Hypoparathyroidism: Consequences, economic impact, and perspectives. A case series and systematic review.

BACKGROUND: Postoperative hypoparathyroidism (PH) is the most common complication after total thyroidectomy. Incidence varies from 2% to 83%, depending on the definition. OBJECTIVE: We performed a systematic review of the literature to determine the medico-economic effects of PH and update understanding of long-term consequences, morbidity, and quality of life related to hypoparathyroidism. METHODS: We considered relevant articles published between 2000 and 2020 concerning long-term consequences of PH and quality of life. All studies concerning the medico-economic assessment of PH were included. We compared data from 2018 to results in the literature. RESULTS: A proportion of 64/403 (16.8%) patients presented with transient PH during 2018, and 7/403 (1.7%) had permanent PH. Seven patients needed supplementation with alfacalcidol at 6-month follow-up. Factors predicting the need for alfacalcidol were age <45, thyroidectomy for goiter, and lymph node dissection. Additional therapy costs related to PH were €9781.10, and additional hospital costs were €230,400. We qualitatively synthesized 41 studies. Most were retrospective studies and only a few reported costs. No series assessed direct or indirect costs of postoperative PH. CONCLUSION: To our knowledge, no previous studies reported the medico-economic impact of PH. Decreasing PH associated with fluorescence usage should be considered, particularly concerning cost-effectiveness.

Medullary thyroid cancer outcomes in patients with undetectable versus normalized postoperative calcitonin levels.

BACKGROUND: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors in medullary thyroid cancer (MTC). This study aimed to evaluate progression-free survival and recurrence rates of MTC associated with undetectable compared with normalized serum Ct levels after surgery. METHODS: This retrospective observational study included patients operated for MTC at the Digestive and Endocrine Surgery Department of Lyon Sud Hospital Centre between 2000 and 2019. Clinical and pathological factors were correlated with postoperative Ct concentrations. Undetectable and normalized Ct concentrations were defined as below 2 pg/ml and 2-10 pg/ml respectively. RESULTS: Overall, 176 patients were treated for MTC, and 127 were considered biochemically cured after surgery. Of these, 24 and 103 had normalized and undetectable Ct concentrations respectively. Patients with Ct level normalization had a 25 per cent risk of disease recurrence, compared with 3 per cent in patients with undetectable Ct levels after surgery. The presence of metastasis in two or more compartments was predictive of failure to achieve undetectable Ct concentrations after surgery and an increased risk of recurrence. CONCLUSION: Among patients with biochemically cured MTC, those with undetectable or normalized Ct concentrations after surgery had different risks of recurrence. Simply assessing postoperative Ct normalization can be falsely reassuring, and long-term follow-up is needed. LAY SUMMARY: Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

Calcitonin (Ct) is a sensitive diagnostic biomarker and one of the most important prognostic factors for medullary thyroid cancer outcomes; however, the significance of postoperative Ct levels remains controversial. This study evaluated the differences between normal and undetectable postoperative Ct levels in patients who had undergone surgical treatment for medullary thyroid cancer. Patients who experienced postoperative Ct level normalization had a higher risk of disease recurrence than those with undetectable Ct levels after surgery.

Additional value of PCA3 density to predict initial prostate biopsy outcome.

PURPOSE: Similar to prostate-specific antigen (PSA) density, PCA3 density (PCA3D: ratio of urinary PCA3 score/prostate volume) can be calculated, but whether it can be an aid to decide biopsy in patients at risk of prostate cancer (PCa) is uncertain. The objective was to demonstrate that PCA3D provides better specificity than PCA3 in predicting initial prostate biopsy outcome. METHODS: Serum and urine samples were obtained from 595 consecutive patients scheduled for initial prostate biopsy. The urinary PCA3 test was performed before biopsy. Additional measures were prostate volume, PSA density (PSAD) and PCA3D. Multivariate logistic regression models including baseline characteristics and the markers were evaluated. The presumed net benefit was assessed through decision curve analyses. RESULTS: PSAD and PCA3D performed better than PSA and PCA3 score, respectively. PCA3D provided the best specificity (76 %). The best calculated cutoff for PCA3D was 1. The risk of positive biopsy significantly increased to 70 % if PCA3D ≥ 1 versus 29 % if PCA3D was <1. Using a cutoff at 0.5 for PCA3D, biopsies could have been avoided in up to 52 % of the patients without PCa while missing 15 % of any PCa and 10 % of PCa with Gleason score ≥7. Decision curve analyses showed that PSAD was the best predictor of Gleason score at biopsy while PCA3D best predicted the proportion of invaded cores. CONCLUSIONS: PCA3D showed a significant increase in specificity when compared with PSA, PSAD and PCA3. PCA3D can be considered an easy-to-use mini-nomogram with a 70 % risk of positive initial biopsy when PCA3D > 1, i.e., PCA3 score > prostate volume.

Influence of nucleophosmin/B23 on DNA binding and transcriptional activity of the androgen receptor in prostate cancer cell.

The promotion and progression of prostate cancer (PCa) are associated with androgen receptor (AR) signalling. AR functions are modulated by a variety of co-factors amongst which we identified the nucleophosmin (NPM/B23), a member of the histone chaperone family. Here, we show that NPM is overexpressed in PCa compared to normal adjacent tissues. AR and NPM interact in vitro and in vivo, and NPM is critical for androgen-dependent transcriptional activation in LNCaP cells as an anti-NPM siRNA downregulates transcription of a transfected androgen response element (ARE)-containing reporter promoter as well as expression of the endogenous androgen responsive prostate-specific antigen (PSA) gene. By investigating the effect of NPM on AR, we have also observed that NPM enhances AR binding to an ARE in vitro in electrophoretic gel mobility-shift assay experiments. Chromatin immunoprecipitation studies further demonstrated that both AR and NPM associate with AREs of the PSA gene in vivo. Altogether, our data suggest that the molecular histone chaperone NPM could regulate AR functions by promoting assembly of AR-containing regulatory complexes and that high levels of NPM might alter AR functions in PCa.

Preservation of prostate during radical cystectomy: evaluation of prevalence of prostate cancer associated with bladder cancer.

OBJECTIVES: To estimate the frequency and characteristics of prostatic lesions discovered incidentally in radical cystoprostatectomy specimens and to determine whether any factors would allow for the detection of prostate cancer preoperatively. METHODS: A total of 100 radical cystoprostatectomy specimens with orthotopic bladder reconstruction were performed for malignant bladder disease between 1990 and 2000. The mean patient age at surgery was 62 +/- 8 years (range 32 to 75). Digital rectal examination and prostate-specific antigen (PSA) assay were done routinely before surgery. During the 10-year study period, the same pathologist examined the prostatic tissues from radical cystoprostatectomy specimens using McNeal's technique on fine slices every 2.5 mm. RESULTS: The overall incidence of prostate cancer discovered incidentally in radical cystoprostatectomy specimens was 51%, of which 29% were microcancers (volume less than 0.5 cm3) and 22% were significantly larger (volume 0.5 cm3 or more). The mean Gleason score was 6. Of the tumors, 24% could be considered "clinically nonsignificant" (less than 0.5 cm3 and Gleason score less than 7). The mean preoperative PSA level was 4.13 +/- 1.36 ng/mL. Of 66 patients with a PSA level of less than 4 ng/mL (mean PSA 1.5 +/- 0.8) and a normal digital rectal examination before surgery, 50% had prostate cancer, of which 69% were microcancers. CONCLUSIONS: The prevalence of prostate cancer (51%) in our series is among the highest in published reports. Furthermore, our results stress that currently no factors are available to enable the detection of "clinically significant" prostate cancer preoperatively.

RET rearrangements in familial papillary thyroid carcinomas.

Familial papillary thyroid carcinoma (FPTC) is an inherited tumor characterized by a more aggressive phenotype than that of its sporadic counterpart. Its mode of inheritance as well as its genetic and molecular bases are still poorly understood. On the contrary, genetic alterations in sporadic papillary thyroid carcinoma (PTC) are better characterized, the most common one involving the activation of the proto-oncogene RET through somatic rearrangements. In the present study, we investigated by interphase fluorescence in situ hybridization the presence of RET rearrangements in a series of 20 FPTC. We show that one FPTC and the adenoma from the same patient carry a RET rearrangement (type PTC1) and that this rearrangement is absent in the germline. Furthermore, we excluded a RET haplotype sharing in two brothers of the same family. These results show that RET rearrangements can indeed be found in FPTC and confirm that RET is not involved in the inherited predisposition to FPTC.

Expression of vascular endothelial growth factor (VEGF) and its two receptors (VEGF-R1-Flt1 and VEGF-R2-Flk1/KDR) in non-small cell lung carcinomas (NSCLCs): correlation with angiogenesis and survival.

The formation of new vessels (angiogenesis) is essential for primary tumour growth and metastasis and is induced by several angiogenic factors, including vascular endothelial growth factor (VEGF). The microvascular density (MVD) in tumours was assessed and the expression of VEGF and its receptors VEGF-R1-Flt1 and VEGF-R2-KDR/Flk1 was investigated in the different cellular compartments in vivo, in order to establish their interrelationship and their prognostic influence. Immunohistochemical study of 69 stage I-II non-small cell lung carcinomas (NSCLCs) was performed on paraffin sections with CD34 antibody to estimate MVD, using a Chalkley eye-piece graticule and VEGF, VEGF-R1, and VEGF-R2 antibodies. There was strong expression of VEGF and its receptors in tumour cells, endothelial cells, and stromal fibroblasts. In tumour cells, the level of VEGF was correlated with that of VEGF-R1 ( p = 0. 018) but not that of VEGF-R2. In fibroblasts, high expression of VEGF was correlated with that of VEGF-R1 ( p = 0.0001) and VEGF-R2 ( p = 0.0001). In endothelial cells, expression of VEGF was correlated with that of VEGF-R1 ( p < 0.0001) and VEGF-R2 ( p = 0.04). The level of VEGF in fibroblasts was correlated with that of VEGF-R1 ( p = 0.0028) and VEGF-R2 ( p = 0.01) in endothelial cells. There was no correlation between the level of MVD and that of VEGF or VEGF-R1 or VEGF-R2. Neither the level of MVD, nor the level of expression of VEGF and VEGF receptors in any compartment influenced the patient's survival. In conclusion, although angiogenesis is essential for tumour growth, this study failed to demonstrate that MVD, VEGF, VEGF-R1, and VEGF-R2 are prognostic markers for stage I-II NSCLC. VEGF, however, might act as a direct autocrine growth factor for tumour cells via VEGF-R1 and angiogenesis could be promoted in a paracrine loop, where VEGF is produced by fibroblasts and tumour cells and then binds to endothelial cells via induced VEGF receptors. VEGF and its receptors thus appear as relevant therapeutic targets in NSCLC.

Cytological aspiration of intraocular retinoblastoma in an 11-year-old boy.

Only a few cases of retinoblastomas in older children have been reported and the clinical diagnosis may be difficult. In case, fine-needle aspiration from an atypical retinal mass of an 11-yr-old boy was performed. The vitreous fluid was stained with Diff-Quik for an immediate cytological examination and the diagnosis of retinoblastoma was suggested. The rest of the specimen was separated into two parts. One was stained with May-Grünwald-Giemsa and the other was centrifuged, embedded in paraffin, and finally stained with hematoxylin-eosin-safran. The undifferentiated blue cells were associated with abundant necrotic debris and portions of capillaries with perivascular tumor cells around. The cytoplasm of the tumor cells was strongly stained with neuron-specific enolase antibody. The diagnosis of retinoblastoma was confirmed. The specimen of enucleation confirmed the diagnosis. In conclusion, cytological aspiration can categorically diagnose suspected intraocular tumors of older children in whom clinical and noninvasive investigations have failed to establish the diagnosis.

Paget's disease versus Toker cell hyperplasia in a supernumerary nipple.

We report the second case of mammary Paget's disease arising in a supernumerary nipple of a 29-year-old woman. The epithelium of the nipple was infiltrated by large cells with abundant and pale-staining cytoplasm. The nuclei had a vesicular chromatin pattern and identifiable nucleoli. The cells were strongly immunoreactive with KL1, CEA and EMA, but did not show reactivity with PS100, HMB45, or erb-B2. The pathogenesis of Paget cells is unclear. In our case, the lesion showed nearly all the clinical, histological and histochemical characteristics of Paget's disease, though without involvement of mammary gland epithelium and underlying carcinoma. The possibility of an intraepidermal origin, either by transformation from epidermal keratinocytes or by derivation from intraepidermal precursor cells, has to be considered. The differential diagnosis against Toker cell hyperplasia is also discussed.

[Glomangioma: an unusual ethmoid-nasal tumor]. / Glomangiome: une tumeur ethmoïdo-nasale inhabituelle.

Glomus tumors are benign vascular tumors usually located in the fingertip dermis. Extracutaneous glomus tumors are extremely rare. A new case of sino-nasal glomangioma is reported and both clinical and histological features and biological behavior of glomus tumors in this exceptional site are described.