glucose level, at least in the cat, could be marginal for rod-mediated retinal function. The results also suggest a marked difference in metabolic mechanisms for cone versus rod photoreceptors.

Internal carotid blood flow velocity in children with cerebral palsy by Doppler Ultrasound method.

Cerebral blood flow assessed noninvasively by Doppler ultrasound technique in 30 children with cerebral palsy. The average maximal blood velocity (A/L) and end-diastolic blood velocity (d) of internal carotid artery were measured before and during brief digital compression of contralateral common carotid artery. Both A/L and d values in children with cerebral palsy were significantly lower than those observed in normal healthy children. In 13 children with spastic hemiplegia, no significant difference in either A/L or d was seen between the non-affected side and affected side both before and during brief digital compression. This data suggests that mean cerebral blood flow decreases in our children with cerebral palsy, and that no lateralization of the decrease in hemispheric cerebral circulation in hemiplegic children may explain by supposing the existence of generalized bilateral brain damage in those subjects.

Antiepileptic effects of clobazam in children.

Many benzodiazepines used as anticonvulsants have nitrogen radicals in positions 1 and 4. Clobazam has nitrogen radicals in positions 1 and 5. We studied the antiepileptic effect of clobazam in 36 patients with intractable epilepsies in childhood. Their ages were 1 year 1 month to 16 years 5 months (mean 8 years). The mean initial dose was 0.33 mg/kg of daily doses and increased up to 0.71 mg/kg. Nine cases (primary generalized epilepsy 2/2, secondary generalized epilepsy 7/29) were completely free from seizures, and another 9 (secondary generalized epilepsy 8/29, partial epilepsy 1/5) experienced a decrease of 50% or more in seizure frequency. Seizure frequency did not change in 16, and increased in the other 2 (secondary generalized epilepsy 2/29). The antiepileptic effects were observed on the first day to 10th day after clobazam treatment. There were recurrences of seizures in 4 out of 9 patients with complete control of seizures, 1 month alter in 3 and 10 months later in one. Mean serum clobazam level of 7 improved cases was 73 ng/ml and that of 3 cases with no response was 94 ng/ml. Although mild clinical side effects such as drowsiness were observed transiently in 17 cases, no abnormality was found in laboratory investigations performed.

Delayed myelination in a patient with 18q- syndrome.

A Japanese boy with the typical manifestations of 18q-syndrome and delayed myelination on magnetic resonance imaging is described. Cytogenetic investigation revealed a deletion at 18q21.3. Three serial magnetic resonance images demonstrated that myelination in the central nervous system was delayed except for the corpus callosum and brainstem. This pattern of delayed myelination appears to be peculiar to the 18q- syndrome. Because the gene for myelin basic protein has been localized to the distal end of the long arm of chromosome 18, we speculate that the abnormal myelination in our patient was partly due to the failure of expression of the myelin basic protein gene.

Antigenic alteration in major piroplasm surface proteins of Theileria sergenti during infection.

Theileria sergenti piroplasms were purified from different parasitemia peaks of cattle infected with parasitized erythrocytes or sporozoites during persistent infection. Their reactivities with monoclonal antibodies 13F5 and C9, which recognize 23 kDa and 32 kDa piroplasm surface proteins, respectively, were analyzed. Antigenic differences were observed among parasites from different parasitemia peaks during persistent infection when cattle were infected with sporozoites. Results of two-dimensional polyacrylamide gel electrophoresis showed that the 23 and 32 kDa proteins were expressed in all samples tested, regardless of their reactivities with the monoclonal antibodies. In contrast, parasites obtained from cattle inoculated with parasitized erythrocytes showed no antigenic alteration over a 2 month observation period. The results suggest that antigenic alteration of T. sergenti during persistent infection is related to whether the parasites proliferate through extraerythrocytic schizont stage in cattle or sporozoite and other sexual stages in tick vector.

Changes in the hybridization patterns of populations of Theileria sergenti during infection.

Restriction fragment length polymorphisms (RFLPs) of Theileria sergenti DNA were analysed using probes of a genomic DNA fragment (pTs 2) and a cDNA corresponding to this genomic probe (C-Ts 2). Each of the probes detected RFLPs in DNA from different stocks of Theileria sergenti. Additionally, using these probes, alterations in hybridization patterns were observed in samples of the parasites harvested at different times after individual calves had been infected with Theileria sergenti. This result suggests that the Theileria sergenti stocks used were mixed parasite populations.

Spectral sensitivity of monochromatic ERG c-wave of chicken under color adaptation.

The spectral sensitivity of the ERG c-wave was studied in the chicken under yellow or red light adaptation of various intensities, ie, 1, 3, 4 and 5 W/m2 at the corneal surface in the former, and 3, 4 and 5 W/m2 in the latter. The peak wavelength of the spectral sensitivity curve of the c-wave amplitude under both yellow and red light adaptations was 520 or 540 nm, being shorter as compared with the peak wavelength (560 nm) under white light adaptation (Fukuda, 1989). Under the yellow or red light adaptation the sensitivity of the c-wave was suppressed at a range of longer wavelength, suggesting a possible isolation of the blue and green cone-driven c-wave responses. The peak (520 or 540 nm) and the shoulder (580 nm) in the spectral sensitivity curves were presumed to be derived from the three cone systems.

Detection and characterization of Theileria sergenti proteinases.

The lysate of Theileria sergenti piroplasms was tested for proteinases using sodium dodecyl sulfate-polyacrylamide gel electrophoresis in which substrate was included in gel matrix. Six proteinases of molecular weight 330, 125, 98, 94, 67 and 58 kilodalton (kDa) were detected. From the results of the Triton X-114 phase partition, 330, 125 and 58 kDa proteinases were partitioned into aqueous phase, which indicated that they were not associated with parasite membranes. All these three enzymes were classified into metalloproteinase family because of their sensitivities to metal-ion chelating compounds, ethylenediaminetetraacetic acid (EDTA) and 1,10-phenanthroline. On the other hand, 98 and 94 kDa proteinases were membrane-associated metalloproteinases which were preferentially inhibited by 1,10-phenanthroline. Another metalloproteinase of 67 kDa which was inhibited by EDTA and 1,10-phenanthroline was not associated with parasite membranes. Proteinases of 98 and 94 kDa degraded heat-denatured hemoglobin.

Gangliosides as a possible receptor on the bovine erythrocytes for Theileria sergenti.

To elucidate whether or not gangliosides on the bovine erythrocytes serve as a receptor for Theileria sergenti merozoites, the reactivities of the T. sergenti piroplasms with gangliosides were studied by the liposome agglutination test. The parasites reacted weakly with I-active ganglioside containing N-acetylneuraminic acid (NeuAc) and strongly with I-active ganglioside containing N-glycolylneuraminic acid (NeuGc). However, none of the other gangliosides expressed on the bovine erythrocytes, such as GM3 (NeuAc), GM3 (NeuGc), sialosylparagloboside (SPG) (NeuAc), SPG (NeuGc), i-active ganglioside (NeuAc), and i-active ganglioside (NeuGc), were recognized. After infection with T. sergenti, furthermore, the content of I-active ganglioside (NeuAc) was less (p < 0.05), and I-active ganglioside (NeuGc) content was much less in the erythrocytes (p < 0.01), though the contents of other NeuAc- and NeuGc-containing gangliosides did not so vary with T. sergenti infection. These results suggest that the parasites recognize the I-active ganglioside as their receptor and bind preferentially to NeuGc-carrying I-active ganglioside rather than to NeuAc-type in the target cell membranes, and that the reduction of the contents of I-active gangliosides (NeuAc and NeuGc) on the erythrocytes was related to T. sergenti infection.

Alteration of ganglioside composition in the erythrocytes associated with Theileria sergenti infection.

The changes in ganglioside composition of bovine erythrocytes associated with Theileria sergenti infection were investigated using the erythrocytes before and after the infection. The erythrocytes before infection with T. sergenti had GM3, sialosylparagloboside (SPG), i-active, and I-active ganglioside as predominant gangliosides. After infection with T. sergenti merozoites, the contents of SPG and i-active ganglioside were slightly less, and I-active ganglioside content was much less in the erythrocytes, though GM3 content did not so vary. The decreased I-active ganglioside content showed a recovery as the parasitemia waned to low level in the infected cattle. The total amount of lipid-bound sialic acid also decreased in the erythrocytes after the infection. Similar changes were also caused by the incubation of liposomes containing ganglioside fraction obtained from bovine erythrocytes with T. sergenti piroplasms. These results suggest that the reduction of the contents of SPG, i-active, and I-active ganglioside on the erythrocytes was related to the T. sergenti infection.

Isolation of bovine coronavirus from feces and nasal swabs of calves with diarrhea.

Fecal and nasal samples were collected from 180 calves with diarrhea and 36 clinically normal co-habitants, and tested for virus using HRT-18 cell cultures derived from human rectal adenocarcinoma. A cytopathic virus was isolated from 5 fecal and 56 nasal samples obtained from diarrheic calves. All calves in which the virus was isolated from diarrheic feces were positive for virus isolation from nasal swabs. The virus was also isolated from the nasal swabs of 10 clinically normal calves that were co-habitants with diarrheic calves. Because they were morphologically similar to coronavirus, agglutinated mouse erythrocytes and serologically identical with the Nebraska calf diarrhea coronavirus, new isolates were identified as bovine coronavirus. The demonstration of viral antigens in nasal epithelial cells by a direct immunofluorescence was in close agreement with the virus isolation in HRT-18 cell cultures. This is the first report on the isolation of bovine coronavirus from newborn calves with diarrhea in Japan. The evidence that the virus was frequently isolated from nasal swabs is of great interest for understanding the pathogenesis of bovine coronavirus infection.

[Changing glucose concentration affects rod-mediated response in the perfused cat eye].

The effects of changing glucose concentration on the ERG b-wave and optic nerve response (ONR) were studied in dark adapted, arterially perfused cat eyes. Changes in glucose concentration in the perfusate induced remarkable effects on both electrical responses. The ERG b-wave and ONR amplitudes were enhanced with increasing the glucose concentration above the standard level (5.5 mM), and were transiently decreased below the control after termination of the increase in glucose. Furthermore, a control perfusate with higher glucose concentrations (8-10 mM) was used, transient addition of glucose failed to elicit consistent increase in amplitudes of the b-wave and ONR. We conclude that the optimal supply of glucose to the mammalian retina is crucial for recording b-wave and ONR in-vitro under dark adaptation. A higher glucose level (8-10 mM) than 5.5 mM in the standard tissue culture medium is suggested for maintaining the retinal function in-vitro.

[Ocular complications after renal transplantation].

Seventy-two post-renal transplant patients were studied for ocular complications. Of 72 patients, 56 (77.8%) showed some ocular abnormality. Steroid cataract was the most common complication, occurring in 45 patients (62.5%). Eleven patients (18 eyes) had undergone operations for cataract. The average of their ages was 39.7 years and the period from renal transplantation to cataract operation was 3.3 years. Postoperative visual acuity was over 20/20 in most cases. Increased intraocular pressure was encountered in 9 patients (12.5%), cytomegalovirus ocular infection in 2 (2.8%), hypertensive retinopathy in 2 (2.8%), branch retinal vein occlusion in 1 (1.4%), and subconjunctival hemorrhage in 15 (20.8%). A new immunosuppressant, cyclosporine, increased renal graft survival more than azathioprine. However, ocular complications such as steroid cataract occurred frequently in spite of the use of cyclosporine, as in the azathioprine era. In conclusion, it is necessary for renal transplant patients to receive a periodical ophthalmological check-up.