Parathyroidectomy for tertiary hyperparathyroidism after second kidney transplantation: a case report.

Successful kidney transplantation usually resolves secondary hyperparathyroidism (SHPT). However, some patients fail to normalize, and their condition is often referred to as tertiary hyperparathyroidism (THPT). Surgical consensus on the timing of post-transplant parathyroidectomy (PTX) for THPT has not been reached. Herein, we report a case of a 58-year-old post-transplant woman, considering the concrete timing of PTX for both SHPT and THPT. She initiated hemodialysis with end-stage renal disease at the age of 24, and underwent first kidney transplantation at the age of 28. When peritoneal dialysis (PD) was induced due to the worsening kidney function at the age of 50, the serum intact parathyroid hormone (iPTH) level remarkably increased (2332 pg/mL). Although cinacalcet was administered, the patient's iPTH levels were not sufficiently suppressed for seven years. Diagnostic images including ultrasound, computed tomography, and 99mTc-methoxyisobutylisonitrile scintigraphy indicated THPT as the reason for prolonged post-transplant hypercalcemia. Therefore, PTX was performed 14 months after the second transplantation. Histology showed nodular hyperplasia of all parathyroid glands, indicating autonomous secretion of parathyroid hormone. In general, patients with more severe THPT are recognized with more severe SHPT prior to transplantation during the dialysis period. We should consider a referral for surgery based on the individual risk factors. We recommend to perform parathyroidectomy earlier, before the kidney transplantation in the clinical suspicion of severe SHPT.

A case of resistance to thyroid hormone diagnosed after total thyroidectomy for thyroid cancer.

This is a case of a woman who was diagnosed with resistance to thyroid hormone after total thyroidectomy for thyroid cancer. Preoperative laboratory examination revealed the syndrome of inappropriate secretion of TSH, however, the patient had no thyrotoxic symptoms and no family history. Based on the results of ultrasonography and fine needle aspiration, she was diagnosed with papillary thyroid carcinoma and underwent total thyroidectomy. After the surgery, she received L-T4 therapy, but her TSH levels remained elevated. MRI was performed on the brain, but no lesions were found in the pituitary gland. Therefore, she was tested for TRß gene, and a previously defined mutation, P453S, was detected. Ultimately, she was diagnosed as RTH and treated with L-T4. In this case, the dose of L-T4 needed to be increased to suppress her TSH levels to the normal range or less, and to prevent stimulating malignant cells. Currently, her dose of L-T4 has been increased, and her TSH levels are still lower than normal, however, she has no thyrotoxic symptoms, recurrence or metastasis of thyroid cancer. The patient is currently under careful observation regarding her circulatory and physiological status. In addition, the results of treatment still need to be monitored and evaluated.

[Small size lung adenocarcinoma with rocal recurrence and port site recurrence 56 months after partial resection].

A lobectomy with systemic lymphadenectomy is a standard surgical procedure for a resectable lung cancer. However there is not a consensus on the limited surgery. A 60-year-old man underwent left upper lobe partial resection for small size lung adenocarcinoma under video assisted thoracic surgery (VATS). Fifty-six months after the operation, a computed tomography (CT) scan showed a local recurrence on the staple-line. A positron emission tomography (PET) scan showed an additional port site recurrence, which wasn't showed by a CT scan. He underwent left upper lobectomy and port site resection.

[Two elderly patients with advanced breast cancer successfully treated by tri-weekly docetaxel].

Case 1: An 86-year-old woman had an invasive breast cancer with dermal infiltration. Bone metastases were found in the femur and lumbar vertebrae. She was treated with 2 courses of 70 mg docetaxel (DOC) chemotherapy every 3 weeks, after which the tumor dramatically decreased in size. Following this treatment, she underwent a radical mastectomy. Case 2: An 80-year-old woman had a 10 cm tumor in the right breast. Lung and bone metastases were also found. Two 80 mg courses of DOC reduced the lung and bone metastases, and the size of the breast tumor. She underwent a local excision. Hormonal therapy is a standard treatment for hormone-sensitive breast cancer in elderly patients. It is suitable for patients who have a declining quality of life (QOL), although chemotherapy shows a higher response rate and takes less time than hormonal therapy. However, it is difficult to continue chemotherapy until pCR is achieved, even for chemotherapy-effective patients because the side effects of chemotherapy are severe. Therefore, local excision after chemotherapy is necessary for breast cancer patients to improve their QOL, even if there are distant metastatic lesions.

A case of a giant phyllodes tumor of the breast with hypoglycemia caused by high-molecular-weight insulin-like growth factor II.

We report the case of a patient who presented with hypoglycemia associated with a giant breast mass and presence of serum high-molecular-weight insulin-like growth factor II (big IGF-II). In July 2005, a 49-year-old woman was admitted because of delirium, transient loss of consciousness, and a giant mass of about 28 cm in diameter on the right breast. She had noticed the mass for more than 2 years, but had refused medical attention at that time. A blood examination indicated hypoglycemia (21 mg/dl) and decreased levels of endogenous insulin. Furthermore, a western blot analysis revealed that big IGF-II (20 kDa) was the predominant serum IGF-II peptide (mature IGF-II is 7.5 kDa). Because we suspected that the big IGF-II was produced by the breast tumor and was likely the cause of the hypoglycemia, a mastectomy was performed. A histological examination determined that the mass was a benign phyllodes tumor. After surgery, the hypoglycemia resolved, and endogenous insulin levels improved. We suspected that the patient had non-islet cell tumor hypoglycemia (NICTH), but the behavioral symptoms of the hypoglycemia caused by NICTH were similar to some mental diseases, which made diagnosis based on the behavior alone difficult. We suggest that co-occurrence of symptoms such as recent appearance of mental disease-like behavior, hypoglycemia, and giant breast tumor may help diagnose NICTH caused by big IGF-II.

[A case of occult breast cancer successfully treated by capecitabine in combination with weekly paclitaxel followed by FEC (75)].

A 78-year-old woman was referred to our hospital complaining of a hard nodule on the left side of her neck. Histological examination of this nodule showed metastatic carcinoma from breast cancer. Further examination revealed paraaortic lymph node swelling and no breast tumors. We diagnosed her tumors as occult breast cancer and its metastasis to lymph nodes (cT0N3cM1, Stage IV). We used weekly paclitaxel followed by a FEC75 regimen. The neck nodule size did not change after administration twice. We added capecitabine to the weekly paclitaxel, which had decreased the size of the nodule immediately. After this chemotherapy, PET-CT revealed that the lymph node metastasis had disappeared completely. It was considered that the addition of capecitabine in the early phase of the regimen was useful for this case.

Genetic analyses in patients with familial isolated hyperparathyroidism and hyperparathyroidism-jaw tumour syndrome.

BACKGROUND: A subset of familial isolated primary hyperparathyroidism (FIHP) is a variant of hyperparathyroidism-jaw tumour syndrome (HPT-JT). AIM/PATIENTS AND METHODS: We investigated the involvement of the HRPT2, MEN1 and CASR genes in 11 provisional FIHP families and two HPT-JT families. RESULTS: Germline mutations of HRPT2 were found in two of the 11 FIHP families and one of the two HPT-JT families. One FIHP family with parathyroid carcinoma and atypical adenomas and another FIHP family with cystic parathyroid adenoma had novel frameshift mutations of 518-521del and 62-66del, respectively. In a patient with HPT-JT, a de novo germline mutation of 39delC was detected. Novel somatic HRPT2 mutations of 70-73del and 95-102del were found in two of five parathyroid tumours in a family with a 518-521del mutation. Biallelic inactivation of HRPT2 by a combination of germline and somatic mutation was confirmed in the parathyroid tumours. The finding that two families diagnosed with FIHP carried HRPT2 mutations suggests that they have occult HPT-JT. In the remaining 10 families, one family had a missense MEN1 mutation. No mutations of CASR were detected. CONCLUSION: Our results confirm the need to test for HRPT2 in FIHP families, especially those with parathyroid carcinomas, atypical adenomas or adenomas with cystic change.

The reduced expression and aberrant methylation of p16(INK4a) in chromate workers with lung cancer.

STUDY OBJECTIVES: It is known that chromium is one of the important inhaled carcinogens that cause lung cancer. Our previous studies revealed a variety of genetic changes in lung cancers from chromate-exposed workers (chromate lung cancer). However, the epigenetic effects of chromium are not understood. MATERIALS AND METHODS: We investigated the methylation of the p16 gene using a methylation-specific PCR method in 30 chromate lung cancers and 38 non-chromate lung cancers, and the expression of the p16 protein using immunohistochemistry in 25 chromate lung cancers. RESULTS: Ten (33%) chromate lung cancers showed methylation of the p16 promoter region. On the other hand, 10 (26%) of the non-chromate lung cancers also showed it. The frequency of p16 methylation in non-chromate lung cancer was 0%, 33% and 30% for low (< or =600), moderate (<600, >1000) and high (> or =1000) Brinkman indexes, respectively. However, the frequency of p16 methylation in chromate lung cancer was constant, irrespective of the Brinkman index. In chromate lung cancer, patients with chromate exposure of less than 15 years never had p16 methylation, while 40% (> or =25 years) or 43% (> or =15, <25 years) of patients with chromate exposure of more than 15 years did. In chromate lung cancer, chromate exposure, not smoking, mainly influenced the p16 methylation. Most of the chromate lung cancers with p16 methylation (85.7%) showed repression of the p16 protein. CONCLUSIONS: We speculate that not only genetic but also epigenetic alterations are involved in the carcinogenesis due to chromium.

Thymidylate synthase and dihydropyrimidine dehydrogenase in non-small cell lung cancer: relationship between mRNA expression and activity.

BACKGROUND: UFT (Tegafur + Uracil) has been reported to be effective for postoperative adjuvant chemotherapy of non-small cell lung cancer (NSCLC) in a randomized prospective study. Recently, many clinical studies have demonstrated that UFT is effective for cancer with a low activity of thymidylate synthase (TS) and dihydropyrimidine dehydrogenase (DPD). In the present study, we investigated TS and DPD activity in resected tumors and corresponding normal lungs and the relationship between the activity and the mRNA expression of TS and DPD in NSCLC. MATERIALS AND METHODS: Seventy-seven patients underwent complete surgical resection and lymph node dissection for NSCLC. The activity of TS was determined by the FdUMP binding assay combined with gel filtration. The activity of DPD was determined by radio-enzymatic assay. Tumor tissues and their paired non-cancerous tissues were assayed. Furthermore, the mRNA expressions of TS and DPD were examined by real-time RT-PCR. RESULTS: The mean TS and DPD activities in NSCLC were approximately 2.4-fold and 5-fold of those in normal lungs. The mean TS and DPD activities of NSCLC were 0.099 pmol/mg and 407 pmol/mg/min, respectively. Although both TS and DPD activities showed a tendency to be high for adenocarcinoma, there was no significant difference between TS and/or DPD activities and any clinical findings (age, gender, stage and histological type). The mRNA expression of DPD was correlated with DPD activity (rs=0.846, p<0.001). The mRNA expression of TS was weakly correlated with TS activity (rs=0.757, p<0.001). CONCLUSION: TS and DPD activities in NSCLC were higher than those in normal lungs. Assay of DPD mRNA and TS mRNA by real-time RT-PCR can be used as an indicator for the use of UFT.

Adult case of accessory cardiac bronchus presenting with bloody sputum.

We report an adult case of accessory cardiac bronchus (ACB) which extended from the carina to the diaphragm. A 32-year-old woman, with a history of frequent respiratory infections since childhood, recently presented with bloody sputum, and was admitted to our hospital. The ACB was detected as a supernumerary bronchus diverging from tracheal bifurcation. Complete resection of the ACB was performed by video-assisted thoracic surgery via minithoracotomy, approaching from the 5th intercostal space. The bloody sputum was caused by chronic inflammation of the ACB. She has been asymptomatic since surgery.

Microsatellite instability and protein expression of the DNA mismatch repair gene, hMLH1, of lung cancer in chromate-exposed workers.

Our previous studies of lung cancer in chromate-exposed workers (chromate lung cancer) have revealed that the frequency of replication error (RER) in chromate lung cancer is very high. We examined whether the RER phenotype of chromate lung cancer is due to an abnormality of DNA mismatch repair protein. We investigated the expression of a DNA mismatch repair gene, hMLH1, and hMSH2 proteins using immunohistochemistry and microsatellite instability (MSI) in 35 chromate lung cancers and 26 nonchromate lung cancers. Lung cancer without MSI or with MSI at one locus was defined as "RER(-)," lung cancer with MSI at two loci was defined as "RER(+)," and lung cancer with MSI at three or more loci was defined as "RER(++)." The repression rate of hMLH1 and hMSH2 proteins in chromate lung cancer was significantly more than that of nonchromate lung cancer (hMLH1: 56% vs. 20%, P = 0.006, hMSH2: 74% vs. 23%, P < 0.0001). In chromate lung cancer, the repression rate for hMLH1 was 43% in RER(-), 40% in RER(+), and 90% in the RER(++) group. The repression rate of hMLH1 protein in the RER(++) group was significantly higher than that in the RER(-) and RER(+) groups (P = 0.039). The inactivation of hMLH1 expression strongly correlated with the microsatellite high instability phenotype in chromate lung cancer. The genetic instability of chromate lung cancer is due to the repression of hMLH1 protein.

WHO histologic classification is a prognostic indicator in thymoma.

BACKGROUND: The histologic classification of thymoma has remained a subject of controversy for many years. In 1999, the World Health Organization Consensus Committee published a histologic typing system for tumors of the thymus. METHODS: We reclassified a series of 100 thymomas resected at Tokushima University Hospital and four affiliated hospitals in Japan between 1973 and 2001 according to the World Health Organization histologic classification and reported its clinicopathologic relationship and prognostic relevance. RESULTS: There were 8 type A, 17 type AB, 27 type B1, 8 type B2, 12 type B3, and 28 type C thymomas. The frequency of invasion to neighboring organs increased according to tumor subtype in the order A (0%), AB (6%), B1 (19%), B2 (25%), B3 (42%), and C (89%). There was no recurrence in patients with type A, AB, or B2 thymoma. The recurrence rates of patients with B1, B3, or C thymoma were 15%, 36%, and 47%, respectively. The disease-free survival rates were 100% for types A and AB, 83% for types B1 and B2, 36% for type B3, and 28% for type C thymoma at 10 years. There were significant differences in disease-free survival between types A and AB and types B1 and B2 (p = 0.0436), and between type B3 and type C (p = 0.042). By multivariate analysis, only Masaoka clinical stage (p = 0.002) showed significant independent effects on disease-free survival. The 10-year survival rates of types A and AB, types B1 and B2, type B3, and type C thymoma were 100%, 94%, 92%, and 58%, respectively. CONCLUSIONS: The current study confirmed the World Health Organization histologic classification as a good prognostic factor.

Microscopic analysis of chromium accumulation in the bronchi and lung of chromate workers.

BACKGROUND: It is known that chromium is an inhaled carcinogen and an important risk factor in the development of lung carcinoma. METHODS: The authors used a microscopic X-ray fluorescence analyzer with transmitted X-ray mapping imaging (Horiba, Kyoto, Japan) to measure the accumulation of chromium in 10 resected lung tissue specimens and 90 biopsy specimens from chromate workers. RESULTS: The maximum chromium accumulation (mean +/- standard deviation) in 10 resected lung tissue specimens was 197 +/- 238 counts per second (cps)/mili ampere (mA) (range, 4-649 cps/mA). Chromium accumulation was scattered in six tissue specimens and diffuse in one specimen. Chromium accumulation in the proximal bronchi was less than in the bronchioles or subpleural regions of the lung. Chromium accumulation was detectable in 63 (70%) of 90 biopsy specimens, and the mean accumulation was 6.5 +/- 9.2 cps/mA (range, 0-46.5 cps/mA). Chromium detected in bronchial tissue specimens was deposited in the bronchial stroma but not in the epithelium. The maximum chromium accumulations in dysplasic (n = 3), squamous metaplastic (n = 10), and normal bronchial epithelia (n = 9) in chromate workers and in normal bronchial epithelia (n = 3) in non-chromate workers were 20.2 +/- 5.4, 18.3 +/- 12.2, 13.2 +/- 13.4, and 3.0 +/- 1.8 cps/mA, respectively. The amount of chromium accumulation significantly increased according to the progression of malignant change of the bronchial epithelium (P = 0.003). CONCLUSIONS: Previous studies found that lung carcinoma with chromate exposure exhibited a variety of genetic abnormalities. Considering genetic aberrations and chromium accumulation in these premalignant lesions is useful for elucidating the process of carcinogenesis in chromium-induced lung carcinoma.

Frequent microsatellite instability in lung cancer from chromate-exposed workers.

Although chromium has been the most extensively investigated metal with respect to mutagenicity and carcinogenicity, its genetic effects in humans are only partly understood. Our previous study demonstrated that lung cancer from chromate-exposed workers infrequently (20%) displayed p53 gene mutations as well as a particular mutation pattern. In the present study, we examined the replication error (RER) and loss of heterozygosity (LOH) in 38 lung cancers from 28 chromate-exposed workers (chromate lung cancer group) and in 26 lung cancer patients without chromate exposure (non-chromate lung cancer group), using six microsatellite markers containing CA repeats: D3S647 (3p23), D3S966 (3p21.3), D3S1289 (3p21.1), D5S346 (5q21-q22), D9S161 (9p21), and TP53 (17p13.1). The RER phenotype was defined as the presence of microsatellite instability (MSI) at two or more loci. Thirty (78.9%) of 38 tumors in the chromate lung cancer group exhibited RER. In contrast, only four (15.4%) of 26 tumors in the non-chromate lung cancer group exhibited RER. The frequency of RER in the chromate lung cancer group was significantly higher than that in the non-chromate lung cancer group (P < 0.0001). By contrast, the frequency of LOH at 3p, 5q, 9p, and 17p loci in tumors with chromate exposure was not significantly different from that in tumors without chromate exposure. In the chromate lung cancer group, the period of chromate exposure in workers with RER (24.5 +/- 6.7 yr) was significantly longer than that in workers without RER (17.0 +/- 3.5 yr) (P = 0.0046). In addition, a longer period of chromate exposure was associated with a tendency toward a higher frequency of MSI. This finding suggests that MSI may play a role in chromium-induced carcinogenesis. In addition to our previous study of p53 mutations, the present findings suggest that the carcinogenic mechanism of chromate lung cancer may differ from that of non-chromate lung cancer.

Localized adiposity of the thyroid, clinically mimicking an adenoma.

A case of localized adiposity of the thyroid in a 35-year-old woman with a long history of steroid therapy for nephrotic syndrome is reported. A well-demarcated yellowish mass measuring 2 cm in diameter was found in the upper portion of the right lobe of the thyroid. Microscopically, this lesion was composed of mature adipose tissue partially mixed with thyroid tissue and had no distinct capsule. The nontumorous thyroid tissue showed features of Hashimoto's thyroiditis. At least two factors-hamartomatous malformation and metabolic disturbance-may be involved in the histogenesis of this localized adiposity.