Optimizing the selection of patients with low rectal cancer for intersphincteric resection by evaluating vertical invasion to the levator and external sphincter.

AIM: The indications for intersphincteric (ISR) anterior resection are not clearly defined. The aim of this study was to evaluate vertical extension of T2 or T3 low rectal cancer treated by rectal amputation to optimize patient selection for ISR. METHOD: The abdominoperineal excision specimens of T2 or T3 low rectal cancer from 53 patients treated between 1992 and 2004 were retrospectively reviewed. Vertical invasion was quantified by measuring the shortest distance between the tumour and the striated muscle (T-SM), assuming that this represented the surgical margin that would have be achieved had an ISR been performed. RESULTS: Involvement of the dentate line (DL) and intramural distal spread were independent risk factors for T-SM ≤ 2 mm. The T-SM was less when the inferior border of the tumour was on the distal side of the DL (r = 0.572, P < 0.001). The probability of involvement of the DL, intramural distal spread or either one of these being associated with T-SM ≤ 2 mm was 43, 46 and 43%, respectively. All patients without both intramural distal spread and involvement of the DL had T-SM > 2. CONCLUSION: We recommend that ISR should only be performed for patients with T2 or T3 low rectal cancer in whom the lowest edge of the tumour is above the DL and there is no intramural distal spread. Such patients are relatively unlikely to have a T-SM ≤ 2 mm.

BRCAness is beneficial for indicating triple negative breast cancer patients resistant to taxane.

AIM: Triple negative breast cancer (TNBC) is a heterogeneous disease and is associated with the cancer stem cell (CSC), basal-like, and BRCA1 function deficient (BRCAness) subtypes. We examined these 3 subtypes in TNBC and compared their chemosensitivity against anthracycline or taxane with a special attention to BRCAness. METHODS: Sixty-six TNBC cases were obtained from a randomized phase II trial comparing TCx6 (TC6) with FEC-Docetaxel (FEC-D) as neoadjuvant chemotherapy. The core needle specimens before chemotherapy were used for subtyping. The basal-like and CSC subtypes were identified by immunohistochemistry; CK5/6 and EGFR staining for the basal-like subtype and ALDH1 staining for the CSC subtype. The BRCAness subtype was examined by Multiplex Ligation-dependent Probe Amplification (MLPA). Correlations between subgroups and pCR rates according to each regimen and subtype were examined. RESULTS: The basal-like and BRCAness subtypes were significantly associated (p = 0.010) with the other subtypes, but not the CSC subtype. The pCR rates were higher with FEC-D than with TC6 in the basal-like (54.5% vs 14.3%, p = 0.081) and BRCAness (56.2% vs 16.7%, p = 0.030) subtypes. Both were not effective in the CSC subtype (18.2% vs 11.8%, p = 1.00). CONCLUSION: BRCAness identified by MLPA was practically useful for treatment selection for avoiding taxane. ALDH1 may be considered as a marker for the CSC subtype requiring novel agents.

Donor site selection and clinical outcomes of nipple-areola skin-sparing mastectomy with immediate autologous free flap reconstruction: A single-institution experience.

BACKGROUND: The objective of this study was to examine the clinical outcomes of immediate breast reconstruction using perforator flaps from different donor sites, and to characterize the trends among these flaps. METHODS: We retrospectively reviewed 136 consecutive patients who underwent immediate breast reconstruction using free flaps after skin-sparing mastectomy (SSM) or nipple-sparing mastectomy (NSM). The whole breast was pathologically analyzed in 5-mm sections. Breast reconstruction was performed using the deep inferior epigastric perforator (DIEP) flap, gluteal artery perforator (GAP) flap, and posterior medial thigh perforator (PMTP) flap. Patient characteristics were compared among donor sites. RESULTS: NSM was converted to SSM because of intraoperative subareolar tumor positivity in 7 of 107 patients. Eleven patients had positive margins in permanent sections. All but one patient had a positive horizontal margin in the peripheral direction. The 5-year recurrence-free survival rate was 91.9%. The locoregional recurrence rate was 5.1% with a mean follow-up observation period of 75 months. DEIP, GAP, and PMTP flaps were used in 64 (47.1%), 38 (27.9%), and 34 (25.0%) patients, retrospectively. DIEP flaps were used in older patients and those with a higher body mass index. GAP flaps were used in younger patients. DIEP and GAP flaps were used for larger breasts, and PMTP flaps for smaller breasts. CONCLUSION: NSM or SSM with immediate perforator flap breast reconstruction is an oncologically acceptable surgical option. We believe that age, desire to have children, body mass index, and excised breast volume are valuable factors for selecting the optimal donor site.

Outcomes of immediate perforator flap reconstruction after skin-sparing mastectomy following neoadjuvant chemotherapy.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on immediate free flap breast reconstruction remains controversial. Furthermore, the oncological outcomes of immediate free flap breast reconstruction after skin-sparing mastectomy (SSM) following NACT remain unclear. This study aimed to investigate the surgical complications and oncological outcomes of immediate perforator flap reconstruction after SSM following NACT. METHODS: A total of 201 consecutive patients with indications for immediate perforator flap reconstruction after SSM were included between 2004 and 2012. Surgical and oncological outcomes were compared between patients with and without NACT. RESULTS: There were 38 patients in the NACT group and 163 in the non-NACT control group. The median age of the NACT group was 39.5 years, which was significantly younger than the control group (43.0 years; P < 0.05). Patients in the NACT group also had more advanced and aggressive disease (P < 0.05). There was no significant difference in the frequency of surgical complications between the groups, no difference in the type of complications, and no significant difference in the frequencies of major and minor complications. No patients in the NACT group had delayed adjuvant therapy. Eight patients (4%) developed recurrences, with a median follow-up time of 3.0 years. Local recurrences occurred in three control patients but no patients in the NACT group. CONCLUSION: NACT does not affect short-term or interim outcomes after immediate perforator flap reconstruction and may thus represent a safe and practical treatment option for the multidisciplinary treatment of breast cancer.

Successful treatment of refractory bronchorrhea by inhaled indomethacin in two patients with bronchioloalveolar carcinoma.

Bronchorrhea in patients with bronchioloalveolar carcinoma is not uncommon. However, to our knowledge, an effective treatment for bronchorrhea in these patients has not been established. Recently, we have confirmed the efficacy of inhaled indomethacin in severe refractory bronchorrhea in comparison to that of other medications in two patients with bronchioloalveolar carcinoma. Despite the administration of a macrolide and corticosteroid, sputum volume increased to 700 mL/d in case 1 and to 200 mL/d in case 2 and hypoxemia and dyspnea deteriorated. Within a few days after the initiation of treatment with inhaled nebulized indomethacin (75 mg/d), sputum volume started to decrease and was controlled to < 100 mL/d, associated with alleviation of dyspnea and hypoxemia. To our knowledge, this is the first report of successfully treated refractory bronchorrhea associated with bronchioloalveolar carcinoma by inhaled indomethacin, resulting in markedly reduced sputum volume, improved quality of life, and prolonged survival.

Expression of the mphB gene for macrolide 2'-phosphotransferase II from Escherichia coli in Staphylococcus aureus.

The genes mphA and mphB encode macrolide 2'-phosphotransferases I and II, respectively, and they confer resistance to macrolide antibiotics in Escherichia coli. To study the expression of these genes in Gram-positive bacteria, we constructed recombinant plasmids that consisted of an mph gene and the pUB110 vector in Bacillus subtilis. When these plasmids were introduced into Staphylococcus aureus, the mphB gene was active and macrolide 2'-phosphotransferase II was produced. The gene endowed S. aureus with high-level resistance to spiramycin, a macrolide antibiotic with a 16-membered ring. Moreover, transcription of the mphB gene in S. aureus began at the promoter that was active in E. coli.

Pharmacological studies on Puerariae Flos. IV: Effects of Pueraria thomsonii dried flower extracts on blood ethanol and acetaldehyde levels in humans.

We investigated the effects of extracts from the dried flower of Pueraria thomsonii on blood ethanol and acetaldehyde levels in humans consuming alcoholic beverages. The extracts of Pueraria thomsonii had no influence on blood ethanol and acetaldehyde concentration in humans. However, the extracts increased the elimination rate constant of blood acetaldehyde, although they had no effect on the elimination of blood ethanol in humans. These results suggest that Pueraria thomsonii promotes the elimination of blood acetaldehyde in humans. The present study clinically suggests that a modest stimulatory effect of Pueraria thomsonii on the elimination of blood acetaldehyde may passively mitigate acetaldehyde toxicity, such as flushing, palpitation, headache, etc., associated with excessive alcohol intake.

Correlation of serum HDL-cholesterol and LCAT levels with the fraction of ionized magnesium in children.

Correlation of serum lipids and apolipoprotein levels with serum total magnesium concentration and whole blood ionized magnesium level was determined in 47 children (14 female and 33 male; mean age, 8.7 +/- 4.2 years). Mean serum concentration of magnesium was 2.19 +/- 0.19 mg/dl, whole blood concentration of ionized magnesium 1.23 +/- 0.08 mg/dl, and fraction of ionized magnesium (ratio of whole blood ionized magnesium to serum total magnesium) 0.56 +/- 0.04. Neither serum total magnesium level nor whole blood ionized magnesium level had any correlation with serum albumin, lipid, and apolipoprotein levels. However, the fraction of ionized magnesium was significantly correlated with HDL-cholesterol (n = 46, r = 0.31, p = 0.0345), apolipoprotein A-1 (n = 41, r = 0.39, p = 0.0124), and lecithin-cholesterol acyltransferase (LCAT) (n = 20, r = 52, p = 0.0184). These results suggest that fraction of ionized magnesium is more closely linked to serum HDL-cholesterol and LCAT level than with the serum total magnesium level or whole blood ionized magnesium.

[A case report of Campylobacter fetus subspecies fetus bacteremia].

An unusual case of Campylobacter fetus subspecies fetus bacteremia was presented. A twenty four year old male was admitted to our hospital due to abdominal pain, general malaise, diarrhea, high fever, and hemoptysis. He was alcoholic and fond of eating raw liver. He had a history of partial gastrectomy and disturbance of pancreatic function. He showed pulmonary empyema, pleuritis, thrombophlebitis of lower legs, jaundice, hepatomegaly, diarrhea, pneumothorax, and low T3 low T4 syndrome. C. fetus subsp. fetus was detected from the venus blood and pleural effusion on admission. He was successfully treated by gentamicin, chloramphenicol, and minocycline. This is the fourth case of C. fetus subsp. fetus bacteremia in the Japanese literature. This microanerophilic gram negative curved bacillus has been increasingly associated with human disease and relapsing in nature, so protracted antimicrobial therapy was recommended.

[An adult case of congenital myopathy--coexistence of nemaline rods and core-like structures].

A 42-year-old female complained of exertional dyspnea and sleep disturbance. Her face was elongated longitudinally and the hard palate was narrow and high-arched. She has slender musculature and kyphoscoliosis. She was dysphonic and could not walk on her heels. Muscles in the face, upper arm, pelvic girdle and thigh were atrophic. Muscle weakness was detected in the neck, tibialis anterior, ilipsoas and other hip muscles, and ranged between 3- and 4 by the manual muscle testing. Electromyography showed definite myogenic abnormalities in all the muscle examined. No abnormality was found on the routine examination of blood, as was the motor and sensory nerve conduction velocity. Her vital capacity was 0.91 L, i.e., 35% of the expected value, suggesting a severe restrictive respiration. The arterial blood gas analysis revealed hypoxia, hypercapnia and desaturation. The blood gas data worsened when she was asleep, because of increased hypoventilation. Muscle biopsy of the biceps brachii showed a marked variation in the muscle fiber size. The type 1 muscle fiber was predominant. Many fibers contained nemaline rods and/or core-like structures. Some fibers contained both nemaline and core-like structures. This core-like structures were not stained with NADH-TR and ATPase reactions, and about 40-100 microns in the longitudinal extension. In this context, typical central cores have not been observed in the present case. No association of nemaline rods and core-like structures in the same muscle fiber has been reported, although a close relationship of the two structures has been suggested.(ABSTRACT TRUNCATED AT 250 WORDS)

[Sputum penetration of levofloxacin and its clinical efficacy in patients with chronic lower respiratory tract infections].

Sputum penetration of levofloxacin (LVFX) was evaluated after a single oral dose of 100 mg or 200 mg to 4 patients with copious purulent sputa. The sputum concentration of LVFX reached maximum levels of 1.27 and 4.36 micrograms/ml at 4 hours, and still remained at concentrations of 0.32 and 1.68 micrograms/ml at 8 hours after administration of 100 mg and 200 mg, respectively. The AUC ratio of sputum/serum was 0.9-1.0, indicating good sputum penetration of LVFX in these patients. The clinical efficacy and the safety of LVFX were also evaluated in a total of 13 patients with respiratory tract infections associated with bronchiectasis, diffuse panbronchiolitis, etc. LVFX was administered orally at a daily dose of 200 mg once a day, 100 mg t.i.d. or 200 mg t.i.d. for 7-28 days (mean 14.7 days). The clinical response to the drug was rated as excellent in 1 case, good in 5, fair in 3, and poor in 2 cases in 11 evaluable cases, thus the efficacy rate was 54.5%. All the 3 strains of Haemophilus influenzae were eradicated. Of the 3 strains of Pseudomonas aeruginosa, eradication, decrease, and unchange was observed for 1 strain each. One strain of Streptococcus pneumoniae remained unchanged. No adverse reaction was observed except for 1 case with slight and temporary increase of eosinophils. The above results suggested that LVFX would be clinically useful in the treatment of chronic lower respiratory tract infections.

[A clinicopathological study of pulmonary cryptococcosis--chest CT and pathologic correlation].

We reviewed the clinicopathological features in 12 patients (7 males and 5 females; mean age 54 yr) with pulmonary cryptococcosis. Eleven of the patients were asymptomatic and the disease was detected by chest radiograph abnormalities. The underlying systemic disease had been diagnosed as diabetes mellitus in two. Chest CT scans showed a solitary nodule in 9 of the 12 patients, multiple nodules in 2, and infiltration in 1. The nodular diameter was less than 2 cm in 10 of the 12. All nodules were located in the subpleural region. On the chest CT, cavitary nodules, scattered nodules, or both, and spiculated nodules were difficult to distinguish from pulmonary tuberculosis and primary lung cancer, respectively. According to McDonnell's pathological classification of pulmonary cryptococcosis, the resected 8 lungs revealed peripheral pulmonary granuloma in 5 and granulomatous pneumonia in 3. It is important to perform a pathological examination for the diagnosis of pulmonary cryptococcosis to avoid misdiagnosis as lung cancer or pulmonary tuberculosis.

[Exogenous lipoid pneumonia induced by inhalation of insecticide].

We report a case of exogenous lipoid pneumonia induced by insecticide. A 67-year-old man was admitted to our hospital with complaints of dyspnea cough, hemoptysis, and shivering 6 hours after inhaling an insecticide. A chest radiograph on admission disclosed consolidation in the right upper lobe. Chest computed tomography showed nodular infiltrates associated with ground-glass opacities. Bronchoalveolar lavage fluid was hemorrhagic and showed neutrophilia. Pathological examination of transbronchial lung biopsy specimens showed numerous vacuolated macrophages in alveolar spaces. Electron microscopy demonstrated lipid droplets in the cytoplasm of these macrophages. These findings together yielded a diagnosis of exogenous lipoid pneumonia induced by insecticide. In addition, we experimentally induced a similar form of lipoid pneumonia in rats by intratracheal instillation of the same insecticide.

[Endocrine disturbances in sleep apnea syndrome].

Sleep apnea may interact endocrine rhythms by a number of mechanisms. Repetitive apneas will cause sleep fragmentation and disorganization of sleep stages and cycles. How this compares with hormonal changes secondary to sleep deprivation is unclear. Hypoxia may have direct central effects on neurotransmitters, which in turn will affect hypothalamic-pituitary hormone production. And, sudden arousal from sleep may produce a central stress response leading to hormonal changes. These factors may interact and lead to changes in the central of sleep and endocrine rhythms. We describe Growth hormone and Androgens secretion during sleep with obstructive sleep apnea patients.

[Breathing during sleep].

Sleep alters breathing pattern and respiratory responses to many external stimuli. These changes permit the development of sleep-related hypoxemia in patients with respiratory diseases and may contribute to the pathogenesis of apneas in patients with sleep apnea syndrome. Many respiratory problems during sleep are related to an abnormal control of ventilation. The impaired ventilatory responses permit the development of hypoventilation during sleep and of sleep-related hypoxemia in patients with hypoxic chronic emphysema post TB sequela and kyphoscoliosis. In all these conditions, the hypoxia is most marked in REM sleep, when the ventilatory responses are at their lowest. The impaired ventilatory responses during sleep may accompanied by a decrease in the response of the upper airway opening muscles to chemostimulation during sleep and both factors may be important in the initiation and continuation of apneas.

Observational study of blue dye-assisted four-node sampling for axillary staging in early breast cancer.

BACKGROUND: The use of radioisotopes (RIs) is regulated and not all institutions have nuclear medicine facilities for sentinel node biopsy (SNB). We previously reported blue dye-assisted four-node axillary sampling (4NAS/dye) to be a suitable method for detecting sentinel nodes (SNs) without RIs. Here, we present an interim report on an observational study of this technique. METHODS: From May 2003 to June 2008, 234 early breast cancer patients underwent SNB with 4NAS/dye. Lymphatic mapping was performed by injection of patent blue, and axillary sampling was performed until 4 SNs were detected. Patients with metastatic SNs underwent axillary lymph node dissection (ALND) at levels I and II, while SN-negative patients did not undergo further axillary procedures. RESULTS: The SN identification rate was 99%. In total, 44 patients were diagnosed with metastatic disease by using the 4NAS/dye technique and underwent ALND; the remaining 189 patients did not undergo ALND (the SNB group). After a median follow-up period of 54 months, only 1 patient (0.5%) in the SNB group developed axillary recurrence. For the 4NAS/dye procedure, blue SNs were harvested in 220 patients (94%) and only unstained SNs were harvested in 13 patients (6%). Among the 44 patients with SN metastases, foci were found in blue SNs in 37 patients (84%), while they were found in only unstained SNs in 7 patients (16%). CONCLUSIONS: SNB with 4NAS/dye is a safe and reliable technique for treatment of early breast cancer patients. This technique may be particularly useful for surgeons who do not have access to radioisotope facilities.