Variability of parvovirus B19 genotype 2 in plasma products with different compositions in the inactivation sensitivity by liquid-heating.

BACKGROUND AND OBJECTIVES: Our previous report showed that parvovirus B19 genotype 1 in different solutions derived from plasma preparations showed different heat-sensitivity patterns during liquid-heating. In this study, we similarly examined B19 genotype 2. MATERIALS AND METHODS: Two plasma samples one containing B19 genotype 1 and the other genotype 2 DNA were used. Four process samples collected immediately before the heat treatment step in the manufacture of albumin, immunoglobulin, haptoglobin and antithrombin preparations were spiked with B19 and subsequently treated at 60°C for 10 h. A low pH immunoglobulin solution was also spiked with B19 and treated at room temperature for 14 days. Infectivity was then measured. RESULTS: B19 genotype 2, similar to genotype 1, showed three patterns of inactivation: (i) a rapid inactivation in the albumin and immunoglobulin preparations, (ii) a slow inactivation in the haptoglobin preparation and (iii) only limited inactivation in the antithrombin preparation. Its sensitivity in the low pH immunoglobulin solutions also resembled that of genotype 1. CONCLUSION: Both genotypes 1 and 2 of B19 varied in sensitivity to liquid-heating and low pH among different plasma preparations.

Role of video capsule endoscopy in patients with constitutional mismatch repair deficiency (CMMRD) syndrome: report from the International CMMRD Consortium.

BACKGROUND AND STUDY AIMS: Constitutional mismatch repair deficiency (CMMRD) syndrome, also known as biallelic mismatch repair deficiency (BMMRD) syndrome is a rare autosomal-recessive genetic disorder that has a high mortality due to malignancy in childhood and early adulthood. The small bowel phenotype in CMMRD is not well described and surveillance protocols for small bowel cancer have not been well established. This study was conducted to evaluate the usefulness and clinical impact of video capsule endoscopy (VCE) for small bowel surveillance. PATIENTS AND METHODS: We retrospectively reviewed the prospectively maintained International CMMRD Consortium database. Treating physicians were contacted and VCE report data were extracted using a standardized template. RESULTS: Among 58 patients included in the database, 38 VCE reports were collected from 17 patients. Polypoid lesions were first detected on VCE at a median age of 14 years (range: 4 - 17). Of these, 39 % in 7 patients (15/38) showed large polypoid lesions (> 10 mm) or multiple polyps that prompted further investigations. Consequently, three patients were diagnosed with small bowel neoplasia including one patient with adenocarcinoma. Small bowel neoplasia and/or cancer were confirmed histologically in 35 % of the patients (6/17) who had capsule surveillance and the lesions in half of these patients were initially visualized on VCE. Multiple polyps were identified on eight VCEs that were completed on three patients. Ten VCEs (28 %) were incomplete due to slow bowel transit; none required capsule removal. CONCLUSIONS: Small bowel surveillance in patients with CMMRD should be initiated early in life. VCE has the potential to detect polyps; however, small bowel neoplasias are often proximal and can be missed, emphasizing the importance of concurrent surveillance with other modalities. MEETING PRESENTATIONS: Digestive Disease Week 2017 and World Congress of Pediatric Gastroenterology, Hepatology and Nutrition 2016.

An Asian variant of intravascular lymphoma: unique clinical and pathological manifestation in the gallbladder.

We here present a rare case of intravascular lymphoma (IVL) in a Japanese man. 4 months after cholecystectomy due to cholecystitis, a diagnosis of intravascular lymphoma (IVL) was strongly suspected. Lymphoma cells were diffusely observed in the bone marrow parenchyma, but were absent in the vascular spaces. The patient died of respiratory failure and at autopsy a small number of lymphoma cells in the extravascular parenchyma of the adrenal gland and bone marrow were seen. Serial sections of the surgically resected gallbladder retrospectively confirmed the diagnosis of IVL. In addition, congestion and edema were observed in the connective tissue layer. It is possible that edema or ischemia in the gallbladder wall or at other anatomic sites due to the circulation disturbance induced by the intravascular obstruction of lymphoma cells may have caused the initial symptoms. In conclusion, clinicians and pathologists should keep in mind that the gallbladder may be initially involved in IVL.

Bridging necrosis and reticulin bridging fibrosis induced by intrahepatic involvement of acute biphenotypic leukemia.

A 47-year-old Japanese woman was diagnosed as having acute biphenotypic leukemia with association of t(9;22)(q34;q11). Cholestatic liver dysfunction arose, and she died of cachexia and intracranial hemorrhage. Autopsy showed unusual hepatic fibrosis. In the liver, bridging infiltration, bridging necrosis and bridging fibrosis by leukemic cells were seen. It seemed that the degree of fibrosis was associated with the number of aggregates of infiltrating leukemic cells. The fibrotic foci were predominantly composed of reticulin and collagen fibers, and distortion of the lobules was observed. Immunohistochemically, dense bundles of alpha-smooth muscle actin (ASMA)-positive stromal cells, namely activated hepatic stellate cells (HSCs), were observed in the immature fibrotic foci as well as along the sinusoids densely infiltrated by leukemic cells. No cells positive for TGF-beta1 or PDGF-BB were identified. In conclusion, extensive intrahepatic involvement by neoplastic cells in adult acute biphenotypic leukemia may cause the unusual "disorganized" hepatic fibrosis.

[Infarct exclusion for postinfarction left ventricular free wall rupture with severe congestive heart failure].

A 70-year-old man was transferred to our hospital with severe congestive heart failure and ventricular arrhythmia due to acute myocardial infarction. He had experienced chest pain 3 weeks previously and was admitted to another hospital for dyspnea, where he required assist ventilation, 1 week prior to the transfer. An echocardiogram revealed a broad anteroseptal infarction and very poor left ventricular function with an ejection fraction (EF) of 22%. He remained in a severe congestive heart failure condition despite a full administration of catecholamines. Coronary angiogram findings revealed an occlusion of the proximal left anterior descending coronary artery and 1 week later severe hypotension was suddenly presented. An echocardiogram showed pericardial effusion with signs of cardiac tamponade. A pericardiocentesis was performed and hemodynamic improvement was obtained for a short time, after which the patient underwent urgent open heart surgery. During the operation, exclusion of the anteroseptal akinetic area using an oval patch was performed under a cardiopulmonary bypass and ventricular fibrillation. Severe cardiac failure remained postoperatively and the patient could not be weaned from cardiopulmonary bypass, therefore, we implanted a percutaneous cardiopulmonary support (PCPS) and started intraaortic balloon pumping (IABP). The patient was weaned from PCPS at 26 days after surgery and from IABP at 30 days. Following hospital release, he has continued to do well without heart failure for 39 months after the operation.

[Mitral valve repair of valve insuffficiency with broad and complex lesions due to infective endocarditis; report of a case].

Surgical intervention is necessary for the treatment of infective endocarditis, although antibiotic therapy has been shown to be effective for treatment of this disorder. Mitral valve infective endocarditis frequently presents with broad and complex lesions, and thus a variety of valve repair is needed. A 40-year-old woman with mitral valve insufficiency due to infective endocarditis underwent mitral valve repair. During the operation, torn chordae, aneurysm with perforation of the anterior leaflet, and torn chordae of the posterior leaflet were found. The chordae of the anterior leaflet were reconstructed and the aneurysm was excised, and autopericardial patch repair was performed. Then, resection and suturing of the prolapsing lesion of posterior leaflet were performed. Mitral valve repair preserves the left ventricular apparatus and function. Therefore, mitral repair results in better prognosis than valve replacement. The repair of the mitral valve should be attempted for the treatment of valve insufficiency due to infective endocarditis.

[Critical hypertrophic obstructive cardiomyopathy patient with improved hemodynamics following mitral valve replacement: report of a case].

A 75-year-old man with dyspnea was admitted to our hospital in critical condition. Catheterization showed normal coronary arteries and good left ventricular function. Transesophageal echocardiography showed left ventricular hypertrophy and severe mitral regurgitation. We decided to perform mitral valve replacement because the patient was in critical condition and it was necessary to complete the operation smoothly. During the operation, we could see the dilated mitral valve annulus and hypertrophic mitral valve, which was restricted. The patient's hemodynamics showed improvement after mitral valve replacement with a mechanical prosthesis, and he was discharged on postoperative day 21. In conclusion, mitral valve replacement is a beneficial method for the treatment of patients with critical hypertrophic obstructive cardiomyopathy.

Prospective and randomized trial of lipiodol-transcatheter arterial chemoembolization for treatment of hepatocellular carcinoma: a comparison of epirubicin and doxorubicin (second cooperative study). The Cooperative Study Group for Liver Cancer Treatment of Japan.

A randomized, controlled clinical trial was conducted to compare the use of epirubicin (EPI) and doxorubicin (DOX) in Lipiodol (Laboratoire Guerbet, Roissy-Charles-de-Gaulle Cedex, France)-transcatheter arterial chemoembolization as a treatment of hepatocellular carcinoma. One hundred ninety-two hospitals participated, and 415 patients were enrolled in the study during the period between October 1989 and December 1990. The patients were randomly allocated to group A (EPI) or group B (DOX) by a centralized telephone registration. The actual doses of EPI and DOX were 72 mg/body and 48 mg/body, respectively. The 1-, 2-, and 3-year survival rates were, respectively, 69%, 44%, and 33% for group A and 73%, 54%, and 37% for group B. There were no statistically significant differences (P = .2296, log-rank test). When each group of patients was classified retrospectively into high-risk and low-risk subgroups based on the severity index calculated by the Cox regression model from the significant prognostic factors (the pretreatment tumor size, the pretreatment serum alpha-fetoprotein level, tumor encroachment, and Child's classification), the survival curve of the low-risk DOX subgroup was significantly superior to that of the low-risk EPI subgroup (P = .0182). However, there was no significant difference between the high-risk subgroups (P = .4606). The change in the serum alpha-fetoprotein level, the extent of Lipiodol accumulation in the tumor, and the extent of tumor reduction after the treatment did not show any significant differences between the groups. The white blood cell count in group B showed a tendency to decrease slightly more than in group A at 3 weeks after Lipiodol-transcatheter arterial chemoembolization. In conclusion, there was no statistically significant difference between the survival curves of the EPI and DOX groups in Lipiodol-transcatheter arterial embolization treatment of hepatocellular carcinoma.

Cancer regression induced by modified CTL therapy is regulated by HLA class II and class I antigens in Japanese patients with advanced cancer.

Autologous cancer-specific bulk CTLs are unlikely to be induced by in vitro CTL generation (ivtCTLG) using peripheral blood mononuclear cells (PBMCs) of cancer patients when autologous cancer cells are used as in vitro stimulators. However, autologous cancer-specific bulk CTLs are frequently activated when allogeneic cancer cells are used as in vitro stimulators, regardless of the type of cancer cell. We have developed a cancer-specific immunotherapy called modified CTL therapy, which involves adoptive immunotherapy of autologous cancer-specific bulk CTLs after active immunization of autologous or allogeneic cancer cells screened as in vitro stimulators according to their ability to induce autologous cancer-specific CTLs (ACS. CTLs). Cancer did not regress in patients in whom ACS.CTLs were not induced by ivtCTLG using the patients' PBMCs in therapy. Cancer regression, albeit temporary, occurred solely in patients under the immunological condition that ACS.CTLs were induced by ivtCTLG using PBMCs through the therapy. The induction of ACS.CTLs by ivtCTLG using patient PBMCs in therapy was related to patients' HLA class II antigens. HLA DR8 was seen more frequently in ACS.CTL-inducible patients than in ACS.CTL-uninducible patients (P=0.051). On the contrary, HLA DQ3 was seen more frequently in ACS.CTL-uninducible patients (P=0.055). On the other hand, the success in therapy, albeit temporary, was related mainly to patients' HLA class I antigens. HLA B61 was seen more frequently in patients whose therapy proved effective than in patients whose therapy proved ineffective (P=0.018). HLA Cw7 was seen more frequently in therapy-ineffective patients (P=0.040).

Simple hypothermic retrograde cerebral perfusion during aortic arch replacement. A preliminary report on two successful cases.

We recently found that hypothermic retrograde cerebral perfusion can be performed by simply elevating the central venous pressure in Trendelenburg's position while the aortic arch is open. In this technique, with an occlusion balloon in the descending aorta, deep hypothermic perfusion of the lower half of the body is performed as oxygen-rich venous blood supplies the brain. Two successful cases are reported: one of dissecting aortic aneurysm, DeBakey type II, with a true aortic arch aneurysm, in a 53-year-old woman, and one of acute aortic dissection, DeBakey type I, in a 53-year-old man. With the brain under retrograde perfusion at a rectal temperature of 15 degrees C and a central venous pressure of 15 mm Hg, replacement of the ascending to the descending aorta in the former case and to the proximal aortic arch in the latter case was successful. Cerebral circulatory arrest times were 81 and 65 minutes, respectively. No neurologic deficit was found postoperatively. It is suggested that this simple technique protected the brain for a long period of cerebral circulatory arrest during the aortic arch operation by supplying it with oxygen and simplifying the operative procedure.

Roles of the respiratory Na+ pump in bioenergetics of Vibrio alginolyticus.

Bioenergetic characteristics of Na+ pump-defective mutants of a marine bacterium Vibrio alginolyticus were compared with those of the wild type and revertant. Generation of membrane potential and motility at pH 8.5 in the mutants were completely inhibited by a proton conductor, carbonylcyanide m-chlorophenylhydrazone, whereas those in the wild type or revertant were resistant to the inhibitor. Motility and amino acid transport were driven by the electrochemical potential of Na+ not only in the wild type or revertant but also in the mutants. In the absence of the proton conductor, motility and amino acid transport of the mutants did not significantly differ from those of the wild type or revertant even at pH 8.5, where the Na+ pump has maximum activity. Therefore, the electrochemical potential of Na+ in the mutants seemed to be maintained at a normal level by a respiration-dependent H+ pump and Na+/H+ antiporter. On the other hand, growth of the mutants became defective as the medium pH increased, especially on minimal medium. These results indicate that the Na+ pump is an important energy-generating mechanism when nutrients are limited at alkaline pH.

Selective portal branch occlusion by balloon catheter during liver resection.

An intraoperative ultrasonographically guided introduction of a balloon catheter into labor or smaller branches of the portal vein within the liver parenchyma made it possible to temporarily occlude them and perform regional staining during resection for tumors. The technique minimized blood loss without hilar dissection for vascular control, and the presence of the catheter facilitated intraparenchymal dissection of the portal stalk to the part of the liver to be resected.

Simple technique for pancreatogastrostomy and the histological findings of pancreatogastric anastomosis.

The leakage of pancreatic juice is the most serious complication after pancreatoduodenectomy. In an attempt to lessen the incidence of this complication, we have developed a simple technique for the anastomosis of pancreatogastrostomy. Since March 14, 1995, we have already performed surgical procedures on 8 cases of pancreatogastrostomy using this technique and as yet have never experienced fatal complications. We report the autopsy findings of pancreatogastric anastomosis histologically. The specimen taken from the anastomosis reveals good mucosal continuity. This result suggests the importance of reliable sutures between the pancreatic parenchyma and the full thickness of the gastric wall for the anastomosis of pancreatogastrostomy.

Distal aortic arch aneurysmectomy and coronary revascularization through a left thoracotomy.

A successful single operation of a distal aortic arch aneurysm and coronary artery disease through a left lateral thoracotomy using a simple hypothermic retrograde cerebral perfusion technique for cerebral protection in a 64-year-old man is reported. During ventricular fibrillation accompanying cooling to 15 degrees C, a left internal thoracic artery was anastomosed with the left anterior descending coronary artery, and the aneurysm was replaced with a patch during hypothermic retrograde cerebral perfusion.

Effects of transcatheter arterial chemoembolization with oral chemotherapy on hepatic neoplasms.

An investigation was carried out into the effects of lipiodol-transcatheter arterial chemoembolization (L-TACE) therapy on hepatocellular carcinoma (HCC) and metastatic liver cancer, as well as the effects of oral 5-fluorouracil administration after L-TACE. For L-TACE, lipiodol mixed with adriamycin (doxorubicin) was injected through a catheter inserted into the tumor feeding artery and this was followed by embolization with a gelatin sponge. Twenty national hospitals throughout Japan participated in this multicenter co-operative open trial. A total of 102 patients became the subjects of study, including 75 HCC patients, 12 metastatic liver cancer patients treated with L-TACE, and 15 HCC patients who had hepatectomy after L-TACE. In 22% of the HCC patients and in 42% of the metastatic liver cancer patients, the tumor size was reduced by more than 50% after L-TACE. 73% of the 63 HCC patients showed a more than 50% reduction of the levels of serum alpha-fetoprotein. Although the survival rates of the HCC patients who had a hepatic resection were better than those who had not, there was no statistically significant difference between the survival rates of the HCC patients and those of the metastatic liver cancer patients treated with L-TACE. The survival rates of the HCC patients after L-TACE did not change as a result of oral 5-fluorouracil administration. It was therefore concluded that L-TACE is an effective way of treating both HCC patients and metastatic liver cancer patients, and that repeated L-TACE should be considered for some patients whose serum levels of alpha-fetoprotein rose again after L-TACE. Further follow-up studies will be needed to discover the effects of oral chemotherapy after L-TACE.

Multimodal treatment of hepatocellular carcinoma.

Our multimodal treatment of hepatocellular carcinoma (HCC) has brought about a significant improvement of the survival rate. It consists of a combination of hepatectomy and transcatheter arterial embolization using lipiodol (L-TAE). In order to facilitate L-TAE, we have developed a special catheter with notches. A group of patients with HCC (124 cases), excluding cases with absolutely non-curative resections and operative deaths, were treated between December 1980 and November 1986. Each case was treated for more than 1 year after hepatectomy. The patients were divided into two groups: A, patients with a single tumor not larger than 5 cm, and B, cases with larger tumors or more than one lesion. Some patients in each group were treated with L-TAE after hepatectomy. In group A, there was no significant difference in survival between treated and non-treated cases. In group B, L-TAE gave a significantly better survival than no postoperative treatment.

A randomized trial of intrahepatic arterial infusion of 4'-epidoxorubicin with Lipiodol versus 4'-epidoxorubicin alone in the treatment of hepatocellular carcinoma.

We conducted a prospective randomized trial to evaluate the efficacy of Lipiodol in intrahepatic arterial infusion chemotherapy for patients with hepatocellular carcinoma (HCC). A total of 38 patients with unresectable HCCs and underlying cirrhosis were entered in this trial, and 36 of them were evaluable. Every 4 weeks, 17 patients received 70 mg of 4'-epidoxorubicin (epirubicin) alone (group A), whereas 19 patients received a Lipiodol emulsion containing the same dose of epirubicin (group B) through the hepatic artery. A tumor response (CR+PR) was observed in 12% of group A patients and in 42% of group B patients. The group B patients showed a significantly higher response rate than the group A patients. There was a tendency for an increased duration of survival (P = 0.09) in the group B patients. These results suggested that the infusion of the Lipiodol emulsion with epirubicin was more effective than epirubicin alone for the treatment of these patients with HCC.

Radiological studies of the cheiro-oral syndrome.

Four cases of the cheiro-oral syndrome are reported, with a review of the clinical symptoms and signs and the neuroradiological methods used to demonstrate the responsible lesion. In each case, angiography, computed tomography (CT) and magnetic resonance imaging (MRI) were performed. The lesion was found in the thalamus in three cases and in the pons in one. Infarction had occurred in three cases and haemorrhage in one. Angiography revealed normal findings in all cases. CT at the onset of the symptoms demonstrated a small haemorrhage in the thalamus in one case but was not helpful in the others, and MRI was required to identify infarction. The anatomical sites responsible for the cheiro-oral syndrome have been reported to be in the central gyrus, in the thalamus, and in the brain stem. The clinical symptoms and signs reported in the literature and in our four cases are reviewed to evaluate aetiological factors and clinical features according to the three different sites of lesions causing this syndrome.

Cisternal drainage after early operation of ruptured intracranial aneurysm.

The authors reviewed 22 cases of intracranial aneurysm of the anterior part of the circle of Willis. All patients presented with the signs and symptoms of subarachnoid hemorrhage (SAH) and were in good neurological condition on admission. In all cases, early operation was performed to obliterate aneurysm. Subarachnoid blood clots were extensively removed and cisternal drainage was done. With topical application of povidone-iodine and intravenous administration of antibiotics, cisternal drainage continued for 14 days or more after the onset of SAH in 21 cases. Five patients developed symptomatic vasospasm, which was treated with hypervolemia and hypertension, and three received shunts later for chronic hydrocephalus. The overall result demonstrated that 21 patients were independent and had returned to their previous social lives. Therefore, it was strongly recommended that patients is good neurological condition after SAH secondary to ruptured intracranial aneurysm be treated with early operation, removal of subarachnoid clots, and long term application of cisternal drainage.