Clinicopathologic features, treatment, prognosis and prognostic factors of neuroendocrine carcinoma of the endometrium: a retrospective analysis of 42 cases from the Kansai Clinical Oncology Group/Intergroup study in Japan / 부인종양

OBJECTIVE: We conducted a retrospective, multi-institutional, collaborative study to accumulate cases of neuroendocrine carcinoma of the endometrium, to clarify its clinicopathologic features, treatment, prognosis and prognostic factors to collate findings to establish future individualized treatment regimens. To our knowledge, this is the largest case study and the first study to statistically analyze the prognosis of this disease. METHODS: At medical institutions participating in the Kansai Clinical Oncology Group/Intergroup, cases diagnosed at a central pathologic review as neuroendocrine carcinoma of the endometrium between 1995 and 2014 were enrolled. We retrospectively analyzed the clinicopathologic features, treatment, prognosis and prognostic factors of this disease. RESULTS: A total of 65 cases were registered from 18 medical institutions in Japan. Of these, 42 (64.6%) cases were diagnosed as neuroendocrine carcinoma of the endometrium based on the central pathological review and thus included in the study. Advanced International Federation of Gynecology and Obstetrics stages (stage III and IV) and pure type small cell neuroendocrine carcinoma cases had a significantly worse prognosis. Upon multivariate analysis, only histologic subtypes and surgery were significant prognostic factors. Pure type cases had a significantly worse prognosis compared to mixed type cases and complete surgery cases had a significantly better prognosis compared to cases with no or incomplete surgery. CONCLUSION: Our findings suggest that complete surgery improves the prognosis of neuroendocrine carcinoma of the endometrium. Even among cases with advanced disease stages, if complete surgery is expected to be achieved, clinicians should consider curative surgery to improve the prognosis of neuroendocrine carcinoma of the endometrium.

The detection of sentinel lymph nodes in laparoscopic surgery for uterine cervical cancer using 99m-technetium-tin colloid, indocyanine green, and blue dye / 부인종양

OBJECTIVE: Our objective was to determine the feasibility and detection rates and clarify the most effective combination of injected tracer types for sentinel lymph node (SLN) mapping in uterine cervical cancer in patients who have undergone laparoscopic surgery or neoadjuvant chemotherapy (NAC). METHODS: A total of 119 patients with cervical cancer underwent SLN biopsy at radical hysterectomy using three types of tracers. The various factors related to side-specific detection rate, sensitivity, and false negative (FN) rate were analyzed. RESULTS: The SLN detection rates using 99m-technetium ((99m)Tc)-tin colloid, indigo carmine, and indocyanine green (ICG) were 85.8%, 20.2%, and 61.6%, respectively. The patients with ≥2-cm-diameter tumors and those who received NAC had lower detection rates than those with <2-cm-diameter tumors (75.7% vs. 91.5%, p<0.01) and those who did not receive NAC (67.9% vs. 86.3%, p<0.01), respectively. Laparoscopic procedures had a higher detection rate than laparotomy (100.0% vs. 77.1%, p<0.01). No factors significantly affected the sensitivity; however, the patients with ≥2-cm-diameter tumors (86.0% vs. 1.4%, p<0.01), NAC (19.4% vs. 2.2%, p<0.01), and those who underwent laparotomy (7.4% vs. 0%, p<0.01) had an unfavorable FN rate. CONCLUSION: Among the examined tracers, (99m)Tc had the highest detection of SLN mapping in patients with uterine cervical cancer. Patients with local advanced cervical cancer with/without NAC treatment might be unsuited for SLN mapping. SLN mapping is feasible and results in an excellent detection rate in patients with <2-cm-diameter cervical cancer. Laparoscopic surgery is the best procedure for SLN detection in patients with early-stage disease.

A study of the triage function of referrals in an urban clinic / 日本プライマリ・ケア連合学会誌

<b>Introduction</b> : To promote disease management in the community, general physicians should refer their patients to specialists in a timely and appropriate manner. In this study, we propose an indicator for evaluation of such referrals.<br><b>Methods</b> : We analyzed all referrals in an urban clinic from September 1, 2011 to August 31, 2012. Symptoms and diagnoses documented by general physicians were collected from medical records, and the final diagnoses by specialists were collected from their reports. The symptoms and diagnoses were classified using the International Classification of Primary Care second edition (ICPC-2). Referral rates, hospitalization rates, and place of referral were analyzed.<br><b>Results</b> : The average number of encounters in the candidate clinic was 1402 per month, and the mean number of referrals was 23 (1.6% of encounters). Of patients who received a referral, 6.75 (29.1%) were admitted to hospitals. The symptoms and diagnoses of the referred patients were distributed across all chapters (A to Z) of ICPC-2. Diagnoses of admitted patients included pneumonia (R81) (24%), urinary tract infection (U70 and U71) (9%), and acute gastroenteritis with dehydration (D73 with T11) (9%).<br><b>Conclusion</b> : We identified the referral rates, hospitalization rates, and distribution of referral patients as indicators of the triage function of primary care physicians. These should be evaluated further as potential indicators of “the quality of medical care.”

Characteristics and mechanisms of low-frequency muscle fatigue: alterations in skeletal muscle / 体力科学

Repeated contractions of skeletal muscle cause fatigue, as manifested by a reduced ability to produce force and slowed contraction. During studies of muscle fatigue, a phenomenon known as low-frequency fatigue (LFF) was observed in human skeletal muscles. It is characterized by a greater loss of force in response to low- versus high-frequency muscle stimulation and a long period of time for full recovery. This force deficit is most likely to be owing to disturbances in sarcoplasmic reticulum (SR) Ca²⁺ release and/or reductions in myofibrillar Ca²⁺ sensitivity. Studies on metabolites have implied that inorganic phosphate and Mg²⁺ might have some role in reduced SR Ca²⁺ release that occurs immediately after fatiguing contraction. In addition, recent experiments have shown that impaired myofibril function may relate to increased nitric oxide and hydroxyl radical production, whereas deterioration of SR function may be attributable to increased superoxide production, elevation of cytoplasmic Ca²⁺ concentration and/or decreased muscle glycogen. Finally, we will discuss possible proteins which are affected and contribute to the development of LFF.

EFFECT OF HIGH-INTENSITY TRAINING AND ACUTE EXERCISE ON Ca²⁺-SEQUESTERING FUNCTION OF SARCOPLASMIC RETICULUM : ROLE OF OXIDATIVE MODIFICATION / 体力科学

To investigate the influences of high-intensity training and/or a single bout of exercise on <i>in vitro</i> Ca²⁺-sequestering function of the sarcoplasmic reticulum (SR), the rats were subjected to 8 weeks of an interval running program (final training : 2.5-min running×4 sets per day, 50 m/min at 10% incline). Following training, both trained and untrained rats were run at a 10% incline, 50 m/min for 2.5 min or to exhaustion. SR Ca²⁺-ATPase activity, SR Ca²⁺-uptake rate and carbonyl group contents comprised in SR Ca²⁺-ATPase activity were examined in the superficial portions of the gastrocnemius and vastus lateralis muscles. For rested muscles, a 12.7% elevation in the SR Ca²⁺-uptake rate was induced by training. Training led to improved running performance (avg time to exhaustion : untrained-191.1 vs trained-270.9 sec ; <i>P</i><0.01). Regardless of training status, a single bout of exercise caused progressive reductions in SR Ca²⁺-ATPase activity and SR Ca²⁺-uptake rate. Increases in carbonyl content only occurred after exhaustive exercise (<i>P</i><0.05). At both point of 2.5-min and exhaustion, no differences existed in SR Ca²⁺-sequestering capacity and carbonyl content between untrained and trained muscles. These findings confirm the previous findings that oxidative modifications may account, at least partly, for exercise-induced deterioration in SR Ca²⁺-sequestering function ; and raise the possibility that in the final phase of acute exercise, high-intensity training could delay the progression of protein oxidation of SR Ca²⁺-ATPase.

RELATIONSHIP BETWEEN OXIDATION OF MYOFIBRILLAR PROTEINS AND CONTRACTILE PROPERTIES IN SOLEUS MUSCLES FROM HYPERTHYROID RAT / 体力科学

We tested the hypothesis that a force reduction in soleus muscles from hyperthyroid rats would be associated with oxidative modification of myofibrillar proteins. Daily injection of thyroid hormone [3, 5, 3’-triiodo-_L-thyronine (T₃)] for 21 days depressed isometric forces in whole soleus muscle across a range of stimulus frequencies (1, 10, 20, 40, 75 and 100 Hz) (<i>P</i><0.05). In fiber bundles, hyperthyroidism also led to pronounced reductions (<i>P</i><0.05) in both K⁺- and 4-chloro-<i>m</i>-cresol-induced contracture forces. The degrees of the reductions were similar between these two contractures. These reductions in force production were accompanied by a remarkable increment (103% ; <i>P</i><0.05) in carbonyl groups comprised in myofibrillar proteins. In additional experiments, we have also tested the efficacy of carvedilol, a non-selective β₁-β₂-blocker that possesses anti-oxidative properties. Treatment with carvedilol prevented T₃-induced oxidation of myofibrillar proteins. However, carvedilol did not improve the hyperthyroid-induced reductions in force production. These data suggest that oxidative modification of myofibrillar proteins may not account for the reductions in force production of hyperthyroid rat soleus muscle.

Characterization of a chitinase gene encoded by virus-sensitive chlorella strains and expressed during virus infection

A chitinase gene [hChti-1] was found and characterized in a few strains of Chlorella species that are sensitive to Chlorella viruses. A cDNA clone of hChti-1 obtained from Chlorella strain NC64A contained a 401 aa [1206 bp] open reading frame, whose amino acid sequence was most similar to that of family 18 catalytic domain I of dual-structured chitinase vChti-1 encoded by Chlorella virus CVK2. The expression of hChti-1 was induced by virus infection and functional chitinase protein was produced. Since the hChti-1 gene was strictly limited to virus-sensitive strains, its occurrence seems to be involved in the virus infection mechanism. This is the first report of chitinase encoded and produced by unicellular algae

CHANGES IN SARCOPLASMIC RETICULUM Ca²⁺-SEQUESTERING CAPACITY DURING RECOVERY FOLLOWING HIGH-INTENSITY EXERCISE / 体力科学

The purpose of this study was to investigate changes in sarcoplasmic reticulum (SR) Ca²⁺-sequestering capacity in rat fast-twitch plantaris (PL) and slow-twitch soleus (SOL) muscles during recovery after high-intensity exercise. The rats were subjected to treadmill runs to exhaustion at the intensity (10% incline at 50 m/min) estimated to require 100% of maximal O₂ consumption. The muscles were excised immediately after exercise, and 15, 30 and 60 min after exercise. Acute high-intensity exercise evoked a 27 % and 38 % depression (<i>P</i><0.05) in SR Ca²⁺-uptake rate in the PL and SOL, respectively. In the PL, uptake rate remained lower (<i>P</i><0.05) at 30 min of recovery but recovered 60 min after exercise. These alterations were paralleled by those of SR Ca²⁺-ATPase activity. On the other hand, SR Ca²⁺-uptake rate in the SOL recovered 15 min after exercise. Unlike the PL, discordant time-course changes between SR Ca²⁺-ATPase activity and uptake occurred in the SOL during recovery. SR Ca²⁺-ATPase activities were unaltered with exercise and elevated (<i>P</i><0.05) by 25, 30 and 30% at 15, 30 and 60 min of recovery, respectively. These results demonstrate that SR Ca²⁺-sequestering ability is restored faster in slow-twitch than in fast-twitch muscle during recovery periods following a single bout of high-intensity exercise and suggest that the rapid restoration of SR Ca²⁺-sequestering ability in slow-twitch muscle could contribute to inhibition of disturbances in contractile and structural properties that are known to occur with raised myoplasmic Ca²⁺ concentrations.

EFFECTS OF THYROID HORMONE ON SARCOPLASMIC RETICULUM Ca2+ UPTAKE AND CONTRACTILE PROPERTIES IN RAT SOLEUS MUSCLE / 体力科学

The effect of hyperthyroidism on the contractile properties and Ca<SUP>2+</SUP> sequestering abilities by the sarcoplasmic reticulum (SR) in the soleus muscles was examined in rats treated with thyroid hormone (3, 5, 3'-triiodo-L-thyronine, T<SUB>3</SUB>) (300μg/kg body weight) for 3, 7 and 21 days. At the end of a given treatment period, the right or left soleus muscle was mounted isometrically at 30°C, and stimulated directly using supramaximal current intensity. A twitch contraction was elicited by a 1 msec square-wave pulse and a tetanic contraction by 20 Hz stimulation for 600 msec. To evaluate fatigue resistance, muscles were stimulated at 40 Hz for 350 msec with tetani repeated at an interval of 2 sec during a 4-min period. Another soleus muscle was used, for analysis of SR Ca<SUP>2+</SUP> -uptake rate and SR Ca<SUP>2+</SUP> -ATPase activity. Pronounced increases in SR Ca<SUP>2+</SUP> -uptake rate and ATPase activity were observed after T<SUB>3</SUB> treatment periods longer than 6 days. These alterations were accompanied by decreases in twitch and tetanic tension, half-relaxation time, and fatigue resistance. The T<SUB>3</SUB>-treated muscles stimulated at 20 Hz relaxed during the interval between successive stimuli, indicating that the mechanical fusion of tetanic contractions was incomplete. SR Ca<SUP>2+</SUP> uptake rate was significantly correlated both to tetanic tension and to fatigue resistance. These data suggest that there may be a causal relationship between changes in SR Ca<SUP>2+</SUP> uptake and the loss of muscular strength in the hyperthyroid soleus.

The Optimum Temperature of the Retrograde Continuous Blood Cardioplegia in Coronary Artery Bypass Grafting / 日本心臓血管外科学会雑誌

Myocardial oxidative stress during retrograde continuous blood cardioplegia (RCBC) was evaluated in 35 patients undergoing elective aortocoronary bypass surgery. The patients were divided into three groups: Group C (<i>n</i>=12) received cold (20°C) RCBC, Group T (<i>n</i>=11) received tepid (30°C) RCBC, and Group W (<i>n</i>=12) received warm (36°C) RCBC. Myocardial oxidative stress was assessed by measuring the release of oxidized glutathione (GSSG), malondialdehyde (MDA), and myeloperoxidase (MPO) in the coronary sinus plasma before aortic clamping, at 1, 5, and 10min after unclamping. Myocardial oxygen uptake and lactate release were assessed at the same times. Both the hemodynamic recovery and the creatine kinase MB (CKMB) activity were measured perioperatively until 24h after unclamping. In Group C, a significant coronary sinus release of GSSG was found in the early reperfusion period in comparison to Groups T and W. However, the peak CK-MB activity was significantly lower in Group T than in Group W. No significant difference in the release of MDA or MPO was noted in the three groups. The recovery of oxygen uptake after unclamping was rapid in Group T. The recovery in the left and right ventricular functions and the myocardial lactate release were similar in the three groups. In conclusion, tepid RCBC is considered to protect the myocardium from ischemia-reperfusion injury better than cold or warm blood cardioplegia under retrograde continuous perfusion.

The Early Results of MIDCAB / 日本心臓血管外科学会雑誌

We herein review the early results of minimally invasive coronary artery bypass (MIDCAB). From April 1994 to November 1998, 23 patients underwent MIDCAB, and 12 patients underwent coronary artery bypass grafting with cardiopulmonary bypass (CABG). We compared and analyzed the findings of these two groups. Regarding preoperative factors, the MIDCAB group included elderly patients, while the CABG group consisted of younger patients. However, the frequency of hemodialysis, respiratory disorders and cerebral vascular accidents did not differ significantly between the 2 groups. Regarding perioperative factors, the MIDCAB group needed a shorter operation time, and also had a lower bleeding volume, and a low incidence of blood transfusion. Regarding the postoperative course, the MIDCAB group needed a shorter artificial respiration time, and a shorter postoperative hospital stay, and no mortality was observed. The graft patency of the MIDCAB group was lower (88%) than the CABG group (100%). However, the graft patency of the MIDCAB group reached 94% after we used a stabilizer in the operation. In conclusion, the operation results of the MIDCAB group were comparatively better than those of the CABG group. Thanks to recent technological advances, the results of MIDCAB continue to improve. Though MIDCAB remains an invaluable operative modality for the treatment of one-vessel disease, surgeons must be careful to select appropriate candidates for this operative method.

Synergistic Action of Amrinone and Dibutyryl Cyclic AMP on Myocardial Metabolism and Hemodynamics in the Early Postoperative Period Following Open-Heart Surgery / 日本心臓血管外科学会雑誌

Effects of amrinone and dibutyryl cyclic AMP (DBcAMP) on hemodynamics and myocardial metabolism were studied in 16 patients in the early postoperative period following open-heart surgery. Amrinone was administered continously at 10μg/kg/min for 5 hours and DBcAMP at 12μg/kg/min was infused concomitantly for the last 1 hour. Amrinone increased SVI, and decreased HR, PCWP, arterial systolic blood pressure, double product and central temperature difference significantly. Following concomitant administration of DBcAMP for 1 hour, further increase of CI, O₂ delivery, blood sugar and insulin were observed. Significant decrease of excess lactate from 9.31±3.27 to -1.31±1.83mg/dl (<i>p</i><0.05) showed that anaerobic metabolism improved in the myocardium after amrinone administration, and the effect improved further to -3.64±1.8mg/dl following concomitant administration of DBcAMP. These data demonstrate that amrinone has beneficial effects on hemodynamics and myocardial metabolism, and following supplementary administration of DBcAMP, further improvement in hemodynamics was observed.

Long-term Evaluation of a "Tighter" Tricuspid Annuloplasty by De Vega's Technique for Secondary Tricuspid Regurgitation / 日本心臓血管外科学会雑誌

The long-term results of a “tighter” tricuspid annuloplasty (TAP) by De Vega's technique for secondary tricuspid regurgitation (TR) were studied. From June 1985 to July 1993, 122 patients underwent TAP following mitral valve surgery in our clinic. The analysis was performed on 50 patients who were followed up for more than 5 years (a mean of 75.1 months ranging from 60 to 96 months). The patients consisted of 13 males and 37 females with a mean age of 53.7 years (range from 28 to 71 years). The echocardiogram taken after long-term follow-up showed that the right ventricular inflow peak velocity at rest was a mean of 0.72m/s ranging from 0.53 to 1.04m/s, while the mean pressure half time was 76.7±14.9msec. Significant residual TR was observed in 16% at 1 month, 6% at 1 year, 10% at 3 years, and 12% at 5 years or more after operations. We conclude that a “tighter” TAP by De Vega's technique for secondary TR seems to be effective for the long-term reduction of residual TR and is not a causative factor for tricuspid stenosis.

Anigioplasty of Isolated Left Coronary Ostial Stenosis-A Case Report / 日本心臓血管外科学会雑誌

A case of isolated left coronary artery ostial stenosis treated successfully by the saphenous vein patch plasty is reported. A 49-year-old woman was referred for surgery because of unstable angina with subendcardial infarction on ECG. Coronary angiogram showed isolated severe stenosis of left coronary artery ostium without stenotic lesion in the periphery and right coronary artery. At surgery, the aorta was incised obliquely downward to the left coronary ostium and this incision was further extended 8mm distally in the main trunk. Atheromatous left coronary ostium was enlarged with the saphenous vein patch. Postoperatively, angina disappeared and aortic root angioram revealed a well dilated ostium. At 1 year follow-up, the patient remains asymptomatic.

Coronary artery bypass grafting in a patient with hypertrophic non-obstructive cardiomyopathy. A case report / 日本心臓血管外科学会雑誌

Preoperatively, hypertrophic non-obstructive cardiomyopathy with asymmetrical septal hypertrophy was found in a 66-year-old man with a chief complain of effort angina whose CAG showed stenosis of 70% in LCA (seg 5) and 100% in RCA (seg 1) with collaterals from LAD. Although graft flows, 240ml to LAD and 28ml/min to RCA, were obtained, it was necessary to place the patient on the assisted circulation and catecholamines when the weaning from CPB was being tried due to “stone heart” despite patient had been on IABP during surgery and short anoxic arrest time of 44min. Postoperative hemodynamic recovery was slow with low cardiac output improved lately by the continuous use of IABP and DBcAMP. Catecholamines and vasodilators often cause disturbance of hemodynamics in hypertrophic obstructive type but seem to be effective in non-obstructive type. Importance of myocardial protection, use of IABP, careful administration of β-stimulants and DBcAMP are discussed in surgery of patients with cardiomyopathy.