Randomized clinical trial of duct-to-mucosa versus invagination pancreaticojejunostomy after pancreatoduodenectomy.

BACKGROUND: The postoperative pancreatic fistula (POPF) rate for duct-to-mucosa and invagination anastomosis after pancreatoduodenectomy is still debated. The aim of this RCT was to investigate the POPF rate for duct-to-mucosa versus invagination pancreaticojejunostomy. METHODS: Patients were stratified by pancreatic texture and diameter of the main pancreatic duct and randomized to the duct-to-mucosa or invagination group. The primary endpoint was the rate of clinically relevant POPF (defined as grade B or C). Secondary endpoints were suture material cost for pancreaticojejunostomy, drain insertion duration and duration of postoperative hospital stay. RESULTS: Some 120 patients undergoing pancreatoduodenectomy were included following consent. Clinically relevant POPF developed in six of 59 patients (10 per cent) in the invagination group and in 14 of 61 patients (23 per cent) in the duct-to-mucosa group (P = 0·077). Duration of drain insertion (6 versus 7 days respectively; P = 0·027) and postoperative hospital stay (19 versus 24 days; P = 0·015) were shorter in the invagination group. Subgroup analysis for 61 patients with a soft pancreas revealed a lower rate of clinically relevant POPF in the invagination group (10 per cent versus 42 per cent in the duct-to-mucosa group; P = 0·010). Among 20 patients with a clinically relevant POPF, the six patients in the invagination group had a shorter duration of drain insertion (38·5 days versus 49 days for 14 patients in the duct-to-mucosa group; P = 0·028) and postoperative hospital stay (42 versus 54·5 days respectively; P = 0·028). CONCLUSION: This study did not demonstrate a superiority of invagination over duct-to-mucosa pancreaticojejunostomy in the risk of POPF. However, in high-risk patients with a soft pancreas, invagination may reduce the risk of clinically relevant POPF compared with duct-to-mucosa. Registration number: UMIN000005890 (http://www.umin.ac.jp).

Down-regulation of the two-component system and cell-wall biosynthesis-related genes was associated with the reversion to daptomycin susceptibility in daptomycin non-susceptible methicillin-resistant Staphylococcus aureus.

Daptomycin (DAP) is widely used in the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infection. The emergence of DAP non-susceptible MRSA strains during therapy is a major concern in clinical settings. Recent studies revealed that MRSA spontaneously reverts to a subsequent methicillin-susceptible S. aureus (MSSA) strain. However, it is not clear whether DAP non-susceptible MRSA has the ability to revert to a susceptible strain. We obtained an MRSA strain pair, DAP non-susceptible strain and subsequent DAP susceptible strain, from a patient. To understand the underlying mechanism by which DAP non-susceptible MRSA reverts to a susceptible strain, we performed genetic and phenotypic analysis in the strain pair. Although whole-genome analysis revealed four missense mutations, including L826F in mprF, in both strains, the net cell-surface charge was similar between the DAP non-susceptible and susceptible strains. However, the thickness of the cell wall was higher in the DAP non-susceptible strain, which was decreased to the same level as the control after reversion to the DAP susceptible strain. Moreover, the non-susceptible strain showed higher mRNA expression of the two-component system (TCS), such as VraSR, yycG and GraS, with the up-regulated transcription levels of cell-wall biosynthesis-related genes. The expression levels of those genes were decreased after reversion to the susceptible strain. These results indicated that DAP non-susceptibility due to up-regulation of the TCS and cell-wall biosynthesis-related genes may be reversible by the discontinuation of DAP, leading to reversion to the DAP susceptible phenotype.

Iatrogenic arteriovenous fistula of the internal mammary artery. Transcatheter intravascular coil occlusion.

We encountered a case of right internal mammary artery to innominate vein fistula following subclavian vein catheterization and the projection of the coil spring was projected after transcatheter intravascular coil occlusion. We were worried about both distal thromboembolism from small thrombi forming on a portion of the coil spring and stenosis of the subclavian artery. However, there was no evidence of thromboembolism of the distal artery, and good patency of the right subclavian artery was shown by an angiogram performed six months later. The patient has been receiving heparin therapy during hemodialysis, which should help prevent thromboembolism of the distal artery.

Sensory ataxia. A residual disability of Guillain-Barré syndrome.

Four patients had idiopathic acute polyradiculoneuritis (Guillain-Barré syndrome) with sensory ataxia as the most prominent symptom. Sensory ataxia remained as a residue even three to five years after onset, despite good recovery of muscle weakness in five to 14 months. Sural nerve biopsy specimens disclosed a severe loss of large myelinated fibers and a high incidence of active axonal degeneration.

Severe orthostatic hypotension in a female carrier of Fabry's disease.

A 21-year-old woman in a family with a history of Fabry's disease showed orthostatic hypotension and whorl-like corneal opacity typical for Fabry's disease. Biochemical studies revealed that she was a heterozygote of the Fabry gene. A variety of autonomic function tests demonstrated both sympathetic and parasympathetic dysfunction. To our knowledge, the present case is the first report of a heterozygous female carrier of Fabry's disease presenting dysfunction of the autonomic nervous system.

HLA and sarcoidosis in the Japanese.

One hundred fourteen patients with sarcoidosis, who were diagnosed as having sarcoidosis histologically, have been typed for HLA class 1 (A, B, and C) and class 2 (DR and DQ) antigens. Controls consisted of 478 healthy Japanese subjects. The frequencies of HLA-A1, HLA-Bw46, HLA-Cx46, HLA-DRw8, HLA-DRw9, and HLA-DRw52 were significantly increased in sarcoidosis compared to control subjects, but only four patients were positive for HLA-A1. Increased frequencies of HLA-Bw46 and HLA-Cx46 were thought to be attributable to linkage disequilibrium with HLA-DRw8. Patients with HLA-DRw52 were the most frequent (84 cases of 113). No significant differences were observed between HLA-DRw52-positive and HLA-DRw52-negative patients in their clinical features, but all of the patients with muscular involvement (six cases) were positive for HLA-DRw52. Among patients positive for HLA-DRw52, those with HLA-DR5 showed a significantly better clinical course and earlier onset of the disease than those with HLA-DRw8. These results suggest that HLA antigens may play an important role in the pathogenesis of sarcoidosis.

Late-onset acid maltase deficiency associated with intracranial aneurysm.

The autopsy findings in a patient with late-onset acid maltase deficiency who died following rupture of a basilar artery aneurysm are reported. The patient developed muscular weakness and wasting at the age of 20 years and died 9 years later after suddenly falling into a coma. At autopsy a giant fusiform aneurysm was found in the basilar artery which had ruptured at the base of the pons, leading to a large haematoma in the pons. The cerebral arteries and arterioles showed extensive vacuolar degeneration of smooth muscle cells in the media. It is suggested that the aneurysm was induced by fragility of the arterial wall due to this smooth muscle change.

[Concurrence of acute autonomic and sensory neuropathy and myasthenia gravis--a case report and pathogenetic considerations].

A 22-year-old woman admitted to the hospital on Mar. 19, 1985 because of syncopal attacks and numbness on the limbs. Examination revealed peripheral sympathetic as well as parasympathetic dysfunctions and loss of myelinated as well as unmyelinated fibers in a biopsied sural nerve. A diagnosis of acute autonomic and sensory neuropathy (AASN) was made. She was treated with prednisolone but did not respond to the therapy. Only L-DOPS was effective on orthostatic hypotension. Recovery of the neurological conditions was insufficient till May 1987, when she complained of easy fatigability when speaking and chewing. Pharmacological and electrodiagnostic tests showed typical myasthenic phenomenon. At this time, serum anti-ACh receptor antibody was 741nmol/l and a diagnosis of myasthenia gravis was confirmed. Anti-ACh receptor antibody was proven to be elevated in the serum collected on April 1985 when the initial symptom of AASN had appeared. A thymectomy resulted in prompt and complete remission of semiologies of both myasthenia gravis and AASN. These suggest that immunological abnormality might play an important role in the pathogenesis of AASN in this case.

[Bilateral abductor vocal cord paralysis (Gerhardt syndrome) in the Shy-Drager syndrome].

Ten consecutive patients with a progressive pan-autonomic failure of the Shy-Drager syndrome were investigated. Movement disorders of the vocal cords were examined with a fiber-optic laryngoscope as well as a video-recorder. Moderate to severe vocal cord paralysis was present in five of ten patients. The vocal cords were almost immobile during inspiration, while there was no limitation of the adduction during phonation. In two cases, grade of vocal cord paralysis was asymmetric. One patient developed peculiar twisting-like dystonic movements of the vocal cord. Polygraphic studies revealed that SaO2 was lowered in spite of tachypnea during sleep. In two cases, the expiratory flow volume curve in effort-dependent portion near TLC showed a plateau and the inspiratory part of the curve also showed a plateau indicating constant flow. These functional disorders suggest an upper airway obstruction probably due to the vocal cord dysfunction. There was no vocal cord paralysis in two patients who had neither snore nor stridor. Development of a severe vocal cord dysfunction usually manifested itself clinically as stridor, snore or respiratory failure requiring tracheostomy. There was little information on the pathology of the vagal nerves and nuclei supplying motor control to the laryngeal muscles. The mechanism of the selective involvement of abductor muscle (posterior muscle) of the vocal cord (Gerhardt syndrome) remains unsolved. Vocal cord paralysis should be looked for since it can result in respiratory failure leading to death.

Unusual findings of M-mode echocardiogram in a case with left ventricular thrombus.

The unusual echo findings of the left ventricular thrombus by M-mode echocardiogram is reported. The patient was a 41-year-old man with hypokinesis of the inferior and inferolateral wall due to acute myocardial infarction. The findings of M-mode echocardiogram revealed dense thick linear echoes just below the anterior wall of the apex, which had a higher density than the myocardium and looked "band like". These abnormal echoes obtained by M-mode echocardiogram were also detected through examinations by 2-dimensional echocardiogram, computed tomogram and left ventriculogram, and were assumed to arise from the index finger-sized thrombus in the left ventricle at the time of surgical procedure. Although this abnormal echo, revealed to have a "band like" feature by M-mode echocardiogram, is usually seen in the left ventricular myxoma, we assume that this "band like" echo by M-mode echocardiogram arose from the left ventricular thrombus under conditions such as myocardial infarction, ventricular aneurysm, dilated cardiomyopathy and long-term congestive heart failure.

[Effects of cefotaxime single administration and of cefotaxime + fosfomycin administration against respiratory tract infections].

Subjects in a cefotaxime (CTX) single administration group and in a CTX + fosfomycin (FOM) administration group were randomly selected for a comparative study on the utility of each product against respiratory tract infections. Overall improvement rates were 81.3% in 32 cases of the CTX single administration group, and 75.6% in 41 cases of the CTX + FOM concomitant administration group. No statistical difference was observed. As for adverse reactions and abnormal laboratory test results, pyrexia, thrombocytopenia, increases in GOT and GPT, and increase in GPT were observed in 4 cases of the CTX single administration group, while angialgia, increases in GOT and GPT (3 cases), and increases in BUN, (totalling 5), were observed in the CTX + FOM group. However, all the symptoms were transient, and none was serious in nature.

[Evaluation of imipenem/cilastatin sodium in the treatment of respiratory tract infections].

Imipenem/cilastatin sodium (IPM/CS) was administered to 55 patients with respiratory tract infections (RTI). A clinical evaluation of IPM/CS was carried out in 51 patients, 28 with pneumonia, 4 with pulmonary abscess, 1 with pyothorax, 6 with bronchitis, 9 with bronchiectasis, 1 with diffuse panbronchiolitis and 2 with RTI with chronic obstructive pulmonary disease, and the clinical efficacy rate was 78.4%. Causative organisms were isolated in 23 strains out of 20 patients, such as Staphylococcus aureus 4 strains, Staphylococcus epidermidis 1 strain, Streptococcus pneumoniae 1 strain, Branhamella catarrhalis 1 strain, Haemophilus influenzae 2 strains, Klebsiella pneumoniae 4 strains, Pseudomonas aeruginosa 6 strains, Pseudomonas sp. 1 strain, Acinetobacter calcoaceticus 1 strain, Acinetobacter sp. 1 strain and glucose non-fermentative Gram-negative rod 1 strain. An eradication rate of 70.6% was obtained. An overall eradication rate of main causative organisms in RTI including S. aureus, S. pneumoniae, H. influenzae and K. pneumoniae was 75.0%. Clinical adverse effects were observed in 5 patients, and these were eruption in 2, itching in 1, vomiting in 1 and drug fever in 1. Abnormalities in laboratory test results were observed in 8 patients. These disappeared or returned to normal values after completion or discontinuation of IPM/CS administration. IPM/CS appears to be a useful antibiotic for the treatment of RTI, especially severe infections.

[Therapeutic efficacy of imipenem/cilastatin sodium on respiratory tract infections in lung cancer patients].

Imipenem/cilastatin sodium (IPM/CS) was used to treat respiratory tract infections (RTI) in 54 patients with lung cancer. Out of the 54 patients studied, 53 were evaluable for the utility of IPM/CS; 42 had pneumonia, 9 had obstructive pneumonia, 1 had a lung abscess and 1 had acute bronchitis. The efficacy rate was 71.7%. Seventeen causative organisms were isolated from 14 patients. They included Staphylococcus aureus 5 strains, Staphylococcus epidermidis 4 strains, Staphylococcus sp. 2 strains, Enterococcus faecalis 1 strain, Pseudomonas aeruginosa 2 strains, Pseudomonas fluorescens 2 strains, Acinetobacter sp. 1 strain, and the eradication rate was 81.8%. Clinical adverse effects (nausea and vomiting) were observed in 1 patient. Abnormalities in laboratory test results were observed in 3 patients. They disappeared or returned to normal values after completion of therapy or discontinuation of IPM/CS administration. IPM/CS appears to be a useful antibiotic for RTI in patients with lung cancer.

[Evaluation of ceftizoxime in the treatment of respiratory tract infections].

Ceftizoxime (CZX) was used for 33 patients with respiratory tract infections; 22 patients with pneumonia, 3 patients with pulmonary abscess, 4 patients with diffuse panbronchiolitis and 4 patients with acute exacerbation of bronchiectasia. Clinical effects of CZX were evaluated in 33 patients; excellent in 16 and good in 14 patients. The efficacy rate was 91%. Bacteriological effects of CZX were prominent in 7 patients infected with S. pneumoniae, H. influenzae, K. pneumoniae and Citrobacter, but not in a patient infected with P. aeruginosa. The elimination rate was 92% (12/13). As the side effects, exanthema in 1 patient and gastrointestinal symptoms (nausea and vomiting) in 1 patient were observed. However, they improved without any treatment by cessation of CZX use. Abnormal laboratory findings were observed in 2 patients with elevated GOT and/or GPT. They normalized after cessation of drug. The usefulness of CZX was 82% (27/33). Therefore, CZX is a very useful drug and its effects are promising in clinical management of respiratory tract infections.

[A case of miliary tuberculosis with skull tuberculosis].

A 47-year old woman was admitted to our hospital with complaints of headache and right occipital swelling. Brain CT scan showed right occipital bone defect with a sequestrum and soft tissue swelling. T1 weighted MRI enhanced by GD-DTPA revealed several nodules. A right occipital craniotomy was performed. Subcutaneous pus and a well-circumscribed yellowish, firm mass which existed under the bone defect was extirpated. Pathologically, this mass was considered to be a tuberculoma and intracranial nodules were suspected to be cerebral tuberculosis. Anti-tuberculous therapy was started. Since her admission fecal occult blood continued and endoscopic examination with biopsy revealed sigmoid colon cancer. Sigmoidectomy was performed and she has been well during 1 year post-operative follow up. Although tuberculous disease are decreasing in number in our country, we must take into account of the existence of skull tuberculosis.

[A case of pulmonary tuberculosis presenting with infected bulla].

A case of pulmonary tuberculosis manifested as infected bulla complicating with tuberculous pneumonia is reported. A 63-year-old male visited our hospital because of chest X-ray abnormality detected by his home doctor. He complained of pyrexia and productive cough. Chest X-ray showed large bulla with air-fluid level, associated with surrounding infiltration at right upper lobe. On the diagnosis of infected bulla empirical antibiotic therapy was started on out-patient basis and continued after admission, but chest X-ray findings worsened, although subjective symptoms were once relieved. Surgical intervention was recommended, but after short interval pulmonary infiltrates rapidly worsened and expanded to other lobes. Sputum was reexamined and Mycobacterium, later proved as Mycobacterium tuberculosis with DNA probe method, was detected in the sputum specimen. Anti-mycobacterial drugs were administered and subjective symptoms, laboratory, and chest X-ray findings improved. Infected bulla caused by Mycobacterium tuberculosis is rare, but when it is resistant to common empirical therapy, Mycobacterium tuberculosis should be considered as one of its causative agents.

[A case of generalized disseminated atypical mycobacteriosis caused by M. avium complex with a giant gravitation abscess].

A case of generalized disseminated atypical mycobacteriosis caused by M. avium complex (MAC) was reported. The case was a female of 52 years of age. She was admitted to our hospital due to high fever and polyarthralgia. Her chest X-ray and CT scan revealed infiltrative shadows in the right S2b and S4 segments, and multiple accumulation shadows were seen on osteoscintigraphy. Pus aspirated from a lesion of the right fifth rib were acid-fast bacilli positive by smear (Gaffky v). The administration of four drugs, INH, RFP, EB and SM, was introduced, then corticosteroid was added, and the case became afebrile. Later, acid-fast bacilli were also isolated from bronchial washing and aspirated specimen from bone marrow, and all of them were identified as MAC. Based on these findings, the case was diagnosed as generalized disseminated mycobacteriosis. After several months remission, tenderness over the fifth lumbar vertebra deteriorated, and MRI scan on lumbar vertebrae showed high-intensity area both on T1-weighted and T2-weighted images. MAC was isolated from the pus of the fifth lumbar vertebra. Lumbar lesions deteriorated gradually, and a giant gravitation abscess which involved right ilium was revealed by CT scan of the pelvis. In spite of vigorous treatment including chemotherapy, aspiration of pus and drainage, general condition of the case deteriorated, and the case finally died of renal insufficiency.

[Evaluation of type IV collagen in patients with various thyroid disease].

Serum level of type IV collagen was measured in 104 patients with various thyroid disease, and the relationship between its level and thyroid hormone level was examined. The type IV collagen was measured by the method of one step sandwich enzyme immunoassay (EIA) using two distinct monoclonal antibodies recognized triple-helical (TH) domain and 7-S domain, respectively. The serum level of type IV collagen was significantly high in the hyperthyroid patients compared with that in normal controls, and a significant positive correlation was found between its value and thyroid hormone levels (T3, T4, FT3, FT4). The elevated level of type IV collagen in hyperthyroid patients was decreased to normal level, when they became to euthyroid after antithyroid drug therapy for hyperthyroidism. The serum level of type IV collagen was in normal range in hypothyroid patients, but the value was increased to high normal range after T4-replacement therapy for hypothyroidism. This evidence indicates that the serum level of type IV collagen is closely related to thyroid hormone level in patient with various thyroid disease. Type IV collagen concentration might be one of the useful variables for evaluating the thyroid function, although its mechanism is not elucidated.

[Estimation of anti-thyroid peroxidase autoantibody (TPOAb) and anti-thyroglobulin autoantibody (TgAb) in patients with various thyroid disease--comparison between histopathological findings and serological results in patients with Hashimoto's thyroiditis].

We compared and evaluated titers of AMC (anti-microsome antibody), and ATG (anti-thyroglobulin antibody) by passive gelatin-agglutination and by radioimmunoassay in 170 sera from 129 patients with various thyroid diseases and 41 normal subjects. The results of conventional ATG and TgAb by RIA correlated (r = 0.731) and those of conventional AMC and TPOAb correlated well (r = 0.907), with discrepancies mostly limited to sera with low antibody titers. Five patients with Hashimoto's thyroiditis showed positive results in AMC, whilst negative in TPOAb. These sera had positive ATG autoantibody and preincubation with thyroglobulin inhibited the agglutination reaction of AMC tests, suggesting ATG producing false positive results in AMC assay. The prevalences of positive TgAb rates were higher than (p < 0.001) ATG in patients with Hashimoto's disease (96.6% vs 50.0%) and Graves' disease (76.9% vs 46.1%). However, the prevalences of positive TPOAb were not different from AMC (Hashimoto's disease 75.9% vs 81.0%: Graves' disease 80.8% vs 76.9%). In patients with Hashimoto's thyroiditis, our study demonstrates the results of TgAb by RIA reflects the pathological findings and the diagnostic sensitivity increases by using in combination with TPOAb.

[Clinical evaluation of serum 1,5AG levels in patients with liver cirrhosis].

We measured serum 1,5 anhydroglucitol (1,5AG) levels by HPLC in 32 patients with liver cirrhosis, 32 with diabetes mellitus and 61 normal subjects. Serum 1,5AG was significantly lower in patients with diabetes mellitus and liver cirrhosis compared with that in normal subjects. Serum levels of type IV collagen were higher in patients with liver cirrhosis than in those without liver cirrhosis. A negative correlation was observed between serum 1,5AG and type IV collagen in patients with liver cirrhosis (r = -0.37, p < 0.05), but not in patients with diabetes mellitus. These data suggest that serum 1,5AG levels reflect the degree of liver cirrhosis.