Substernal goiter. Report of 212 cases

AIM OF THE STUDY: The aim of this retrospective study was to report the results of the surgical treatment in a series of 210 patients operated on for substernal goiters. PATIENTS AND METHOD: From 1982 to 1996, 210 patients with substernal goiters, including 80% of women, were operated on via a cervical approach in 208 cases, via a sternotomy in two cases. Two patients with operative contra-indications were not operated on. Twenty-five were operated on for a substernal recurrence of a goiter. In 160 cases, extraction of the substernal portion was easy. In 48 cases, removal of the substernal portion was facilitated by the discovery of the recurrent nerve at its entering into the larynx and a downward dissection of the tracheal attachments of the lobe. The complete dissection of the cervical portion made easier the ascension of the substernal portion even in very large substernal components. RESULTS: Three papillary carcinomas were diagnosed. A transient laryngeal nerve palsy occurred in 7.2% of the patients and a transient hypoparathyroidism in 13.4%, A definitive laryngeal nerve palsy occurred in 1.2% of the patients, and a persistent hypoparathyroidism in 2.1%. Of the 25 patients who underwent surgery for recurrence of a goiter, three (12%) developed a transient laryngeal nerve palsy, one (4%) a permanent nerve palsy, four (20%) a transient hypoparathyroidism and one (4%) a persistent hypocalcemia. CONCLUSION: CT scan and MRI are the best explorations to evaluate intrathoracic extension of substernal goiters. Thyroidectomy was performed via a cervical incision in 208 patients and via a sternotomy in two patients only. The complete dissection of the cervical portion with discovery of the recurrent nerve at its entering into the larynx, facilitates the ascension of the substernal portion even in very large substernal goiters.     

Phase II study of proteasome inhibitor bortezomib in relapsed or refractory B-cell non-Hodgkin's lymphoma.

PURPOSE: Evaluate efficacy and toxicity of bortezomib in patients with relapsed or refractory B-cell non-Hodgkin's lymphoma. PATIENTS AND METHODS: Patients were stratified, based on preclinical data, into arm A (mantle-cell lymphoma) or arm B (other B-cell lymphomas) without limitation in number of prior therapies. Bortezomib was administered as an intravenous push (1.5 mg/m2) on days 1, 4, 8, and 11 every 21 days for a maximum of six cycles. RESULTS: Sixty patients with a median number of prior therapies of 3.5 (range, one to 12 therapies) were enrolled; 33 patients were in arm A and 27 were in arm B, including 12 diffuse large B-cell lymphomas, five follicular lymphomas (FL), three transformed FLs, four small lymphocytic lymphomas (SLL), two Waldenstrom's macroglobulinemias (WM), and one marginal zone lymphoma. In arm A, 12 of 29 assessable patients responded (six complete responses [CR] and six partial responses [PR]) for an overall response rate (ORR) of 41% (95% CI, 24% to 61%), and a median time to progression not reached yet, with a median follow-up of 9.3 months (range, 1.7 to 24 months). In arm B, four of 21 assessable patients responded (one SLL patient had a CR, one FL patient had a CR unconfirmed, one diffuse large B-cell lymphoma patient had a PR, and one WM patient had a PR) for an ORR of 19% (95% CI, 5% to 42%). Grade 3 toxicity included thrombocytopenia (47%), gastrointestinal (20%), fatigue (13%), neutropenia (10%), and peripheral neuropathy (5%). Grade 4 toxicity occurred in nine patients (15%), and three deaths from progression of disease occurred within 30 days of withdrawal from study. CONCLUSION: Bortezomib showed promising activity in relapsed mantle-cell lymphoma and encouraging results in other B-cell lymphomas. Future studies will explore bortezomib in combination with other cytotoxic or biologic agents.     

The MDR1 (P-glycoprotein) and MRP (P-190) transporters do not play a major role in the intrinsic multiple drug resistance of Jurkat T lymphocytes

The response of T cells in relation to the cell cycle has not been extensively studied. We have attempted to address this question using Jurkat T cells treated with cytostatic drugs known to arrest cells at various transition points of their cycle. We tested several concentrations of drugs that act at G1/S (hydroxyurea, lovastatin, thymidine), early S (aphidicolin, cyclosporin A, rapamycin) or G2+M (colchicine, nocodazole) in 24 h cultures. Cytofluorimetric analyses showed that cycling Jurkat cells were equally distributed between the G1 (44.9 ± 6.5%) and S (42.3 ± 8.0%) phases. Cell distribution in G2+M was 12.7 ± 2.8%. Hydroxyurea but not lovastatin increased the percentage of cells in S phase to ≈60–70% and both drugs decreased it to ≈30% in G1. Thymidine had no effects. Aphidicolin increased the distribution in S phase to ≈70% with a decrease in G1 to ≈30%. Cyclosporin A and rapamycin increased the percentage of the cells in G1 to ≈70% and decreased it to ≈25% in S phase. Nocodazole increased cell distribution in G2+M to ≈60% and induced a decrease in G1 to ≈10%. The effects of the drugs were not related to their toxicity and their limited efficiency raised the possibility that Jurkat cells possessed an intrinsic resistance to these xenobiotics. Time-course analysis showed (scanning electron microscopy) that the early morphological changes induced by colchicine were reversible. Drug efflux experiments (vinblastine) suggested that an ATP-dependent process could be involved. However, Northern blot analyses showed a weak signal for MDR1 (P-glycoprotein). In contrast, a probe for MRP (P-190) showed a strong signal in Jurkat and peripheral lymphocytes. The presence of drugs (cyclosporin A, nocodazole, thymidine) (24 h) did not upregulate its message and cell treatment with -butathione (S,R)-sulfoximine only moderately affected the efficiency of the glutathione S-conjugate MRP transporter. Our data suggest that the intrinsic multidrug resistance of leukemic Jurkat T cells does not appear to involve the MDR1 and MRP members of the ABC family of reverse drug transporters and these observations raise the possibility of the involvement of multifaceted mechanisms.     

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome: clinical description and genetics

The Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is characterized by congenital aplasia of the uterus and the upper part (two-third) of the vagina. It may be isolated (type I) or associated with other malformations (type II or MURCS association). These latter involve the upper urinary tract, the skeleton and, to a lesser extent, the otologic sphere or the heart. The incidence of MRKH syndrome has been estimated as 1 in 4500 women. The prime feature is a primary amenorrhea in women presenting otherwise with normal development of secondary sexual characteristics and normal external genitalia. However, the vagina is reduced to a vaginal dimple with variable depth. The ovaries are normal and functional as well as the endocrine status. Karyotype is 46,XX, with no visible chromosome modification. The phenotypic manifestations of MRKH syndrome overlap with various other syndromes or malformations and thus require accurate delineation as well as differential diagnosis. For a long time, the syndrome has been considered as a sporadic anomaly, but increasing familial cases now support the hypothesis of a genetic cause currently under investigation. The syndrome appears to be transmitted as an autosomal dominant trait with incomplete penetrance and variable expressivity.     

Prevalence and Predictors of Liver Fibrosis in People Living with Hepatitis B in Senegal

Hepatitis B virus (HBV) infection is the first cause of liver cirrhosis and cancer in West Africa. Although the exposure to additional environmental and infectious risk factors may lead to the faster progression of liver disease, few large-scale studies have evaluated the determinants of HBV-related liver fibrosis in the region. We used transient elastography to evaluate the prevalence of liver fibrosis and assessed the association between HBV markers and significant liver fibrosis in a cohort of people living with HBV in Dakar, Senegal. The prevalence of significant liver fibrosis was 12.5% (95% confidence interval [CI] 9.6%–15.9%) among 471 people with HBV mono-infection (pwHBV) and 6.4% (95% CI 2.6%–12.7%) in 110 people with HIV/HBV co-infection (pwHIV/HBV) on tenofovir-containing antiretroviral therapy (p = 0.07). An HBV viral load > 2000 IU/mL was found in 133 (28.3%) pwHBV and 5 (4.7%) pwHIV/HBV, and was associated with significant liver fibrosis (adjusted odds ratio (aOR) 1.95, 95% CI 1.04–3.66). Male participants (aOR 4.32, 95% CI 2.01–8.96) and those with elevated ALT (aOR 4.32, 95% CI 2.01–8.96) were especially at risk of having significant liver fibrosis. Our study shows that people with an HBV viral load above 2000 IU/mL have a two-fold increase in the risk of liver fibrosis and may have to be considered for antiviral therapy, independent of other disease parameters.     

Percutaneous blade and balloon atrioseptostomy as a supplement to extracorporeal membrane oxygenation as a bridge to heart transplantation

In patients with severe ventricular dysfunction, the extracorporeal membrane oxygenation (ECMO) could be insufficient to discharge the left ventricle. The percutaneous blade and balloon atrioseptostomy that requires transeptal catheter-based experience could be an advisable technique to supplement assistance as a bridge to partial recovery or to heart transplantation. We present a case of a young male who presented for cardiogenic shock with a huge thrombus in the left main coronary artery in whom blade and balloon atrioseptostomy in addition to the ECMO was helpful to bail out and to perform heart transplantation.