Relevance of level IIb neck dissection in patients with papillary thyroid carcinoma.

BACKGROUND: Cervical nodal metastasis is a key prognostic factor in patients with papillary thyroid carcinoma. The role of lymph nodes in papillary thyroid carcinoma management and prognosis remains controversial. METHODS: Level IIb lymph nodes obtained from 44 patients with papillary thyroid carcinoma were histopathologically examined retrospectively. Specimens were classified as ipsilateral or contralateral. The number of dissected nodes and prevalence of level IIb metastasis were compared according to pre-operative clinical nodal stage. RESULTS: In the node-negative neck, the prevalence of contralateral and ipsilateral IIb nodes was 0 out of 20 and 0 out of 3, respectively. In the node-positive neck, the prevalence of contralateral and ipsilateral IIb nodes was 1 out of 13 (7.70 per cent) and 3 out of 41 (7.32 per cent), respectively. Clinically determined and pathologically confirmed level IIb node negativity were significantly associated. Thirty-four patients (77.3 per cent) developed accessory nerve complications from level IIb dissection. CONCLUSION: Level IIb neck dissection for papillary thyroid carcinoma may be required if pre-operative examination reveals multilevel, level IIa or suspicious level IIb metastasis.

Primary Lymphangiosarcoma of the Urinary Bladder in a Dog.

Abdominal ultrasonographical and computed tomography examinations of a 12-year-old neutered female toy poodle revealed a protruding mass, approximately 2 cm in diameter, at the apex of the bladder. The mass was firm and haemorrhagic with a homogeneously brownish-yellow cut surface. Microscopically, it was unencapsulated and located in the muscle layer with invasion of the extra-muscular layer. It was composed of spindloid to oval neoplastic cells that formed irregular clefts and diffuse sheets that dissected bundles of collagen. Immunohistochemically, the neoplastic cells were positive for vimentin and lymphatic vessel endothelial hyaluronan receptor 1 antigens, but negative for cytokeratin AE1/AE3, factor VIII-related antigen, CD31, CD34, Prox-1, S100, desmin, α-smooth muscle actin and MyoD1. Negative immunolabelling for laminin antigen supported the absence of evidence of a basal lamina on ultrastructural examination. Based on these findings, this tumour was identified as a lymphangiosarcoma. To the best of our knowledge, this case is the first report of lymphangiosarcoma arising from the bladder in a dog.

Randomized clinical trial of extensive intraoperative peritoneal lavage versus standard treatment for resectable advanced gastric cancer (CCOG 1102 trial).

BACKGROUND: A survival benefit of extensive intraoperative peritoneal lavage (EIPL) has been reported in patients with gastric cancer with positive peritoneal cytology. The hypothesis of this study was that EIPL may reduce peritoneal recurrence in patients with advanced gastric cancer who undergo surgery with curative intent. METHODS: This was an open-label, multi-institutional, randomized, phase 3 trial to assess the effects of EIPL versus standard treatment after curative gastrectomy for resectable gastric cancer of T3 status or above. The primary endpoint was disease-free survival (DFS); secondary endpoints were overall survival, peritoneal recurrence-free survival and incidence of adverse events. RESULTS: Between July 2011 and January 2014, 314 patients were enrolled from 15 institutions and 295 patients were analysed (145 and 150 in the EIPL and no-EIPL groups respectively). The 3-year DFS rate was 63·9 (95 per cent c.i. 55·5 to 71·2) per cent in the EIPL group and 59·7 (51·3 to 67·1) per cent in the control group (hazard ratio (HR) 0·81, 95 per cent c.i. 0·57 to 1·16; P = 0·249). The 3-year overall survival rate was 75·0 (67·1 to 81·3) per cent in the EIPL group and 73·7 (65·9 to 80·1) per cent in the control group (HR 0·91, 0·60 to 1·37; P = 0·634). Peritoneal recurrence-free survival was not significantly different between the two groups (HR 0·92, 0·62 to 1·36; P = 0·676). No intraoperative complications related to EIPL were observed. CONCLUSION: EIPL did not improve survival or peritoneal recurrence in patients who underwent gastrectomy for advanced gastric cancer. Registration number: 000005907 (http://www.umin.ac.jp/ctr/index.htm).

ANTECEDENTES: Se ha descrito que un lavado peritoneal extenso intraoperatorio (extensive intraoperative peritoneal lavage, EIPL) proporciona un beneficio en la supervivencia en pacientes con cáncer gástrico con citología peritoneal positiva. La hipótesis de este estudio era que el EIPL podría disminuir la recidiva peritoneal en pacientes con cáncer gástrico avanzado sometidos a cirugía con intención curativa. MÉTODOS: Ensayo clínico fase 3, abierto, multicéntrico y aleatorizado para evaluar los efectos de un lavado peritoneal extenso intraoperatorio (EIPL) frente a tratamiento estándar tras gastrectomía curativa por cáncer gástrico ≥T3 resecable. La variable de resultado primaria fue la supervivencia libre de enfermedad (disease-free survival, DFS), y las variables de resultado secundarias fueron la supervivencia global (overall survival, OS), la supervivencia libre de recidiva peritoneal y la incidencia de efectos adversos. RESULTADOS: Entre julio de 2011 y enero de 2014, se reclutaron 314 pacientes de 15 instituciones y se analizaron los datos de 295 pacientes (145 en el grupo con EIPL y 150 en el grupo sin EIPL). La DFS a los 3 años fue 63,9% (i.c. del 95% 55,5-71,2) en el grupo con EIPL y 59,7% (i.c. del 95% 51,3-67,1) en el grupo control (cociente de riesgos instantáneos, hazard ratio, HR 0,81 (i.c. del 95% 0,57-1,16), P = 0,249). La OS a los 3 años fue 75,0% (i.c. del 95% 67,1-81,3) en el grupo con EIPL y 73,7% (i.c. del 95% 65,9-80,1) en el grupo control (HR 0,91 i.c. del 95% 0,60-1,37), P = 0,634). No se observaron diferencias estadísticamente significativas entre los dos grupos en la supervivencia libre de recidiva peritoneal (P = 0,676, HR 0,92 (i.c. del 95% 0,62-1,36). No se observaron complicaciones intraoperatorias relacionadas con EIPL. CONCLUSIÓN: El EIPL no mejoró la supervivencia o la recidiva peritoneal en pacientes sometidos a gastrectomía por cáncer gástrico avanzado.

Prognostic factors for survival in patients with pT1 N+ or T2-3 N0 gastric cancer in Japan.

BACKGROUND: The outcome for pT1 N+ or pT2-3 N0 gastric cancer is favourable, but some patients suffer from recurrent disease. The aim of this study was to identify prognostic factors in patients with pT1 N+ or pT2-3 N0 gastric cancer. METHODS: This was a multicentre, retrospective cohort study. All patients with pT1 N+ or pT2-3 N0 gastric cancer who underwent curative gastrectomy at five high-volume, specialized cancer centres in Japan between 2000 and 2008 were included. Demographic, clinical, surgical and pathological data were collected. Independent prognostic factors were identified using a Cox proportional hazards regression model. RESULTS: Some 1442 patients were included. The 5-year overall survival rate for patients with pT1 N+ or pT2-3 N0 gastric cancer was 92·0 per cent. Multivariable analysis for overall survival identified age (hazard ratio (HR) 2·67, 95 per cent c.i. 2·09 to 3·43), sex (HR 0·57, 0·39 to 0·83) and clinical tumour depth (cT) (HR 1·45, 1·06 to 1·98) as independent prognostic factors. CONCLUSION: Survival of patients with pT1 N+ or pT2-3 N0 gastric cancer is good. Age 65 years or above, male sex and cT2-4 category are associated with worse overall survival.

Ultraviolet photochemical reaction of [Fe(III)(C2O4)3](3-) in aqueous solutions studied by femtosecond time-resolved X-ray absorption spectroscopy using an X-ray free electron laser.

Time-resolved X-ray absorption spectroscopy was performed for aqueous ammonium iron(III) oxalate trihydrate solutions using an X-ray free electron laser and a synchronized ultraviolet laser. The spectral and time resolutions of the experiment were 1.3 eV and 200 fs, respectively. A femtosecond 268 nm pulse was employed to excite [Fe(III)(C2O4)3](3-) in solution from the high-spin ground electronic state to ligand-to-metal charge transfer state(s), and the subsequent dynamics were studied by observing the time-evolution of the X-ray absorption spectrum near the Fe K-edge. Upon 268 nm photoexcitation, the Fe K-edge underwent a red-shift by more than 4 eV within 140 fs; however, the magnitude of the redshift subsequently diminished within 3 ps. The Fe K-edge of the photoproduct remained lower in energy than that of [Fe(III)(C2O4)3](3-). The observed red-shift of the Fe K-edge and the spectral feature of the product indicate that Fe(III) is upon excitation immediately photoreduced to Fe(II), followed by ligand dissociation from Fe(II). Based on a comparison of the X-ray absorption spectra with density functional theory calculations, we propose that the dissociation proceeds in two steps, forming first [(CO2 (•))Fe(II)(C2O4)2](3-) and subsequently [Fe(II)(C2O4)2](2-).

Genetic polymorphism of IGF-I predicts recurrence in patients with gastric cancer who have undergone curative gastrectomy.

BACKGROUND: To our knowledge, no reports have evaluated the effects of genetic polymorphisms of insulin-like growth factor-I (IGF-I) on clinical outcomes of gastric cancer patients. METHODS: We retrospectively analyzed the impact of IGF-I polymorphisms on recurrence-free survival (RFS) in 430 patients with gastric cancer who underwent curative gastrectomy between 2001 and 2005 in our institution. RESULTS: Among the 430 gastric cancer patients, 345 were pathological stage I or II, while 85 were stage III or IV. The median 5-year RFS rate was 85.3% (95% confidence interval [CI] 81.4-88.5). In a multivariate Cox model (adjusted for age, gender, histology, pathological stage, adjuvant chemotherapy, and history of diabetes), two IGF-I polymorphisms, rs1520220 and rs2195239, were significantly associated with RFS (hazard ratio [HR] 0.60, 95% CI 0.40-0.91; and HR 0.60, 95% CI 0.41-0.89, respectively, in a per-allele model). When stratified by stage (I-II versus III-IV), rs1520220 in particular was associated with RFS in patients with stage III-IV disease, with a P-value for interaction of 0.01. CONCLUSIONS: Our findings indicate that genetic polymorphisms of IGF-I may have a substantial effect on recurrence for gastric cancer patients who have undergone curative gastrectomy. This information may help identify population subgroups that could benefit from IGF-I-targeting agents.

Galanin and galanin receptor type 1 suppress proliferation in squamous carcinoma cells: activation of the extracellular signal regulated kinase pathway and induction of cyclin-dependent kinase inhibitors.

Galanin receptor 1 (GALR1) maps to a common region of 18q loss in head and neck squamous cell carcinomas and is frequently inactivated by methylation. To investigate effects of GALR1 and its signaling pathways, we stably expressed hemaglutinin-tagged GALR1 in a human oral carcinoma cell line (UM-SCC-1-GALR1) that expresses no endogenous GALR1. In transfected cells, galanin induced activation of the extracellular-regulated protein kinase-1/2 (ERK1/2) and suppressed proliferation. Galanin stimulation mediated decreased expression of cyclin D1 and increased expression of the cyclin-dependent kinase inhibitors (CKI), p27(Kip1) and p57(Kip2). Pretreatment with the ERK1/2-specific inhibitor U0126 prevented these galanin-induced effects. Phosphatidylinositol 3-kinase (PI3K) pathway activation did not differ in UM-SCC-1-GALR1 and UM-SCC-1-mock cells after galanin treatment. Pertussis toxin and LY294002 inhibition demonstrated that galanin and GALR1 induce ERK1/2 activation via Galphai, not the PI3K pathway-linked to the Gbetagamma subunit. Galanin and GALR1 also inhibit colony formation and tumor growth in vivo. Our results implicate GALR1, a Gi protein-coupled receptor, as a tumor suppressor gene that inhibits cell proliferation via ERK1/2 activation.

New procedure for purse-string suture in thoracoscopic esophagectomy with intrathoracic anastomosis.

BACKGROUND: In endoscopic surgery, one of the greatest problems is the difficulty with the reconstructive procedure. This problem frequently makes operating times longer. The authors have performed thoracoscopic esophagectomy and intrathoracic esophagogastric anastomosis for reconstruction using a circular stapler for the esophageal cancer. Although the circular stapler is a useful device for gastrointestinal anastomosis, it was difficult to place a purse-string suture and to fixate the anvil into the proximal esophagus endoscopically. METHODS: The authors devised a new procedure for the placement of the purse-string suture by using an Endo-Stitch device along with a new method to incise the esophageal wall and thereby facilitate fixation of the anvil. RESULTS: The authors attempted this procedure for five patients. The anastomoses were performed successfully. CONCLUSIONS: The new procedure can make endoscopic intrathoracic anastomosis feasible and safe. In addition, this procedure can be applied widely to other endoscopic reconstructions.

A retroperitoneal bronchogenic cyst: laparoscopic treatment.

Subdiaphragmatic bronchogenic cysts are rare, and those located retroperitoneally are exceptional. We describe a retroperitoneal cyst presenting as an asymptomatic adrenal mass which was treated with laparoscopic surgery with three trocars.

Transient hematopoietic stem cell rescue using umbilical cord blood for a lethally irradiated nuclear accident victim.

We performed stem cell rescue and allogeneic skin transplantation on a lethally neutron-irradiated nuclear accident victim. HLA-DRB1 mismatched unrelated umbilical cord blood cells (2.08 x 10(7)/kg recipient body weight) were transplanted to an 8-10 Gy equivalent neutron-irradiated patient because of a lack of a suitable bone marrow or peripheral blood donor. Pre-transplant conditioning consisted of anti-thymocyte gamma-globulin alone, and GVHD prophylaxis was a combination of cyclosporine (CYA) and methylprednisolone (mPSL). Granulocyte colony-stimulating factor (G-CSF), erythropoietin (EPO), and thrombopoietin (TPO) were concurrently administered after transplantation. The absolute neutrophil count reached 0.5 x 10(9)/l on day 15, the reticulocyte count rose above 1% on day 23, and the platelet count was over 50 x 10(9)/l on day 27, respectively. Cytogenetic studies of blood and marrow showed donor/recipient mixed chimerism. Rapid autologous hematopoietic recovery was recognized after withdrawal of CYA and mPSL. Repeated pathological examinations of the skin revealed no evidence of acute GVHD. Eighty-two days after the irradiation, skin transplantation was performed to treat radiation burns. Almost 90% of the transplanted skin engrafted. Immunological examination after autologous hematopoietic recovery revealed an almost normal T cell count. However, immune functions were severely impaired. The patient died from infectious complication 210 days after the accident.

Prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by X-ray irradiation in rats.

1. In the present study, we investigated the prophylactic effects of pilocarpine hydrochloride on xerostomia models induced by either single (15 Gy) or repeated (8.6 Gy x3 days) X-ray irradiation in rats. Pilocarpine hydrochloride was administered orally 90 min before each irradiation session. Then, 7 days later, salivary volume, amylase activity and protein concentration in the saliva secreted from the right parotid gland were measured before and after a subsequent administration of pilocarpine hydrochloride (intraduodenal). 2. In irradiated no-pretreatment rats, irradiation induced a significant reduction in both spontaneous and pilocarpine hydrochloride-stimulated secretion (both total salivary volume and flow rate), regardless of the protocol used for X-ray exposure. In irradiated, pilocarpine hydrochloride-pretreated rats, salivary secretion was increased after stimulation by pilocarpine hydrochloride (intraduodenal) to a degree that depended on the pretreatment dose of pilocarpine hydrochloride (p.o.) in both xerostomia models. 3. There were no differences in amylase or protein concentrations between irradiated rats pretreated with pilocarpine hydrochloride and irradiated no-pretreatment control rats. 4. A decrease in the weight of the parotid gland was observed in rats exposed to either the single dose or repeated irradiation protocols. Changes in the submandibular gland were less marked than those in the parotid gland. These changes in gland weight were not affected by pilocarpine hydrochloride pretreatment. 5. The responsiveness of the parotid gland to subsequent stimulation with pilocarpine hydrochloride was apparently preserved in both xerostomia models by pretreatment with pilocarpine hydrochloride, which itself increased salivary secretion. This suggests that pilocarpine hydrochloride may exert functional protective effects against xerostomia that occurs following irradiation therapy through a stimulation of salivary secretion.

[Laparoscopic adrenalectomy at Shinshu University School of Medicine].

We report our experience with transperitoneal laparoscopic adrenalectomy in 26 cases (mean age 45 years). We experienced primary aldosteronism in 19 cases, Cushing syndrome in 6 cases and non-functioning tumor in one case. There was no significant difference in the operation time between right and left, men and women, primary aldosteronism and Cushing syndrome. The blood loss decreased with training. There were no severe complications during and after the operation. The weight of the resected adrenal glands increased. The blood loss decreased significantly compared with the open surgery. Transperitoneal laparoscopic adrenalectomy is becoming the safe and standard surgery for the adrenal gland tumor, and the number of suitable cases for this procedure is expected to increase in the future.

Immunohistochemical analysis of small cell carcinoma of the head and neck: a report of four patients and a review of sixteen patients in the literature with ectopic hormone production.

Small cell carcinoma (SCC) occurs mostly in the lung, and in some patients is accompanied by production of ectopic hormones. Small cell carcinoma of the head and neck is very rare. We report 4 patients with SCC of the head and neck (larynx, tonsil, maxillary sinus, and parotid gland). The patient with SCC of the maxillary sinus demonstrated a high level of plasma serotonin and overexpression of parathyroid hormone; however, he did not show any related symptoms. The patient with SCC of the tonsil showed the syndrome of inappropriate secretion of antidiuretic hormone associated with antidiuretic hormone hyperproduction at the terminal stage. In the literature, 16 patients with SCC of the head and neck with ectopic hormone production have been reported. Antidiuretic hormone and adrenocorticotropic hormone were the hormones that caused clinical symptoms (paraneoplastic syndromes). We believe that the evaluation of hormonal syndromes is valuable for diagnosis and treatment.

Effect of KAD-1229, a nonsulfonylurea hypoglycemic agent, on plasma glucose and insulin in streptozotocin-induced diabetic dogs.

Hypoglycemic agents with a rapid onset and short duration of action should be useful for controlling postprandial hyperglycemia. Our aim was to establish a diabetes mellitus model in dogs, and then during an oral glucose tolerance test to compare the hypoglycemic effect and insulinotropic action of KAD-1229, a new hypoglycemic agent, with that of gliclazide, a conventional sulfonylurea. In this model, KAD-1229 reduced the increase in plasma glucose level without producing hypoglycemia. Gliclazide had a weaker effect on reduction of the glucose increase and caused hypoglycemia via a significantly raised insulin secretion in the late phase. A rapid insulinotropic action of KAD-1229 was clearly observed in the portal venous blood. The results suggest that in type 2 diabetes caused by, at least, insulin deficiency, KAD-1229 may improve impaired insulin secretion in the early phase and attenuate hyperglycemia without causing a sustained hypoglycemia.

[Useful tools for prone position: ProneView and OPTI-GARD].

For prone position except for neurosurgery or cervical spinal surgery, head and neck are usually turned sideways on the pillow. This position has a risk of injuries to eyes, nose, lips, ears, or facial nerve and inducing neck pain after surgery. We introduce new tools to avoid these complications from prone position. The ProneView consists of a plastic helmet with a window for eyes, nose and mouth, a sponge to fit the face attached to the helmet, and a mirror to watch eyes, nose and lips. The OPTI-GARD is the glasses made by a sponge with a plastic windows to protect eyes. Using the ProneView and the OPTI-GARD together, patient's neck and head can be kept at neutral position with eyes, nose, lips, and ears being kept free from any pressure. In addition, we can check the position of the face easily by mirror. Therefore, the ProneView and the OPTI-GARD must be useful to decrease injuries to eyes, nose, lips, ears, and facial nerve, and neck pain in prone position.

A simple method for classifying genes and a bootstrap test for classifications.

A new simple method for classifying genes is proposed based on Klastorin's method. This method classifies genes into monophyletic groups which are made distinct from each other by evolutionary changes. The method is applicable as long as the phylogenetic tree of genes is obtained. There is a fast algorithm for obtaining the classification. A bootstrap test of a classification is also presented. As an example, we classified opsin genes. The classification obtained by this method is the same as the previous classification based on the function of opsins.

[A case report of TS-1 in a patient with advanced gastric cancer].

TS-1 is an oral anticancer drug that produces biochemical modulation. TS-1 is composed of FT (tegafur), CDHP (gimestat, which inhibits 5-FU degradation enzyme), and Oxo (otastat potassium, which reduces 5-FU gastrointestinal toxicities), in a molar ratio of 1:0.4:1. We administered TS-1 to a 68-year-old female gastric cancer patient, after distal gastrectomy (Stage IV, cur C). As a result of abdominal CT, the diameter of metastatic lymph node increased before and after surgery, and before TS-1 (45 x 35 mm), but it was reduced after 1 course of TS-1 (37 x 25 mm), 2 courses of TS-1 (35 x 20 mm), 3 courses of TS-1 (30 x 20 mm), 4 courses of TS-1 (30 x 20 mm), and 6 months after 4 courses of TS-1 (20 x 20 mm). The reduction rate is 74.6%. The value of CA125 was reduced 74.4 to 8.6 after TS-1. Anorexia and back pain, which occurred after operation, disappeared after TS-1. There was no side effect over grade 3.

Origin and evolution of the colonial volvocales (Chlorophyceae) as inferred from multiple, chloroplast gene sequences.

A combined data set of DNA sequences (6021 bp) from five protein-coding genes of the chloroplast genome (rbcL, atpB, psaA, psaB, and psbC genes) were analyzed for 42 strains representing 30 species of the colonial Volvocales (Volvox and its relatives) and 5 related species of green algae to deduce robust phylogenetic relationships within the colonial green flagellates. The 4-celled family Tetrabaenaceae was robustly resolved as the most basal group within the colonial Volvocales. The sequence data also suggested that all five volvocacean genera with 32 or more cells in a vegetative colony (all four of the anisogamous/oogamous genera, Eudorina, Platydorina, Pleodorina, and Volvox, plus the isogamous genus Yamagishiella) constituted a large monophyletic group, in which 2 Pleodorina species were positioned distally to 3 species of Volvox. Therefore, most of the evolution of the colonial Volvocales appears to constitute a gradual progression in colonial complexity and in types of sexual reproduction, as in the traditional volvocine lineage hypothesis, although reverse evolution must be considered for the origin of certain species of Pleodorina. Data presented here also provide robust support for a monophyletic family Goniaceae consisting of two genera: Gonium and Astrephomene.

Prognostic value of vascular endothelial growth factor (VEGF) in head and neck squamous cell carcinomas.

Vascular endothelial growth factor (VEGF) has been identified as the substance that increases the permeability and proliferation of vascular endothelial cells. We examined the clinical significance of VEGF expression in 60 head and neck squamous cell carcinomas using the methods of Western blot, immunohistochemistry, and reverse transcriptase-polymerase chain reaction (RT-PCR), comparatively, and analysed the relationship between VEGF status in Western blot and tumour size, lymph-node status, histologic grade and disease-free survival (DFS) rate. Western blot analysis revealed high VEGF expressors (tumour/normal tissue density >/= 3-fold) in 26 patients (43%) and low VEGF expressors (< 3-fold) in 34 patients (57%). The results of the Western blot analysis correlated significantly with those of the RT-PCR (P = 0.00007) or immunohistochemistry (P = 0. 00006). High VEGF expressors are associated with the progression of lymph-node spread (P = 0.0009), which are correlated with poor DFS. The 2-year DFS rate of high VEGF expressors (30%) was significantly lower than that of low VEGF expressors (78%) (P = 0.0008). Multivariate analysis showed VEGF expression and stage were independent predictors for the DFS (P = 0.045 and 0.041, respectively). VEGF expression may play an important role in progression of HNSCC.