Long-term survival after an aggressive surgical resection and chemotherapy for stage IV pulmonary giant cell carcinoma

BACKGROUND: Pulmonary giant cell carcinoma is one of the rare histological subtypes with pleomorphic, sarcomatoid or sarcomatous elements. The prognosis of patients with this tumor tends to be poor, because surgery, irradiation and chemotherapy are not usually effective. CASE PRESENTATION: We herein report a patient with pulmonary giant cell carcinoma with stage IV disease in whom aggressive multi-modality therapy resulted in a long-term survival. A 51-year-old male underwent an emergent operation with a partial resection of small intestinal metastases due to bleeding from the tumor. The patient also underwent a left pneumonectomy due to hemothorax as a result of the rapid growth of the primary tumor. Thereafter, two different regimens of chemotherapy and a partial resection for other site of small intestinal metastases and a splenectomy for splenic metastases were performed. The patient is presently doing well without any evidence of recurrence for 3 years after the initial operation. CONCLUSION: This is a first report of a rare case with stage IV pulmonary giant cell carcinoma who has survived long-term after undergoing aggressive surgical treatment and chemotherapy

Structural basis for the substrate recognition of aminoglycoside 7′′-phosphotransferase-Ia from Streptomyces hygroscopicus

Hygromycin B (HygB) is one of the aminoglycoside antibiotics, and it is widely used as a reagent in molecular-biology experiments. Two kinases are known to inactivate HygB through phosphorylation: aminoglycoside 7′′-phosphotransferase-Ia [APH(7′′)-Ia] from Streptomyces hygroscopicus and aminoglycoside 4-phosphotransferase-Ia [APH(4)-Ia] from Escherichia coli. They phosphorylate the hydroxyl groups at positions 7′′ and 4 of the HygB molecule, respectively. Previously, the crystal structure of APH(4)-Ia was reported as a ternary complex with HygB and 5′-adenylyl-β,γ-imidodiphosphate (AMP-PNP). To investigate the differences in the substrate-recognition mechanism between APH(7′′)-Ia and APH(4)-Ia, the crystal structure of APH(7′′)-Ia complexed with HygB is reported. The overall structure of APH(7′′)-Ia is similar to those of other aminoglycoside phosphotransferases, including APH(4)-Ia, and consists of an N-terminal lobe (N-lobe) and a C-terminal lobe (C-lobe). The latter also comprises a core and a helical domain. Accordingly, the APH(7′′)-Ia and APH(4)-Ia structures fit globally when the structures are superposed at three catalytically important conserved residues, His, Asp and Asn, in the Brenner motif, which is conserved in aminoglycoside phosphotransferases as well as in eukaryotic protein kinases. On the other hand, the phosphorylated hydroxyl groups of HygB in both structures come close to the Asp residue, and the HygB molecules in each structure lie in opposite directions. These molecules were held by the helical domain in the C-lobe, which exhibited structural differences between the two kinases. Furthermore, based on the crystal structures of APH(7′′)-Ia and APH(4)-Ia, some mutated residues in their thermostable mutants reported previously were located at the same positions in the two enzymes

Precise Three-Dimensional Morphology of the Male Anterior Anorectum Reconstructed From Large Serial Histologic Sections: A Cadaveric Study

BACKGROUND: Deep anatomic knowledge of the male anterior anorectum is important to avoid urethral injury and rectal perforation in intersphincteric resection or abdominoperineal resection for very low rectal cancer. However, its structure is difficult to understand, because the anorectum, muscles, and urogenital organs are complicatedly and 3-dimensionally arranged. OBJECTIVE: The purpose of this study was to revisit the anatomic information of the male anterior anorectum for intersphincteric resection and abdominoperineal resection with a focus on the spatial muscular morphology. DESIGN: This was a descriptive cadaveric study. SETTINGS: The study was conducted at Ehime and Kyoto universities. PATIENTS: Tissue specimens from 9 male cadavers were included. MAIN OUTCOME MEASURES: Specimens around the anterior anorectum were serially sectioned in the horizontal, sagittal, or frontal plane; large semiserial histologic sections were created at 250-μm intervals. The series were stained with Elastica van Gieson, and some sections from the series were studied by immunohistochemistry to detect smooth and striated muscles. Two series were digitalized and reconstructed 3-dimensionally. RESULTS: Two regions without a clear anatomic border were elucidated: 1) the anterior region of the external anal sphincter, where the external anal sphincter, bulbospongiosus muscle, and superficial transverse perineal muscle were intertwined; and 2) the rectourethralis muscle, where the smooth muscle of the longitudinal muscle continuously extended to the posteroinferior area of the urethra, which became closest to the anorectum at the prostatic apex level. A tight connection between the striated and smooth muscles was identified at the anterior part of the upper external anal sphincter and anterolateral part of the puborectalis muscle level. LIMITATIONS: This study involved a small sample size of elderly cadavers. CONCLUSIONS: This study clarified the precise spatial relationship between smooth and striated muscles. The detailed anatomic findings will contribute more accurate step-by-step anterior dissection in intersphincteric resection and abdominoperineal resection, especially with the transanal approach, which can magnify the muscle fiber direction and contraction of striated muscle by electrostimulation. MORFOLOGÍA TRIDIMENSIONAL PRECISA DEL ANORRECTO ANTERIOR MASCULINO RECONSTRUIDO A TRAVÉS DE SECCIONES MAYORES HISTOLÓGICAS EN SERIE: UN ESTUDIO CADAVÉRICO: El conocimiento anatómico amplio del anorrecto anterior masculino es importante para evitar lesiones de uretra y perforación de recto en la resección interesfinterica o la resección abdominoperineal para cáncer de recto bajo. Sin embargo, su estructura es difícil de entender porque el anorrecto, los músculos y los órganos urogenitales están aliñados en forma complexa tridimensional. OBJETIVO: Revisar de nuevo el conocimiento anatómico del anorrecto anterior masculino relevante a la resección interesfinterica y la resección abdominoperineal con un enfoque en la morfología muscular espacial. DISEÑO:: Estudio descriptivo cadavérico. ENTORNO: Ehime y la Universidad de Kyoto. SUJETOS: Tejido especímenes de nueve cadáveres masculinos. PUNTOS FINALES DE VALORACIÓN:: Las muestras alrededor del anorrecto anterior se seccionaron en serie en planos horizontal, sagital y coronal. Se crearon mayores secciones histológicas en serie a intervalos de 250 μm. Los especímenes fueron teñidos con Elástica van Gieson, y algunas secciones de la serie se estudiaron mediante inmunohistoquímica para detectar músculos lisos y estriados. Dos series fueron digitalizadas y reconstruidas tridimensionalmente. RESULTADOS: Se demostraron dos regiones sin un borde anatómico definido: (i) la región anterior del esfínter anal externo, donde se entrelazaron el esfínter anal externo, el músculo bulbospongoso y el músculo perineal transverso superficial; y (ii) músculo rectouretral, donde el músculo liso del músculo longitudinal se extiende continuamente a la zona posteroinferior de la uretra, que se acerca más al anorrecto a nivel del ápice prostático. La conexión estrecha entre los músculos estriados y lisos se identificó en la parte anterior del esfínter anal externo superior y la parte anterolateral del nivel del músculo puborrectal. LIMITACIÓN:: Este estudio incluyó una muestra pequeña de cadáveres ancianos. CONCLUSIÓN:: Este estudio aclaró la relación espacial precisa entre los músculos lisos y estriados. Los hallazgos anatómicos detallados ayudarán para una disección anterior paso a paso más precisa en la resección interesfintérica y la resección abdominoperineal, especialmente con el abordaje transanal, que puede magnificar la dirección de las fibras musculares y la contracción del músculo estriado utilizando electroestimulación

Prognostic value of visceral pleural invasion in resected non–small cell lung cancer diagnosed by using a jet stream of saline solution

AbstractObjectiveVisceral pleural invasion caused by non–small cell lung cancer is a factor in the poor prognosis of patients with that disease. We investigated the relationship between the diagnosis of visceral pleural invasion by using a jet stream of saline solution, which was previously reported as a new cytologic method to more accurately detect the presence of visceral pleural invasion, and prognosis.MethodsFrom January 1992 through December 1998, 143 consecutive patients with peripheral non–small cell lung cancer that appeared to reach the visceral pleura underwent a surgical resection at the Department of Thoracic Oncology, National Kyushu Cancer Center. The surface of the visceral pleura in patients undergoing lung cancer resection was irrigated with a jet stream of saline solution. The diagnosis of visceral pleural invasion was determined by means of either a pathologic examination or by means of a jet stream of saline solution. In addition, a cytologic examination of the pleural lavage fluid obtained immediately after a thoracotomy was evaluated.ResultsForty-nine (34%) resected tumors were identified as having visceral pleural invasion. The diagnosis of visceral pleural invasion in 31, 6, and 12 patients was determined by using a jet stream of saline solution alone, pathologic examination alone, or both, respectively. The visceral pleural invasion and positive findings of intrapleural lavage cytology were linked. Although there was no significant difference between the incidence of distant metastases in the patients with visceral pleural invasion and those without visceral pleural invasion, the incidence of local recurrence, especially regarding carcinomatous pleuritis (malignant pleural effusion, pleural dissemination, or both), in the patients with visceral pleural invasion was significantly higher than in those without visceral pleural invasion. The recurrence-free survival of patients with visceral pleural invasion was significantly shorter than that of patients without visceral pleural invasion (P = .004), even patients with stage I disease (P = .02). There was also a significant difference between the patients with or without visceral pleural invasion in the overall survival (P = .02). Visceral pleural invasion was independently associated with a poor recurrence-free survival on the basis of multivariate analyses (P = .03), as were sex (P = .03), age (P = 002), and the stage of the disease (P < .0001).ConclusionsThis study confirmed that the jet stream of saline solution method in addition to ordinary pathologic examination was useful for detecting visceral pleural invasion, which is considered to be one of the causes of local recurrence, especially in carcinomatous pleuritis

Limitation in the Photosynthetic Acclimation to High Temperature in Canopy Leaves of Quercus serrata

As temperature dependence in many biological processes is generally a bell-shaped curve, warming may be benefitial at cooler climate but deterimental at warmer climate. Although warming responses are expected to vary between different temperature regimes even in the same species, such variations are poorly understood. We established open-top canopy chambers, in which average daytime leaf temperature was increased by ca. 1.0°C, at the canopy top of Quercus serrata in a deciduous forest in high (HL) and low (LL) latitude sites and studied temperature dependence of photosynthesis in the leaves across seasons. In control leaves, photosynthetic rates were higher in LL than in HL. Reponse to warming was different between HL and LL; an increase in growth temperature increased photosynthetic rates at higher leaf temperatures in HL but decreased in LL. Lower photosynthetic rate in the warming treatment in LL was partly explained by lower leaf mass per area and leaf nitrogen content per unit leaf area. Optimal temperature that maximizes photosynthetic rate (Topt) linearly increased with increasing growth temperature (GT) in HL, whereas it was saturating against GT in LL, suggesting that Topt in Q. serrata has an upper limit. The variation in Topt was explained by the activation energy of the maximum carboxylation rate (EaV). Our results suggest an upper limit in temperature acclimation of photosynthesis, which may be one of the determinants of southern limitation of the distribution

Plasma pharmacokinetics after combined therapy of gemcitabine and oral S-1 for unresectable pancreatic cancer

<p>Abstract</p> <p>Background</p> <p>The combination of gemcitabine (GEM) and S-1, an oral 5-fluorouracil (5-FU) derivative, has been shown to be a promising regimen for patients with unresectable pancreatic cancer.</p> <p>Methods</p> <p>Six patients with advanced pancreatic cancer were enrolled in this pharmacokinetics (PK) study. These patients were treated by oral administration of S-1 30 mg/m²twice daily for 28 consecutive days, followed by a 14-day rest period and intravenous administration of GEM 800 mg/m²on days 1, 15 and 29 of each course. The PK parameters of GEM and/or 5-FU after GEM single-administration, S-1 single-administration, and co-administration of GEM with pre-administration of S-1 at 2-h intervals were analyzed.</p> <p>Results</p> <p>The maximum concentration (Cmax), the area under the curve from the drug administration to the infinite time (AUCinf), and the elimination half-life (T1/2) of GEM were not significantly different between GEM administration with and without S-1. The Cmax, AUCinf, T1/2, and the time required to reach Cmax (Tmax) were not significantly different between S-1 administration with and without GEM.</p> <p>Conclusion</p> <p>There were no interactions between GEM and S-1 regarding plasma PK of GEM and 5-FU.</p

Formation of two-dimensional weak localization in conducting Langmuir-Blodgett films

We report the magnetotransport properties up to 7 T in the organic highly conducting Langmuir-Blodgett(LB) films formed by a molecular association of the electroactive donor molecule bis(ethylendioxy)tetrathiafulvalene (BEDO-TTF) and stearic acid CH$_3$(CH$_2$)$_{16}$COOH. We show the logarithmic decrease of dc conductivity and the negative transverse magnetoresistance at low temperature. They are interpreted in the weak localization of two-dimensional (2D) electronic system based on the homogeneous conducting layer with the molecular size thickness of BEDO-TTF. The electronic length with phase memory is given at the mesoscopic scale, which provides for the first time evidence of the 2D coherent charge transport in the conducting LB films.Comment: 5 pages, 1 Table and 5 figure

Relationship between serum concentrations of saturated fatty acids and unsaturated fatty acids and the homeostasis model insulin resistance index in Japanese patients with type 2 diabetes mellitus

Background : Consumption of polyunsaturated fatty acids (PUFA) improves the lipid metabolism of diabetics, leading to prevents of arteriosclerosis. Exact relationship between saturated fatty acids (SFA) or PUFA and the insulin resistance of diabetics are unknown. Subjects and Methods : We investigated the relationship between the serum concentrations of saturated and unsaturated fatty acids and the homeostasis model insulin resistance index (HOMA-R) in Japanese patients with type 2 diabetes mellitus. Results : The SFA, i.e., lauric acid, myristic acid, palmitic acid, and stearic acid ; the monounsaturated fatty acids (MUFA), i.e., palmitoleic acid, oleic acid, and erucic acid ; and the PUFA, i.e., eicosadienoic acid, dihomo-γ-linolenic acid, docosatetraenoic acid, and docosapentaenoic acid were positively correlated with HOMA-R. However, no correlations were found between HOMA-R and SFA, i.e., arachidic acid, behenic acid, and lignoceric acid ; the MUFA, i.e., eicosenoic acid and nervonic acid ; and the PUFA, i.e., linoleic acid, γ-linolenic acid, linolenic acid, 5-8-11 eicosatrienoic acid, arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. Conclusions : Some PUFA as well as SFA were positively correlated with HOMA-R. These results indicate that the intake of diet fatty acid must be well balanced in diabetic patients and it is not always true to refrain from taking SFA and increase the unsaturated fatty acids in their diets