Paolo Goffredo

Presence and Number of Lymph Node Metastases Are Associated With Compromised Survival for Patients Younger Than Age 45 Years With Papillary Thyroid Cancer

PURPOSE Cervical lymph node metastases are recognized as a prognostic indicator only in patients age 45 years or older with papillary thyroid cancer (PTC); patients younger than age 45 years are perceived to have low-risk disease. The current American Joint Committee on Cancer staging for PTC in patients younger than age 45 years does not include cervical lymph node metastases. Our objective was to test the hypothesis that the presence and number of cervical lymph node metastases have an adverse impact on overall survival (OS) in patients younger than age 45 years with PTC. PATIENTS AND METHODS Adult patients younger than age 45 years undergoing surgery for stage I PTC (no distant metastases) were identified from the National Cancer Data Base (NCDB; 1998-2006) and from SEER 1988-2006 data. Multivariable models were used to examine the association of OS with the presence of lymph node metastases and number of metastatic nodes. RESULTS In all, 47,902 patients in NCDB (11,740 with and 36,162 without nodal metastases) and 21,855 in the SEER database (5,188 with and 16,667 without nodal metastases) were included. After adjustment, OS was compromised for patients with nodal metastases compared with patients who did not have them (NCDB: hazard ratio (HR), 1.32; 95% CI, 1.04 to 1.67; P = .021; SEER: HR, 1.29; 95% CI, 1.08 to 1.56; P = .006). After adjustment, increasing number of metastatic lymph nodes was associated with decreasing OS up to six metastatic nodes (HR, 1.12; 95% CI, 1.01 to 1.25; P = .03), after which more positive nodes conferred no additional mortality risk (HR, 0.99; 95% CI, 0.99 to 1.05; P = .75). CONCLUSION Our results suggest that cervical lymph node metastases are associated with compromised survival in young patients, warranting consideration of revised American Joint Committee on Cancer staging. A change point of six or fewer metastatic lymph nodes seems to carry prognostic significance, thus advocating for rigorous preoperative screening for nodal metastases.

Hurthle cell carcinoma: a population-level analysis of 3311 patients.

Hurthle cell carcinoma (HCC) is an uncommon and more aggressive thyroid cancer. To date, there is a paucity of data at a population level. In this study, demographic, clinical, and pathologic characteristics of HCC were investigated and compared with other types of differentiated thyroid cancers (ODTCs). The authors also evaluated disease‐specific survival and compliance with American Thyroid Association (ATA) management guidelines from 2009.

Malignant pheochromocytoma and paraganglioma: A population level analysis of long-term survival over two decades†‡

Pheochromocytoma (PHEO) and paraganglioma (PGL) are rare tumors. Aims of this study were to describe and to compare demographic, clinical, pathologic, and survival characteristics of malignant PHEO and PGL.

Impact of extent of surgery on survival for papillary thyroid cancer patients younger than 45 years.

CONTEXT Papillary thyroid cancer (PTC) patients <45 years old are considered to have an excellent prognosis; however, current guidelines recommend total thyroidectomy for PTC tumors >1.0 cm, regardless of age. OBJECTIVE Our objective was to examine the impact of extent of surgery on overall survival (OS) in patients <45 years old with stage I PTC of 1.1 to 4.0 cm. DESIGN, SETTING, AND PATIENTS Adult patients <45 years of age undergoing surgery for stage I PTC were identified from the National Cancer Data Base (NCDB, 1998-2006) and the Surveillance, Epidemiology, and End RESULTS dataset (SEER, 1988-2006). MAIN OUTCOME MEASURE Multivariable modeling was used to compare OS for patients undergoing total thyroidectomy vs lobectomy. RESULTS In total, 29 522 patients in NCDB (3151 lobectomy, 26 371 total thyroidectomy) and 13 510 in SEER (1379 lobectomy, 12 131 total thyroidectomy) were included. Compared with patients undergoing lobectomy, patients having total thyroidectomy more often had extrathyroidal and lymph node disease. At 14 years, unadjusted OS was equivalent between total thyroidectomy and lobectomy in both databases. After adjustment, OS was similar for total thyroidectomy compared with lobectomy across all patients with tumors of 1.1 to 4.0 cm (NCDB: hazard ratio = 1.45 [confidence interval = 0.88-2.51], P = 0.19; SEER: 0.95 (0.70-1.29), P = 0.75) and when stratified by tumor size: 1.1 to 2.0 cm (NCDB: 1.12 [0.50-2.51], P = 0.78; SEER: 0.95 [0.56-1.62], P = 0.86) and 2.1 to 4.0 cm (NCDB: 1.93 [0.88-4.23], P = 0.10; SEER: 0.94 [0.60-1.49], P = 0.80). CONCLUSIONS After adjusting for patient and clinical characteristics, total thyroidectomy compared with thyroid lobectomy was not associated with improved survival for patients <45 years of age with stage I PTC of 1.1 to 4.0 cm. Additional clinical and pathologic factors should be considered when choosing extent of resection.

Combined hepatocellular‐cholangiocarcinoma: A population‐level analysis of an uncommon primary liver tumor

Combined hepatocellular‐cholangiocarcinoma (cHCC‐CC) is a rare primary liver cancer. Our aims were to analyze the demographic, clinical, and pathological characteristics of cHCC‐CC at a population level and to investigate the effects of these features as well as different management strategies on the prognosis. The Surveillance, Epidemiology, and End Results (SEER) database was analyzed for 1988‐2009. Data analyses were performed with chi‐square tests, analyses of variance, Kaplan‐Meier curves, and Cox proportional hazards regression. Four hundred sixty‐five patients with cHCC‐CC, 52,825 patients with hepatocellular carcinoma (HCC), and 7181 patients with cholangiocarcinoma (CC) were identified. cHCC‐CC was more common in patients who were white, male, and older than 65 years. Treatment was more frequently nonsurgical/interventional. Patients with cHCC‐CC, HCC, and CC had 5‐year overall survival (OS) and disease‐specific survival rates of 10.5%, 11.7%, and 5.7% (P < 0.001) and 17.8%, 21.0%, and 11.9% (P < 0.001), respectively. For cHCC‐CC patients, an increasing invasiveness of the therapeutic approach was significantly associated with prolonged survival (P < 0.001). In a multivariate model, black race, a distant SEER stage, and a tumor size of 5.0 to 10.0 cm were independently associated with lower survival for cHCC‐CC patients; a year of diagnosis after 1995 and surgical treatment with minor hepatectomy, major hepatectomy (MJH), or liver transplantation (LT) were independently associated with better survival for cHCC‐CC patients. Patients diagnosed with cHCC‐CC, HCC, and CC and treated with LT had 5‐year OS rates of 41.1%, 67.0%, and 29.0%, respectively (P < 0.001). In conclusion, cHCC‐CC patients appear to have intermediate demographic, clinical, and survival characteristics in comparison with HCC and CC patients. cHCC‐CC patients undergoing LT showed inferior survival in comparison with HCC patients, and the role and indications for LT in cHCC‐CC have yet to be defined. At this time, MJH may be considered the best therapeutic approach for such patients. Liver Transpl 20:952–959, 2014.

Aggressive Variants of Papillary Thyroid Microcarcinoma Are Associated with Extrathyroidal Spread and Lymph-Node Metastases: A Population-Level Analysis

BACKGROUND Tall cell variant (TCV) and diffuse sclerosing variant (DSV) of papillary thyroid cancer are aggressive subtypes, for which tumors ≤1 cm have not been exclusively studied. METHODS The SEER database (1988-2009) was used to compare characteristics of TCV ≤1 cm (mTCV) and DSV ≤1 cm (mDSV) with classic papillary thyroid microcarcinoma (mPTC). Survival was analyzed with the Kaplan-Meier method and log-rank test, and risk factors for nodal metastases with chi-square analysis and binary logistic regression. RESULTS There were 97 mTCV, 90 mDSV, and 18,260 mPTC patients. mTCV incidence increased by 79.9% (p=0.153) over the study period, while mDSV incidence decreased by 10.3% (p=0.315). Compared to classic mPTC, mTCV tended to be larger on average (7.1 mm vs. 5.3 mm, p<0.001), with higher rates of multifocality (47.2% vs. 34.0% respectively, p=0.018) and lymph-node examination (63.9% vs. 39.2% respectively, p<0.001), while in mDSV, nodal metastases were more frequent (57.1% vs. 33.1% respectively, p=0.007). Both aggressive variants had higher rates of extrathyroidal extension (27.8% mTCV vs. 13.3% mDSV vs. 6.1% mPTC, p<0.001). Aggressive variants also received radioactive iodine more frequently (39.2% mTCV vs. 40.0% mDSV vs. 29.1% mPTC, p<0.001). However, they were not statistically more likely to receive thyroidectomy over lobectomy compared to classic mPTC. There were no significant differences in overall and disease-specific survival between the histologies. In mTCV, after adjustment, extrathyroidal extension was independently associated with size >7 mm (odds ratio (OR) 4.4 [CI 1.5-13.6]) and nodal metastasis with multifocality (OR 5.4 [CI 1.3-23.4]) and extrathyroidal extension (OR 5.8 [CI 1.3-25.4]). No statistically significant predictors of extrathyroidal extension or nodal metastasis in mDSV were observed. CONCLUSIONS Aggressive variants of mPTC tend to exhibit more aggressive pathologic characteristics than classic mPTC, but survival appears to be similar. Treatment with total thyroidectomy and central lymphadenectomy may be warranted if the diagnosis can be made pre- or intraoperatively.

The value of repeat biopsy in the management of lupus nephritis: an international multicentre study in a large cohort of patients

BACKGROUND The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification represents the gold standard for the histological evaluation of Systemic Lupus Erythematosus (SLE) nephritis. A repeat biopsy (RB) might be an important tool to provide information on long-term renal outcomes and optimal therapy. Aims of this study were to evaluate the use of the ISN/RPS classification and the role of RB in routine clinical practice. METHODS A total number of 142 patients with SLE nephritis and with adequate reference and RB samples were included in this multicentre retrospective study. A meticulous histological examination was centrally performed on first and RB and compared with clinical variables and follow-up data. RESULTS Morphological features of the ISN/RPS classification: at first and RB, significant differences were observed between segmental classes (III, IV-S) and Class IV-G in mesangial proliferation, wire loops and tuft necrosis. Clinical features and ISN/RPS classification: the correlation between serum creatinine, proteinuria, blood pressure levels and histological classes at first and RB demonstrated more severe renal disease in Class IV-G, both at first and RB. Agreement between ISN/RPS classification at first and RB: 40.8% of patients changed the histological class. Fifty per cent of Class II (mild mesangial form) were reclassified as Class IV-G at RB, whereas 18.9% of Class IV-G were reclassified as Class II. The transition among segmental (III/IV-S) and mesangial forms (II/IV-G) was extremely rare. The comparison between the clinical parameters at the final follow-up and the ISN/RPS classification confirmed that the trend of serum creatinine and proteinuria between the different classes was better described at the RB (higher in Class IV-G) than on the first biopsy. CONCLUSIONS The histopathological data suggest that morphological differences between segmental and global forms do exist, possibly due to different pathogenetic mechanisms. An RB strategy could provide additional information on long-term renal outcomes. A strategy of protocol biopsies could be useful in perspective future trials to better understand the therapeutic response and the natural history of this disease.

Malignant Struma Ovarii: A Population-Level Analysis of a Large Series of 68 Patients

BACKGROUND Malignant struma ovarii (MSO) is a germ cell tumor of the ovary histologically identical to differentiated thyroid cancers. There is a paucity of data on this neoplasm, with fewer than 200 reported cases. The primary objective of this study was to examine the survival rate of women diagnosed with MSO using data from the Surveillance, Epidemiology, and End RESULTS (SEER) database. Secondary objectives were to describe the demographic, clinical, pathologic, and treatment characteristics of this population. METHODS A retrospective analysis was performed of prospectively collected cancer registry data. A total of 68 patients were identified in the SEER database, 1973-2011. The chi-square test, Students t-test, and Kaplan-Meier curves were employed for data analyses. RESULTS All 68 patients were females with a mean age at diagnosis of 43.0 years. Nearly 33% underwent unilateral oophorectomy, 28.6% bilateral oophorectomy, and 28.6% oophorectomy and omentectomy, and 4.8% were treated with debulking surgery. Pelvic radiation was administered to 12.3% of patients. The mean tumor size was 52.8 mm; 80% of malignant struma ovarii were SEER staged as local. Overall survival rates at 5, 10, and 20 years were 96.7%, 94.3%, and 84.9% respectively. Among the patients, there were six deaths recorded; only one was attributed to MSO. Six individuals (8.8%) had a concomitant or subsequent diagnosis of thyroid cancer. Four patients underwent total thyroidectomy, three patients had radioactive iodine, and one patient underwent external beam radiation. Two thirds of thyroid cancers extended outside the thyroid gland. All six patients with thyroid cancer were alive at the end of follow-up. CONCLUSIONS It was observed that patients with malignant struma ovarii had an excellent disease-specific survival rate, regardless of the management strategy employed. However, MSO patients had a high risk for developing aggressive thyroid cancers. Therefore, MSO patients may benefit from routine thyroid imaging once the diagnosis of MSO is established.

Same thyroid cancer, different national practice guidelines: When discordant American Thyroid Association and National Comprehensive Cancer Network surgery recommendations are associated with compromised patient outcome.

BACKGROUND The American Thyroid Association (ATA) and National Comprehensive Cancer Network (NCCN) guidelines have discordant recommendations for managing patients with differentiated thyroid cancer (DTC). We hypothesized that physician adherence to either of the 2009 extent of surgery guidelines of the ATA or NCCN was associated with improved survival, and that practice is most standardized nationally when guidelines are concordant. METHODS Adult patients undergoing surgery for DTC were included from the National Cancer Database. Multivariable modeling was used to identify factors associated with nonadherence to the 2009 ATA or NCCN guidelines (2010-2011) and hypothetically examine the association of retrospective adherence to guidelines with survival (1998-2006). RESULTS A total of 39,687 patients with DTC were included; 2,249 were not treated in accordance with ATA or NCCN guidelines. Factors independently associated with nonadherence were discordance between ATA and NCCN recommendations, black race, and treatment at nonacademic centers (P < .01). After adjustment, care not in accordance with either set of guidelines was associated with compromised survival (hazard ratio 1.16, P = .02). CONCLUSION A minority of patients received surgery for DTC not aligned with guidelines; nonadherent care was associated with compromised survival. Discordance in recommendations between guidelines is associated with reduction in adherent care, suggesting that standardizing guidelines could decrease confusion, increase adherence, and thereby may improve outcomes.

Risk factors for 30-day readmission after adrenalectomy

Background: Readmissions represent a substantial burden to the health care system. Risk factors for 30‐day readmission after adrenalectomy were examined. Methods: Patients who underwent adrenalectomy were selected from the American College of Surgeons National Surgical Quality Improvement Program database from 2011 to 2015. Results: Among 4,221 patients who underwent adrenalectomy, 216 (5.1%) were readmitted. On multivariate analysis, pre‐operative predictive factors associated with readmission were American Society of Anesthesiologists classification (odds ratio [OR] 1.4, confidence interval [CI] 1.1–1.8), disseminated cancer (OR 1.6, CI 1.1–2.5), and adrenal injury (OR 10.9, CI 1.8–68.9). Elective procedures had fewer readmissions (OR 0.50, CI 0.33–0.76). and procedures with greater relative value units had greater readmission rates (OR 1.01, CI 1.004–1.02). An open adrenalectomy (21% of patients) had a higher rate of readmission than a laparoscopic approach (8.0% vs 4.3%, OR 1.5, CI 1.1–2.0). Postoperative risk factors affecting readmission included reoperations (OR 3.2, CI 1.3–8.0), wound complications (OR 6.6, CI 3.8–11.7), systemic infection (OR 6.5, CI 3.9–10.7), renal complications (OR 7.1, CI 2.6–19.2), venous thrombotic events (OR 11.3, CI 5.6–22.6), and discharge to home (OR 0.40, CI 0.22–0.73). Conclusion: Encouraging the appropriate use of laparoscopic adrenalectomy, preventing venous thrombotic events and surgical infections, and improving early post‐operative follow‐up in high‐risk patients may decrease readmissions.