PTEN loss is associated with follicular variant of Middle Eastern papillary thyroid carcinoma.

BACKGROUND: PTEN gene at chromosomes 10q23.3 is a tumour suppressor gene that is inactivated in many types of human cancers. The known mechanisms of PTEN inactivation are rendered to mutation, epigenetic silencing by aberrant methylation or gene deletion. Although PTEN role has been documented in many cancers, PTEN alteration in papillary thyroid carcinoma (PTC) has not been fully elucidated. The aim of this study is to comprehensively investigate PTEN alterations in a large cohort of Middle Eastern papillary thyroid cancer by immunohistochemistry and fluorescent in situ hybridisation (FISH). METHODS: PTEN protein expression was analysed by immunohistochemistry in a tissue microarray (TMA) format in a large cohort of more than 1000 patients with papillary thyroid cancer. Copy number changes in PTEN were analysed by FISH and data were correlated with clinicopathological parameters along with survival analysis. RESULTS: PTEN inactivation reflected by complete absence of staining was seen in 24.5% of PTC samples, whereas PTEN deletion was seen only in 4.8% of the tested samples by FISH. No association was seen between PTEN loss of protein expression and PTEN gene deletion. However, interestingly, PTEN loss of expression was significantly associated with the follicular variant subset of papillary thyroid cancer. CONCLUSION: Our study confirmed that PTEN might have a role in pathogenesis in a subset of PTC. PTEN loss of protein expression is a more common event in follicular variant of papillary thyroid cancer. Lack of association between PTEN loss of protein expression and PTEN gene deletion might indicate that gene deletion may not be the sole cause for PTEN loss of expression and these results might raise the possibility of other mechanism such as promoter methylation-mediated gene silencing to be responsible for PTEN inactivation.

Prognostic value of postoperative and post-ablative serum thyroglobulin levels in patients with differentiated thyroid cancer.

BACKGROUND: The study was designed to examine the value of post-operative and post-ablative serum thyroglobulin levels and diagnostic whole body scan in predicting remission in patients with differentiated thyroid carcinoma. METHODOLOGY: Serum TG levels and diagnostic iodine-123 whole body scans performed prior to and 6-12 months after 131I ablation for DTC were evaluated in 100 consecutive patients at King Faisal Specialist Hospital Riyadh. Patients were followed up for a period of 7.6 years (range 7-10 years). All patients underwent total thyroidectomypriorto 131I ablation. RESULTS: Patients with serum TG levels < 8 ng/ml post thyroidectomy (50 patients) also maintained low TG < 8 ng/ml after 131I ablation and had better outcome (60%) remission. On the other hand DTC subjects with higher TG > 8 ng/ml post thyroidectomy (50 patients) 40% remained in remission X2 = 4.00, p = 0.046. For the group with initial high post-operative TG, it became < 8 ng/ml in 34/50 (68%) patients after ablation with 131I and in this subgroup, remission was seen in 16/34 (47%) of patients in contrast to 4/16 (25%) remission rate in those who continue to have TG > 8 ng/ml after ablation. At the end of follow up, 123I-WBS was positive in 4% and 10% of patients with initial TG < 8 ng/ml and TG > 8 ng/ml respectively; X2 = 1.38, p= 0.24. CONCLUSION: Post-operative and post-ablative serum TG levels -but not follow up diagnostic WBS- have predictive values and permit selection of patients with higher risk for persistent/recurrent disease.

Impact of cervical lymph node dissection on serum TG and the course of disease in TG-positive, radioactive iodine whole body scan-negative recurrent/persistent papillary thyroid cancer.

In the management of papillary thyroid cancer (PTC), surgery is indicated for locoregional recurrent/persistent disease. In this study, we examined the effect of such surgery on serum TG and the course of the disease in 21 patients with PTC (mean age 38.5 yr), who after the initial surgery and radioactive iodine (RAI) ablation developed high TG (>10 ng/ml) and negative 123I whole body scan (DxWBS). All patients had neck persistent/recurrent PTC that was confirmed by ultrasound-guided fine needle aspiration. Prior to neck re-exploration, radiological studies (chest X-rays, CT scan of the chest, and fluoro-18-deoxyglucose positron emission tomography [FDG-PET]) showed no evidence of distant metastases. TG autoantibodies were negative in 19 patients. Second surgery consisted of unilateral (13 patients) or bilateral (8 patients) modified neck dissection. The mean+/-SE TG prior to neck re-exploration was 184.8+/-79.0 ng/ml and declined after surgery to 127.5+/-59.0 ng/ml (p=0.25). The corresponding TSH values were 150.6+/-23.0 and 143.4+/-20.0 mU/l, respectively (p=0.34). After a mean follow-up of 20.7+/-3 months, TG increased to 168+/-68.0 ng/ml. This increase, however, was NS (p=0.67). The corresponding TSH values were 143.4+/-20.0 and 132.0+/-22.0 mU/l (p=0.27). Following second surgery, only 4 patients achieved remission, the other 17 patients received one or more of the following therapies; RAI (10 patients), third surgery (5 patients), and/or external radiation (7 patients). Thirteen patients continued to have persistent disease and 4 patients showed progressive course of their disease (distant metastases or grossly palpable neck disease). In conclusion, second surgery for recurrent/persistent PTC leads to remission in only a minority of cases but the course of the disease tends to be stable in most cases.

Partial laparoscopic adrenalectomy for aldosterone-producing adenoma: short-and long-term results.

BACKGROUND AND PURPOSE: Laparoscopic surgery for adrenal gland tumors is the gold standard operative approach now. Adrenal-sparing surgery has special indications. We demonstrated the safety and feasibility of performing adrenal-sparing surgery by means of laparoscopy for aldosterone-producing adenoma (Conn's syndrome). PATIENTS AND METHODS: Between 1995 and 1999, seven patients with Conn's syndrome had laparoscopic adrenal-sparing resection of their tumors. These patients were followed up by means of radiology and biochemistry. RESULTS: All seven patients had successful laparoscopic surgery without complications. Most patients were discharged in 2 to 6 days (mean 3 days). At follow-up, the six patients investigated had normal blood pressure. No recurrences have been encountered with a median follow-up of 12 months in these six patients. CONCLUSIONS: Adrenal-sparing resection of tumors causing primary hyperaldosteronism is technically feasible by means of laparoscopy. This procedure has the advantage of keeping a greater reserve of normal adrenal tissue and of rapid postoperative recovery.

Locally advanced breast cancer in Saudi Arabia: high frequency of stage III in a young population.

In the Kingdom of Saudi Arabia (KSA), breast cancer constitutes 18% of all cancers in Saudi women. Whilst locally advanced breast cancer disease is unusual in Western countries, it constitutes more than 40% of all non-metastatic breast cancer in KSA. The relative frequency of locally advanced disease among our breast cancer population and the lack of a uniform consensus in the literature about its optimal management have prompted this retrospective analysis of the medical records of patients with Stage III breast cancer patients seen at King Faisal Specialist Hospital and Research Center between 1981 and 1991. In all, 315 patients were identified. Their median age +/- SD was 46 +/- 11.6 years which is distinctly different from the 60-65 years median age in industrial Western nations. Most patients were younger than 50 years (64%) and premenopausal (62%). Patients were approximately equally divided between Stage IIIA and Stage III B. Patients received multimodality treatment, including surgery, adjuvant chemotherapy, tamoxifen, and adjuvant radiotherapy. Sixty-one patients were excluded from survival analysis as they were considered lost to follow-up. Of the remaining 254 patients, 73 (29%) were alive and disease free, and 18 patients (7%) were alive but with evidence of the disease. The remaining 163 (64%) had died from breast cancer or its related complications. Their median overall survival (OS) was 54 months, (95% CI, 27 to 121 months) and the median progression-free survival (PFS) was 28.8 months (95% CI, 14.2 to 113 months). Cox proportional hazard model identified Stage III B and the number of positive axillary lymph nodes as poor predictors of OS and PFS. Radiotherapy was the only adjuvant modality that affected survival favourably. The prognosis of patients with Stage III disease remains poor despite the use of a multimodality approach. The overall young age of our patients may have contributed to the poor outcome. Moreover, the adverse effect of Stage III B disease (as compared with Stage III A) and axillary nodal status was evident. Whilst the favourable effect of radiotherapy on survival was demonstrated, the lack of independent efficacy of other modalities (adjuvant chemotherapy and tamoxifen) or the apparent deleterious effect of neoadjuvant chemotherapy should be addressed with discretion in such retrospective analysis. Optimal management of patients with locally advanced breast cancer disease should be appraised in well designed, prospective, randomised studies.

Extent of lumpectomy for breast cancer after diagnosis by stereotactic core versus wire localization biopsy.

BACKGROUND: Stereotactic core biopsy of mammographically defined breast abnormalities is an alternative to wire localization biopsy. The purpose of this study was to evaluate the extent of lumpectomy in patients diagnosed by stereotactic core versus wire localization biopsy. METHODS: A total of 67 consecutive patients diagnosed with invasive cancers or ductal carcinoma in situ (DCIS) were retrospectively reviewed. Thirty-four were diagnosed by core biopsy and the remaining 33 by wire localization biopsy. RESULTS: Approximately 65% of patients subsequently had breast-conserving surgical therapy. Seventy-nine percent of patients undergoing wire localization biopsies had positive surgical margins. Achievement of negative surgical margins for lumpectomies performed after wire localization or stereotactic core biopsies was 100% and 89%, respectively, which was not significantly different. However, the total volume of breast tissue removed for breast conservation in patients undergoing lumpectomy after wire localization versus core biopsies was 183 cm3 and 104 cm3, respectively, which was significantly different (P = .003). CONCLUSIONS: Diagnosis by stereotactic core biopsies resulted in less tissue removal to achieve margin-negative lumpectomies for breast conservation. Stereotactic core biopsy is the method of choice for biopsying nonpalpable, suspicious breast lesions.

Detection of metastatic parathyroid carcinoma with Tc-99m sestamibi imaging.

PURPOSE: To assess the use of Tc-99m sestamibi to localize recurrent and metastatic parathyroid carcinoma. METHODS: A patient with a history of parathyroid carcinoma that was resected 6 months before had high serum calcium and high serum parathyroid hormone levels. Tc-99m sestamibi imaging was performed to localize the recurrence. RESULTS: Tc-99 sestamibi imaging detected the recurrence and the metastatic lymph nodes. These findings were confirmed surgically and pathologically. CONCLUSION: Tc-99m sestamibi can be useful in diagnosing and localizing metastatic parathyroid carcinoma.

Desensitization in normal and neoplastic human thyroid cell lines.

Because some papillary thyroid cancers continue to grow when thyroid-stimulating hormone (TSH) levels are suppressed, we questioned whether desensitization (i.e., a decreased cAMP response to repeat stimulation with TSH) occurs in normal and neoplastic thyroid tissue. If desensitization does occur, is it similar or different in these human thyroid cells? Normal and papillary thyroid cancer cells from the same patient were cultured as we have previously described. Normal and neoplastic thyroid tissues responded to TSH (0.01-10.0 mU/ml) by increasing cAMP production and growth in a dose-dependent manner. In normal cells there was an 11-fold mean increase in cAMP production at 4 hours, and all thyroid cultures responded. In neoplastic cells cAMP production increased from 1.5-fold to 3.0-fold with a mean 2.0-fold increase at 4 hours. In normal thyroid cells the cAMP response to a second TSH stimulus (desensitization) decreased up to 75% (range 25-75%), and desensitization occurred in all normal thyroid cell cultures. In neoplastic thyroid cells, however, the cAMP response to a second TSH stimulus decreased up to 17% (range 0-17%); and desensitization occurred in only two of the five neoplastic thyroid cell cultures. Thus when normal thyroid and neoplastic cells from the same patients were studied, greater desensitization occurred in the normal cells (75% vs. 17%). These studies document that there is greater desensitization in normal tissue than in neoplastic thyroid tissue, which may account for the increased growth of thyroid neoplasms in the presence of ever-changing low levels of TSH.

Management of thyroid carcinosarcoma.

BACKGROUND: Thyroid carcinosarcoma is a rare and aggressive malignant thyroid tumor that has been described pathologically, but there is little clinical information regarding tumor behavior. METHODS: We retrospectively analyzed the course of our patient and 16 others reported in the literature to determine optimal management. We review the case history of our patient and the literature concerning patients with carcinosarcoma of the thyroid. RESULTS: Seventeen patients, 52 to 80 years of age (mean, 60 years), have had a thyroid carcinosarcoma of the thyroid. Five of seven patients for whom the information is available were treated by partial thyroidectomy and two by total thyroidectomy. Among these patients five (71%) died within the first 3 months and two (29%) survived more than 6 months. The mean survival was 5 months. At autopsy in seven patients, six had lymph node or distant metastases. CONCLUSIONS: Carcinosarcoma of the thyroid is a very aggressive tumor with a clinical course similar to anaplastic thyroid carcinoma. Like patients with anaplastic thyroid carcinoma, few survive more than 6 months despite aggressive multimodal treatment. Our patient's exposure to raw phosphorus, radiation, and 1,3-bis-(2-chloroethyl)-1-nitrosourea may have predisposed her to this aggressive tumor.