Randomized controlled trial on efficacy of oligomeric formula (HINE E-GEL®) versus polymeric formula (MEIN®) enteral nutrition after esophagectomy for esophageal cancer with gastric tube reconstruction.

The efficacy of early enteral nutrition after esophageal cancer surgery has been reported. However, the choice of formula and management of diarrhea are important to achieve the goal of enhanced recovery after surgery. The aim of this study is to assess the frequency of diarrhea/completion rate of enteral nutrition regimen as primary endpoints and the postoperative nutritional status/body composition analysis/operative morbidity as secondary endpoints was compared between the two nutrition groups. Among the 122 patients who underwent esophagectomy for esophageal cancer between December 2015 and September 2017, 67 patients who met the eligibility criteria were randomly assigned to receive enteral nutrition with either HINE E-GEL® (HINE group; n = 33) or MEIN® (MEIN group; n = 34). The incidence of diarrhea was significantly lower in the HINE group (18.2 % vs. 64.7 %, P < 0.001). The score of Bristol scale of POD 6/7 was significantly lower in the HINE group (P = 0.019/P = 0.006, respectively). The completion rate of enteral nutrition regimen was significantly higher in the HINE group (97.4 % vs. 86.6 %, P = 0.002). The Controlling Nutritional Status scores and total protein levels at 6 months after surgery were significantly better in the HINE group (P = 0.030 and P = 0.023, respectively), indicating improved tendency in nutritional status in the HINE group. However, there were no significant differences in Prognostic Nutritional Index values, blood test results, rapid turnover proteins, body mass index, or body composition between the two groups. HINE E-GEL compared with MEIN may reduce the frequency of diarrhea, enabling patients to adhere to the scheduled enteral nutrition plan. Also, maintenance of nutritional status with HINE E-GEL was comparable or potentially better in some nutrition components to that with MEIN, indicating that HINE E-GEL can be an option for enteral nutrition following esophageal surgery to achieve the goal of successful completion of scheduled enteral nutrition and smooth transition to the normal diet.

Intrahepatic cholangiocarcinoma and portal hypertension developing in a patient with multicystic biliary microhamartomas.

INTRODUCTION: We report a case of intrahepatic cholangiocarcinoma and portal hypertension developing in a liver with biliary microhamartomas (von Meyenburg's complex). CASE REPORT: The patient was a 55-year-old man who had a past medical history of diffuse multiple liver abscesses. During follow-up examination, a hypovascular nodule measuring 2.1 cm in diameter was incidentally found in segment 8 of the liver. Surgical resection was performed based on a suspected diagnosis of hepatocellular carcinoma. A gastrofiberscopy examination detected characteristic findings of portal hypertensive gastropathy. During the laparotomy, multiple tiny cystic lesions were observed in a diffuse pattern across the liver surface. The liver parenchyma was slightly fibrotic and haemorrhagic. A histopathological examination revealed intrahepatic cholangiocarcinoma with vascular invasions in von Meyenburg's complex. Multiple biliary adenomas were also observed among the biliary microhamartomas adjacent to the main tumour, suggesting that the malignant transformation of the biliary adenomas might have been responsible for the development of the intrahepatic cholangiocarcinoma. The histopathologic examination also revealed sinusoidal dilation and abnormal spacing of the portal tracts and central veins as evidence of portal hypertension.

Portal vein embolization improves rate of resection of extensive colorectal liver metastases without worsening survival.

BACKGROUND: Most patients requiring an extended right hepatectomy (ERH) have an inadequate standardized future liver remnant (sFLR) and need preoperative portal vein embolization (PVE). However, the clinical and oncological impact of PVE in such patients remains unclear. METHODS: All consecutive patients presenting at the M. D. Anderson Cancer Center with colorectal liver metastases (CLM) requiring ERH at presentation from 1995 to 2012 were studied. Surgical and oncological outcomes were compared between patients with adequate and inadequate sFLRs at presentation. RESULTS: Of the 265 patients requiring ERH, 126 (47·5 per cent) had an adequate sFLR at presentation, of whom 123 underwent a curative resection. Of the 139 patients (52·5 per cent) who had an inadequate sFLR and underwent PVE, 87 (62·6 per cent) had a curative resection. Thus, the curative resection rate was increased from 46·4 per cent (123 of 265) at baseline to 79·2 per cent (210 of 265) following PVE. Among patients who underwent ERH, major complication and 90-day mortality rates were similar in the no-PVE and PVE groups (22·0 and 4·1 per cent versus 31 and 7 per cent respectively); overall and disease-free survival rates were also similar in these two groups. Of patients with an inadequate sFLR at presentation, those who underwent ERH had a significantly better median overall survival (50·2 months) than patients who had non-curative surgery (21·3 months) or did not undergo surgery (24·7 months) (P = 0·002). CONCLUSION: PVE enabled curative resection in two-thirds of patients with CLM who had an inadequate sFLR and were unable to tolerate ERH at presentation. Patients who underwent curative resection after PVE had overall and disease-free survival rates equivalent to those of patients who did not need PVE.

Thrombotic microangiopathy after living-donor liver transplantation.

Thrombotic microangiopathy (TMA) is an infrequent but severe life-threatening disorder in solid organ transplant recipients. Few studies of TMA in living donor liver transplant (LDLT) recipients, however, have been reported. We investigated the clinical characteristics and prognostic factors of TMA after LDLT. Among 393 adult LDLT recipients, 30 patients (7.6%) were identified to have TMA. The 1-, 3- and 5-year survival rates of these patients were lower (60.6%, 52.5% and 47.7%, respectively) than those of patients without TMA (93.0%, 89.0% and 87.3%, respectively). Multivariate analysis confirmed that reduced administration of fresh frozen plasma and sensitization against HLA are closely related with TMA (odds ratio [OR]: 2.6 and 16.1, respectively). However, a review of the cases revealed that individual responses to treatment varied considerably and the main etiologies were difficult to determine. A comparison of the clinical factors suggested that late onset (>30 days), poor response to treatment and delayed diagnosis and/or treatment are associated with a poor outcome. Because the prevention of TMA in LDLT patients is difficult, early diagnosis and initiation of intensive therapies may be crucial to improve the prognosis.

Efficacy of immunoadsorbent devices for maintaining hepatic function in ex vivo direct xenogenic hemoperfusion.

We have developed a new system for direct xenogenic hemoperfusion of a bioartificial liver support system adopting two types of immunoadsorbent devices. In this study, we compared the efficacy of each immunoadsorbent device in maintaining porcine hepatocyte function during 3 h perfusion treatment in a canine liver failure model. Suppression of humoral immunity by the immunoglobulin adsorber prevented immunogenic hepatocyte injury more effectively, and the system showed higher hepatic function when compared with suppression of cell-mediated immunity by the leukocyte adsorber. However, single use of immunoglobulin adsorber was less effective in reducing patients' systemic ammmonia levels and modulating the Fischer's ratio compared with the case of combined use of both immunoadsorbent devices. These results suggest that suppression of humoral immunity was of primary importance in preventing immunogenic hepatocyte injury, however the adsorption of leukocytes may have a synergic effect on maintaining hepatocyte function in direct xenogenic hemoperfusion.

[Two cases of multi-drug-resistant pulmonary tuberculosis with para-aminosalicylic acid (PAS)-induced hypothyroidism].

Two cases of multi-drug-resistant pulmonary tuberculosis with para-aminosalicylic acid (PAS)-induced hypothyroidism were reported. Case 1; a 73-year-old male, complaining of edema, was admitted to our hospital. He had been treated for his multi-drug-resistant pulmonary tuberculosis during the past 1 year with an antituberculous regimen consisting of ethambutol (EB), ethionamide (ETH) and PAS. A thyroid profile performed when he was admitted to our hospital showed several marked abnormalities: serum thyroid stimulating hormone (TSH) was elevated (69.4 microIU/ml: normal, 0.4-4.2 mIU/ml), free thyroxine level (T4) (0.01 ng/dl; normal, 0.70-1.60 ng/dl) and free triiodothyronine level (Ts) (0.60 pg/ml; normal, 2.3-4.1 pg/ml) were low. PAS was discontinued after he was admitted to our hospital, since PAS was believed to be the cause of the hypothyroidism. A thyroid profile that was repeated after the exclusion of PAS from treatment showed the following results: the TSH level was decreased (13.4 mIU/ml), the free T4 (0.93 ng/dl) were normal. During treatment with PAS, he had never received thyroid replacement therapy. Case 2; A 22-year-old female, complaining of hemosputum. She had been treated for her multi-drug-resistant pulmonary tuberculosis during the past 11 months with an antituberculous regimen consisting of EB, ETH and PAS. A thryoid profile performed when she was admitted to our hospital showed several marked abnormalities: elevated serum TSH (112.7 mIU/ml), and low T4 (2.0 micrograms/dl) and T3 (1.1 ng/ml). A thyroid profile that was repeated after the exclusion of PAS from treatment showed the following results: the TSH level was decreased (5.1 mIU/ml). Drug-induced hypothyroidism is an infrequent side effect of therapy with PAS, and only a few cases of PAS-induced hypothyroidism have been reported so far. In this report, we describe patients with hypothyroidism who were receiving therapy for multi-drug-resistant tuberculosis, tuberculosis namely, resistant to at least isoniazid (INH) and rifampicin (RFP), with a regimen that contained PAS.

[A case of tuberculous peritonitis diagnosed by a direct smear of ascitic fluid complicated with an active pulmonary tuberculosis and intestinal tuberculosis].

We sometimes encounter difficulties in differentiating tuberculous peritonitis from other inflammatory disorders or ascites due to carcinomatous peritonitis. Acid-fast bacilli are very rarely detected in ascites. In this study, we reported a case of tuberculous peritonitis accompanied with active pulmonary tuberculosis in which acid-fast bacilli were detected in ascites. The patient was a 37-year-old single man who had been admitted to our hospital on February 28, 2000, because acid-fast bacilli were detected in sputum, faces and ascites by a direct smear. He had a lower abdominal distention and pain. His serum CA 125 level was high, 121 U/ml. Abdominal ultrasonography showed marked ascites in Douglas pouch. However adenosine deaminase level was not high in his ascites. During treatment by the combination chemotherapy with INH, RFP, EB, and PZA, serum CA 125 level was decreased.

[Bronchiolo-alveolar cell carcinoma arising after active pulmonary tuberculosis' report of two cases].

We report on two patients diagnosed as having active pulmonary tuberculosis who later developed lung cancer. In both cases, the lung cancer was detected during the treatment of pulmonary tuberculosis. Both patients were initially considered to be experiencing exacerbation of pulmonary tuberculosis. Case 1 was seen in a 74-year-old man. His chest roentgenogram revealed microscopic cavitary lesions with infiltration into both lung fields. His sputum tested positive for acid-fast bacilli. Although he was treated with isoniazid (INH), rifampicin (RFP), ethambutol (EB) and pyrazinamide (PZA), his general condition deteriorated, and the infiltrative shadows in the lung fields had expanded on subsequent chest radiography. Transbronchial lung biopsy (TBLB) yielded findings compatible with a diagnosis of bronchiolo-alveolar cell carcinoma. Case 2 occurred in a 52-year-old man. His chest radiograph revealed cavitary lesions with infiltration into both lung fields. His sputum also tested positive for acidfast bacilli. Despite medication with INH, RFP, EB and PZA, the infiltrative shadow in his chest radiograph increased in size. Bronchiolo-alveolar cell carcinoma was confirmed after examination of the sputum cytology. Case 1 was diagnosed as lung cancer 10 months after being admission to the hospital, and Case 2, seven months after hospitalization. Recent discussion concerning the simultaneous occurrence of pulmonary tuberculosis and bronchogenic carcinoma suggests a high frequency of coexistence of the two diseases. However, the coexistence of active tuberculosis with bronchiolo-alveolar cell carcinoma, as in our cases, is rare.

[A case of tuberculous pericarditis developing constrictive pericarditis].

A case of constrictive pericarditis which developed after the onset of clinical manifestation of tuberculous pericarditis was reported. A 75-year-old male, complaining of anorexia, was admitted to our hospital. Adenosinedeaminase (ADA) level in pericardial effusion was found to be increased, and the culture of pericardial effusion was positive for tubercle bacilli. Diagnosed as having tuberculous pleuritis and pericarditis, he underwent chemotherapy for tuberculosis. However, massive pleural effusion developed later and pleural effusion drainage was carried out. Despite repeated drainage, pleural effusion continued to recur. Chest CT revealed apparent pericardial thickening, in addition, cardiac catheterization revealed elevation of mean right atrial pressure and marked deterioration of cardiac functions including decrease of cardiac output. These findings were compatible with constrictive pericarditis. After these investigations a diagnosis of constrictive pericarditis was established, and the patient underwent a pericardiectomy. Pathological examination of resected specimens revealed tuberculous inflammation.

[A case of pulmonary eosinophilic granuloma arising rapidly 30 years after the start of smoking and remitting spontaneously without smoking cessation].

A case of pulmonary eosinophilic granuloma which arose rapidly after 30 years of smoking and remitted spontaneously without smoking cessation is reported. The patient was a 54-year-old man complaining of a dry cough who had been smoking 30 cigarettes a day for 30 years. Chest roentgenography showed multiple nodular shadows and cystic lesions in the upper and middle fields of both lungs. Chest computed tomography revealed multiple small cysts and small nodular lesions, mainly in both upper lung fields. CT findings strongly suggested pulmonary eosinophilic granuloma. A transbronchial lung biopsy (TBLB) was performed and 4 specimens were obtained, of which 3 showed granulomatous lesions with eosinophils and histiocytes. Furthermore, the granulomatous lesions were positive for S-100 protein staining. The symptoms and radiographic findings improved markedly within about 6 months after the onset of symptoms without treatment. Many cases of this disease were diagnosed in the past by open lung biopsy, but the number of cases diagnosed by TBLB is now increasing. The effectiveness of open lung biopsy has been emphasized in the diagnosis of pulmonary eosinophilic granuloma, but TBLB is also useful for diagnosis, especially in the active or early stage of the disease.

[Inhibitory effects of AA-2414, a thromboxane (Tx) A2 receptor antagonist, on U-46619-, prostaglandin (PG) D2- and 9 alpha, 11 beta PGF2-induced contractions of guinea pig tracheas and isolated human bronchi].

The effects of a novel TXA2 receptor antagonist, AA-2414 [(+-)-7-(3,5,6-trimethyl-1,4-benzoquinone-2-yl)-7-phenyl-heptanoic acid], on U-46619-, PGD2- and 9 alpha, 11 beta-PGF2 alpha-induced contractions of isolated guinea pig tracheas and human bronchi were investigated. AA-2414 competitively inhibited the contractile responses of both human and guinea pig preparations induced by U-46619 with similar pA2 values (7.7 and 7.6, respectively). In addition, the compound also inhibited the contractions of both preparations caused by PGD2 and 9 alpha, 11 beta-PGF2 alpha, the IC50 values of which were 1.2 x 10(-7) and 1.8 x 10(-7) M in guinea pig tracheas and 2.8 x 10(-8) and 8.5 x 10(-8) M in human bronchi. These results suggest that AA-2414 may be a therapeutically useful drug for bronchial asthma.

[Effects of cepharanthin on leukopenia and thrombocytopenia induced by chemotherapy in lung cancer patients].

We studied the effects of Cepharanthin (CEP) on bone marrow suppression induced by chemotherapy in 18 primary lung cancer patients (14 NSCLC, 4 SCLC). NSCLC patients received IP (IFM+CDDP) therapy and SCLC patients received ION (IFM+VCR+ACNU) therapy. For the control, we chose the first course and we administered CEP (1 mg/kg) during the second course. The rate of leukopenia and neutropenia was significantly lower during the CEP course than during the control (p less than 0.01). The recovery rate (at 3 weeks) of leukopenia and neutropenia was significantly higher during the CEP course than during the control (p less than 0.05). But, obvious effects of CEP for lymphopenia and thrombocytopenia were not obtained. Side effects by CEP were not observed in this study. These data suggest that the large dose of CEP contributes to the prevention of leukopenia, especially neutropenia, in patients who receive a sufficient amount of anticancer drugs.

Recovery time course of airway hyperresponsiveness to acetylcholine after ovalbumin challenge in guinea pigs.

Sequential changes in airway and adrenergic responsiveness after ovalbumin (OA) challenge were studied in guinea pigs. Airway responsiveness, alpha 1- and beta-adrenoceptor numbers and adenylate cyclase activity was determined after increasing doses of acetylcholine aerosol were administered before, 0, 3, 7, and 14 days after exposure to 2 percent OA or physiologic saline solution for 10 consecutive days. The antiasthmatic agent, azelastine (1 mg/kg/day, intraperitoneal), was administered for 14 days after the tenth exposure to OA in some animals. Airway responsiveness increased significantly after OA exposure, beta-adrenoceptor numbers decreased by 35 percent, and adenylate cyclase activity decreased by 54 percent (p less than 0.01). Values remained significantly different than control animals for 7 days and required 14 days to normalize completely. Azelastine decreased the recovery period to seven days. Azelastine may affect airway responsiveness, at least in part, by increasing beta-adrenergic responsiveness.

[Desquamative interstitial pneumonia-like changes in idiopathic pulmonary fibrosis].

A 61-year-old man was admitted to our hospital with fever, cough and dyspnea on exertion. The chest X-ray showed diffuse reticulo-granular infiltrates. Deterioration of clinical features and remarkable elevation of BALF lymphocytes (64.3%) suggested active interstitial pneumonia. The open lung biopsy specimen showed chronic interstitial pneumonia with DIP-like pathologic change. There was a remarkable clinical, physiological and roentgenographic improvement associated with decrease of BALF lymphocytes in response to steroid therapy. BAL is useful for monitoring disease activity and tapering steroids in patients with interstitial pneumonia who respond to steroid therapy.

Time course of recovery of beta- and alpha 1-adrenoceptors in experimental asthma.

1. The time course of recovery of reduced beta-adrenoceptors caused by ovalbumin (OA) challenge was investigated using guinea-pigs. 2. The effects of prednisolone on the recovery time course were also evaluated. 3. beta- and alpha 1-receptor assays were performed using lung membranes. Adenylate cyclase activity was also measured. 4. OA challenge reduced the number of beta-adrenoceptors by 35%, and a significant decrease (13%) persisted for 7 days. The number of beta-adrenoceptor recovered after 14 days. 5. OA challenge elevated the number of alpha 1-adrenoceptors. A significant increase (24%) was observed after 7 days, and it took a further 7 days for the recovery. 6. After OA challenge there was a significant decrease in adenylate cyclase activity after 7 days, which recovered after a further 7 days. 7. Inhalation of prednisolone accelerated the recovery of beta-adrenergic responsiveness, though it did not affect the recovery of the number of alpha 1-adrenoceptors. Prednisolone inhalation also elevated beta-adrenergic responsiveness in non-asthmatic subjects. 8. It is concluded that reduced beta-adrenergic responsiveness caused by OA challenge persisted for 7 days and recovered after a further 7 days. Steroid hormone increased beta-adrenoceptors.

Effects of sodium channel blockers on electrical field stimulation-induced guinea-pig tracheal smooth muscle contraction.

The effects of sodium channel blockers, a conventional one: tetrodotoxin, and clinically available ones: cibenzoline, flecainide and SUN 1165 [N-(2,6-dimethylphenyl)-8-pyrrolizidine-acetamide hydrochloride hemihydrate] on electrical field stimulation-induced and carbachol-induced guinea-pig tracheal smooth muscle contraction were investigated. Electrical field stimulation was performed at 50 V with 20 Hz and 0.8 msec square pulse duration. Carbachol (5 x 10(-8) M) was used for induction of tracheal contractions. All agents were administered before electrical field stimulation or carbachol administration. Electrical field stimulation-induced tracheal smooth muscle contraction was dose-dependently reduced by all sodium channel blockers used. The effects of sodium channel blockers on electrical field stimulation-induced contraction were greater than those on carbachol-induced contractions, except for SUN 1165 which reduced similarly both electrical field stimulation- and carbachol-induced contractions. These results indicate that the sodium influx is closely related to the acetylcholine release, resulting in smooth muscle contraction. Since the parasympathetic nervous system may be involved in the genesis of various pathological conditions, such as bronchial asthma, sodium channel blockers could contribute to the management of these conditions.