Evaluation of malignant parathyroid tumours in two European cohorts of patients with sporadic primary hyperparathyroidism.

PURPOSE: Parathyroid carcinoma (PC) is remarkable for its rare occurrence and challenging diagnostics. PC accounts for 0.1-5 % cases of primary hyperparathyroidism (PHPT). The differentiation from benign tumours is difficult even by morphological criteria. To address these issues, we assessed the PC frequency in two separate European PHPT cohorts and evaluated the demographic, clinical, morphological and molecular background. METHODS: A retrospective study was carried out, using continuously maintained database (2005-2014) of PHPT patients from two tertiary referral university hospitals in Europe. The demographic, clinical data and frequency of PC among surgically treated PHPT was detected. Immunohistochemistry (IHC) was performed to detect parafibromin, representing protein product of HRPT2 gene and proliferation marker Ki-67. RESULTS: Both PHPT cohorts were characterised by close mean age values (58.6 and 58.0 years) and female predominance. The frequency of PC differed significantly between the cohorts: 2.1 vs. 0.3 %; p = 0.004. PC was characterised by invariable complete loss of parafibromin contrasting with parathyroid adenomas. The proliferation fraction was similar in both PC cohorts (10.6 and 11.0 %). PC showed significantly higher proliferation fraction than typical parathyroid adenomas (1.6 %), atypical adenomas (1.6 %) or adenomas featuring focal loss of parafibromin (2.2 %). CONCLUSIONS: PC frequency can range significantly between the two European cohorts. The differences can be attributable to selection bias of patients referred for surgery and are not caused by discordant definition of malignant parathyroid histology. Diffuse loss of parafibromin and increased proliferation fraction by Ki-67 are valuable adjuncts in PC diagnostics due to significant differences with various clinical and morphological subtypes of adenoma.

Is the covering of the resection margin after distal pancreatectomy advantageous?

BACKGROUND: In recent years, many advances in pancreatic surgery have been achieved. Nevertheless, the rate of pancreatic fistula following pancreatic tail resection does not differ between various techniques, still reaching up to 30% in prospective multicentric studies. Taking into account contradictory results concerning the usefulness of covering resection margins after distal pancreatectomy, we sought to perform a systematic, retrospective analysis of patients that underwent distal pancreatectomy at our center. METHODS: We retrospectively analysed the data of 74 patients that underwent distal pancreatectomy between 2001 and 2011 at the community hospital in Neuss. Demographic factors, indications, postoperative complications, surgical or interventional revisions, and length of hospital stay were registered to compare the outcome of patients undergoing distal pancreatectomy with coverage of the resection margins vs. patients undergoing distal pancreatectomy without coverage of the resection margins. Differences between groups were calculated using Fisher's exact and Mann-Whitney U test. RESULTS: Main indications for pancreatic surgery were insulinoma (n=18, 24%), ductal adenocarcinoma (n=9, 12%), non-single-insulinoma-pancreatogenic-hypoglycemia-syndrome (NSIPHS) (n=8, 11%), and pancreatic cysts with pancreatitis (n=8, 11%). In 39 of 74 (53%) patients no postoperative complications were noted. In detail we found that 23/42 (55%) patients with coverage vs. 16/32 (50%) without coverage of the resection margins had no postoperative complications. The most common complications were pancreatic fistulas in eleven patients (15%), and postoperative bleeding in nine patients (12%). Pancreatic fistulas occurred in patients without coverage of the resection margins in 7/32 (22%) vs. 4/42 (1011%) with coverage are of the resection margins, yet without reaching statistical significance. Postoperative bleeding ensued with equal frequency in both groups (12% with coverage versus 13% without coverage of the resection margins). The reoperation rate was 8%. The hospital stay for patients without coverage was 13 days (5-60) vs. 17 days (8-60) for patients with coverage. CONCLUSIONS: The results show no significant difference in the fistula rate after covering of the resection margin after distal pancreatectomy, which contributes to the picture of an unsolved problem.

Cinacalcet effects on the perioperative course of patients with secondary hyperparathyroidism.

PURPOSE: Since its registration in 2004, the calcimimetic agent cinacalcet has been established as an alternative treatment for secondary hyperparathyroidism (SHPT). Working by allosteric activation of the calcium-sensing receptor, cinacalcet can lower parathyroid hormone (PTH) and calcium (Ca) in patients with SHPT. The influence of calcimimetics on the perioperative course has been unclear so far. METHODS: We retrospectively analyzed the data of patients with primary operation for SHPT between 2004 and 2011, comparing the perioperative course of patients with and without preoperative cinacalcet treatment. RESULTS: Fifty-six patients had cinacalcet therapy, and 54 patients had no calcimimetic medication prior to surgery. Gender, age, hemodialysis, and medical treatment were similar in both groups. Also, PTH levels were similar preoperatively and postoperatively (preoperative, 1,249 ± 676 vs. 1,196 ± 601 pg/ml; postoperative, 86 ± 220 vs. 62 ± 91 pg/ml). Patients with cinacalcet preoperatively had significant lower Ca levels preoperatively (2.49 ± 0.25 vs. 2.61 ± 0.24 mmol/l) and postoperatively (1.75 ± 0.37 vs. 1.86 ± 0.35 mmol/l) and had a higher rate of oral Ca substitution postoperatively (93 vs. 74 %). The risk for postoperative persistent disease was slightly higher in these patients compared to those without preoperative cinacalcet therapy (5 vs. 0 %, not significant). CONCLUSIONS: In our experience, cinacalcet did not alter the perioperative course in SHPT patients.

The impact of intraoperative neuromonitoring (IONM) on surgical strategy in bilateral thyroid diseases: is it worth the effort?

BACKGROUND: Intraoperative nerve monitoring (IONM) of the recurrent laryngeal nerve and the vagal nerve can detect nonfunctioning nerves (recurrent laryngeal nerve palsy, RLNP) that are visibly intact. The use of IONM is questionable, however, as we still lack evidence that it reduces the rate of postoperative nerve injuries. Since negative IONM results after thyroid dissection of the first side could change our surgical strategy and thus could prevent patients from bilateral RLNP, we questioned whether IONM results are reliable enough to base changes in surgical strategy and whether this has any effect on surgical outcome. METHODS: We retrospectively analyzed the data of 1333 consecutive patients with suggested benign bilateral thyroid disease who had been operated on under a defined protocol, including the use of a specific IONM technique (tube electrodes and stimulation of the vagal nerve and the inferior recurrent nerve before and after thyroid resection), between January 1, 2006 and December 31, 2008. RESULTS: In four patients the IONM system did not work, two nerves had not been found, and in eight patients the tube had to be readjusted. Of five permanent nerve injuries, four were visible during surgery and one was suspected. Sensitivity of IONM in detecting temporary nerve injuries of macroscopically normal-appearing nerves was 93%. Specificity was 75-83% at first side of dissection and 55-67% at the second side, with an overall specificity of 77%. In 11 of 13 patients (85%) with known nerve injury (preexisting or visible) and in 20 of 36 patients (56%) with negative IONM stimulation at the first side of dissection, the surgical strategy was changed (specific surgeon or restricted resection) with no postoperative bilateral RLNP. This was in contrast to 3 of 18 (17%) bilateral RLNP (p < 0.05), when surgeons were not aware of a preexisting or highly likely nerve injury at the first side of thyroid dissection. CONCLUSIONS: Failed IONM stimulation of the vagal or recurrent laryngeal nerve after resection of the first thyroid lobe is specific enough to reconsider the surgical strategy in patients with bilateral thyroid disease to surely prevent bilateral RLNP.

Does multiple gland disease in primary hyperparathyroidism correlate with age or sex?

PURPOSE: Paediatric primary hyperparathyroidism (PHPT) patients suffer more often from multiple gland disease (MGD) than adults. The question occurs whether MGD in adult PHPT patients also correlates with age or sex and whether familial PHPT plays a decisive role. This is significant, as it would influence our decision for a focused approach or the bilateral cervical exploration. MATERIALS AND METHODS: We retrospectively analysed 465 consecutive PHPT patients who underwent surgery in our department between September 2001 and December 2008. RESULTS: PHPT patients aged 40 years or younger suffered significantly more often from MGD than older patients (22.9% versus 11.0%). If familial PHPT disorders, which were more common in young patients, were excluded, the divergence between these two groups vanished (12.5% versus 10.0%). There was no statistical significant difference in the frequency of MGD between men (12.2%) and women (12.3%). CONCLUSIONS: If familial PHPT can be ruled out, the frequency of MGD in adult PHPT patients does not correlate with age or with sex. Therefore, age and sex do not imply specific surgical approaches in adult PHPT patients.