Pancreatoduodenectomy with or without prophylactic falciform ligament wrap around the hepatic artery for prevention of postpancreatectomy haemorrhage: randomized clinical trial (PANDA trial).

BACKGROUND: Postpancreatectomy haemorrhage (PPH) is a rare but potentially fatal complication after pancreatoduodenectomy. Preventive strategies are lacking with scarce data for support. The aim of this study was to investigate whether a prophylactic falciform ligament wrap around the hepatic and gastroduodenal artery can prevent PPH from these vessels. METHODS: In a randomized, controlled, multicentre trial, patients who were scheduled for elective open partial pancreatoduodenectomy with pancreatojejunostomy between 5 November 2015 and 2 April 2020 were randomly allocated in a 1 : 1 ratio to undergo pancreatoduodenectomy with (intervention) or without (control) a falciform ligament wrap around the hepatic artery. The primary endpoint was the rate of clinically relevant PPH from the hepatic artery or gastroduodenal artery stump within 3 months after pancreatoduodenectomy. Secondary endpoints were the rates of associated postoperative complications, for example postoperative pancreatic fistula (POPF) and PPH. RESULTS: Altogether, 445 patients were randomized with 222 and 223 in each group. Among the patients included in modified intention-to-treat analysis (207 in the intervention group and 210 in the control group), the primary endpoint was observed in six of 207 in the intervention group compared with 15 of 210 in the control group (2.9 versus 7.1 per cent respectively; odds ratio 0.39 (95 per cent c.i. 0.15 to 1.02); P = 0.071). Per protocol analysis showed a significant reduction in the intervention group (odds ratio 0.26 (95 per cent c.i. 0.09 to 0.80); P = 0.017). A soft pancreas texture (43 per cent) and the rate of a clinically relevant POPF were evenly (20 per cent) distributed between the groups. The rate of any clinically relevant PPH including the primary endpoint and other bleeding sites was not significantly different between intervention and control groups (9.7 versus 14.8 per cent respectively). CONCLUSION: A falciform ligament wrap may reduce PPH from the hepatic artery or gastroduodenal artery stump and should be considered during pancreatoduodenectomy. REGISTRATION NUMBER: NCT02588066 (http://www.clinicaltrials.gov).

Thyroid Carcinoma: Do We Need to Treat Men and Women Differently?

BACKGROUND: For differentiated thyroid carcinoma, gender-specific differences exist in regard to incidence, age at onset, tumor stage, and recurrence, but causative factors remain to be elucidated. Possible and likely contributors are genetic and hormonal differences. While some of these factors are known to be differently distributed between the sexes, like, for example, BRAF-mutation and estrogen levels, their role in thyroid cancer initiation or promotion awaits further investigation. SUMMARY: Apart from generally accepted risk factors for differentiated thyroid carcinoma, an apparent gender disparity of thyroid cancer with a general female predominance, an age-dependent difference in growth acceleration during the reproductive years, and a peak at the time of entering menopause have been demonstrated. Hormonal status and hormonal receptor mediation seem to be most likely to contribute to the differences in thyroid cancer phenotypes of males and females. However, specific cause-and-effect pathways have not yet been determined. KEY MESSAGES: Female gender is overrepresented in the incidence of differentiated thyroid carcinoma, as it is in the more favorable tumor stages. Besides the assumption of gender-specific differences in general health awareness and behavior, hormonal age-dependent and gender-specific factors appear to be contributory. In the advanced stage of thyroid cancer, males are overrepresented. Therefore, the real cause of gender differences in thyroid cancer is likely due to a mixed effect. Present knowledge does not favor different treatment modalities of thyroid carcinoma according to gender.

100-Year evolution of precision medicine and surgery for multiple endocrine neoplasia type 2A.

PURPOSE: To determine whether published disease penetrance estimates of 50% for pheochromocytoma and 20-30% for primary hyperparathyroidism in multiple endocrine neoplasia (MEN 2A), conceivably reflecting overrepresentation of index patients with completely developed MEN 2A, may be too high. METHODS: Cross-sectional study of carriers at high risk of MEN 2A from a tertiary referral center. RESULTS: There were 213 carriers of RET mutations in codon 634, born between 1922 and 2014. Median age of thyroidectomy was 17 years, with MTC being present in 76.5%; pheochromocytoma in 31.0% at a median of 34 years in the first, and in 18.8% at a median of 35 years in the second adrenal; and primary hyperparathyroidism in 10.8% at a median of 39 years. MTC, pheochromocytoma and primary hyperparathyroidism, stratified by year of birth, were diagnosed earlier over time: for MTC from 51 to 4 years; for pheochromocytoma from 51 to 22.5 years in the first, and from 51 to 29.5 years in the second adrenal, and for primary hyperparathyroidism from 46 to 12 years (P ≤ 0.008). This decline in age was paralleled by diminishing tumor diameters, more strongly in the thyroid (from 20 to 1.8 mm; P < 0.001) than in the adrenals (from 43 to 30 mm in the first, and from 20-57.5 to 30.5 mm in the second adrenal; statistically nonsignificant). CONCLUSIONS: The lower disease penetrance estimates and sluggish decline of adrenal tumor diameters call for more widespread adoption of adrenal-sparing and parathyroid preservation surgery based on early and regular biochemical screening.

Disease impacts more than age on operative morbidity in children with Graves' disease after total thyroidectomy.

BACKGROUND: In pediatric Graves' disease, operative morbidity after total thyroidectomy remains ill defined. The present study aimed to clarify whether total thyroidectomy entails greater operative morbidity in children with Graves' disease, in particular when they are very young, as compared with an age-matched reference group of children with hereditary C-cell disease who underwent total thyroidectomy at the same time. METHODS: Operative morbidity after total thyroidectomy for Graves' disease was determined in relation to the child's age and in comparison with a reference group of age-matched children with hereditary C-cell disease. RESULTS: Included in the study were 58 children with Graves' disease (51 girls and 7 boys) and 108 children with hereditary C-cell disease (59 girls and 49 boys). When children with Graves' disease and children with hereditary C-cell disease were compared across and within the 4 age increments (≤ 3, 4-6, 7-12, and 13-18 years), operative mortality did not differ significantly among and within age increments. Children with Graves' disease had a 1.7-fold greater overall risk of transient hypoparathyroidism (29% versus 17%; P = .073) than children with hereditary C-cell disease. Permanent hypoparathyroidism was nil in either group. Transient recurrent laryngeal nerve palsy, wound hemorrhage, and wound infections were infrequent (≤ 3% each), resolving spontaneously and after reoperation, respectively. CONCLUSION: Disease impacts more than age on operative morbidity in children with Graves' disease after total thyroidectomy but is fairly low overall and rarely permanent in experienced hands.

Impact of central node dissection on postoperative morbidity in pediatric patients with suspected or proven thyroid cancer.

BACKGROUND: Pediatric risk factors for postoperative morbidity after central node dissection are ill-defined. METHODS: This outcome study aimed to evaluate operative morbidity in patients aged ≤18 years after total thyroidectomy with or without central node dissection for suspected or proven thyroid cancer. RESULTS: Included were 102 patients with hereditary C-cell hyperplasia, 66 patients with medullary, 60 patients with papillary, and 2 patients with follicular thyroid cancer. In all 230 patients, 131 of whom underwent central node dissection, transient recurrent laryngeal nerve palsy was significantly associated only with central node dissection (100% vs 55%; P = .010). Transient and permanent hypoparathyroidism were significantly associated with age (means of 11.9 years versus 7.8 years, and 12.9 years versus 8.5 years; P ≤ .002); central node dissection (80% vs 50%, and 100% vs 54%; P ≤ .001); and the number of central lymph nodes cleared (means of 12.2 nodes versus 5.4 nodes, and 26.9 nodes versus 5.8 nodes, P < .001). These effects were stronger for permanent than transient hypoparathyroidism. Correlations between permanent hypoparathyroidism and the number of nodes cleared on central node dissection (r = 0.35) were closer than those between permanent hypoparathyroidism and age (r = 0.15), but similar for transient hypoparathyroidism (r = 0.22 and r = 0.25). CONCLUSION: Owing to the incremental morbidity from central node dissection, the extent of a neck operation, in experienced hands, should be tailored to the extent of the underlying disease regardless of the child's age. The notion that the experience of the center and surgeons may be more important than the age of the child requires validation in independent series across different health care settings.

Hypercalcitoninemia in thyroid conditions other than medullary thyroid carcinoma: a comparative analysis of calcium and pentagastrin stimulation of serum calcitonin.

PURPOSE: Calcitonin screening aims at uncovering occult medullary thyroid cancer (MTC) in patients with nodular thyroid disease. Elevated basal calcitonin serum levels call for calcitonin stimulation, the level of which may direct the extent of surgery. Because pentagastrin has become restricted, calcium has increasingly been used instead for stimulation. This study identified a new spectrum of patients demonstrating a false-positive hypercalcitoninemia in the absence of C-cell disease, carrying multinodular goiter (MNG), thyroiditis, and non-MTC thyroid malignancy, and endeavored to explore the feasibility of extrapolating pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. METHODS: Altogether, 43 (9.5 %) of 455 patients with nodular thyroid disease revealed increased basal calcitonin serum levels between 2005 and 2012, for which they underwent intravenous stimulation with pentagastrin (31 patients) or calcium gluconate (12 patients) before and after primary thyroidectomy. RESULTS: Stimulation with calcium gluconate resulted in significantly higher and more variable preoperative calcitonin serum levels after 2 (241.2 vs. 104.9 pg/mL; P = 0.018) and 5 min (240.6 vs. 87.4 pg/mL; P = 0.007) than stimulation with pentagastrin. Stimulation with calcium gluconate produced 10-fold (nodular goiter), 15-fold (thyroiditis), and 21-fold (thyroid neoplasia other than MTC) calcitonin increases over baseline, as opposed to 5-fold, 10-fold, and 8-fold increases after stimulation with pentagastrin. None of the 43 patients, all of whom reverted to undetectable calcitonin serum levels after thyroidectomy, had immunohistochemical evidence of C-cell disease. Subgroup analyses according to gender and thyroid disease, being limited by the low number of patients in each subgroup, did not yield significant differences. CONCLUSIONS: Calcium stimulation yields significantly greater calcitonin levels than pentagastrin stimulation, precluding generalization of pentagastrin-stimulated to calcium-stimulated calcitonin thresholds. After calcium stimulation, false-positive findings appear to be more common in patients of female gender and patients with thyroiditis and thyroid neoplasia other than MTC, potentially effecting surgical overtreatment.