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.

Hemodynamic stabilizing effects of L-carnitine in chronic hemodialysis patients.

BACKGROUND: The effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients have been debated. In order to clarify the effect of administered L-carnitine on cardiac function and hypotensive episodes during the hemodialysis procedure, a randomized double-blind placebo-controlled study was performed for 3 months. METHODS AND RESULTS: TWENTY STABLE OUTPATIENTS UNDERGOING HEMODIALYSIS TREATMENT WERE DIVIDED INTO TWO GROUPS: controls (placebo) and treated patients (L-carnitine 900 mg p.o. daily). After 3 months, cardiac function was reevaluated by echocardiography, and hypotensive episodes during hemodialysis were assessed. Free and acyl carnitine levels increased significantly from 22.3 ± 7.1 to 140.3 ± 57.5 µmol/l and from 15.8 ± 2.8 to 94.8 ± 50.4 µmol/l, respectively, in the treated group. The ejection fraction significantly increased from 61.8 ± 16.0 to 64.4 ± 13.8% (p < 0.05) in the treated group. However, there was no difference in other echocardiographic parameters between the two groups. Hypotensive episodes significantly decreased from 4.0 ± 1.7 to 1.3 ± 0.9 times per month (p < 0.05), although patients' body weight did not change significantly. CONCLUSIONS: Beneficial effects of L-carnitine on the hemodynamic state of chronic hemodialysis patients were observed. L-Carnitine supplementation might be considered especially for chronic hemodialysis patients with unstable hemodynamic conditions.

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.

Pathological examination with two-millimetre serial sectioning for sentinel lymph node biopsies in breast cancer.

AIMS: To compare enhanced pathology with serial sectioning and the transcription-reverse transcription concerted reaction (TRC) for detecting sentinel node (SN) metastasis in breast cancer cases. METHODS: In total, 115 SN samples from 32 breast cancer cases were investigated by pathological examination with 2.0-mm serial sectioning and by quantitative analysis of carcinoembryonic antigen messenger RNA with the TRC. RESULTS: The results were concordant in 98.3% of these cases. Two histologically metastatic nodes tested negative by TRC, whereas none tested positive by TRC alone. CONCLUSION: Pathological examination with 2-mm sectioning showed superior performance to TRC under the study conditions.

Transcription-reverse transcription concerted reaction and minimal residual disease in axillary sentinel nodes of breast cancer.

AIMS: To investigate the use of transcription-reverse transcription concerted reaction (TRC) to detect axillary lymph node metastases. METHODS: Metastases in 423 lymph nodes obtained from 50 breast cancer patients were investigated by routine pathological hematoxylin and eosin (H and E) staining and quantitative analysis of carcinoembryonic antigen (CEA) mRNA by TRC. Enhanced pathological studies, serial sectioning and immunohistochemistry were conducted for cases which were negative by routine pathology, but positive by TRC. RESULTS: Pathological examination identified metastatic disease in 67 lymph nodes. TRC CEA mRNA results were concordant with 89.8% of these cases at a threshold of 100 copies. TRC identified 30 false negative nodes, which was reduced to 15 by excluding node biopsies yielding less than 40 microg total RNA. Twelve nodes were histologically negative for cancer, but positive according to TRC. Serial sectioning and immunohistochemical analysis of these nodes revealed macrometastatic lesions in three, micrometastasis in one, and isolated tumor cells in two. CONCLUSION: TRC for the detection of CEA mRNA may complement routine pathological examination by sentinel lymph node biopsy (SNB) in early breast cancer. We have started an enhanced pathological examination with serial sectioning on all excised sentinel nodes to set the best threshold for the TRC method.

Blue-dye technique complements four-node sampling for early breast cancer.

AIMS: To examine four-node axillary sampling assisted by a blue dye (4NAS/dye) technique as a sentinel node biopsy (SNB) for breast cancer. METHODS: Lymphatic mapping was performed by injection of patent blue for 33 consecutive cases with breast cancer. Axillary sampling was performed until four nodes were obtained. This was followed by back-up axillary lymph node dissection to examine the feasibility of 4NAS/dye. The same study with 30 cases was conducted at an independent hospital to confirm the feasibility of this method. This method was then applied to 101 consecutive clinically node-negative patients to avoid axillary-node dissection, with intraoperative diagnosis made by frozen section examination. RESULTS: The median numbers of blue-stained nodes and nodes excised by 4NAS/dye were 1.7 and 3.4, respectively. The identification rate of sentinel lymph nodes (SNs) was 81.8% using the dye alone and 97.0% when the combination was used. Pathological examination revealed that the nodal status was correctly predicted by the dye alone in 62.5% of cases with metastasis, whereas in 100% by 4NAS/dye. The dye alone was not sufficient to identify SNs, especially in cases with prior excisional biopsy. The identification rate of SNs and the accuracy rate in another feasibility study were 100% and 92.5% in 30 consecutive cases, respectively. 4NAS/dye successfully detected SNs in 100 of 101 cases of the subsequent observational study with an acceptable post-operative axillary morbidity and thus succeeded as an SNB. CONCLUSIONS: The 4NAS/dye method is reliable for the detection of SNs. This method could be applied to observational studies without radio-isotope.

Markers of malignant transformation of sinonasal inverted papilloma.

AIM: To measure HPV status, epidermal growth factor receptor (EGFR) and transforming growth factor-alpha (TGF-alpha) expression and Ki-67 index in exophytic papilloma (EP), inverted papilloma (IP) with dysplasia, IP with carcinoma and invasive squamous cell carcinoma (SCC). METHODS: Forty-four patients with sinonasal papilloma and invasive SCC were selected. The nasal tissues were stained with monoclonal antibodies to EGFR, TGF-alpha and Ki-67. The results were analysed using quantitative immunohistochemical analysis. In situ hybridization studies for HPV DNA for 6/11, 16/18 and 31/33 were also performed on the tissue. RESULTS: Significant increase of EGFR and TGF-alpha was observed in IP with severe dysplasia, IP with carcinoma and invasive SCC compared to IP with mild dysplasia and control nasal mucosa. And a serial upreguration in terms of Ki-67 index in IP with dysplasia was observed. Among IP, HPV 6/11-positive was present in 42% tumour and HPV 16/18-positive was present in 31% of tumours. Among HPV 6/11 and 16/18-positive IP, significant increase of EGFR and Ki-67 index were observed. CONCLUSION: Pre-cancerous lesions of IP exhibited elevated levels of EGFR and TGF-alpha and these expression may be associated with early events in IP carcinogenesis. HPV infection may be an early event in a multistep process of malignant formation of IP.

Lamivudine treatment for reverse seroconversion of hepatitis B 4 years after allogeneic bone marrow transplantation.

Reverse seroconversion of hepatitis B virus (HBV) after allogeneic BMT is rare. We present a case of HBV reactivation late after allogeneic BMT which responded well to lamivudine therapy. A 35-year-old woman with CML received an allogeneic BMT. Before BMT, the patient had immunity to HBV, with serum antibodies against hepatitis B surface antigen (HBsAb), and the donor was completely negative for HBV. Four years after BMT, acute hepatitis occurred with a detectable level of HBV-DNA. Lamivudine rapidly reduced transaminase and bilirubin levels, and serum HBV-DNA decreased to negative. Retrospective analysis revealed that there had been a gradual decrease in serum HBsAb titers after BMT. Administration of lamivudine immediately after HBV replication may be more effective than vaccination of hepatitis B surface antigen-negative donors before BMT.

Successful allogeneic bone marrow transplantation from an HBV-positive donor into an HBV-positive recipient using lamivudine.

A 21-year-old woman with severe aplastic anemia underwent allogeneic bone marrow transplantation from an HLA-identical sibling donor. The patient also had chronic hepatitis B and the donor was an HBV carrier. To decrease HBV and improve hepatic dysfunction before BMT, the patient had received lamivudine for 6 months. After marrow transfusion, administration of lamivudine was continued to inhibit replication of donor-derived HBV. The patient showed hematological engraftment on day 13 without any serious liver dysfunction. Eight months after BMT, she is now alive and well without chronic liver GVHD or reactivation of hepatitis B. HBV-DNA was not detected in the patient's serum. Administration of lamivudine to a BMT recipient with chronic hepatitis B may be a safe and promising way to prevent fatal liver dysfunction in the setting of allogeneic BMT, even in the event of BMT from an HBV-positive donor.

An Arabidopsis SNF1-related protein kinase, AtSR1, interacts with a calcium-binding protein, AtCBL2, of which transcripts respond to light.

AtSR1 is a protein kinase of Arabidopsis thaliana, which belongs to the SNF1-related protein kinase subfamily 3. We previously showed accumulation of its transcripts to be responsive to light. In this study, we examined the interaction between AtSR1 and six calcineurin B like proteins of Arabidopsis and found that AtSR1 prominently interacts with one of them, AtCBL2, by yeast two-hybrid assay. Interaction between AtSR1 and AtCBL2 could also be directly confirmed in vitro by pull down assay. RNA blot and reverse transcription-polymerase chain reaction analyses showed that transcripts of AtCBL2, and also of AtCBL1, another CBL, increased upon illumination of leaves. The physiological meaning of the interaction of AtSR1and AtCBL2 is not clear, but they presumably function in signal transduction of light.

Correlation of diversity of leg morphology in Gryllus bimaculatus (cricket) with divergence in dpp expression pattern during leg development.

Insects can be grouped into mainly two categories, holometabolous and hemimetabolous, according to the extent of their morphological change during metamorphosis. The three thoracic legs, for example, are known to develop through two overtly different pathways: holometabolous insects make legs through their imaginal discs, while hemimetabolous legs develop from their leg buds. Thus, how the molecular mechanisms of leg development differ from each other is an intriguing question. In the holometabolous long-germ insect, these mechanisms have been extensively studied using Drosophila melanogaster. However, little is known about the mechanism in the hemimetabolous insect. Thus, we studied leg development of the hemimetabolous short-germ insect, Gryllus bimaculatus (cricket), focusing on expression patterns of the three key signaling molecules, hedgehog (hh), wingless (wg) and decapentaplegic (dpp), which are essential during leg development in Drosophila. In Gryllus embryos, expression of hh is restricted in the posterior half of each leg bud, while dpp and wg are expressed in the dorsal and ventral sides of its anteroposterior (A/P) boundary, respectively. Their expression patterns are essentially comparable with those of the three genes in Drosophila leg imaginal discs, suggesting the existence of the common mechanism for leg pattern formation. However, we found that expression pattern of dpp was significantly divergent among Gryllus, Schistocerca (grasshopper) and Drosophila embryos, while expression patterns of hh and wg are conserved. Furthermore, the divergence was found between the pro/mesothoracic and metathoracic Gryllus leg buds. These observations imply that the divergence in the dpp expression pattern may correlate with diversity of leg morphology.

Protective effect of gamma-glutamylethylamide (theanine) on ischemic delayed neuronal death in gerbils.

We examined the protective effect of gamma-glutamylethylamide (theanine) on ischemic delayed neuronal death in field CA1 of the gerbil hippocampus. One microliter of theanine from each three concentrations (50, 125 and 500 microM) was administered through the lateral ventricle 30 min before ischemia. Transient forebrain ischemia was induced by bilateral occlusion of the common carotid arteries for 3 min under careful control of brain temperature at approximately 37 degrees C. Seven days after ischemia, the number of intact CA1 neurons in the hippocampus was assessed. Ischemia-induced neuronal death in hippocampal CA1 region was significantly prevented in a dose-dependent manner in the theanine-pretreated groups. These findings indicate that theanine might be useful clinically for preventing ischemic neuronal damage.

Inhibiting effects of theanine on caffeine stimulation evaluated by EEG in the rat.

In this study, the inhibiting action of theanine on the excitation by caffeine at the concentration regularly associated with drinking tea was investigated using electroencephalography (EEG) in rats. First, the stimulatory action by caffeine i.v. administration at a level higher than 5 micromol/kg (0.970 mg/kg) b.w. was shown by means of brain wave analysis, and this level was suggested as the minimum dose of caffeine as a stimulant. Next, the stimulatory effects of caffeine were inhibited by an i.v. administration of theanine at a level higher than 5 micromol/kg (0.781 mg/kg) b.w., and the results suggested that theanine has an antagonistic effect on caffeine's stimulatory action at an almost equivalent molar concentration. On the other hand, the excitatory effects were shown in the rat i.v. administered 1 and 2 micromol/kg (0.174 and 0.348 mg/kg) b.w. of theanine alone. These results suggested two effects of theanine, depending on its concentration.

Mobile intracardiac calcinosis: a new risk of thromboembolism in patients with haemodialysed end stage renal disease.

Cardiac calcinosis is a common complication of end stage renal disease. A newly observed risk of thromboembolism is reported in four patients with mobile cardiac calcinosis, treated with long term dialysis. Rapidly growing mobile calcification was confirmed by echocardiography. Each patient had an imbalance in serum calcium x inorganic phosphate (Ca x P product >/= 50); this imbalance could not be treated due to the sudden death of the patient or the need for surgical resection to prevent recurrent cerebral thromboembolism. Histological examination revealed intracardiac calcinosis in three cases, and each case showed haemodialysis hypoparathyroidism (intact PTH < 160 pg/ml). Thromboembolism in such cases is rare, however it indicates a need for cautious echocardiographic monitoring in end stage renal disease in patients with an uncontrolled Ca x P product.

Case report: A case of lymphoepithelioma-like carcinoma of the oesophagus and review of the literature.

A 78-year-old Japanese female was admitted to our hospital with dysphagia and weight loss. An oesophageal tumour was demonstrated radiologically and endoscopically, and was diagnosed as oesophageal cancer by biopsy. Histologically, the resected tumour showed poorly differentiated squamous cell carcinoma with prominent lymphoid stroma and was diagnosed as the so-called lymphoepithelioma-like carcinoma (LELC). Epstein-Barr virus in the tumour was negative by polymerase chain reaction and in situ hybridization. Oesophageal LELC is extremely rare. The cases in the literature, as well as the one reported here, presented with gross features of a submucosal tumour-like appearance. Although the differentiation of the tumour cells is often poor, prognosis seems to be better than for other types of oesophageal cancer. Oesophageal LELC has characteristic clinicopathological features and should be classified by criteria independent of other types of tumour.

[Efficacy of granisetron as anti-emetic agent for emesis induced by intra-arterial injection therapy for hepatocellular carcinoma].

The effect of granisetron in preventing nausea and emesis induced by intraarterial chemotherapy was comparatively studied with a historical control group (46 cases) in 50 patients with hepatocellular carcinoma receiving intraarterial anti-tumor drugs such as cisplatin and doxorubicin. Emesis was perfectly controlled in 39 out of 50 patients in the treatment group (78%), in comparison to 33 out of 46 patients (71.7%) in the historical control group. This represented no statistical significance between the two groups. In terms of the severity of nausea, however, the granisetron group demonstrated significant superiority to the control group with 27 out of 50 patients (54%) being free of symptoms compared with 16 out of 46 patients (34.8%) in the control group. A stratified analysis of the data also demonstrated significant superiority of the granisetron group over the historical group in the number of emetic episodes and the severity of nausea in female patients, who are more predisposed to emesis. The above results confirm the usefulness of granisetron as an antiemetic agent used for the prevention of acute nausea and emesis induced by intraarterial chemotherapy.

The association of physical activity level characteristics and other lifestyles with obesity in Nagoya University alumni, Japan.

Improving daily-life habits is considered to be effective in treating obesity. We have examined obesity in regular physical examinations in university students since 1974. In this study, the subjects were 199 students regarded as obese (Broca's index: more than 120%) and 326 non-obese students randomly selected (525 subjects in total) among students who underwent regular physical examinations at Nagoya University, Japan, between 1974 and 1978. Here we report our follow-up survey of obese university students and non-obese individuals who were students of the same university during the same period. This study was carried out for the purpose of clarifying the relationship between changes in lifestyle and body weight 20 years after graduation. Concerning eating behavior, a higher proportion of subjects cared about diet intake in the current non-obese group than in the current obese group (P<0.05). The meal-time in the obese was shorter than that in the non-obese group (P<0.01). Ten percent of subjects in the obese group and 24.4% of subjects in the non-obese group selected class II (moderate) or higher as indicative of the intensity of their daily physical activity. There was a significant difference in distribution between the groups (P<0.05). In the group showing improvement in obesity over time, a higher proportion of subjects cared about diet intake than in the group with continued obesity (P<0.05). Concerning intensity of physical activity, 11.8% of subjects in the group with continued obesity selected class II (moderate) or higher, while 45.5% of subjects in the group showing improvement in obesity chose class II (moderate) or higher. A significant difference in distribution existed between the groups (P<0.01). These findings suggest that the eating behavior of ending meals before feeling satiety and a lifestyle change to enhance the intensity of daily physical activity including walking, even if not having any special sports habits, are effective in decreasing body weight.

Calcitonin-producing pancreatic somatostatinoma: report of a case.

A 59-year-old woman was hospitalized due to a 1-year history of diarrhea and weight loss. Echography and computed tomography of the abdomen revealed a 10 x 7 cm solid mass in the tail of the pancreas and gallstones, while selective celiac angiography revealed the presence of a hypervascular mass. High levels of somatostatin and calcitonin were detected in the plasma, 70 pg/ml (normal range <28 pg/ml) and 5550 pg/ml (normal range 37 +/- 8 pg/ml), respectively. This tumor was thus removed by means of a distal pancreatectomy and a splenectomy. After the pancreatic tumor was removed, the elevated levels of plasma somatostatin and calcitonin returned to the normal ranges, and the persistent diarrhea also dramatically disappeared. A postoperative immunohistochemical study showed the tumor cells to be diffusely positive for somatostatin and calcitonin. These results clearly indicate this patient to be a case of calcitonin-producing pancreatic somatostatinoma.