Bilateral breast desmoid-type fibromatosis, case report and literature review.

Background: Breast desmoid-type fibromatosis (BDF) is a rare mesenchymal tumor accounting for only 0.2% of solid breast tumors. It is classified as an intermediate tumor because it is locally aggressive but has no metastatic potential. Its diagnosis is often difficult because it shares many clinical and radiologic aspects with breast carcinomas and therefore relies on anatomopathological analysis which may be supplemented by genetic analysis. The treatment of BDF has considerably evolved in the past years. While surgery was the cornerstone of the management prior to the 2000s, recent data have shown the value of active surveillance (AS) from the time of diagnosis. Indeed, after 2 years of AS, the progression-free survival (PFS) of the disease is identical or superior to surgery. Moreover, spontaneous regression has been observed in 30% of patients undergoing AS. In case of disease progression, surgery can be considered on a case-by-case basis, as well as systemic treatments. Case Description: We present a case of bilateral BDF affecting a 20-year-old woman for whom the first suggested treatment was bilateral mastectomy with reconstruction. After a second opinion, the decision was revised and AS was initiated. Almost 3 years after the onset of AS, tumors have shown a continuous regression. Conclusions: This case demonstrates the need for experience in the management of mesenchymal tumors to avoid overtreatment by mutilating surgeries which promote recurrence. Moreover, to our knowledge, very few cases of bilateral BDF have been published to date. It thus seemed relevant for us to report this rare case which supports the interest of AS for DF, as recently advised by the Desmoid Tumor Working Group guidelines.

The closure of arteriovenous fistula in kidney transplant recipients is associated with an acceleration of kidney function decline.

Background: The creation of arteriovenous fistula (AVF) may retard chronic kidney disease progression in the general population. Conversely, the impact of AVF closure on renal function in kidney transplant recipients (KTRs) remains unknown. Methods: From 2007 to 2013, we retrospectively categorized 285 KTRs into three groups: no AVF (Group 0, n = 90), closed AVF (Group 1, n = 114) and left-open AVF (Group 2, n = 81). AVF closure occurred at 653 ± 441 days after kidney transplantation (KTx), with a thrombosis:ligation ratio of 19:95. Estimated glomerular filtration rate (eGFR) was determined using the Modification of Diet in Renal Disease equation. Linear mixed models calculated the slope and intercept of eGFR decline versus time, starting at 3 months post-KTx, with a median follow-up of 1807 days (95% confidence interval 1665-2028). Results: The eGFR slope was less in Group 1 (-0.081 mL/min/month) compared with Group 0 (-0.183 mL/min/month; P = 0.03) or Group 2 (-0.164 mL/min/month; P = 0.09). Still, the eGFR slope significantly deteriorated after (-0.159 mL/min/month) versus before (0.038 mL/min/month) AVF closure (P = 0.03). Study periods before versus after AVF closure were balanced to a mean of 13.5 and 12.5 months, respectively, with at least 10 observations per patient ( n = 99). Conclusions: In conclusion, a significant acceleration of eGFR decline is observed over the 12 months following the closure of a functioning AVF in KTRs.

Asporin Is a Fibroblast-Derived TGF-ß1 Inhibitor and a Tumor Suppressor Associated with Good Prognosis in Breast Cancer.

BACKGROUND: Breast cancer is a leading malignancy affecting the female population worldwide. Most morbidity is caused by metastases that remain incurable to date. TGF-ß1 has been identified as a key driving force behind metastatic breast cancer, with promising therapeutic implications. METHODS AND FINDINGS: Employing immunohistochemistry (IHC) analysis, we report, to our knowledge for the first time, that asporin is overexpressed in the stroma of most human breast cancers and is not expressed in normal breast tissue. In vitro, asporin is secreted by breast fibroblasts upon exposure to conditioned medium from some but not all human breast cancer cells. While hormone receptor (HR) positive cells cause strong asporin expression, triple-negative breast cancer (TNBC) cells suppress it. Further, our findings show that soluble IL-1ß, secreted by TNBC cells, is responsible for inhibiting asporin in normal and cancer-associated fibroblasts. Using recombinant protein, as well as a synthetic peptide fragment, we demonstrate the ability of asporin to inhibit TGF-ß1-mediated SMAD2 phosphorylation, epithelial to mesenchymal transition, and stemness in breast cancer cells. In two in vivo murine models of TNBC, we observed that tumors expressing asporin exhibit significantly reduced growth (2-fold; p = 0.01) and metastatic properties (3-fold; p = 0.045). A retrospective IHC study performed on human breast carcinoma (n = 180) demonstrates that asporin expression is lowest in TNBC and HER2+ tumors, while HR+ tumors have significantly higher asporin expression (4-fold; p = 0.001). Assessment of asporin expression and patient outcome (n = 60; 10-y follow-up) shows that low protein levels in the primary breast lesion significantly delineate patients with bad outcome regardless of the tumor HR status (area under the curve = 0.87; 95% CI 0.78-0.96; p = 0.0001). Survival analysis, based on gene expression (n = 375; 25-y follow-up), confirmed that low asporin levels are associated with a reduced likelihood of survival (hazard ratio = 0.58; 95% CI 0.37-0.91; p = 0.017). Although these data highlight the potential of asporin to serve as a prognostic marker, confirmation of the clinical value would require a prospective study on a much larger patient cohort. CONCLUSIONS: Our data show that asporin is a stroma-derived inhibitor of TGF-ß1 and a tumor suppressor in breast cancer. High asporin expression is significantly associated with less aggressive tumors, stratifying patients according to the clinical outcome. Future pre-clinical studies should consider options for increasing asporin expression in TNBC as a promising strategy for targeted therapy.

Mutations of calcium-sensing receptor gene: two novel mutations and overview of impact on calcium homeostasis.

OBJECTIVE: Genetic disorders of calcium metabolism arise in a familial or sporadic setting. The calcium-sensing receptor (CASR) plays a key role in maintaining calcium homeostasis and study of the CASR gene can be clinically useful in determining etiology and appropriate therapeutic approaches. We report two cases of novel CASR gene mutations that illustrate the varying clinical presentations and discuss these in terms of the current understanding of CASR function. PATIENTS AND METHODS: A 16-year-old patient had mild hypercalcemia associated with low-normal urinary calcium excretion and normal-to-high parathyroid hormone (PTH) levels. Because of negative family history, familial hypocalciuric hypercalcemia was originally excluded. The second patient was a 54-year-old man with symptomatic hypocalcemia, hyperphosphatemia, low PTH, and mild hypercalciuria. Familial investigation revealed the same phenotype in the patient's sister. The coding region of the CASR gene was sequenced in both probands and their available first-degree relatives. RESULTS: The first patient had a novel heterozygous inactivating CASR mutation in exon 4, which predicted a p.A423K change; genetic analysis was negative in the parents. The second patient had a novel heterozygous activating CASR mutation in exon 6, which predicted a p.E556K change; the affected sister of the proband was also positive. CONCLUSIONS: We reported two novel heterozygous mutations of the CASR gene, an inactivating mutation in exon 4 and the first activating mutation reported to date in exon 6. These cases illustrate the importance of genetic testing of CASR gene to aid correct diagnosis and to assist in clinical management.

Adrenal ganglioneuroma.

BACKGROUND: A 20-year-old man was referred after having been discovered a left adrenal incidentaloma. Characteristics on magnetic resonance imaging (MRI) suggested the diagnosis of adrenal ganglioneuroma or carcinoma. Pathological examination after adrenalectomy concluded it was an adrenal ganglioneuroma. We studied the characteristics of adrenal ganglioneuroma. METHODS: We retrospectively reviewed hormonal status, computed tomography and MRI features, and histological findings of our series of 8 adrenal ganglioneuromas. RESULTS: Specific features were: (1) no hormonal hypersecretion; (2) presence of calcifications, no vessel involvement; and a non-enhanced attenuation of less than 40 Hounsfield units on computed tomography; and (3) low non-enhanced T1-weighted signal, a slightly high and heterogeneous T2-weighted signal, and a late and gradual enhancement on dynamic MRI, especially if associated with a whorled pattern. CONCLUSIONS: Even if many aggressive tumors share some of those radiological features, the presence of all or most of them must lead the clinician to consider the diagnosis of adrenal ganglioneuroma.

Carcinoid tumor of the appendix: a consecutive series from 1237 appendectomies.

AIM: To report the experience of the CHU Sart Tilman, University of Liege, Belgium, in the management of appendiceal carinoid tumor. METHODS: A retrospective review of 1237 appendectomies performed in one single centre from January 2000 to May 2004, was undertaken. Analysis of demographic data, clinical presentation, histopathology, operative reports and outcome was presented. RESULTS: Among the 1237 appendectomies, 5 appendiceal carcinoid tumors were identified (0.4%) in 4 male and 1 female patients, with a mean age of 29.2 years (range: 6-82 years). Acute appendicitis was the clinical presentation for all patients. Four patients underwent open appendectomy and one a laparoscopic procedure. One patient was reoperated to complete the excision of mesoappendix. All tumors were located at the tip of the appendix with a mean diameter of 0.6 cm (range: 0.3-1.0 cm). No adjuvant therapy was performed. All patients were alive and disease-free during a mean follow-up of 33 mo. CONCLUSION: Appendiceal carcinoid tumor most often presents as appendicitis. In most cases, it is found incidentally during appendectomies and its diagnosis is rarely suspected before histological examination. Appendiceal carcinoid tumor can be managed by simple appendectomy and resection of the mesoappendix, if its size is

Subtotal parathyroidectomy as an adequate treatment for primary hyperparathyroidism in multiple endocrine neoplasia type 1.

HYPOTHESIS: The most appropriate surgical approach for hyperparathyroidism (HPT) in multiple endocrine neoplasia type 1 remains controversial. It has been advocated that reoperations for recurrent disease are easier to perform after total parathyroidectomy (TP) with autotransplantation than after subtotal parathyroidectomy (SP). In view of our large experience in patients with secondary HPT for whom TP with autotransplantation did not simplify reoperations, SP remains our preferred treatment for patients with HPT and multiple endocrine neoplasia type 1. DESIGN: Retrospective cohort study. SETTING: Tertiary referral medical center. PATIENTS: A total of 29 consecutive patients (22 women, 7 men; mean age, 42.2 years) with multiple endocrine neoplasia type 1 who underwent definitive cervical exploration for HPT. MAIN OUTCOME MEASURES: Temporary and permanent hypocalcemia, pattern of parathyroid disease, and sites and timing of recurrent HPT. Definitive primary surgery included SP in 21 patients, TP with autotransplantation in 4 patients, and less-than-subtotal parathyroidectomy in 4 selected patients. RESULTS: The mean follow-up was 88.5 months (range, 8-285 months). Four patients died during follow-up; 2 of these deaths were related to multiple endocrine neoplasia. No patients had persistent HPT. Temporary hypocalcemia occurred in 12 SP cases (57%), 4 TP with autotransplantation cases (100%), and 0 less-than-subtotal parathyroidectomy cases. Permanent hypocalcemia requiring long-term treatment occurred in 2 SP cases (10%), 1 TP with autotransplantation case (25%), and 0 less-than-subtotal parathyroidectomy cases. Four patients developed recurrent disease, including 1 with SP, 2 with TP with autotransplantation, and 1 with less-than-subtotal parathyroidectomy at 57 months, 197 and 180 months, and 164 months, respectively, representing 14% of all of the patients and 43% of patients with more than 10 years of follow-up. CONCLUSIONS: Recurrent HPT occurs many years after definitive primary surgery (median, 14.3 years). Surgical treatment should therefore aim to minimize the risk of permanent hypocalcemia and facilitate future surgery. When correctly performed, SP fulfills these objectives.

Risk of upper gastrointestinal cancer after bariatric operations.

The authors discuss the potential influence of obesity surgery on the risk of cancer, focusing on the upper GI tract directly affected by operations. There is currently no substantiation for an increased risk of cancer after bariatric surgery, because there are only about 25 reports of subsequent cancer of the esophagus and the stomach. However, this review emphasizes the need to detect potential precancerous conditions before surgery. Candidates for postoperative endoscopic surveillance may include patients >15 years after gastric surgery, but also patients symptomatic for gastroesophageal reflux disease in whom a high incidence of Barrett's metaplasia has been reported. The greatest concern is a delay in diagnosis from inadequate investigation due to mistaking serious upper GI symptoms as a consequence of the past operation.

Immediate and medium-term results of intraoperative parathyroid hormone monitoring during video-assisted parathyroidectomy.

HYPOTHESIS: Using an intraoperative parathyroid hormone (IOPTH) assay during video-assisted parathyroidectomy by lateral approach is useful in patients with sporadic primary hyperparathyroidism, and the medium-term results of surgery are excellent. DESIGN: Retrospective study of patients with sporadic primary hyperparathyroidism following video-assisted parathyroidectomy by lateral approach with IOPTH measurement. PATIENTS: Of 394 patients with sporadic primary hyperparathyroidism, 200 (67%) were eligible for video-assisted parathyroidectomy by lateral approach: patients in whom a single enlarged gland was clearly localized by ultrasonography, sestamibi scintigraphy, or both. MAIN OUTCOME MEASURES: An IOPTH assay was used in 198 patients. Intraoperative parathyroid hormone was measured at induction, skin incision, ablation, and 5 and 15 minutes after ablation. RESULTS: The immediate results of the IOPTH assay were true positive in 187 cases (94.4%), true negative in 8 cases (4%), false negative in 2 cases (1%), and false positive in 1 case (0.5%). The overall accuracy of the IOPTH assay was 98.5%. All patients were normocalcemic postoperatively. The median follow-up was 20.5 months in 150 reviewed: 149 patients (99.4%) were normocalcemic, 17 patients (11.3%) had an elevated PTH level with normocalcemia, and 1 patient (0.6%) had recurrent primary hyperparathyroidism. CONCLUSIONS: In our experience, IOPTH monitoring during video-assisted parathyroidectomy by lateral approach is useful in detecting multiple gland disease not suspected by preoperative localization studies. Overall, IOPTH monitoring predicts medium-term normocalcemia with a success rate of 98.5% in patients with sporadic primary hyperparathyroidism.

Negative preoperative localization studies are highly predictive of multiglandular disease in sporadic primary hyperparathyroidism.

BACKGROUND: The development of localization studies and quick parathyroid hormone assay (QPTH) has allowed the development of focused surgery in sporadic primary hyperparathyroidism. The aim of this investigation was to determine whether localization studies select a specific population of patients. METHODS: From 1999 to 2001, 213 patients underwent surgery for sporadic primary hyperparathyroidism. All were investigated with sestamibi scanning and ultrasonography. When at least 1 study showed a positive result (n=175), the patient underwent a video-assisted approach with QPTH. When results were negative (n=38), the patient underwent cervicotomy and exploratory procedures of all 4 parathyroid glands. RESULTS: All patients are cured (mean follow-up, 17.8+/-10.3 months [SD]). Patients with negative preoperative study results had a high risk of multiglandular disease (12/38 patients; 31,6%), compared with patients with 1 positive study result (3/83 patients; 3.6%; P<.0001) and those with 2 concordant positive study results (0/92 patients; P<.0001). CONCLUSION: When preoperative localization study results are negative, the patient has a high risk of multiglandular disease, and a conventional cervicotomy with identification of the 4 glands is recommended strongly. When only 1 localization study is positive, the risk of multiglandular disease justifies the use of QPTH during a focused approach. When positive localization study results are concordant, the use of QPTH is questionable during a focused approach.

Primary hyperparathyroidism in MEN 1--how radical should surgery be?

Primary hyperparathyroidism is the most common manifestation of MEN 1 syndrome. The management of these patients is complex due to the underlying disease process, which predisposes patients to persistent and recurrent disease. The surgical treatment of patients with MEN 1 and hyperparathyroidism can therefore be considered to be palliative in nature. The basic principles of surgery include (1) obtaining and maintaining normocalcaemia for the longest time possible, avoiding persistent/recurrent hypercalcaemia, (2) avoiding surgically induced hypocalcaemia, and (3) facilitating future surgery for recurrent disease. Two approaches have been described as the best practice for patients with hyperparathyroidism in MEN 1: subtotal parathyroidectomy, leaving a remnant of no more than 60 mg in the neck, and total parathyroidectomy with immediate autotransplantation of 10-20 1 mm(3) pieces of parathyroid tissue. Both approaches should be combined with efforts to exclude supernumerary glands and ectopic parathyroid tissue by including resection of fatty tissue from the central neck compartment and thymectomy in all patients. Cryopreservation of parathyroid tissue should be performed whenever facilities are available. In patients with persistent or recurrent disease, an attempt to obtain total elimination of cervical parathyroid tissue is justified, combined with cryopreservation of parathyroid tissue. As radical as surgery is for hyperparathyroidism in MEN 1, the surgeon must take steps to avoid permanent hypoparathyroidism, which in young patients may be worse than the disease itself.