Incidence of the CHEK2 Germline Mutation and Its Impact on Clinicopathological Features, Treatment Responses, and Disease Course in Patients with Papillary Thyroid Carcinoma.

The CHEK2 gene is involved in the repair of damaged DNA. CHEK2 germline mutations impair this repair mechanism, causing genomic instability and increasing the risk of various cancers, including papillary thyroid carcinoma (PTC). Here, we asked whether CHEK2 germline mutations predict a worse clinical course for PTC. The study included 1547 unselected PTC patients (1358 women and 189 men) treated at a single center. The relationship between mutation status and clinicopathological characteristics, treatment responses, and disease outcome was assessed. CHEK2 mutations were found in 240 (15.5%) of patients. A CHEK2 I157T missense mutation was found in 12.3%, and CHEK2 truncating mutations (IVS2 + 1G > A, del5395, 1100delC) were found in 2.8%. The truncating mutations were more common in women (p = 0.038), and were associated with vascular invasion (OR, 6.91; p < 0.0001) and intermediate or high initial risk (OR, 1.92; p = 0.0481) in multivariate analysis. No significant differences in these parameters were observed in patients with the I157T missense mutation. In conclusion, the CHEK2 truncating mutations were associated with vascular invasion and with intermediate and high initial risk of recurrence/persistence. Neither the truncating nor the missense mutations were associated with worse primary treatment response and outcome of the disease.

Effective Preoperative Plasmapheresis Treatment of Severe Hyperthyroidism in a Patient with Giant Toxic Nodular Goiter and Methimazole-Induced Agranulocytosis.

Agranulocytosis is a rare but very serious complication of thyrostatic therapy. In severe hyperthyroidism, the removal of circulating thyroid hormones by plasmapheresis may be an effective therapeutic option. This report describes the therapeutic difficulties and successful preoperative treatment with plasmapheresis in a 63-year-old patient admitted to the Endocrinology Clinic with severe hyperthyroidism, during the course of giant toxic nodular goiter and agranulocytosis, which occurred after 2 weeks of taking methimazole. During hospitalization, methimazole treatment was discontinued and therapy with steroids, a beta blocker, propylthiouracil, Lugol's solution, lithium carbonate, and antibiotics were initiated. Granulocyte colony growth stimulating factor was also used to resolve agranulocytosis. Due to the failure to achieve euthyreosis using this approach, we decided to conduct thyroid surgery, as a life-saving action, after preparation of the patient by plasmapheresis. Two plasmapheresis procedures were performed, resulting in a decrease in the concentration of free thyroid hormones. Total thyroidectomy was performed and there were no complications during surgery. We conclude that plasmapheresis may be considered as an effective alternative treatment option for the preparation of patients with hyperthyroidism for surgery, when the clinical situations prevent the use of conventional treatments for hyperthyroidism and when immediate life-saving surgery is necessary.

Surgery quality and tumor status impact on survival and local control of resectable liposarcomas of extremities or the trunk wall.

BACKGROUND: The 5-year survival rates for localized liposarcomas reportedly vary from 75% to 91% with histologic grade as the most important prognostic factor. However, it is unclear which other factors, including the initial surgery quality and recurrent tumors, influence survival in localized liposarcomas (LPS). QUESTIONS/PURPOSES: We analyzed factors (including AJCC staging system) influencing survival and local control of resectable LPS of the extremities/trunk wall and the impact of surgery quality and tumor status and type of disease recurrences according to pathological subtype. METHODS: We retrospectively reviewed 181 patients with localized LPS: 110 were treated for primary tumors, 50 for recurrent tumors, and 21 for wide scar resection after unplanned nonradical resection. We determined survival rates and examined factors influencing survival. The minimum followup was 4 months (median, 52 months; range, 4-168 months). RESULTS: Five-year disease-specific (DSS), disease-free (DFS), and local relapse-free survival (LRFS) rates were: 80%, 58%, and 75%, respectively. Five-year local relapse-free survival rates for primary versus clinically recurrent tumor versus scar after nonradical resection were: 86.1%, 52.1%, and 73.3%, respectively. The following were independent negative prognostic factors for DSS (AJCC Stage ≥ IIb), DFS (Grade 3; clinical recurrence; skin infiltration), and LRFS (clinical recurrence; R1 resection). An unplanned excision, although influencing local relapse-free survival, had no impact on disease-specific survival (calculated from date of first excision 5-year rate of 80%, considering impact of combined treatment of clinical recurrence/scar). CONCLUSIONS: We confirmed the value of AJCC staging for predicting disease-specific survival in extremity/trunk wall LPS. Radical reresection of scar after nonradical primary tumor resection (+ radiotherapy) seems to improve disease-free and local relapse-free survival in liposarcomas. Patients with unplanned excision can be cured when referred to a sarcoma unit. LEVEL OF EVIDENCE: Level IV, prognostic study. See the Guidelines for Authors for a complete description of levels of evidence.

Melanoma without a detectable primary site with metastases to lymph nodes.

OBJECTIVE: To compare outcomes of patients with clinical nodal melanoma metastases that occurred without a detectable primary tumor (melanoma of unknown primary site; MUP) with those with a known primary site (KPM). METHODS: We included data from 459 consecutive patients treated from 1994 to 2007 with radical therapeutic lymph node dissection (LND; stage IIIB, C) due to clinically palpable and pathologically confirmed lymph node metastases (229 axillary; 230 ilioinguinal). The median follow-up was 49 months. RESULTS: LND was performed in 59 cases (12.9%; 29 men, 30 women) due to MUP nodal metastases, including 33 axillary (14.4%) and 26 ilioinguinal (11.3%). In the MUP group, the 3- and 5-year survival rates were 48% and 41%, respectively. Similar rates were observed in patients with KPM, even with matched-pair analyses. Established prognostic factors (number of metastatic nodes, p=.005; extracapsular extension of metastases, p=.002) influenced survival in the MUP group. Relapses occurred in 31 (53%) and 299 (74.7%) cases in the MUP and KPM groups, respectively. CONCLUSIONS: Survival rates in the MUP and KPM groups were similar, and the same prognostic factors affected both. Thus, all MUP cases should be treated as standard stage III melanomas.