Esophageal squamous cell carcinoma: Pathology and prognosis

Between 1985 and 1992 a total of 403 patients with resected thoracic esophageal squamous cell carcinoma were evaluated histopathologically, and various pathologic findings related to survival were examined. Concerning depth of tumor invasion, 8 (2%) cases were pTis, 110 (27%) were pT1, 48 (12%) were pT2, 202 (50%) were pT3, and 35 (9%) were pT4. Lymphatic invasion was detected in 299 cases (74%), blood vessel invasion in 200 cases (49%), intramural metastasis in 45 (11%), and lymph node metastasis in 232 (58%). In pT1 carcinoma cases, 4% of mucosal carcinomas and 30% of submucosal carcinomas had lymph node metastasis. Tumors with deeper invasion had a higher incidence of lymph node metastasis: 74% of pT3 carcinomas and 83% of pT4 carcinomas. The sites of lymph node metastasis were divided into mediastinal, cervical, and abdominal fields; and rates of lymph node metastasis were 49%, 14%, and 41%, respectively. In all resected cases, the operative mortality rate was 3.2%, and the overall 5-year survival rate was 44.8%. The 5-year survival rate of patients with curative resection (R₀ and R₁) was 49.5%, whereas patients with palliative resection (R₂) did not survive more than 3 years. There was no significant difference in survival relative to tumor location. In curatively resected cases, the significant prognostic factors by multivariate analysis were pT category, vascular invasion, lymph node metastasis, and intramural metastasis. Prognosis of lymph node-positive cases did not depend on the positive node site. Patients with only one positive node had a better prognosis, and those with six or more positive nodes had a poor prognosis. Concerning lymph node metastasis, other factors that worsened prognosis were a positive node larger than 1 cm, two- to three-field metastasis, and positive cervical nodes in cases of lower-third esophageal carcinoma.

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Resumen Se analizaron desde el punto de vista histopatológico 403 pacientes, 348 hombres y 55 mujeres, sometidos a resección de carcinoma escamocelular del esófago torácico en el período 1985 a 1992, y se examinaron diversos hallazgos patológicos en relación a sobrevida. En cuanto a profundidad de invasión tumoral, 8(2%) casos fueron Tis, 110(38%) p T1, 48(12%) p T2, 202(50%) p T3 y 35(8%) p T4. Se detectó invasión linfática en 299 casos (74%), invasión de vasos sanguíneos en 200 (49%), metástasis intramurales en 45(11%) y metástasis ganglionares en 232 (58%). Entre los casos en estado p T1, 4% de los carcinomas mucosos y 30% de los submucosos tenían metástasis ganglionares.Los tumores con invasión más profunda exhibieron una mayor incidencia de metástasis ganglionares, 74% en los pacientes en estado pT3 y 83% en los estados pT4. La ubicación de las metástasis ganglionares fue dividida en tres campos: mediastinal, cervical y abdominal, y las ratas de metástasis ganglionares correspondientes fueron 49%, 14%, y 41%. La tasa de mortalidad operatoria fue 3.2% y la tasa global de sobrevida a 5 años fue 44.8%; para los casos con resección curativa (R0 y R1) ésta fue de 49.5%, en tanto que ninguno de los pacientes con resección paliative (R2) sobrevivió más allá de 3 años no se hallaron diferencias significativas en lo relativo a ubicación del cáncer.En los pacientes con resección curativa, los factores pronóstico de importancia significativa determinados por análisis multivariado fueron el estado pT, la invasión vascular, las metástasis ganglionares y las metástasis intramurales. El pronóstico en los pacientes con ganglios positivos no dependió de la ubicación de los ganglios afectados, y los pacientes con sólo un ganglio afectado tuvieron un mejor pronóstico, en tanto que aquellos con 6 o más ganglios afectados tuvieron un pronóstico pobre.En lo relativo a las metástasis ganglionares, otros factores que ensombrecieron el pronóstico fueron los ganglios mayores de 1 cm, metástasis a 2–3 campos y ganglios cervicales positivos cuando el carcinoma primario era del tercio inferior del esófago.

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Résumé Entre 1985 et 1992, 403 patients ayant eu une résection de leur cancer épidermoïde de l'oesophage thoracique ont eu une évaluation histopathologique corrélée avec la survie. En ce qui concerne la profondeur de l'invasion, huit cas (2%) étaient des pTis, 110 (38%) étaient des pT1, 48 (12%) étaient des pT2, 202 (50%) étaient des pT3, et 35 (8%) étaient des pT4. L'atteinte lymphatique a été détectée chez 299 (74%) patients, une invasion vasculaire dans 200 (49%) des cas, une résurgence intramurale dans 45 (11%) des cas et une atteìnte ganglionnaire chez 232 (58%) des cas. Dans le cas des tumeurs pT1, 4% des cancers de la muqueuse, et 30% des cancers de la sous-muqueuse étaient accompagnées de métastases ganglionnaires. Des tumeurs ayant une invasion plus profonde, les pT3 et les pT4 étaient associées à des métastases ganglionnaires dans 74% et 83% des cas. Les sites des métastases ganglionnaires étaient le médiastin, les chaînes cervicales, et l'abdomen chez, respectivement, 49%, 14% et 41% des cas. Parmi les cas de résection, la mortalité opératoire était de 3.2% et la survie globale à 5 ans étaient de 44.8%. La survie à 5 ans des patients ayant eu une résection à visée curative (R0 et R1) était de 49.5% alors qu'aucun des patients ayant eu une résection palliative (R2) n'étaient en vie à 3 ans. Il n'y avait aucune différence de survie selon la localisation tumorale. Chez les patients réséqués de façon curative, les facteurs pronostiques significatifs étaient la classe pT, l'invasion vasculaire, la métastase lymphatique, et l'invasion intramurale. Le pronostic des patients ayant une métastase ganglionnaire était indépendant de la localisation. Le pronostic des patients ayant un seul ganglion envahi était meilleur que le pronostic des patients ayant six ou plus de ganglions envahis. Le pronostic était moins bon lorsque la métastase ganglionnaire était plus grande que 1 cm, intéressait plus de 2–3 champs différents et lorsqu'elle intéressait la chaîne cervicale en cas de cancer du tiers inférieur de l'oesophage.

     

The interaction of neuromuscular relaxants with rabbit lung muscarinic receptors

The interaction of muscle relaxants with airway muscarinic receptors of rabbit lung was investigated in vitro by the [3H]QNB binding technique. Pancuronium, vecuronium, alcuronium and succinyl choline chloride (SCC) inhibited the binding of [3H]QNB to rabbit lung muscarinic receptors in a dose-dependent manner. The values of IC50 (the concentration giving 50% inhibition) of pancuronium, vecuronium, alcuronium and SCC were 1.54 x 10(-5), 2.52 x 10(-5), 8.40 x 10(-5), and 4.00 x 10(-3) mol/l respectively. As the values of Kd increased with minimal change in the value of Bmax, while not influencing the number of receptors, these muscle relaxants had an inhibitory action on the affinity of muscarinic receptors to [3H]QNB in the order: pancuronium greater than or equal to vecuronium greater than alcuronium greater than SCC. Applying IC50 values to human conditions, clinical doses of these muscarinic relaxants are unlikely to exhibit any significant vagolytic action in lung tissue.     

Rapid tolerance to focal cerebral ischemia in rats is attenuated by adenosine A1 receptor antagonist.

Two types of ischemic tolerance in the brain, rapid and delayed, have been reported in terms of the interval between the conditioning and test insults. Although many reports showed that delayed-phase neuroprotection evoked by preconditioning is evident after 1 week or longer, there have been a few investigations about rapidly induced tolerance, and the reported neuroprotective effects become ambiguous 7 days after the insults. The authors examined whether this rapid ischemic tolerance exists after 7 days of reperfusion in a rat focal ischemic model, and investigated modulating effects of the adenosine A 1 receptor antagonist DPCPX (8-cyclopentyl-1,3-dipropylxanthine). Preconditioning with 30 minutes of middle cerebral artery occlusion reduced infarct volume 7 days after 180 minutes of subsequent focal ischemia given after 1-hour reperfusion. The rapid preconditioning also improved neurologic outcome. These beneficial effects were attenuated by pretreatment of 0.1 mg/kg DPCPX, which did not influence the infarct volume after conditioning (30 minutes) or test (180 minutes) ischemia when given alone. The results show that preconditioning with a brief focal ischemia induces rapid tolerance to a subsequent severe ischemic insult, the effect of which is still present after 7 days of reperfusion, and that the rapid ischemic tolerance is possibly mediated through an adenosine A 1 receptor-related mechanism.     

Clustered components of the metabolic syndrome and platelet counts in Japanese females.

BACKGROUND: Blood platelet counts (PCs) play a role in the development of cardiovascular disease (CVD). The metabolic syndrome (MS) is also associated with high CVD risk. However, the connection between PCs and MS has not yet been thoroughly investigated in relation to various biosocial factors that can affect both PCs and the pathophysiology of MS. METHODS: A total of 152 asymptomatic female subjects (mean age 50 years) with almost normal levels of hemoglobin and white blood cell counts were recruited. MS was diagnosed according to the NCEP-ATP III criteria with a minor modification. The relationships between PCs and MS were analyzed according to the number of MS components (0, 1-2, > or =3). Biosocial factors including age and some lifestyle factors (smoking, alcohol intake and physical activity) were included in the analyses. RESULTS: PCs in subjects with > or =3 MS components (233+/-43 [SD]x10(9) /L) were strikingly and significantly higher than in subjects with 0 (194+/-34 x 10(9)/L) or 1-2 MS components (207+/-38 x 10(9)/L). General linear model analysis for PCs, adjusted for all biosocial factors and number of MS components, revealed a significant and positive correlation between PCs and number of MS components (p<0.0001). CONCLUSIONS: The results suggest that PCs may be a potential marker associated with clustered MS components, independent of some biosocial factors, in Japanese females.     

Importance of anti-siphon devices in the treatment of pediatric hydrocephalus

The effects of an antisiphon device (ASD) on shunt flow and intracranial pressure (ICP) in 16 children with hypertensive hydrocephalus were examined using quantitative radionuclide shuntography (^99mTc) with the children in supine and sitting positions. The average age of these patients was 9.5 years. Results were compared with those recorded in 36 patients with adult normal-pressure hydrocephalus (NPH). The closing pressure levels of shunt valve used were low in 8 cases, medium in 7 and high in 1. Half the children (8) had shunt systems with, and the other 8 without, ASD. In the children who had the shunt system without ASD, sitting shunt flow was significantly greater than supine shunt flow, which indicated overdrainage. Conversely, in children who had the shunt system with ASD, supine shunt flow was greater than sitting shunt flow. Because ASD prevented overdrainage, ICP was higher with the shunt system with ASD than with the shunt system without ASD. Without ASD, sitting shunt flow of children was lower than that of adult patients with NPH because of the lower hydrostatic pressure, which correlated with their height. Conversely, in the presence of a shunt system with ASD, sitting shunt flow of children was greater than that of adults, because of the higher ICP and lower hydrostatic pressure. The effect of ASD was smaller in children than in adults, because positive pressure over the ASD was greater (hypertension vs normal pressure) and negative pressure under the ASD was less (short vs tall) in children than in adults. Thus, in children the ASD was effective in preventing overdrainage. An overfunction of the ASD, which has sometimes been observed in adult patients with NPH, was not encountered. The relationships among the function of the ASD and ICP, height and position of the ASD are discussed.Presented at the Consensus Conference: Hydrocephalus '92, Assisi, Italy, 26–30 April 1992     

USEFUL ENDOSCOPIC ULTRASONOGRAPHY TO ASSESS THE EFFICACY OF NEOADJUVANT THERAPY FOR ADVANCED ESOPHAGEAL CARCINOMA: BASED ON THE RESPONSE EVALUATION CRITERIA IN SOLID TUMORS

Objective: The aim of the present study was to assess the usefulness of endoscopic ultrasonography (EUS) for evaluating the efficacy of neoadjuvant therapy for advanced esophageal carcinoma based on the Response Evaluation Criteria in Solid Tumors (RECIST). Patients and Methods: Sixty‐two patients with advanced esophageal carcinoma underwent surgical resection after neoadjuvant therapy. The maximal tumor thickness was measured by EUS before and after neoadjuvant therapy, and the percent reduction was compared with the pathological response. Based on the RECIST, PD‐SD (progressive disease‐stable disease) was defined as < 30% reduction of tumor thickness on EUS, PR (partial response) as ≥ 30% reduction of tumor thickness, and CR (complete response) as no detectable tumor (100%). Results: The percent reduction of the thickness of Grade 0–1, Grade 2 and Grade 3 tumor was 11.5 ± 21.0%, 48.2 ± 17.0% and 74.9 ± 21.1%, respectively. There were significant differences in the extent of reduction among the three groups. Based on the RECIST, 80% of Grade 0–1 cases, 91% of Grade 2 cases and 22% of Grade 3 cases were PD‐SD, PR, and CR according to EUS, respectively. EUS correctly identified 80% of non‐responders and 94% of responders. Conclusions: The percentage reduction of tumor thickness on EUS closely reflected the pathological evaluation. EUS evaluation based on the RECIST seems to be useful for monitoring neoadjuvant therapy in patients with esophageal carcinoma.     

Spermatozoon and mitochondrial DNA

In eukaryotic cells, mitochondria are the major site of ATP production, which is achieved through the electron-transport chain and oxidative phosphorylation, according to the energy demand. Mitochondria contain their own genome (mitochondrial DNA, mtDNA) on which a limited number of genes are encoded. In the human sperm, mitochondria helically wrap the midpiece of the tail and supply the energy for the driving force of motility. While various mutations in mtDNA in somatic cells are found to be associated with a wide spectrum of diseases, it is also reported that the abnormal mtDNA causes astenozoospermia and male infertility. At fertilization, the paternal mitochondria and mtDNA are rapidly degraded early in embryogenesis, thus, only maternal mtDNA is transmitted to the descendant. We briefly review here the basic characteristics of mtDNA and its maternal transmission during fertilization, as well as male infertility. (Reprod Med Biol 2002; 1 : 41–47)     

Angiographic neovascularization after bypass surgery in moyamoya disease: our experience at Hiroshima University Hospital

In this study, we investigated the effect of different bypass procedures on postoperative neovascularization in patients with moyamoya disease at Hiroshima University Hospital. Fourteen cerebral hemispheres of seven patients with moyamoya disease were investigated. Five of the 14 hemispheres underwent direct bypass surgery and the remaining 9 underwent indirect bypass. The neovascularization after bypass surgery was evaluated by cerebral angiography. The extent of angiographic neovascularization after direct or indirect bypass surgery was graded as good, fair or poor. Postoperative neovascularization status (good, fair or poor) was compared with the bypass procedure (direct and indirect bypass). Good neovascularization was observed in 8 hemispheres and the remaining 6 had poor neovascularization. Direct bypass surgery was significantly more effective for angiographic neovascularization than the indirect procedure in moyamoya patients (chi2-test, p<0.05). Therefore, we concluded that the direct bypass procedure is a better choice for moyamoya disease as evidenced by angiographic neovascularization.