Search

Among the several prognostic factors of papillary thyroid carcinoma (PTC), age is the most prominent. It is well known that elderly PTC patients have poorer prognoses. Here we investigated the prognostic impact of young age in univariate and multivariate analyses. We retrospectively analyzed 5,733 PTC patients without distant metastasis at presentation, who underwent initial surgery at Kuma Hospital. The median follow-up period was 150 months. We classified the patients into three groups: young (< 30 years), middle-aged (30-59), and older patients (≥ 60 years). The tumor size was larger and clinical node positivity was higher in the young patients, and significant extrathyroid extension was higher in the older patients compared to the other two groups. In the univariate analysis, the young patients showed poorer extrathyroidal locoregional and distant recurrence rates than the middle-aged patients, but not cause-specific survival rates. In the multivariate analysis, age < 30 years was an independent or marginal predictor of extrathyroidal locoregional and distant recurrence, but not of carcinoma-related death. Age ≥ 60 years independently affected PTC recurrence and death. Taken together, we should carefully treat young PTC patients because of the likeliness of extrathyroidal locoregional and distant recurrence, which may not be life-threatening.

A permanent hypoparathyroidism is a problematic complication of total thyroidectomy. In this study, we investigated its incidence and how to avoid it at the time of completion total thyroidectomy after hemithyroidectomy. Eight of the 154 patients who underwent completion total thyroidectomy as the second surgery (5%) after hemithyroidectomy (two-surgery group) showed a permanent hypothyroidism. Patients without parathyroid autotransplantation either at initial or second surgery were more likely to show a permanent hypoparathyroidism. In the subset of 74 patients in two-surgery group, who underwent bilateral central dissection, 6 (8%) had a permanent hypoparathyroidism. The incidence was higher than those in control group who underwent total thyroidectomy with bilateral central dissection at one time, which was 2%. However, all 6 patients showing a permanent hypoparathyroidsm underwent bilateral central dissection in initial surgery and none of the patients who underwent bilateral central dissection in twice had a permanent hypoparathyroidism. Taken together, we can conclude that 1) in initial surgery of hemithyroidectomy, we have to carefully search the parathyroid glands and if dissected, they should retrieved and autotransplanted to save the patients from a permanent hypoparathyroidism when they undergo second surgery in future, and 2) hemithyroidectomy with bilateral central dissection significantly increases the risk of permanent hypoparathyroidism and only ipsilateral dissection is better when we do not perform total thyroidectomy.

Papillary thyroid cancer occasionally occurs in women of childbearing age. As papillary thyroid microcarcinoma (PTMC) rarely grows or becomes clinically apparent, observation without surgery is an appropriate strategy for patients with low-risk PTMC. Human chorionic gonadotropin possesses weak thyroid-stimulating activity. The aim of this study was to assess the effect of pregnancy on PTMC.We studied 9 patients with PTMC who became pregnant between 2005 and 2011. Twenty-seven age-matched nonpregnant female PTMC patients from a database we used in our previous report served as controls. Tumor enlargement was defined as an increase in the diameter of the tumor of 3 mm or more.PTMC enlargement occurred in 44.4% (4/9 patients) of the pregnant subjects, whereas it occurred only in 11.1% (3/27 patients) of the controls (p=0.0497). Three of the pregnant patients who exhibited tumor enlargement underwent surgery after delivery. No relationship was detected between the changes in the serum thyroglobulin level, the serum thyrotropin level, and tumor size during pregnancy. Immunohistochemical examinations did not detect the estrogen receptor in the tumors of the three patients who underwent surgery.This study is an initial report indicating that the risk of PTMC enlargement might increase during pregnancy. PTMC should be carefully followed-up for possible disease aggravation during pregnancy. Even if a PTMC enlarges during pregnancy, the patient's prognosis will probably not worsen.

Adenomyoepithelioma of the breast is a rare lesion, and has a bicellular pattern of epithelial and myoepithelial cells which are regularly distributed in the tubular structures based on the histologic and ultrastructural features. It is thought to be a benign or a low-grade malignant disease. We herein describe a case of malignant adenomyoepithelioma of the breast with lung metastases in an 86-year-old woman. A primary massive tumor in the left breast grew rapidly within a short period of time. A simple mastectomy with sampling of the axillary lymph nodes was performed. The obtained lymph nodes did not include any metastatic lesions. Malignancy was evidenced by the presence of a high mitotic rate and severe nuclear atypia. Three months after the operation, radiology showed multiple lung metastases, and the patient died 2 weeks thereafter. Reviewing the literature, nine similar cases were reported, and the prognosis of malignant adenomyoepithelioma of the breast with distant metastases was very poor with the time of recurrence varying after initial treatments. Malignant adenomyoepithelioma should be followed up with careful screening for distant metastases.

We report the first case of granulomatous tubulointerstitial nephritis induced by all-trans retinoic acid (ATRA) in a patient with acute promyelocytic leukemia (APL). Acute renal failure during treatment with ATRA has been previously reported as a part of an ATRA syndrome or a thrombotic complication of a hypercoagulable state. This case indicates an alternative mechanism of acute renal failure occurring during ATRA therapy.

To prevent postoperative hypoparathyroidism following total thyroidectomy, the parathyroid glands are preserved in situ and/or resected or devascularized parathyroid glands are autotransplanted. We conducted a retrospective investigation utilizing biochemical and specific endocrine assessments to evaluate the difference in recovery of parathyroid function between the two operative methods. A total of 92 patients underwent total thyroidectomy at our hospital during the period between 1990 and 1997. These patients were divided into a preservation group (n = 83), with one or more preserved glands in situ, and an autotransplantation group (n = 9), with only transplanted glands. The level of intact parathyroid hormone (PTH) was completely restored by 1 year postoperatively in 83% (69/83) of the preservation group patients. In the remaining 14 patients (17%), the intact PTH had fallen below detectable levels on postoperative day (POD) 1, then subsequently recovered to 70% of the preoperative levels. Comparatively, in the autotransplantation group, the mean level of intact PTH recovered to only 43% of the preoperative levels. The results of this study suggest that parathyroid glands should be preserved in situ whenever possible, and that when intact PTH levels fall below detectable limits on POD 1, they may never recover to the preoperative levels in those patients.

Anaplastic thyroid carcinoma has a dismal prognosis. At present, there is no established therapy for anaplastic carcinoma of the thyroid. Our therapeutic guidelines give priority to chemotherapy and radiotherapy over surgery. We retrospectively reviewed our experience to identify prognostic factors influencing survival. Between 1984 and 1998, 462 patients with thyroid carcinoma were seen at our institution. 15 (3.2%) had anaplastic thyroid carcinoma in this series. Of these, 11 were reviewed in this study. All but one patient died. There was a median survival of 273 days, and the 1-year survival rate was 27.3%. Complete resection and tumor size were significant prognostic factors, whereas age, sex, enlarged lymph nodes, distant metastasis, radiotherapy and chemotherapy demonstrated no significant differences in the survival rate. In conclusion, complete resection should be performed for small anaplastic carcinoma of the thyroid.

Intracystic tumors of the breast prove to benign more often than malignant, and most intracystic lesions are benign papillomas. Generally, the cyst with intracystic papilloma of the breast is small, and there are few cases of intracystic papilloma of the breast forming a giant cyst in the literature. We report the case had the intracystic papilloma of the breast with a giant cyst (diameter of 15.0 cm). Imaging examinations showed two intracystic components in the cyst, and suggested that they were malignancy. Cytological examinations revealed no malignant cell. In spite of many aspirations of the cyst fluid, the size was not changed finally. The surgical resection was performed, and histological examination revealed two intracystic papillomas. In review of the literatures, it is difficult to distinguish between intracystic papilloma and intracystic papillary carcinoma by imaging or cytologic examinations preoperatively. Surgery should be recommended to confirm diagnosis and treatment.

Abstract —Molecular variants of the angiotensinogen gene, a key component of the renin-angiotensin system, are considered genetic risk factors for primary hypertension. A relation between the angiotensinogen gene locus and hypertension has been found in whites, Japanese, and African Caribbeans but not in Chinese. The lack of a consistent association between M235T polymorphism at exon 2 and hypertension has suggested that another site in linkage disequilibrium with M235T is the causal mutation. We studied the relations among plasma angiotensinogen concentrations, blood pressure, related clinical variables, and mutations of the 5′ upstream core promoter region of the human angiotensinogen gene in 274 subjects recruited from our outpatient clinic. We confirmed that plasma angiotensinogen concentration was significantly correlated with A−20C mutation and percent body fat and found that systolic and diastolic blood pressures were significantly correlated with G−6A and T+68C mutations. These results suggest that mutations near the transcription start site may be associated with increased blood pressure.

多発性消化管重複症に発生した腺癌の1例を経験したので報告する. 症例は74歳の女性で, 突然右下腹部痛が出現した. 画像検査では右下腹部に腫瘍が示された. 腹部腫瘤の診断にて開腹手術を施行したところ, 回盲部漿膜側に11×4cm大の腫瘍様病変を認め, 術中迅速病理検査にて腺癌と診断された. なんらかの悪性腫瘍の腹膜転移と考え, 回盲部上行結腸切除術を施行した. 切除標本にて腫瘍様病変は回腸と盲腸に開口する2本の重複腸管であり, そのうち盲腸に開口する重複腸管から腺癌を認めた. 近年, 消化管重複症の報告例は増加しているが, 術前診断は困難とされている. また, 本症の多発例や悪性化例の報告はまれである. 自験例のごとく多発性消化管重複症に発生した癌の報告例は検索しえた限りではみられなかった. 自験例が第1例目であると思われる.

A rare case of Salmonella enteritis presented with acute abdomen as well as rhabdomyolysis and acute renal failure is reported.A 65-year-old man was admitted to the hospital because of sudden onset of upper abdominal pain and diarrhea with renal dysfunction in shock status peritoneal signs such as muscular defense and rebound tenderness were present. Panperitonitis with an upper intestinal perforation was suspected. Though an emergency laparotomy was taken to mind, no definitive findings of intestinal perforation could be obtained, and the operation was not performed. Labolatory data demonstrated elevations in serum creatin phosphokinase and myoglobin after admission, and so acute renal failure was thought to be attributed to rhabdomyolysis and dehydration. Antibiotics and hydration therapies were started and symptomatic remission as well as improvement in laboratory data was attained. Blood purification therapy was required only once. Salmonella enteritidis was isolated in the fecal culture. There have been sporadic reports that described Salmonella infection with difficult differentiation from surgical acute abdomen in the literature. It is important to recognize that Salmonella infection may be occasionally a serious and lethal disease and that is not an unrelated disease to surgeons.

A 56-year-old man presented with transient anemia in minimal-change nephrotic syndrome. Following nephrotic syndrome, anemia suddenly appeared without renal dysfunction. The anemia might be attributable to hemodilution because of significant correlations between the values of hemoglobin concentration and serum total protein or blood urea nitrogen during the clinical course. A low serum level and a low urinary excretion of erythropoietin were found, and when nephrotic syndrome ameliorated with steroid therapy, urinary erythropoietin excretion and anemia disappeared. This case indicated disappearance of the exponential increase of endogenous erythropoietin in acute anemia in nephrotic syndrome probably due to urinary losses and altered biosynthesis of erythropoietin. We report a case of the simultaneous improvement of both nephrotic syndrome and anemia with steroid therapy.

Abstract —This study examined expression of renin-angiotensin system (RAS) component mRNAs in angiotensinogen gene knockout ( Atg −/−) mice. Wild-type ( Atg +/+) and Atg −/− mice were fed a normal-salt (0.3% NaCl) or high-salt (4% NaCl) diet for 2 weeks. Angiotensinogen, renin, angiotensin-converting enzyme (ACE), angiotensin II type 1a receptor (AT 1A ), and angiotensin II type 2 receptor (AT 2 ) mRNA levels were measured by Northern blot analysis. In Atg +/+ mice, activities of circulating RAS and renal angiotensinogen mRNA level were decreased by salt loading, whereas levels of renal and cardiac ACE; renal, brain, and cardiac AT 1A ; and brain and cardiac AT 2 mRNA were increased by salt loading. Although activities of circulating RAS were not detected in Atg −/− mice, salt loading increased blood pressure in Atg −/− mice. In Atg −/− mice, renal renin mRNA level was decreased by salt loading; in contrast, salt loading increased renal AT 1A and cardiac AT 2 mRNA levels in Atg −/− mice, and these activated levels in Atg −/− mice were higher than those in Atg +/+ mice fed the high-salt diet. Thus, expression of each component of the RAS is regulated in a tissue-specific manner that is distinct from other components of systemic and local RAS and that appears to be mediated by a mechanism other than changes in the circulating or tissue levels of angiotensin peptides.

Circulating and cardiac renin-angiotensin systems (RAS) play important roles in the development of cardiac hypertrophy. Mechanical stretch of cardiac myocytes induces secretion of ANG II and evokes hypertrophic responses. Angiotensinogen is a unique substrate of the RAS. This study was performed to examine the regulation of the angiotensinogen gene in cardiac myocytes in response to ANG II and stretch. ANG II and stretch significantly increased the levels of angiotensinogen mRNA in cardiac myocytes. Actinomycin D completely inhibited ANG II- and stretch-mediated increases in angiotensinogen mRNA. Although CV-11974 abolished ANG II-mediated increases in mRNA level and promoter activity of the angiotensinogen gene, the inhibition of stretch-mediated activation by CV-11974 was significant but not complete. These results indicate that ANG II activates transcription of the angiotensinogen gene exclusively via ANG II type 1-receptor pathway and that stretch activates such transcription mainly via the same pathway in cardiac myocytes. Furthermore, factors other than ANG II may also be involved in stretch-mediated activation of the angiotensinogen gene in cardiac myocytes.

Expression of neuronal type nitric oxide synthase and renin in the juxtaglomerular apparatus of angiotensin type-1a receptor gene-knockout mice. Angiotensin type-1a (AT1a) receptor gene-knockout ( AT1a -/- ) mice exhibit chronic hypotension and renin overproduction. In the kidneys of AT1a -/- mice, the activity of neuronal type nitric oxide synthase (N-NOS) was histochemically detected by nicotinamide adenine dinucleotide phosphate (NADPH) diaphorase (NADPHd) reaction combined with N-NOS immunohistochemistry. The localization of renin was detected by immunohistochemistry and the results were analyzed morphometrically. The levels of N-NOS and renin mRNA in the renal cortical tissue were determined by reverse transcription-PCR and Northern blot analysis, respectively. In the renal sections from wild-type mice, NADPHd activity and N-NOS immunoreactivity were localized to the discrete region of the macula densa in contact with the parent glomerulus. In contrast, N-NOS-positive macula densa cells were distributed beyond the original location of the macula densa, occasionally extending to the opposite side of the distal tubules. The mean number of N-NOS positive macula densa cells was significantly increased in AT1a -/- mice (186 per 100 glomeruli) compared with wild-type mice (65 per 100 glomeruli). AT1a -/- mice showed 1.4-times higher N-NOS mRNA levels in the renal cortical tissues than wild-type mice. The plasma renin activity was significantly higher in AT1a -/- mice (205.5 ± 26.1 ng/ml/hr) than in wild-type mice (8.0 ± 0.2 ng/ml/hr). The renin-positive areas per glomerulus and renal renin gene expression were 12-times and 2.6-times higher in AT1a -/- mice than in wild-type mice, respectively. These abnormalities, however, were less remarkable in AT1a -/- mice compared with angiotensinogen-knockout mice. When AT1a -/- mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively-stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. Dietary salt loading produced a parallel decrease in plasma renin activity, renal renin-immunoreactive areas, and the levels of renin mRNA without affecting systemic blood pressure. These results provide evidence for the possible involvement of N-NOS at the macula densa in the increased renin production in AT1a -/- mice.

This study was conducted to examine whether imidaprilat, an active diacid of the angiotensin-converting enzyme (ACE) inhibitor imidapril, preferentially inhibits angiotensin I degradation rather than bradykinin degradation, and whether imidapril is less active than other ACE inhibitors in inducing cough in patients with hypertension. The effect of imidaprilat on the inhibition of pressor response to angiotensin I and augmentation of depressor response to bradykinin was compared with that of enalaprilat and captopril in anesthetized rats. To determine the incidence of cough associated with imidapril, patients with a history of ACE inhibitor-induced dry cough were enrolled in a randomized, open-labeled, crossover trial with two 6-week periods to be treated with imidapril or amlodipine, a calcium-channel blocker. The recurrence of cough was assessed during both treatments. In the animal study, there were no significant differences in the ratio of inhibition of pressor response to angiotensin I and the augmentation of depressor response to bradykinin among the ACE inhibitors. In the cough-challenge trial, a total of 60 patients with hypertension were enrolled in the study. Cough and cough related symptoms recurred in 98.3% of the patients (59/ 60) during imidapril therapy. In contrast, only two patients reported cough during treatment with amlodipine. These results indicate that imidapril has no selectivity in inhibiting angiotensin I- and bradykinin-degradation in rats, and that clinically it is not different from other ACE inhibitors in inducing cough in patients with hypertension.

The present study investigates whether neuronal type nitric oxide synthase (N-NOS) in the macula densa participates in the regulation of renal renin expression during altered dietary salt intake in angiotensinogen gene-knockout (Atg-/-) mice. Wild-type (Atg+/+) and Atg+/+ mice were fed a low-salt (0.04% NaCl), normal-salt (0.3% NaCl), or high-salt (4% NaCl) diet for 2 wk. Histochemical staining for NADPH diaphorase (NADPHd) and renin were analyzed morphometrically. Levels of N-NOS and renin mRNA in renal cortical tissues were determined by reverse transcription-PCR and Northern blot analysis, respectively. In animals fed a normal-salt diet, the renal expressions of N-NOS and renin were markedly increased in Atg-/- mice compared with Atg+/+ mice. When mutant mice were fed a high-salt diet, the signal intensity of the NADPHd reaction and the number of positively stained macula densa cells were significantly decreased. The levels of renal cortical N-NOS mRNA were also suppressed by the treatment. These changes were paralleled by decreases in renal renin-immunoreactive areas and the levels of renin mRNA. On the other hand, salt restriction did not produce further significant increases in the renal N-NOS and renin expressions in mutant mice, whereas a parallel inverse relationship was observed between these enzyme expressions and the levels of salt intake in wild-type mice. These results suggest that the N-NOS expression in the macula densa is inversely regulated by salt intake and that the enzyme activity is functionally linked to renal renin production. Salt-modulated renal N-NOS and renin expressions are independent on angiotensin formation in Atg-/- mice.

Genetic deficiency of angiotensinogen produces an impaired urine concentrating ability in mice. Angiotensinogen gene-knockout ( Atg −/− ) mice lacking angiotensin II exhibit chronic hypotension. The present study was designed to investigate pathophysiology of Atg −/− mice from the renal functional view. Wild-type ( Atg +/+ ) and Atg −/− mice at 10 weeks of age were housed in metabolic cages for 24-hour urine collection. When provided free access to water, Atg −/− mice showed an increased urine output and a decreased urine osmolality compared with Atg +/+ mice. Urinary excretion and plasma levels of vasopressin were significantly higher in mutant mice than in wild-type mice. On the other hand, urinary excretion of aldosterone in mutant mice was suppressed to the levels under the detection limit of the assay system. The mean plasma aldosterone level of Atg −/− mice was suppressed to 30% of that of Atg +/+ mice. Plasma levels of creatinine, endogenous creatinine clearance, and urinary electrolyte excretion were not different between these mice. In Atg +/+ mice, urine osmolality was markedly increased from 1929 ± 21 to 3314 ± 402 mOsm/kg during water deprivation, whereas this parameter in Atg −/− mice did not change significantly (from 1413 ± 121 to 1590 ± 92 mOsm/kg). Urinary vasopressin excretion increased during water deprivation from 0.24 ± 0.04 and 0.70 ± 0.08 to 0.42 ± 0.06 and 2.31 ± 0.35 ng/mg creatinine in wild-type and mutant mice, respectively. Histologic study revealed interstitial inflammation, and atrophic changes in the tubules and papilla in Atg −/− mice. In conclusion, a genetic deficiency of angiotensinogen produced an impaired urine concentrating ability and tubulointerstitial lesions, indicating the critical role of angiotensinogen in developing normal tubular function and construction.

Abstract —Two subtypes of angiotensin II (Ang II) receptors, type 1 (AT 1 -R) and type 2 (AT 2 -R), have been identified in the heart. However, little is known about the regulation of cardiac AT 1 -R and AT 2 -R by Ang II in vivo. Thus, we examined cardiac AT 1 -R and AT 2 -R in angiotensinogen-deficient ( Atg-/- ) mice that are hypotensive and lack circulating Ang II. Cardiac Ang II receptors (Ang II-R) were assessed by radioligand binding with 125 I-[Sar 1 ,Ile 8 ]–Ang II in plasma membrane fractions. AT 1 -R and AT 2 -R were distinguished using their specific antagonists CV-11974 and PD123319 , respectively. Total densities of Ang II-R and AT 1 -R density were significantly greater in the Atg-/- mice than Atg+/+ mice (31.1±2.8 versus18.8±2.1, 28.7±3.0 versus16.9±2.3 fmol/mg protein, P 2 -R showed a slight but not significant increase in Atg-/- mice relative to Atg+/+ control animals. K d values were not different between the two groups. In contrast to binding experiments, levels of Ang II type 1a receptor (AT 1a -R) and AT 2 -R mRNA did not differ between Atg-/- and Atg+/+ mice. These results suggest that lack of Ang II may upregulate AT 1 -R through translational and/or posttranslational mechanisms in Atg-/- mice.

Fermentability of dietary cellulose, sodium alginate, chitin, α-starch and kaolin (non-fermentable control) by gut microbes was compared in a tilapia, Oreochromis niloticus, fed a diet containing one of the above supplements (150 g · kg−1) for 14 days. The thickness of the tunica muscularis was also compared among fish fed these diets. The concentration of short-chain fatty acids (SCFA) in gut contents was higher in fish fed the α-starch than in fish fed the sodium alginate, chitin, or kaolin diets. Intestinal contents from fish fed the kaolin (control) diet were incubated in batch culture with each of the other supplements. The volume of released gas and production of SCFA for 24 hr was greater with a α-starch as a substrate than in those with the other substrates. The thickness of the tunica muscularis differed among dietary groups but villus height did not. Fish fed chitin or α-starch had a thicker tunica muscularis than those fed cellulose or sodium alginate. These results suggest that this detritivorous fish digests α-starch to produce SCFA in the intestine by microbial fermentation.

The protein product of the retinoblastoma susceptibility gene, RB, is a nuclear phosphoprotein that modulates transcription of genes involved in growth control via interactions with transcription factors. Renin is a rate-limiting enzyme of the renin-angiotensin system that regulates blood pressure and water-electrolyte balance. Renin gene expression is regulated in a tissue-specific and developmentally linked manner. Similarly, the expression of RB is controlled in a differentiation-linked manner. Thus, to investigate whether RB is involved in the regulation of renin gene expression, we examined the effects of RB on transcriptional activity of the mouse renin (Ren-1C) promoter. The Ren-1C promoter contains two transcriptionally important elements; the RU-1 (-224 to -138) and RP-2 (-75 to -47) elements. RB activated the Ren-1C promoter in human embryonic kidney cells. The promoter element responsible for RB-mediated transcriptional regulation was the RP-2 element. The results of DNA-protein binding experiments showed that RB increased nuclear binding activity to the RP-2 element, and site-directed mutation which disrupted binding of nuclear factors to the RP-2 element markedly reduced RB-mediated activation of Ren-1C promoter in human embryonic kidney cells. These results indicate that the RP-2 element plays an important role in RB-mediated transcriptional regulation of Ren-1C promoter activity in human embryonic kidney cells, thereby suggesting an interesting mechanism by which RB may modulate the renin-angiotensin system.

Objective: The effects of slow diurnal hemodialysis (slow HD) on amino acid losses and nitrogen balance were studied. Design: Slow HD was conducted for 10 h during the day at the dialysate flow rate of 30 ml/min. The patients received total parenteral nutrition including 40 g of amino acids (6.08 g of nitrogen). The amino acid concentrations in plasma and dialysate were determined and the daily nitrogen balance was calculated from the urea nitrogen appearance. Patients: Six critically ill patients with renal failure were entered into the study. Results: Slow HD eliminated 48.5±4.4 mmol (6.2±0.6 g) of amino acids, representing 16% of the daily amino acid load. The estimated nitrogen balance was –2.3±1.3 g/day. Amino acid nitrogen lost in the dialysate was 1.0±0.1 g, contributing 43% of the daily negative nitrogen balance. Conclusion: The amount of amino acid losses during slow HD should be taken into consideration when designing nutritional schedules for maintaining positive nitrogen balance in critically ill patients.

頸部リンパ節結核によるrHuEPO抵抗性を示した53歳女性の血液透析患者の1例を報告する.本例は1986年慢性腎盂腎炎による慢性腎不全にて血液透析導入となった. 必要と判断された場合には鉄剤の投与を行いながら, 腎性貧血に対し1990年よりrHuEPOを週4500単位より投与開始した. 1991年からは週6000単位に増量したが, Htは上昇せず24%以上に維持されることはなかった. 1992年3月に頸部リンパ節結核を発症したため, isoniazid 0.4g/日およびrifampicin 0.45g/日の投与を開始した. 服薬は不規則であり臨床症状は改善しなかった. 1993年1月streptomycin 2g/週, 5週間の投与を開始した. これにより症状が改善すると同時にrHuEPOに対する反応性が良好となり, rHuEPo週4500-9000単位の投与量にてHt28-30%に維持されるようになった. isoniazidおよびrifampicinの投与はそれぞれ1993年5月, 11月まで行った. 現在のところ結核再発の兆候は認められていない. 本例は頸部リンパ節結核発症以前にすでにrHuEPO抵抗性を示していた. その原因として結核菌の持続感染の存在が考慮された. 結核は, 血液透析患者においてrHuEPO抵抗性を生じうると考えられた.

The BRAFV600E mutation has been adopted as a prognostic factor in papillary thyroid carcinoma (PTC). However, it remains unclear whether routine BRAF mutation analysis is useful in establishing a prognosis for PTC patients. In the present study we investigated BRAF mutation analysis in a large number of PTC patients with long-term follow-up. We enrolled 766 patients from our hospital who underwent initial surgery for PTC without distant metastasis at diagnosis between 1996 and 2001, and whose BRAF mutation of primary lesions could be analyzed. The average age and follow-up period were 51 years and 130 months, respectively. To date, 77 (10 %) and 37 (5 %) patients have developed lymph node and distant recurrence, respectively, and 10 (1 %) have died of PTC. The BRAF mutation was positive in 281 patients (37 %), and it had no prognostic impact on lymph node recurrence-free (LNRFS) (p = 0.700), distant recurrence-free (DRFS) (p = 0.696), and cause-specific (CSS) (p = 0.125) survival in our entire series. However, CSS of BRAF mutation-positive high-risk patients based on AMES (p = 0.030), MACIS (score >6) (p = 0.017), the UICC stage (IVa) (p = 0.021), CIH classification (Sugitani et al. Surgery 135:139–148, 2004) (p = 0.015), and our own classification system (Ito et al. World J Surg 34:2570–2580, 2010) (p = 0.010) were significantly poorer than CSS of mutation-negative high-risk patients. The BFAF mutation did not affect CSS of non-high-risk patients, although the incidence of the BRAF mutation did not significantly differ between high-risk and non-high-risk groups based on these classification systems. The BRAF mutation was not related to LNRFS and DRFS in the subsets of high-risk and non-high-risk patients. BRAF mutation analysis is useful in estimating the CSS of high-risk PTC patients based on the representative classification systems. It was not related to the prognosis in non-high-risk patients, at least those living in Japan.

Increased bone mineral density (BMD) has been reported in patients with postsurgical permanent hypoparathyroidism. Hypoparathyroidism may attenuate the high-turnover bone loss in postmenopausal women. We reported previously that patients who had transient hypoparathyroidism postoperatively were at subclinical hypoparathyroid (hP) status even 5 years after surgery. We hypothesized that patients with transient hypoparathyroidism (ThP) may have altered BMD.A total of 140 women who underwent total thyroidectomy had BMD measurements of the lumbar spine, femoral neck, and radius 3 years after surgery. At surgery, 99 patients were ≥50 years and 41 were50 years. They were divided into three groups according to their postoperative parathyroid function: There were 80 patients in the no hP (NhP) group, 54 in the ThP group, and 6 in the permanent hP (PhP) group.Among the 99 patients aged ≥50 years, 36 ThP patients had median Z scores of the BMD in all three areas (lumbar spine, femoral neck, radius) that were significantly higher (by 1.083, 0.533, and 1.047, respectively) than those in the 60 NhP patients aged ≥50 years. The BMDs in the three PhP patients ≥50 years were higher than those in the NhP and ThP patients, but the difference did not reach significance except for in the femoral neck. Multivariate logistic regression analyses showed that Z scores0 were significantly associated only with the presence of ThP postoperatively. In the patients50 years, the BMD values were not significantly different among the three groups except at the radius in PhP patients, which was significantly lower than those of the other patients.We found that ThP was associated with increased BMD in postmenopausal women. This may be due to attenuation of the high-turnover bone loss in postmenopausal women.

There are some tracheal surgeries for invasive papillary thyroid carcinoma (PTC) requiring tracheal resection. We create an airtight tracheocutaneostomy (TCS) by suturing the tracheal hole to the skin when window resection of the trachea is required. Here, we present the outcomes of PTC patients who underwent surgery with airtight TCS.We enrolled 109 patients (18 males and 91 females) who underwent initial surgery for PTC and TCS after partial window resection of the trachea between 1987 and 2010. The average patient age was 61 and the average follow-up was 99 months. The TCS was closed using a local skin flap 3-6 months after surgery in 78 patients, and it closed spontaneously in 13 patients. The TCS of the remaining 18 patients was not closed for various reasons, such as a poor general condition, permanent bilateral vocal cord paralysis, and loss to follow-up.None of the 109 patients showed any serious complications of TCS. Minor wound infection, partial skin necrosis, granulation, and air leakage were observed in 12 (11 %), 2 (2 %), 7 (6 %), and 4 (4 %) patients, respectively. Infection was more likely to occur in patients whose cricoid cartilage was resected (p = 0.0456). Although macroscopically curative surgery was performed for all patients, 38 patients (35 %) had a suspiciously positive margin in the resected tracheal mucosa. Five margin-positive (13 %) and five margin-negative (7 %) patients showed excision site recurrence, but the margin status did not directly affect the prognosis. External beam radiation therapy (EBRT) (50-60 Gy) was administered to nine patients, none of whom showed excision site recurrence, although eight were microscopically margin-positive. Among various clinicopathological features, tumor size 4 cm and age ≥ 60 years were significant (p = 0.0281) and marginal (p = 0.0771) predictors of excision site recurrence on univariate analysis. On multivariate analysis, age ≥ 60 years (p = 0.0484) and tumor size 4 cm (p = 0.0763) were independent and marginal predictors of excision site recurrence, respectively. To date, 14 and 17 patients have shown lymph node and distant recurrence, respectively, and nine have died of PTC.Tracheocutaneostomy is a safe surgical technique after partial window resection of the trachea, although we have to be careful of infection when resecting the cricoid cartilage. Large tumor size and old age are risk factors for excision site recurrence. EBRT may be useful to prevent excision site recurrence, especially in patients with a suspected positive margin.

Background The recurrent laryngeal nerve (RLN) may be involved by thyroid cancer even in patients with functioning vocal cords preoperatively. In such cases, we try to preserve the nerve with sharp dissection. As a result of the dissection, the nerve may become thinner than its original thickness. Here we call this operative procedure “partial layer resection of the RLN,” if the thickness of the preserved nerve is less than half of its original size. However, there is no report on postoperative vocal cord function after this procedure. Methods We report on 4,585 patients with papillary thyroid cancer who underwent their initial surgery in Kuma Hospital. Among them, 18 patients underwent “partial layer resection of the RLN.” We also performed histologic examinations on the RLNs resected because of cancer invasion in 3 other patients. Results Postoperatively, 2 patients had functioning vocal cords, 13 had transient vocal cord paralysis, and the remaining 3 had permanent paralysis. Thus, 83% (15/18) of the present patients who underwent partial layer resection of the RLN had functioning vocal cords 1 year after surgery. In patients with transient paralysis, the phonation efficiency index (PEI) 1 year after operation recovered to normal range from the low PEI immediately after operation. Histologic examinations of resected RLN revealed that 78–82% of the cross-section of the nerve is composed of perineural connective tissue surrounding the nerve fibers. Conclusion An unexpectedly high proportion (83%) of the patients who underwent partial layer resection of the RLN achieved functioning vocal cords and nearly normal phonation postoperatively.

Thyroid nodules with cystic content or mixed sponge-like aspect on ultrasonography and a concordant cytology are strongly predictive of benignity.We present 8 patients with honeycomb-like papillary thyroid carcinoma with multiple small cysts on ultrasonography.The patients were 6 women and 2 men aged between 30 and 57 years. The tumors of these patients showed honeycomb-like multiple small cysts that were aggregated in some area of the thyroid gland on ultrasonography. Histopathological examination indicated a well-differentiated type of papillary thyroid carcinoma with multiple small cysts and a small solid lesion. The cysts were lined with papillary carcinoma cells, and normal thyroid tissue lay between the cysts.There is a peculiar type of papillary thyroid carcinoma that histopathologically shows honeycomb-like multiple small cysts in the thyroid gland. Ultrasonography can be used to identify characteristic features of honeycomb-like multiple small cysts in the thyroid gland in such patients.One should be aware of this peculiar type of papillary thyroid carcinoma with honeycomb-like multiple small cysts on ultrasonography, although thyroid nodules with cystic lesions are generally regarded as benign in clinical management.

Effects of slowly performed daytime hemodialysis (slow HD) using a high-flux hemodialyzer on the pharmacokinetics of vancomycin were determined in 5 critically ill patients with renal failure. Following intravenous administration of 0.5 g of vancomycin, concentrations in the serum and dialysate were monitored. Pharmacokinetic parameters were calculated after fitting individual concentration-time curves to a two-compartment model. The volume of distribution at steady state was 0.58 +/- 0.12 liters/kg. Total body clearance was 37.46 +/- 3.20 ml/min with an elimination phase half-life of 8.72 +/- 0.99 h. Slow HD clearance was 20.19 +/- 2.30 ml/min. During a 10-hour session of slow HD, the serum vancomycin concentration decreased from 44.2 +/- 3.8 to 10.0 +/- 5.0 mg/l and 30.10 +/- 5.34% of the dose was eliminated. Dialyzer clearance of this drug and urea was 18.71 +/- 1.40 and 28.77 +/- 1.77 ml/min, respectively. Slow HD may effectively eliminate vancomycin by a diffusive mechanism and this elimination should be taken into consideration for designing the dosage schedule during the treatment.

We describe a rare case of ACE inhibitor-induced angioedema during long-term therapy in a 51-year-old male patient with essential hypertension; and this is the third case reported of this adverse reaction in Japan. The patient received enalapril for 66 months, and complained of a dry cough which was mild and tolerable. Recently, he noted tenderness of his mouth, face, swelling of lips and tongue for 3 to 4 h after taking his morning dose of enalapril. These symptoms abated spontaneously, so he continued taking the drugs. He again noted similar episodes of angioedema 29 days after the first experience. He had no further episodes of angioedema or dry cough after cessation of enalapril. This case of angioedema developed during long-term therapy with enalapril administered as 19,930 mg of enalapril maleate. We emphasize that angioedema may occur at any time during the use of enalapril. (Jpn Circ J 1996; 60: 166 - 170)

We examined the effects of dietary lactosucrose (20 mg · kg body mass −1 · day −1 ) on body mass gain and the thickness of intestinal tunica muscularis in artificially reared red seabream fed a commercial diet. Lactosucrose did not affect body mass gain. Fish fed lactosucrose had thicker and tougher intestinal tunica muscularis than control fish. In vitro batch culture of intestinal contents of these fish showed that gut fermentation exists in this marine carnivorous teleost. The fermentation can utilize lactosucrose as a substrate, at least in vitro .

Tumor metastasis to the hypophyseal system has rarely been reported with either clinical or radiographic evidence. A 52-year-old woman presented with polydipsia, polyuria, and loss of appetite. She was diagnosed as having diabetes insipidus caused by pituitary micrometatasis of lung adenocarcinoma. After she had been treated with radiation therapy to the pituitary gland, the gland size was reduced as confirmed by magnetic resonance imaging, and her urine volume decreased. However, meningitis carcinomatosa appeared later. This was a rare case of secondary diabetes insipidus due to pituitary metastasis of lung cancer.

ObjectiveThyroidal production of triiodothyronine (T3) is absent in patients who have undergone total thyroidectomy. Therefore, relative T3 deficiency may occur during postoperative levothyroxine (l-T4) therapy. The objective of this study was to evaluate how the individual serum T3 level changes between preoperative native thyroid function and postoperative l-T4 therapy.MethodsWe retrospectively studied 135 consecutive patients with papillary thyroid carcinoma, who underwent total thyroidectomy. Serum free T4 (FT4), free T3 (FT3), and TSH levels measured preoperatively were compared with those levels measured on postoperative l-T4 therapy.ResultsSerum TSH levels during postoperative l-T4 therapy were significantly decreased compared with native TSH levels (P4 levels were significantly increased (P3 levels were significantly decreased (P=0.029). We divided the patients into four groups according to postoperative serum TSH levels: strongly suppressed (less than one-tenth of the lower limit); moderately suppressed (between one-tenth of the lower limit and the lower limit); normal limit; and more than upper limit. Patients with strongly suppressed TSH levels had serum FT3 levels significantly higher than the native levels (P3 levels equivalent to the native levels (P=0.51), and patients with normal TSH levels had significantly lower serum FT3 levels (PConclusionsSerum FT3 levels during postoperative l-T4 therapy were equivalent to the preoperative levels in patients with moderately suppressed TSH levels. Our study indicated that a moderately TSH-suppressive dose of l-T4 is required to achieve the preoperative native serum T3 levels in postoperative l-T4 therapy.

Papillary thyroid carcinoma (PC) can occasionally include a squamous cell carcinoma (SCC) component. In this study, we evaluated the effect of weekly paclitaxel chemotherapy in 3 patients with PC including an SCC component. None of these patients had lesions of anaplastic carcinoma on pathological examination. Weekly paclitaxel chemotherapy was performed as an induction chemotherapy for 2 patients. All 3 patients underwent locally curative surgery and weekly paclitaxel chemotherapy after surgery as an adjuvant therapy. The response to the chemotherapy was evaluated based on the RECIST guideline (version 1.1). Two patients had partial responses (PRs) and the remaining 1 had stable disease (SD). The response rate was 67% and the clinical benefit rate (PR+SD) was 100%. One patient died of the growth of lung metastases that had been detected before surgery 22 months after the diagnosis. The remaining 2 are still alive, 14 and 22 months after the diagnosis, respectively. Taken together, weekly paclitaxel may be one of the effective adjuvant therapies for PC with an SCC component.

Papillary thyroid carcinoma (PTC) often has poorly differentiated components, and it is discriminated from others and classified as an independent entity in the General Rules for the Description of Thyroid Cancer by Japanese Society of Thyroid Surgery (JSTS). In this study, we compared the prognostic significance between this type of poorly differentiated carcinoma (PDC-JSTS) and our risk classification system based on pre- and intraoperative findings in a series of PTC patients. The 10-year lymph node- and distant organ recurrence-free survival (LN-DFS and DRFS) and cause-specific survival (CSS) of high-risk patients were much poorer than in PDC-JSTS patients. In multivariate analysis, PDC-JSTS independently predicted a poor prognosis, but prognostic impacts for LN-DFS, DRFS, and CSS of high-risk in our risk classification were stronger than those of PDC-JSTS. In conclusion, it is appropriate that PDC-JSTS is defined as a subtype of PTC rather than as an independent entity.

Measurement of gene expression levels in thyroid tumor cells in aspirates was difficult because it is interfered with peripheral blood cells or infiltrating lymphocytes. In this study, we established a novel method to separate thyroid tumor cells from blood cells efficiently with mesh filtration. The expression level of trefoil factor 3 (TFF3) mRNA was estimated using LGALS3 mRNA as an internal control (T/G ratio) in 148 preoperative thyroid aspirates. Intra-assay coefficients of variation (CV) of T/G ratio for high, moderate, and low samples were 6.5%, 2.5%, and 9.7%, respectively, and inter-assay CV for high, moderate, and low samples were 27.7%, 21.9%, and 38.2%, respectively. Nondiagnostic samples in terms of T/G ratio and cytology were 12.2% and 16.9%, respectively. We observed no interference with the data by contaminating blood cells. Among these patients, 12 patients received more than two repeated aspirations. We did not observe a marked day-to-day variation except in two cases. All 13 preoperative aspirates diagnosed as malignant by cytology showed an extremely low T/G ratio, whereas 93 aspirates diagnosed as benign by cytology showed extremely varied T/G ratios and 21.5% of them showed a T/G ratio below the cut-off value. Eleven cases underwent surgery. All nodules showing a low T/G ratio were diagnosed as papillary carcinoma by pathological diagnosis. However, one nodule diagnosed as follicular adenoma after surgery showed a high T/G ratio. Our present method may be a promising preoperative test for measuring mRNAs in thyroid aspirates.

Objective The purpose of this study is to evaluate the role of ultrasonography (US) in the management of thyroid nodules when the cytology is benign tumor on fine needle aspiration biopsy (FNAB). Methods Between 2006 and 2011, we investigated 13,972 patients who had solitary thyroid nodule with cytological findings of benign. Surgery was performed according to our criteria for surgical indication. Of these patients, 1877 (13%) patients who underwent surgery were enrolled in this study. We compared the results of clinical findings including US classification and final histopathological diagnosis. Results One hundred seven (6%) after surgery were diagnosed as malignancy pathologically. Large nodule or high serum thyroglobulin level were not associated with an increased risk of malignancy. Ultrasonographic evaluation as malignancy was directly linked to pathological diagnosis as thyroid carcinoma (p Conclusion US may help to play a role in deciding whether surgical treatment is necessary for cytologically benign thyroid nodules.

In papillary thyroid carcinoma (PTC), extrathyroid extension (Ex) and clinical lymph node metastasis (N) significantly affect the prognosis. We investigated the prognosis of patients with PTC 1 cm or less (1,220 patients), 1.1-2 cm (2,101 patients), 2.1-3 cm (1,249 patients), 3.1-4 cm (645 patients), and larger than 4 cm (563 patients). We classified N factor into three categories: N0, no clinical node metastasis: N1, clinical node metastasis smaller than 3 cm and without extranodal tumor extension requiring at least partial excision of adjacent organs for node dissection: and N2, clinical node metastasis 3 cm or larger or showing extranodal tumor extension. N2 markedly affected lymph node and distant recurrence-free survivals and cause-specific survival, regardless of the tumor size. N1 also adversely affected lymph node and distant recurrence-free survival but not cause-specific survival. Ex did not affect patients' prognosis with PTC 1 cm or less. It became a prognostic factor with PTC larger than 1 cm, and worsened lymph node and distant recurrence-free survival not only for N0 but also for N1 PTC larger than 3 cm and larger than 2 cm, respectively. However, its influence is limited for N2 PTC patients. Furthermore, Ex worsened the CSS with PTC larger than 2 cm in combination with N2. We have to note that the prognostic significance for lymph node and distant recurrence-free and cause-specific survival of Ex and N varies according to the tumor size in order to accurately predict the clinical outcomes and establish therapeutic strategies for PTC patients.

Medullary thyroid carcinoma (MTC) accounts for 1.4% of all thyroid malignancies in Japan. Here, we studied the validity of a staging system evaluated preoperatively (Stage), intraoperatively (intra-Stage), and pathologically (pStage) based on the 6(th) and 7(th) UICC TNM classifications. One hundred and nineteen MTC patients who did not show distant metastasis at diagnosis and underwent locally curative surgery were enrolled in this study (average follow-up period: 173.4 months). Twenty-year clinical (not biochemical) disease-free survival (DFS) rates of Stage I, II, III, and IVA patients based on the 6(th) edition were 100, 88.2, 66.8, and 38.9%, respectively. DFS of Stage IVA patients was significantly poorer than that of Stage III patients (p = 0.03137). However, using the 7(th) edition, only 1 patient was classified with Stage III. Intra-Stage III patients based on the 6th edition showed a significantly poorer DFS (20-year DFS 50.0%) than intra-Stage II patients (92.9%) (p = 0.02668), and DFS of intra-Stage IVA patients (38.9%) tended to be poorer than that of intra-Stage III patients (p = 0.05439). Only one patient was classified with intra-Stage III using the 7(th) edition. In pStage, as many as 56 patients (47.1%) were classified with pStage IVA employing both editions. Taken together, Stage and intra-Stage were more useful to accurately discriminate high-risk patients than pStage, and their 6(th) editions were better than 7(th) editions. Although the number of patients was small, our data showed the possibility that intra-Stage in the 6(th) edition was the best staging system for MTC patients.

Age is an important prognostic factor in papillary thyroid carcinoma (PTC). In this study, we investigated the difference in prognosis of 7 subsets of PTC patients without distant metastasis at presentation or a history of radiation exposure (20 years or younger, 21-30 years, 31-40 years, 41-50 years, 51-60 years, 61-70 years, and older than 70 years). The lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years. Distant recurrence and carcinoma death rates significantly elevated in patients older than 60 years. The incidence of significant extrathyroid extension markedly increased with age, although that of large node metastasis or extranodal tumor extension did not differ much among the 7 subsets. With the Kaplan-Meier method, lymph node recurrence rate was poor in patients 20 years or younger and in those older than 60 years. Poor distant recurrence-free and cause specific survivals of patients older than 60 years were identified in the series of PTC patients with and without these aggressive features. It is therefore suggested that 1) Lymph node recurrence rate was high in patients 20 years or younger and those older than 60 years and 2) prognosis, including distant recurrence-free survival and cause-specific survival, of patients older than 60 years was poor regardless of clinicopathological features of PTC at initial surgery.

Slow hemodialysis (HD) was performed for 10 h during the day in 11 critically ill patients with renal failure. The dialysis method was a modification of the pump-driven continuous venovenous HD. A nonsterile bicarbonate-containing hemodialysate was passed into the EVAL membrane dialyzer at a flow rate of 30 ml/min. No patient developed further hemodynamic instability during the treatment. The serum urea level was maintained below 20 mmol/l within 4 days of initiating the treatment. It allowed the patients to rest without interruption at night. This method was safely conducted by general nursing staff under the supervision of nephrologists on duty during the day. This schedule offers an approach to renal replacement therapy for hemodynamically unstable patients without any potential problem in the extracorporeal circulation at night.

Identification and characterization of adenosine A 1 receptor-cAMP system in human glomeruli. Although adenosine is known to affect renal function through stimulating adenosine receptors, little is known about A 1 receptors in human glomeruli. Thus, we attempted to identify the adenosine A 1 receptor-cyclic AMP (cAMP) system in human glomeruli. Normal renal cortical tissues were obtained at nephrectomy of patients with renal cell carcinoma. Glomeruli were isolated using a graded sieving method or dissected manually under a stereomicroscope. Radioligand binding assay using 2-chloro-N-[ 3 H] cyclopentyl adenosine ([ 3 H]CCPA, an A 1 agonist ligand) was performed at 30°C for 90 minutes. Cyclic AMP (cAMP) produced in glomeruli was measured after incubation with different concentrations of N 6 -cyclohexyladenosine (CHA; A 1 agonist) and a phosphodiesterase inhibitor. The specific binding was saturated within 60 minutes and reversible by adding 1 mM of theophylline. Scatchard plot analysis revealed a single class of binding site (K d = 1.78 ± 0.21 nM, B max = 271.7 ± 35.8 fmol/mg protein). The specific binding was inhibited dose-dependently by various agents in an order suggesting A 1 receptor specificity. CHA inhibited the production of cAMP in microdissected human glomeruli. This inhibitory effect was antagonized by 8-cyclopentyl-1,3-dipropylxanthine (DPCPX; A 1 antagonist). This is the first study revealing the presence of the A 1 receptor-cAMP system in human glomeruli using a radioligand binding assay method and by measuring the cAMP production.