Propensity score-matched comparison of oncological outcomes between laparoscopic and open distal pancreatic resection.

BACKGROUND: Selected studies have reported improved outcomes in laparoscopic compared with open distal pancreatic resection. Concerns regarding failure to achieve proper oncological resection and compromised long-term outcomes remain. This study investigated whether postoperative outcomes and long-term survival after laparoscopic distal pancreatectomy are comparable to those after an open procedure. METHODS: This retrospective case-control study included patients who underwent distal pancreatectomy for resectable pancreatic adenocarcinoma between 2010 and 2013, identified from the National Cancer Database. Propensity score nearest-neighbour 1 : 1 matching was performed between patients undergoing laparoscopic or open distal pancreatectomy based on all relevant co-variables. The primary outcome was overall survival. RESULTS: Of 1947 eligible patients, 605 (31·1 per cent) underwent laparoscopic distal pancreatectomy. After propensity score matching, two well balanced groups of 563 patients each were analysed. There was no difference in overall survival at 3 years after laparoscopic versus open distal pancreatectomy (41·6 versus 36·0 per cent; hazard ratio 0·93, 95 per cent c.i. 0·77 to 1·12; P = 0·457). The overall conversion rate was 27·3 per cent (165 of 605). Patients who underwent laparoscopic distal pancreatectomy had outcomes comparable to those of patients who had an open procedure with regard to median time to chemotherapy (50 versus 50 days; P = 0·342), median number of nodes examined (12 versus 12; P = 0·759); 30-day mortality (1·2 versus 0·9 per cent; P = 0·562); 90-day mortality (2·8 versus 3·7 per cent; P = 0·403), 30-day readmission rate (9·6 versus 9·2 per cent; P = 0·838) and positive margin rate (14·9 versus 18·5 per cent; P = 0·110). However, median duration of hospital stay was shorter in the laparoscopic group (6 versus 7 days; P < 0·001). CONCLUSION: Laparoscopic distal pancreatectomy is an acceptable alternative to open distal pancreatectomy with no detriment to survival.

Accuracy of fine-needle aspiration cytology in patients with radiation-induced thyroid neoplasms.

BACKGROUND: Fine-needle aspiration cytology (FNAC) is useful for selecting patients with thyroid nodules for thyroidectomy. Its value in patients who have been exposed to low-dose therapeutic radiation is questionable because these patients have an increased risk of multifocal benign and malignant tumours, and thyroid cancer is common in such patients. METHODS: Between 1960 and 1999, 171 patients with one or more thyroid nodules who had a history of exposure to radiation underwent operation; 49 of these patients had preoperative FNAC. The cytology results in these 49 patients were compared with those of an age- and sex-matched control group of patients with thyroid nodules who did not have a history of radiation exposure. RESULTS: Of those who had been exposed to radiation, six of 20 patients with 'benign' cytology by FNAC and six of 16 patients with 'suspicious' cytology had thyroid cancer. All 13 specimens considered to be malignant on FNAC were indeed malignant. There was a higher rate of false-negative cytological examinations among patients with a history of irradiation that in those without. CONCLUSION: FNAC of thyroid nodules in patients with a history of irradiation is not as accurate as that in non-irradiated patients, primarily because of coexisting occult thyroid cancers.

Completely resected anaplastic thyroid carcinoma combined with adjuvant chemotherapy and irradiation is associated with prolonged survival.

BACKGROUND: The prognosis of anaplastic thyroid carcinoma (ATC) has been dismal. The objective of this study was to identify prognostic factors in patients who had prolonged survival. METHODS: Patients with ATC were identified from a computer database at a tertiary referral center. Univariate and multivariate analyses for survival differences were performed using the Kaplan-Meier log-rank statistic and the Cox proportional hazards model, respectively. RESULTS: Of the 33 evaluable patients, median survival was 3.8 months. Median age was 69 years. Prior goiter was present in 6 patients (18%), and 6 (18%) had prior thyroid carcinoma. Median tumor size was 6 cm, and 12 (36%) had adjacent well-differentiated carcinoma. Of the 26 patients who underwent neck exploration, 8 patients were potentially cured and received postoperative chemotherapy and irradiation; 4 (50%) were surgically macroscopically free of disease, and 4 (50%) patients had minimal residual disease after total thyroidectomy and resection of tumor adherent to adjacent structures. Four of these 8 patients survived longer than 2 years; their 5-year survival estimate was 50%. Eighteen patients underwent palliative resection of neck disease, leaving macroscopic residual disease or distant metastases; postoperative adjuvant chemotherapy and irradiation were administered in 16 of these 18 patients. Seven patients were treated with only chemotherapy and irradiation. In patients treated with potentially curative resection, median survival was 43 months compared with 3 months with palliative resection (P =0.002); the median survival of 3.3 months with only chemotherapy and irradiation was no different than palliative resection (P =0.63). No association was found between survival and age, prior goiter, prior thyroid carcinoma, adjacent differentiated carcinoma, or tumor size. CONCLUSIONS: Although the prognosis of most patients with ATC continues to be poor, complete resection of ATC combined with postoperative adjuvant chemotherapy and irradiation resulted in long-term survival, even with persistent minimal disease that remained on vital structures. An aggressive attempt at maximal tumor debulking followed by adjuvant therapy was found to be warranted in patients with localized ATC.

Can localization studies be used to direct focused parathyroid operations?

BACKGROUND: There is considerable controversy today concerning the most appropriate surgical approach for patients with primary hyperparathyroidism. The conventional surgical operation involves a bilateral neck exploration through a collar incision with identification of all parathyroid tissue and removal of abnormal parathyroid glands while the patient is under general anesthesia. The success rate of this operation is about 95% or greater in the hands of an experienced endocrine surgeon. Preoperative localization techniques are generally considered to be unnecessary before initial parathyroid operations. The purpose of this investigation was (1) to evaluate the individual and combined accuracy of ultrasonography and technetium 99m sestamibi scans in localizing abnormal parathyroid glands and (2) to determine whether such scans could be used to direct a focused operation. METHODS: We retrospectively studied 338 patients with sporadic primary hyperparathyroidism who had preoperative neck localization studies, ultrasonography and/or technetium 99m sestamibi scans, and parathyroid exploration (238 patients or, reexploration, 60 patients) from January 1996 to April 2000 at the University of California San Francisco/Mount Zion Medical Center. The preoperative localization studies were recorded as true-positive, false-positive, and false-negative and compared with the surgical and pathologic findings and with the outcome of the operation. RESULTS: All of the abnormal parathyroid glands were correctly identified by ultrasonography in 184 of 303 patients (60.7%) and by technetium 99m sestamibi scanning in 183 of 237 patients (77.2%). The sensitivities of ultrasonography and sestamibi were 65% and 80%, respectively. Among the 202 patients who received both ultrasonography and sestamibi scans, a parathyroid tumor was identified at the same site in 105 (52%) of them. When both techniques identified a parathyroid tumor at the same site, the tests were correct in 101 of 105 patients and the sensitivity increased to 96%. CONCLUSIONS: When both the ultrasonography and sestamibi scans identified the same, solitary parathyroid tumor in patients with sporadic primary hyperparathyroidism, this was the only abnormal parathyroid gland in 96% of the patients. A focused parathyroidectomy could therefore be performed in such patients with an acceptable ( approximately 95%) success rate.

Coexisting chronic lymphocytic thyroiditis and papillary thyroid cancer revisited.

The effect of chronic lymphocytic thyroiditis (CLT) on the behavior of papillary thyroid cancer (PTC) remains unclear. In recent studies the presence of CLT in patients with PTC was reported to be associated with a lower recurrence rate and an improved survival rate. Furthermore, patients with PTC and tumor infiltrating lymphocytes (TILs) have been reported to have lower recurrence rates and a lower frequency of distant metastases. Because of these and other observations, a tumor immune response in PTC has been suggested. The aim of our study was to determine: (1) the relative frequency of CLT in PTC; (2) the prognostic significance of CLT in patients with PTC; and (3) if TIL occurs independently or in association with CLT. A 10-year retrospective study of patients who underwent initial thyroidectomy for PTC from 1986 to 1996 was completed. The extent of thyroid lymphocytic infiltration was determined within the tumor, surrounding the tumor, and in the distant parenchyma by two independent observers blinded to the clinical data. Dense focal/diffuse lymphoid aggregates throughout the thyroid gland were diagnostic of CLT and when present within or surrounding the tumor were designated TILs. A total of 136 patients with PTC (typical and follicular variant of PTC histologic subtypes) were identified with a mean follow-up of 4.4 years and a 8% mortality rate at 10 years. Thirty percent of the patients with PTC had coexisting CLT, and 65% of these patients with CLT had positive anti-thyroglobulin antibodies. Patients with coexisting CLT and PTC were younger (p < 0.05), more likely to be female (p < 0.05), and more likely to have multicentric tumors (p < 0.001) compared to patients without CLT. Only 5% of patients had TILs without CLT, but 82.5% of patients with CLT had TILs identified (p < 0.0001). By univariate analysis CLT, age, gender, stage of PTC, tumor multicentricity, and tumor size were significant prognostic factors. Only age and TNM stage of PTC remained independent prognostic factors by multivariate analysis. We found a similar frequency (30%) of coexisting CLT and PTC as reported by others; but, more importantly, the presence of TILs primarily occurred in association with CLT. The presence of CLT in patients with PTC correlated with an improved prognosis. It was not an independent prognostic factor, however, and was not associated with a lower recurrence rate or a lower frequency of distant metastasis.

Association between residual thyroid carcinoma and diffuse hepatic uptake of 131I following radioiodine ablation in postoperative total thyroidectomy patients.

In patients with differentiated thyroid cancer (DTC) total or near-total thyroidectomy, postoperative 131I ablation, and thyroid suppression therapy are reported to be associated with fewer recurrences than other treatments. Many patients with DTC after total thyroidectomy and radioablation therapy have diffuse hepatic uptake of radioiodine, and its clinical importance is debated. Some investigators report that diffuse liver uptake correlates with uptake in the thyroid bed or the presence of metastatic thyroid cancer somewhere in the body, whereas others note no such correlation. The purpose of this research was to determine the clinical importance of diffuse hepatic uptake of radioiodine after 131I ablative therapy in patients with DTC. We retrospectively reviewed 141 posttherapy scans done in 118 patients with DTC. Patients had had total thyroidectomy and were hypothyroid when serum thyroglobulin (Tg) levels were obtained, and they were treated with 30 to 200 mCi of 131I. Scans were performed 3 to 21 days after radioablation therapy. Information was collected regarding the patients' age and gender, the interval between the ablation therapy and scan, uptake of radioiodine, serum thyroglobulin level, thyroid-stimulating hormone (TSH) level, thyroglobulin antibodies, TNM classification, mortality, and recurrence. Diffuse liver uptake was classified from 0 to 4 depending on hepatic brightness. Radioiodine scans were done to determine whether there was uptake in the thyroid bed or elsewhere. Statistical analyses included analysis of variance and Kaplan-Meier survival analysis. Diffuse hepatic uptake was observed (grades 1-4) in 96.4% of the patients; thus 3.6% had no hepatic uptake. There was no significant association between liver uptake and the uptake in the thyroid bed, the dose of 131I administered for ablation therapy, thyroglobulin levels, age, stage of the disease, presence of local or distant metastases, recurrence, or survival. Diffuse hepatic uptake was therefore not associated with residual normal thyroid or metastases as suggested by some but not all previous investigators.

Is familial non-medullary thyroid carcinoma more aggressive than sporadic thyroid cancer? A multicenter series.

BACKGROUND: The aggressiveness of familial non-medullary thyroid cancer (FNMTC) has been a subject of debate. The purpose of the study was to determine whether FNMTC is more aggressive than sporadic thyroid cancer. METHODS: A multicenter retrospective matched-case control study of FNMTC versus sporadic non-medullary thyroid cancer was conducted. Disease-free survival (time to recurrence) for both groups was compared. RESULTS: Forty-eight familial cases were compared with 144 age-, gender-, and stage-matched controls. Patients with FNMTC had a significantly shorter disease-free survival compared with sporadic non medullary thyroid cancer. Patients with FNMTC who presented with evidence of distant metastasis, or who were from families with more than 2 thyroid cancer-affected members, had the worst prognosis. The available staging systems were less likely to predict the outcome in patients with FNMTC than in patients with sporadic non-medullary thyroid cancer unless one accounted for the strength of family history in the staging system. CONCLUSIONS: FNMTC is more aggressive than sporadic non-medullary thyroid cancer. The best predictors of a poor outcome in patients with FNMTC are the number of family members affected by thyroid cancer and evidence of distant metastasis.

Death from thyroid cancer of follicular cell origin.

BACKGROUND: Although patients with differentiated thyroid cancer (DTC) of follicular cell origin usually have an excellent prognosis, some patients die from progressive tumor. Numerous postoperative criteria have been used to predict prognosis in patients with DTC. The purpose of this investigation was to determine whether the TNM and metastases, age, completeness of resection, invasion, size (MACIS) classifications predicted survival time and why patients died from DTC. The extent of initial treatment and causes of death were also evaluated in these patients who died from thyroid cancer. STUDY DESIGN: Between 1965 and 1995, 102 of 1,224 patients with DTC treated at the University of California at San Francisco (UCSF) and UCSF/Mount Zion Medical Centers died from DTC. Risk factors including age at diagnosis, gender, histologic characteristics, TNM and MACIS classifications, the intervals among initial treatment, recurrence, and death, and the initial and subsequent treatments were documented in these 102 patients. RESULTS: Among the 102 patients who died of DTC 50% were men and 50% were women. The mean age of patients with DTC at diagnosis was 58 years at recurrence, 62 and 65 years at death. Thirty percent of these patients initially had unilateral thyroid operations and 70% had a bilateral operation. Tumors at presentation ranged from 0.6 to 13.0 cm (mean 4.4 cm); 46% of patients presented with late-stage tumors (TNM stage III, IV; MACIS score > 8). At presentation 46% of the patients had locally recurrent disease or regional metastases and 18% had distant metastases. Patients with persistent disease had a significantly shorter survival time than those with recurrent disease (p < 0.001). Both TNM and MACIS classifications were good predictors of survival time. Reoperations were performed in 51% of papillary, 26% of follicular, and 67% of Hürthle cell thyroid cancer patients. Fifty percent of patients with papillary thyroid cancer, 50% of patients with Hürthle cell thyroid cancer, and 11% of patients with follicular cell thyroid cancer died of locally advanced disease. CONCLUSIONS: As expected, patients with local or regional recurrence and those with TNM stage I or MACIS score < 6 survived longer than patients with distant metastasis and TNM stage III or IV, MACIS score > 6, but some patients thought to be at low risk (TNM stage I; MACIS < 6) also died from thyroid cancer.

Medullary thyroid carcinoma: clinical characteristics, treatment, prognostic factors, and a comparison of staging systems.

BACKGROUND: The clinical courses of patients with medullary thyroid carcinoma (MTC) vary, and a number of prognostic factors have been studied, but the significance of some of these factors remains controversial. METHODS: The study group consisted of 104 patients with MTC or C-cell hyperplasia managed at the hospitals of the University of California, San Francisco, between January 1960 and December 1998. Patients were classified as having sporadic MTC, familial non-multiple endocrine neoplasia (MEN) MTC, MEN 2A, or MEN 2B. The TNM, European Organization for Research and Treatment of Cancer (EORTC), National Thyroid Cancer Treatment Cooperative Study (NTCTCS), and Surveillance, Epidemiology, and End Results (SEER) extent-of-disease stages were determined for each patient. The predictive values of these staging or prognostic scoring systems were compared by calculating the proportion of variance explained (PVE) for each system. RESULTS: Fifty-six percent of the patients had sporadic MTC, 22% had familial MTC, 15% had MEN 2A, and 7% had MEN 2B. The overall average age at diagnosis was 38 years, and patients with sporadic MTC presented at an older age (P < 0.05). Thirty-two percent of the patients with hereditary MTC were diagnosed by screening (genetic and/or biochemical). These patients had a lower incidence of cervical lymph node metastasis (P < 0.05) and 94.7% were cured at last follow-up (P < 0.0001) compared with patients not screened. Patients with sporadic MTC who had systemic symptoms (diarrhea, bone pain, or flushing) had widely metastatic MTC and 33.3% of those patients died within 5 years. Overall, 49.4% of the patients were cured, 12.3% had recurrent MTC, and 38.3% had persistent MTC. The mean follow-up time was 8.6 years (median, 5.0 years) with 10.7% (n=11) and 13.5% (n=14) cause specific mortality at 5 and 10 years, respectively. Patients with persistent or recurrent MTC who died of MTC lived for an average of 3.6 years (ranging from 1 month to 23.7 years). Patients who had total or subtotal thyroidectomy were less likely to have persistent or recurrent MTC (P < 0.05), and patients who had total thyroidectomy with cervical lymph node clearance required fewer reoperations for persistent or recurrent MTC (P < 0.05) than patients who underwent lesser procedures. In univariate analysis, age, gender, clinical presentation, TNM stage, sporadic/hereditary MTC, distant metastasis, and extent of thyroidectomy were significant prognostic factors. Only age and stage, however, remained independent prognostic factors in multivariate analysis. The TNM, EORTC, NTCTCS, and SEER staging systems were all accurate predictors of survival, but the EORTC prognostic scoring system had the highest PVE in this cohort. CONCLUSIONS: Screening for MTC and early treatment (total thyroidectomy with central neck lymph node clearance) had nearly a 100% cure rate. Patients with postoperative hypercalcitoninemia without clinical or radiologic evidence of residual tumor after apparently curative surgery may enjoy long term survival but have occult MTC. Only patient age at presentation and TNM stage were independent predictors of survival. The EORTC criteria, which included the greatest number of significant prognostic factors in our cohort, had the highest predictive value.

Classification and treatment of follicular thyroid neoplasms are discordant between and within medical specialties.

BACKGROUND: The histologic criteria to classify follicular thyroid neoplasms are controversial. Criteria used for diagnosis and treatment varies both within and between specialty groups. This discordance makes it difficult to compare disease and management practice. This is especially problematic in issues concerning reoperations and survival. To determine the degree of disparity, we surveyed 3 groups of specialists. METHODS: A questionnaire describing 10 histologic scenarios was sent to an equal number of thyroidologists, endocrine surgeons, and endocrine pathologists. Individuals were randomly selected from rosters of 3 corresponding societies. Each item asked for a rating of a diagnosis and treatment. Questionnaires were distributed and received by facsimile, and responses were kept confidential. The response rate was 60%. RESULTS: Responses were analyzed by nonparametric statistical tests. Two scenarios had significant disagreement among specialties in both diagnosis and treatment: one scenario involved the assessment of neoplasms with minimal capsular invasion; the other scenario involved Hürthle cell features. In both scenarios pathologists tended to be more conservative in assigning the term carcinoma and recommending total thyroidectomy. Significant disagreement within specialty groups was also noted. Two other scenarios dealt with the distinction between minimally and widely invasive carcinoma; significantly, pathologists viewed tumors as less invasive. CONCLUSIONS: This study indicates that much disparity exists among specialists in pathology, endocrinology, and surgery and among experts in each of these disciplines. It highlights that there is no uniform classification. If multicenter trials to evaluate treatment options are to occur, a universal classification must be accepted.

Psychosocial mediators of racial differences in nighttime blood pressure dipping among normotensive adults.

Shallow declines in nocturnal compared with diurnal blood pressure (BP dipping) have been associated with cardiovascular disease. In U.S. samples, Blacks demonstrate less BP dipping compared with Whites. In a sample of 60 Black and 60 White normotensive adults we examined stress, social integration (including parental status), social support, and hostility as potential mediators of the association between race and BP dipping. The effect of race on diastolic BP dipping was partially mediated by parental status. The effect of race on heart rate dipping was partially mediated by stressful life events. No psychosocial factors mediated the relation between race and systolic BP dipping. Although psychosocial factors appear to account for some of the observed racial differences in nocturnal blood pressure decline, our data suggest that these differences cannot be attributed entirely to covarying psychosocial effects.