Treatment of Philadelphia chromosome-positive acute lymphoblastic leukemia: a pilot study which raises important questions

Acute lymphoblastic leukemia (ALL) patients with a Philadelphia chromosome (Ph+ ALL) were treated with a combination of antineoplastic drugs recommended for both myeloid and lymphoid leukemia (BHAC-DMPV: behenoylcytosine arabinoside, daunorubicin, 6-mercaptopurine, prednisolone, and vincristine). Ph+ ALL patients with chromosome breaks which occur within the major breakpoint cluster region (M-BCR rearranged Ph+ ALL) were treated with natural interferon-alpha (IFN-alpha) after entering complete remission. In this study, four of seven patients with Ph+ ALL had M-BCR rearrangement, and all achieved complete remission with karyotypic normalization. Subsequent cytogenetic analysis during complete remission in two ALL patients with M-BCR rearrangement revealed that the percentage of bone marrow cells with the Ph chromosome increased, while the bone marrow maintained remission status. This cytogenetic-hematological discrepancy led us to consider that M-BCR rearranged Ph+ ALL might be a variant of chronic myelogenous leukemia, therefore, three Ph+ ALL patients with M-BCR rearrangement were treated with IFN-alpha after achieving complete remission. In contrast, only one of three patients with M-BCR non-rearranged Ph+ ALL obtained complete remission.     

Low-molecular-weight protein tyrosine phosphatase expression as a prognostic factor for men with metastatic hormone-naïve prostate cancer

Objectives

Recent studies have demonstrated that up-front docetaxel combined with androgen deprivation therapy (ADT) prolongs survival in some patients with metastatic hormone-naïve prostate cancer (mHNPC). However, new biomarkers for selecting personalized treatment strategies for mHNPC are warranted. We evaluated the value of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression as a prognosticator in men with mHNPC.

Transient vocal cord palsy caused by hypoperfusion of unilateral hemisphere

We report a 68-year-old man who exhibited mild dysarthria and mild right hemiparesis resulted from hypoperfusion of the left hemisphere. An MR angiography showed a severe stenosis at the second portion of left middle cerebral artery (MCA). After the beginning of treatment, the patient suffered from hoarseness, followed by breathing failure. The laryngeal fiber exhibited right vocal cord paresis. Unilateral cortico-bulbar tract dysfunction does not typically cause vocal cord palsy. However, several cases indicate the involvement of a dominant projection from the contralateral cortico-bulbar tract to the vocal cord. In the present case, hypoperfusion of the left hemisphere might have temporarily produced right vocal cord palsy, considering the stenosis of the left MCA.     

Stratifying the risk of lymph node metastasis in undifferentiated-type early gastric cancer

AIM:To study how lymph node metastasis(LNM) risk is stratified in undifferentiated-type early gastric cancer(undiff-EGC) dependent on combinations of risk factors.METHODS:Five hundred and sixty-seven cases with undiff-EGC undergoing gastrectomy with lymphadenectomy were examined retrospectively.Using clinicopathological factors of patient age,location,size,an endoscopic macroscopic tumor form,ulceration,depth,histology,lymphatic involvement(LI) and venous involvement(VI),LNM risk was examined and stratified by conventional statistical analysis and datamining analysis.RESULTS:LNM was positive in 44 of 567 cases(7.8%).Univariate analysis revealed > 2 cm,protrusion,submucosal(sm),mixed type,LI and VI as significant prognostic factors and > 2 cm and LI-positive were independent factors by multivariate analysis.In preoperatively evaluable factors excluding LVI,sm and > 2 cm were independent factors.According to the depth and size,cases were categorized into the low-risk group [m and ≤ 2 cm,0%(LNM incidence)],the moderaterisk group(m and > 2 cm,5.6%; and sm and ≤ 2 cm,6.0%),and the high-risk group(sm and > 2 cm,19.3%).On the other hand,LNM occurred in 1.4% in all LI-negative cases,greatly lower than 28.2% in all LI-positive cases,and LNM incidence was low in LInegative cases even in the moderate- and high-risk groups.CONCLUSION:LNM-related factors in undiff-EGC were depth and size preoperatively while those were LI and size postoperatively.Among these factors,LI was the most significantly correlated factor.     

Low-dose flunitrazepam for conscious sedation for EGD: a randomized double-blind placebo-controlled study

BACKGROUND: EGD with conscious sedation is a safe procedure, but complications such as hypoxia can occur. The efficacy and safety of low-dose flunitrazepam (0.25 mg) was compared with a standard dose of flunitrazepam (0.5 mg) for moderate sedation during EGD. METHODS: In a randomized, double-blind, placebo-controlled trial, 75 outpatients (40 men, 35 women, mean age 45 [11] years) undergoing screening EGD were randomly assigned to one of 3 treatment arms: 0.25 mg of flunitrazepam (F0.25 group), 0.5 mg of flunitrazepam (F0.5 group), or placebo (normal saline solution), each administered intravenously. Patient tolerance was scored by using self-assessment questionnaires with visual analogue scales. Cardiopulmonary complications were assessed by monitoring blood pressure, heart rate, oxygen saturation, and the electrocardiogram during the procedure. RESULTS: The patient tolerance scores in the F0.25 and F0.5 groups, respectively 2.1 (2.1) and 2.3 (2.5), were significantly lower than that for the placebo group (6.5 [3.0]); there was no significant difference between F0.25 and F0.5. Cardiopulmonary complications in the F0.25 group were significantly lower than in the F0.5 group. Oxygen desaturation (oxygen saturation < 90%) was noted in two of 25 patients in the F0.5 group. Post-procedure drowsiness was observed in two of 24 (8.3%) patients in the F0.25 group and 3 of 21 (14.3%) in the F0.5 group (p = 0.2438). CONCLUSIONS: Patient tolerance of EGD with low-dose flunitrazepam (0.25 mg intravenously) was similar to that with a standard dose (0.5 mg intravenously) and significantly better than in the placebo group. Oxygen desaturation was observed only in the group that received the standard dose, suggesting that sedation with low-dose flunitrazepam is efficacious and safe for EGD.     

Airway responsiveness to intravenous and inhaled acetylcholine in the guinea pig after cigarette smoke exposure

Exposure of conscious guinea pigs to cigarette smoke results in bronchial hyperresponsiveness. To examine the mechanisms involved, we measured airway responses to increasing doses of intravenous or inhaled acetylcholine in guinea pigs exposed to cigarette smoke (n = 20) or to air (n = 20). After exposure the guinea pigs were anesthetized, paralyzed, and studied in a pressure-sensitive body plethysmograph while ventilated through a tracheostomy. Two and 6 puffs of an aerosol of increasing concentrations (0.05 to 500 micrograms/ml) of acetylcholine were delivered via the tracheostomy. Intravenous acetylcholine was delivered in boluses of 0.1 ml of increasing concentrations (0.5 to 50,000 micrograms/ml) via a catheter in an external jugular vein. Pulmonary resistance (RL), dynamic compliance (Cdyn), and heart rate (HR) were measured at baseline (after aerosolized or intravenous saline) and after each dose of acetylcholine. The peak responses to both inhaled and intravenous acetylcholine were rapid in onset (less than 15 s), short-lived (3 to 4 breaths), and were noncumulative. The baseline RL, Cdyn, and HR were not different in the smoke and air exposure groups. In the intravenous acetylcholine group, there were no differences in RL, Cdyn, and HR responses between the air and smoke exposure groups. In the inhaled acetylcholine group, the dose-response curve was shifted to the left (p less than 0.05) and reached a higher maximal response (p less than 0.01) after smoke exposure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Variant forms of glucokinase gene in Japanese patients with late-onset type 2 diabetes

We have applied the technique of single-strand conformation polymorphism analysis to detect mutations of the glucokinase gene in 50 Japanese patients with lateonset type 2 diabetes and in 50 normal Japanese subjects. Out of the 50 patients with late-onset type 2 diabetes, we observed three kinds of variant patterns: one in exon 1b, one in exon 4, and one in exon 5. The incidence of these patterns was one in exon 1b, two in exon 4 and one in exon 5. Direct sequencing of exon 1b and exon 5 revealed mutations in intron areas at the 12th nucleotide downstream from the 5 splice points in two cases. Direct sequencing of exon 4 revealed a heterozygous silent mutation, CCP[Pro]CCG[Pro] at codon 145. In contrast, 50 normal Japanese subjects showed no variant patterns in any exons. Our results showed that although 8% (4 out of 50) of Japanese patients with late-onset type 2 diabetes have variant forms of the glucokinase gene, none is expected to cause apparent qualitative changes in glucokinase. We think that the frequency of mutations of the glucokinase gene which could cause qualitative change is very low in Japanese patients with late-onset type 2 diabetes.     

Chemotherapy-induced sclerosing cholangitis as a rare indication for resection: Report of a case

Bile duct stricture due to chemotherapy-induced sclerosing cholangitis (CISC) is a potentially fatal complication of hepatic arterial infusion chemotherapy (HAIC). It is managed primarily with medical treatment and biliary stenting. We report a rare case of a CISC-related biliary stricture requiring resection. The patient had been receiving adjuvant HAIC for 11 months after a curative liver resection for hepatocellular carcinoma, when clinically overt cholangitis developed. Radiologic and biopsy findings suggested a CISC-related biliary stricture limited to the common hepatic duct. We discontinued HAIC and started corticosteroid treatment, which finally became ineffective. Endoscopic biliary stenting was impossible because of her severe biliary sclerosis, necessitating resection of the stricture, which was confirmed histologically to be secondary sclerosing cholangitis. The patient has shown no signs of recurrent cholangitis for 12 postoperative months since her operation. Thus, resection could be a treatment option for a CISC-related biliary stricture in selected patients.     

Nd:YAG laser therapy for infertility with a contact-type probe

Laparoscopic Nd:YAG laser surgery for tubal adhesiolysis, hydrosalpinx and other disorders is an effective treatment for female infertility that causes relatively little tissue damage. In initial studies using contact-type probes, the 0.4-mm-diameter probe and 10 mm/sec incision speed were found to cause less tissue degeneration than did other combinations (P less than .05). Fifteen infertile women were treated at laparoscopy with a Nd:YAG laser; one of six with hydrosalpinx achieved pregnancy after salpingostomy using a contact-type probe, two of three with tubal adhesions achieved pregnancy after adhesiolysis with the Nd:YAG laser, and three of six with polycystic ovaries achieved pregnancy after wedge resection using a contact-type probe. Five of fifteen infertile women conceived after Nd:YAG laser surgery with a contact-type probe under laparoscopy. We confirmed that contact irradiation with a ceramic incising probe is capable of creating an adequate incision at low power levels and that laparoscopic Nd:YAG laser surgery for infertile women is an effective treatment.