Clinical characteristics and treatment outcomes of germ cell tumor in Jordan: A tertiary center experience.

Objective: In the Middle East, there is a paucity of data regarding germ cell tumor characteristics and treatment outcomes. Herein, we aim to present the largest series in Jordan reporting our cancer center experience managing GCT. Methods: Between 2010 and 2020, a total of 241 patients with a pathological diagnosis of GCT were treated at our cancer center. Demographic, epidemiologic, and pathological data were retrospectively collected. In addition, survival and relapse outcomes based on tumor stage and adjuvant treatment were collected. Results: A total of 241 patients were diagnosed with GCT, of whom 108 (44.8%) had seminoma and 133 (55.2%) had non-seminoma tumors (NSGCT). Median age (interquartile range) at diagnosis was 31 years (25-36). Patients with seminoma (68.5%) had pT1 disease post orchiectomy, while only 37.5% of patients with NSGCT had pT1 on final pathology. Elevated tumor markers such as beta-human chorionic gonadotropin were present in 10% of seminomas. Following radical orchiectomy and staging, 88 (36.5%) went for active surveillance while 153 patients (63.5%) received adjuvant treatment. With regard to pathology slides read outside, rereading by our genitourinary pathologist yielded a discrepancy on GCT type in 41 (19.3%) out of 212 patients. The median follow-up was 36 (24-48) months. Twenty-two patients relapsed after an average follow-up time of 39 months. The 5-year overall survival for stage I, II, and III was 98%, 94%, and 87%, respectively, and 3-year recurrence-free survival for stage I, II, and III was 94.8%, 78%, and 67%, respectively. Conclusion: Our data on testicular GCT including demographic, histological, and treatment outcomes were comparable to that of developed countries. In light of the pathology discrepancy rate revealed in our study, authors recommend a second review by expert genitourinary pathologists to ensure proper classification and management of GCT.

Quality of life and other patient-reported outcomes in adult Lebanese patients with type 2 diabetes during COVID-19 pandemic.

INTRODUCTION: Several studies have shown that COVID-19 pandemic has a negative impact on type 2 diabetic mellitus (T2DM) patients' quality of life (QoL). However, very few studies were performed in Middle Eastern countries. AIM: The aim of the current study was to assess, the QoL and diabetes-specific QoL, treatment satisfaction and psychological distress of Lebanese patients with T2DMs using: the Audit of Diabetes-Dependent Quality of Life (ADDQoL), Diabetes Treatment Satisfaction Questionnaire status version (DTSQs) and Kessler 10 (K10) questionnaires and to compare results to those obtained during the pre-COVID-19 period. RESULTS: 461 patients with T2DM participated in the study; 52.6% men, 47.4% women; median age 59 years old. The respective median ADDQoL and DTSQs scores were - 2.2 (interval interquartile range (IQR) - 3.9, - 0.8) (range from - 9 maximum negative impact to + 3 maximum positive impact) and 30(IQR22-36) (range from 0 maximum dissatisfaction to 36 maximum satisfaction). K10 median score was 26(IQR18-35) (range from minimum score of 10 indicating no distress to maximum score of 50 indicating severe distress). Rural dwelling, lack of exercise, current smoking, diabetic complications, injectable diabetes treatment, and previous COVID-19 infection were all associated with significantly worse ADDQoL, DTSQs, and K10 score indicating greater distress. A significant worsening of ADDQoL scores followed onset of the pandemic with no significant change in DTSQs scores. CONCLUSION: During the COVID-19 pandemic, T2DM Lebanese patients experienced more negative impact of diabetes on QoL and mental health. Those infected with COVID-19 also reported worse QoL, treatment satisfaction and mental health. This highlights the need for community and individual support.

[Perioperative use of antithrombotic agents: recommendations of the American College of Chest Physicians (ACCP) and the French Superior Health Authority (HAS)]. / La prise en charge périopératoire des traitements antithrombotiques. Des recommandations de l'American College of Chest Physicians (ACCP) à celles de la Haute Autorité de santé (HAS).

The purpose of this work was to analyse management practices for patients given anticoagulants or antiplatelet agents such as aspirin, clopidogrel and who are to undergo an invasive procedure or surgery. The modalities for the transition from oral agents to low-molecular-weight-heparin (LMWH) or unfractionated heparin (UFH) are studied. The recommendations or suggestions using the ACCP score: grade 1 recommendations are strongly motivated and indicate whether the benefit overbalances or not the risk, the burden, and the cost of the treatment. Grade 2 recommendations are considered to be suggestions. They imply that the individual physician chooses between different therapeutic strategies. For the purpose of this work, the most important recommendations are the following:

Coexistence of acute cellular rejection and lymphoproliferative disorder in a lung transplant patient.

We report the case of a 37-year-old man who underwent bilateral lung transplantation for end-stage cystic fibrosis. Two months after his operation, a computed tomographic scan showed multifocal nodules throughout both lungs. Endobronchial biopsies revealed an Epstein-Barr virus-associated B-cell lymphoproliferation. Transbronchial biopsies revealed perivascular lymphoid infiltrates composed of predominantly small T lymphocytes. These perivascular infiltrates were retrospectively considered to be an acute cellular rejection rather than the periphery of the lymphoproliferative disorder. This opinion was based on several arguments: (a) a decrease in dosage of maintenance immunosuppression led to total regression of the lymphoproliferation but did not affect the perivascular lymphoid infiltrates; (b) the treatment of the acute cellular rejection temporarily induced the disappearance of the perivascular infiltrates; (c) the expression of Epstein-Barr virus was not detected in the perivascular infiltrates; and (d) on autopsy, performed 1 year later, severe obliterative bronchiolitis lesions were discovered, for which acute cellular rejection is the main risk factor. These observations point to the possibility that acute cellular rejection and an Epstein-Barr virus-associated lymphoproliferative disorder may coexist.

The thrombophilic state in cancer patients.

Thrombosis and disseminated intravascular coagulation are common complications of cancer. Specific conditions associated with cancer such as stasis due to immobilization or blood flow obstruction, surgery, infections, endothelium damage due to chemotherapeutic agents and abnormalities of blood coagulation contribute to the hypercoagulable and thrombophilic state of cancer patients. This procoagulant state in cancer arises mostly from the capacity of tumor cells to express and release procoagulant activities (cancer procoagulant and tissue factor). Decreased levels of inhibitors of coagulation, impaired fibrinolysis, the presence of antiphospholipid antibodies and an acquired activated protein C resistance contribute to the hypercoagulable state. The activation of coagulation is also implicated in tumor proliferation through interactions of coagulation with inflammation and increased tissue factor pathway inhibitor. Laboratory diagnosis of the thrombophilic state include (1) elevation of clotting factors, fibrinogen/fibrin degradation products, hyperfibrinogenemia and thrombocytosis and (2) elevation of specific markers of activation of coagulation: fibrinopeptide A, fragment 1 + 2, thrombin-antithrombin complexes and D-dimers. However, none of the tests has any predictive value for the occurrence of thrombotic events in one individual patient. In patients with venous thromboembolism a noninvasive screening for occult cancer is able to detect a relatively high incidence of hidden cancer and the search for thrombophilia seems important in patients without known cancer.

Contralateral lung transplantation: a left lung implanted in the right thorax.

Since the inception of lung transplantation in 1982, it has been standard practice to implant donor lungs on the ipsilateral side in the recipient. The development of the techniques of lobar and bilateral lobar transplantation has shown that lung morphology may adapt to the shape of the thorax. Thus, variations in implantation have become possible. We describe a case of a 30-year-old man with severe bronchiectasis due to ciliary dyskinesis which required a left lower lobectomy at the age of 11 years and a left completion pneumonectomy 10 years later. His disease progressed and he was listed for a right lung transplantation. At the time of transplantation, the donor right lung was noted to be edematous and unfit for transplantation. This required grafting the donor left lung in the right thorax of the recipient. Follow-up at 7 years shows good exercise capacity and excellent functional tests without evidence of rejection.

Treatment of B-lymphoproliferative disorder with a monoclonal anti-interleukin-6 antibody in 12 patients: a multicenter phase 1-2 clinical trial.

Severe T-cell immunodeficiency after solid organ or bone marrow transplantation may result in the uncontrolled outgrowth of latently Epstein-Barr virus-infected B cells, leading to B-lymphoproliferative disorder (BLPD). Given the potentially important pathogenic role of IL-6 in BLPD, it was tested whether the in vivo neutralization of IL-6 by a monoclonal anti-IL-6 antibody could contribute to the control of BLPD. Safety and efficacy were assessed in 12 recipients of transplanted organs who had BLPD refractory to the reduction of immunosuppression over 8 days. Five patients received 0.4 mg/kg per day. The next 7 patients received 0.8 mg/kg per day. Treatment was scheduled to last 15 days. It was completed in 10 patients, and in the other 2 patients was discontinued early (days 10 and 13, respectively) because of disease progression. Treatment tolerance was good, and no major side effects were observed. High C-reactive protein levels were found in 9 patients before treatment but were normalized under treatment in all patients, demonstrating efficient IL-6 neutralization. Complete remission (CR) was observed in 5 patients and partial remission (PR) in 3 patients. Relapse was observed in 1 of these 8 patients in whom remission was observed. This relapse was unresponsive to treatment. Disease was stable in 1 patient, but it progressed in 3 patients. Seven patients are alive and well. Two patients died because of disease progression, and 3 patients died while in CR (chronic rejection in 2 patients and BLPD sequelae in 1 patient). These data suggest that the anti-IL-6 antibody is safe and should be further explored in the treatment of BLPD.

[How to provide practical treatment for ambulatory patients with deep venous thrombosis]. / Comment traiter en pratique une thrombose veineuse profonde en ambulatoire?

Much interest has been focused on low molecular weight heparins (LMWH), light weight fragments of standard heparin, for the management of deep vein thrombosis (DVT) without pulmonary embolism (PE). LMWHs offer several advantages: predictable anticoagulant activity, better bioavailability, longer half-life, better patient and caretaker comfort, safety and efficacy at least comparable to continuous intravenous heparin. Ambulatory treatment is quite attractive and a large number of patients with DVT are now being managed as outpatients. There are however certain precautions which must be taken to avoid unsatisfactory anticoagulation and subsequent consequences which have nevertheless been shown to be exceptional in well-designed and well-conducted trials excluding patients with high risk for hemorrhage and based on attentive medical control. The purpose of this review is to propose clear and simple protocols for everyday practice aimed at a global diagnostic and therapeutic management of venous thromboembolism. The review of the literature draws attention to the need for confirmation of the clinical suspicion of DVT, practical application of the anticoagulant treatment, and the importance of the etiology search in order to avoid missing a congenital or acquired state of thrombophilia or an occult cancer revealed by DVT. Half of all cases of thrombosis are caused by these two etiologies. In addition, with the development of noninvasive methods for diagnosing DVT, the efficacy of clear therapeutic regimens and the simplification of coagulation tests warrant outpatient management in many cases of DVT in compliance with certain rules of good clinical practice: confirmation of the diagnosis and regular treatment controls. An essential element is the close collaboration between the patient, the physician, the nursing staff, the laboratory and the pharmacist.

Swyer-James syndrome documented by spiral CT angiography and high resolution inspiratory and expiratory CT: an accurate single modality exploration.

Spiral CT angiography was performed in a patient suspected of having pulmonary embolism. The right pulmonary system was normal. The left arterial system was small but patent. The left upper lobe was small and hyperlucent. The left lower lobe was collapsed and contained bronchiectasis. The bronchi were patent. High resolution CT in inspiration and expiration confirmed air trapping in the left upper lobe. A diagnosis of Swyer-James syndrome of the left upper lobe was made.

Pulmonary bipartitioning and lobar transplantation: a new approach to donor organ shortage.

The scarcity of small donors has significantly limited lung transplantation for pediatric and small adult patients. Use of single lobes procured from size-unmatched donors has overcome this difficulty, but only in a few selected cases and, in addition, it represents a waste of lung tissue. In an animal model we have shown that it is possible to divide one lung with careful partitioning of the vascular and bronchial structures and thus obtain two viable lobar grafts suitable for bilateral implantation in a smaller animal. We have now applied this procedure clinically in seven patients operated on between May 1993 and November 1994. The indications were cystic fibrosis in three children, primary pulmonary hypertension in two adults, bronchiectasis in one, and idiopathic pulmonary fibrosis in one. There were three children aged 13 to 17 years (median 14) and four adults aged 40 to 53 years (median 45). There was a 46% to 50% discrepancy for weight between recipient and donor and a 12% to 17% discrepancy for height. The surgical technique consisted of careful partitioning of the left donor lung, bilateral anterior thoracotomy in the recipient, and, with the use of cardiopulmonary bypass, implantation of the lower lobe in the left hemithorax and the upper lobe in the right hemithorax. Vascular and bronchial connections were facilitated by leaving a long pedicle on the recipient side. The pulmonary artery anastomosis for the donor left upper lobe was done with the "fissure" side of the artery to ensure an anastomosis without tension. An end-to-end bronchial anastomosis overcame the problem of size discrepancy. Six patients are alive and well 10 to 27 months (median 19) after operation. One patient with cystic fibrosis died of systemic aspergillosis infection. All were discharged from the hospital within the first or second postoperative month. No technical problems were identified: repeated bronchoscopy has demonstrated satisfactory healing without early stricture formation. All patients remain well subjectively with good exercise tolerance and all patients achieve greater than 70% of predicted values of forced expiratory volume in 1 second. Perfect adaptation of the transplanted lobes to the recipient pleural space has been demonstrated by postoperative computed tomographic scan. In conclusion, bilateral lobar transplantation from a single donor lung is possible in small adults or children when there is a large size discrepancy with the donor. This may help resolve the problem of donor availability in the pediatric population.

Combined heart-lung-liver, double lung-liver, and isolated liver transplantation for cystic fibrosis in children.

Between June 1990 and September 1995, 8 of 24 children with cystic fibrosis (CF) who were accepted either for combined transplantation or isolated liver transplantation died while waiting for a graft; 11 underwent transplantation and 5 are currently on the waiting list. Of the 11 children who had surgery, 7 (group 1) underwent one of the following procedures: heart-lung-liver (n = 4), sequential double lung-liver (n = 2), or bilateral lobar lung from a split left lung and reduced liver (n = 1). During the same period, the four other children (group 2) underwent isolated liver transplantation (three full-size livers, one partial liver). There was one perioperative death in each group. Pulmonary infection was the most common cause of morbidity in group 1. Other complications in group 1 included tracheobronchial stenosis (n = 2), biliary stricture (n = 2), and severe ascites (n = 2). All were successfully treated. Obliterative bronchiolitis developed in three patients. This was treated with FK 506. In group 2, pulmonary function tests improved or remained stable after liver transplantation. Surgical complications in group 2 included severe ascites (n = 1), biliary stricture (n = 1), and abscess of the liver (n = 1). Actuarial survival was 85.7% +/- 2% in group 1 at 1 year; it remained unchanged at 3 years and was 64.2% at 5 years.

Combined lung and liver transplantation in patients with cystic fibrosis. A 4 1/2-year experience.

Patients with cystic fibrosis who have end-stage respiratory failure and associated liver cirrhosis have been considered poor candidates for lung transplantation because of high morbidity and mortality resulting from hepatic insufficiency after the operation. Since April 1989, our policy has been to combine heart-lung or lung and liver transplantation in this group of patients. Between June 1990 and March 1995, among 25 patients accepted in the program for combined transplantation, nine died awaiting transplantation and 10 underwent one of the following procedures: heart-lung-liver transplantation (n = 5), en bloc double lung-liver transplantation (n = 1), sequential double lung-liver transplantation (n = 3), and bilateral lobar lung transplantation from a split left lung and reduced liver transplantation (n = 1). There were 5 male and 5 female patients. The ages of the recipients ranged from 10 to 24 years. Mean forced expiratory volume in 1 second was 29% and mean forced vital capacity was 35% of predicted values. All patients were infected with resistant Pseudomonas, three with Pseudomonas cepaceia, and two patients had Aspergillus species in addition. All patients had severe cirrhosis with portal hypertension. Four patients had a history of esophageal variceal bleeding and two had had previous portosystemic shunts. The operation was performed as a two-stage procedure, the intrathoracic operation being completed before the abdominal stage was begun. Cardiopulmonary bypass was used in all patients because of poor clinical condition. Immunosuppression consisted of azathioprine, cyclosporine, and prednisone, as for isolated lung transplantation. There were two perioperative deaths, one caused by primary liver failure and the second by early lung dysfunction. For the first 3 months after transplantation pulmonary infection was the most common cause of morbidity. Other complications included tracheal stenosis (n = 1), bronchial stenosis (n = 1), biliary stricture (n = 2), and severe ascites (n = 3). All were successfully treated. Obliterative bronchiolitis developed in three patients. This was stabilized with FK 506 in two patients; the other patient underwent retransplantation at 38 months but eventually died of bleeding. Actuarial survival was 70% at 1 year and remained unchanged at 3 years. Significant functional improvement was observed in all survivors. For patients who have chronic respiratory failure with advanced cirrhosis, lung transplantation combined with liver transplantation can be performed with a satisfactory outcome.

Treatment of active refractory rheumatoid arthritis with humanized monoclonal antibody CAMPATH-1H administered by daily subcutaneous injection.

OBJECTIVE: To investigate the dose tolerance and potential clinical activity of a humanized antilymphocyte monoclonal antibody, CAMPATH-1H (C1H), in patients with active, refractory rheumatoid arthritis (RA). METHODS: Thirty adult patients with active, refractory RA were treated in an open-label, 3-center, dose-escalation study of subcutaneously injected C1H. Six patients were assigned to each of 5 dosage groups (0.3, 1.0, 3.0, 10.0 or 30.0 mg/day), and received 10 daily injections of C1H over a 12-day period. RESULTS: Side effects occurred primarily during the first 1-2 days of dosing, and included mild fever, chills, nausea, vomiting, headache, and, in a minority of patients, hypotension. All patients developed some discomfort at the injection site. Self-limited infections occurred in 5 patients during the 6-month study period. Peripheral blood lymphocyte counts fell promptly after initial dosing and recovered slowly, usually over 2-3 months. Serum antibodies to C1H developed in 54% of patients following treatment. Clinical improvement was observed in 56% of patients, based on the composite Paulus criteria, with a median time-to-response of 22 days and a median response duration of 32 days. CONCLUSION: C1H is a lymphocyte-depleting antibody that exhibits biologic potency when administered subcutaneously to patients with refractory RA. Its use is associated with mild to moderate toxicity and short-term amelioration of disease activity.

Rheumatoid vasculitis manifesting as intra-abdominal hemorrhage.

Rheumatoid vasculitis, an extra-articular component of rheumatoid arthritis, causes a wide spectrum of manifestations that range from clinically insignificant to life-threatening disease. As a systemic necrotizing arteritis, rheumatoid vasculitis is usually characterized by end-organ ischemia. Herein we describe a patient with abdominal pain and syncope due to intra-abdominal hemorrhage from a ruptured aneurysm of the inferior pancreaticoduodenal artery in the setting of rheumatoid vasculitis. Although the intra-abdominal hemorrhage was the unusual manifestation of rheumatoid vasculitis in this patient, he had a history of prior extra-articular rheumatoid disease, including pulmonary fibrosis and Sjögren's syndrome with associated parotid lymphoproliferative disease. In patients with rheumatoid arthritis who have abdominal pain and an unexplained rapidly decreasing hemoglobin concentration, the diagnosis of intra-abdominal hemorrhage from a ruptured visceral aneurysm due to rheumatoid vasculitis should be considered, even in the absence of other indications of systemic vasculitis.

Giant cell arteritis involving the facial artery.

Jaw claudication in giant cell (temporal) arteritis (GCA) is believed to be due to vasculitic obstruction or stenosis of the arteries supplying the muscles of mastication, notably the facial and internal maxillary arteries and their branches. However, histologic documentation of this is rarely available because GCA is usually diagnosed by temporal artery biopsies. We describe a patient with jaw claudication and other clinical features of GCA in whom a facial artery biopsy confirmed involvement by GCA.

The use of clinical characteristics to predict the results of temporal artery biopsy among patients with suspected giant cell arteritis.

OBJECTIVE: To develop a mathematical model which predicts temporal artery biopsy results. METHODS: We collected clinical and laboratory data as well as biopsy results among a consecutive cohort of all individuals who underwent temporal artery biopsy at Mayo Medical Center between January 1, 1988 and December 31, 1991. All biopsies were independently reviewed by one pathologist. Logistic regression was used to identify a set of variables which best predicted the biopsy results. This model was then used to identify patients who were highly likely (> or = 95% predictive value) to have either a negative or a positive biopsy. A receiver operating characteristic (ROC) curve was generated using the best fit model. RESULTS: Of the 525 people in the study, there were 187 men and 338 women. The logistic regression model and the ROC curve generated from this model were of modest value in predicting biopsy results from prebiopsy clinical characteristics. However, this model identified 60 (11%) individuals who had a > or = 95% probability of having a negative biopsy. None of these individuals had any symptoms of claudication, only 5 of 60 (8%) had temporal artery abnormalities on examination, 45 (75%) had synovitis (suggesting an alternate diagnosis), and their median erythrocyte sedimentation rate was only 31 mm/h (Westergren). CONCLUSIONS: In individuals with these findings, we recommend a careful search for other diagnoses before temporal artery biopsy.

How does previous corticosteroid treatment affect the biopsy findings in giant cell (temporal) arteritis?

OBJECTIVE: To determine the effect of previous corticosteroid treatment on the results of temporal artery biopsy. DESIGN: Consecutive case series. SETTING: Tertiary care center. PATIENTS: A consecutive cohort of 535 patients who had temporal artery biopsies at Mayo Clinic, Rochester, Minnesota, between 1 January 1988 and 31 December 1991. MEASUREMENTS AND RESULTS: The dose and duration of corticosteroid treatment received before temporal artery biopsy and detailed clinical and laboratory data were obtained from the patients' medical records. All temporal artery biopsy slides were re-evaluated by a pathologist blinded to clinical data, previous corticosteroid treatment information, and the original pathologic diagnosis. Biopsy specimens were classified as negative for arteritis, positive for typical temporal arteritis, or positive for atypical temporal arteritis. Biopsy results were positive for 31% of patients (89 of 286) who did not receive corticosteroids before biopsy and for 35% of those (86 of 249) who did receive corticosteroids before biopsy (P = 0.4; 95% confidence interval for the difference, -4.7% to 11.5%). Patients who received corticosteroids before biopsy tended to have clinical features more suggestive of arteritis. A multiple logistic regression analysis model, controlling for these differences in clinical and laboratory features, showed that the biopsy positivity rate was unrelated to previous corticosteroid treatment. CONCLUSIONS: Although these results do not prove that histologic features are unaffected by corticosteroids, they show that, in this large, consecutive sample, the positivity rates of temporal artery biopsy were similar in untreated and corticosteroid-treated patients. Temporal artery biopsy may show arteritis even after more than 14 days of corticosteroid therapy in the presence of clinical indications of active disease.

[Severe methotrexate poisoning]. / Intoxication grave au méthotrexate.

Methotrexate toxicity is rare but extremely severe. When complete, it consists of ulcerations of the gastrointestinal mucosae responsible for necrotizing enteritis, erythroderma, bone marrow aplasia, interstitial pneumonia, hepatitis and organic renal failure with diuresis. Toxicity is facilitated by pre-existing renal impairment, third sector and abstention or underdosage of foliculinic acid prescribed as antagonist. The diagnosis rests on serum assays, the results of which must be interpreted taking into account the assay method and the time elapsed between the injection of methotrexate and its assay in serum. The multivisceral pathology observed may totally regress, as in the case reported here. Treatment is based on symptomatic measures, starting with maintenance of an abundant and alkaline diuresis, and on the parenteral administration of folinic acid in doses that vary with the authors.