Extra-pancreatic manifestations of IgG4-related systemic disease: a single-centre experience of treatment with combined immunosuppression.

BACKGROUND/AIM: IgG4-related systemic disease (IgG4-RSD) is a systemic inflammatory disease distinguished by tissue infiltrates of IgG4(+) plasma cells and elevated serum IgG4 levels. While IgG4-RSD often involves the pancreas, extra-pancreatic organs are also frequently affected. Here, we review the presentation and management of patients with extra-pancreatic IgG4-RSD. METHODS: A retrospective analysis was performed on patients diagnosed with extra-pancreatic IgG4-RSD identified from a single centre. RESULTS: Six patients with extra-pancreatic IgG4-RSD were identified. The median age of the patients was 64 years. The range of involved organs included lymph nodes (three patients), ocular adnexa, lung, kidneys, meninges and exocrine glands. The median delay in diagnosis was 13.5 months (4-60 months). Four patients had elevated serum IgG4 levels at diagnosis. Five symptomatic patients were commenced on combination immunosuppression, which included corticosteroids. Maintenance therapy with azathioprine was used in one patient, methotrexate and mycophenolate were each used in two patients, and cyclophosphamide in one patient. Four treated patients went into remission, while two patients had persistent radiological disease. One patient experienced two relapses. CONCLUSION: IgG4-RSD can manifest in a variety of organs. Lack of awareness regarding this entity may delay diagnosis. Combination treatment of corticosteroids and conventional immunosuppression is effective.

A prospective, randomized, controlled trial of covered expandable metal stents in the palliation of malignant esophageal obstruction at the gastroesophageal junction.

OBJECTIVE: Palliation of malignant esophageal obstruction is an important clinical problem. Expandable metal stents are a major advance in therapy, but many stents become obstructed because of tumor ingrowth. The aim of this study was to compare a new, membrane-covered expandable metal stent to conventional prostheses in a randomized controlled trial. METHODS: Sixty-two patients with malignant inoperable esophageal obstruction at the gastroesophageal junction participated in the study. Patients were randomly assigned to covered or uncovered stents. The principal outcome measure was the need for reintervention because of recurrent dysphagia or migration. Secondary endpoints were relief of dysphagia measured by a dysphagia score (grade 0 = no dysphagia, grade 1 = able to eat solid food, grade 2 = semisolids only, grade 3 = liquids only, grade 4 = complete dysphagia) and the rate of complications and functional status. All patients were observed at monthly intervals until death or for 6 months. RESULTS: One week after stenting the dysphagia score improved significantly in both the uncovered (n = 32, 3 +/- 0.1 to 1 +/- 0.1 [means +/- SEMs], p < 0.001) and covered (n = 30, 3 +/- 0.1 to 1 +/- 0.2 [means +/- SEMs], p < 0.001) stents. Obstructing tumor ingrowth was significantly more likely in the uncovered stent group (9/30) than in the covered group (1/32) (p = 0.005). Significant stent migration occurred in 2/30 patients with uncovered stents, as compared with 4/32 patients in the covered group (p = 0.44). Reinterventions for tumor ingrowth were significantly greater in the uncovered stent group (27%), as compared with 0% in the covered group (p = 0.002). Life table analysis showed similar survival in both groups. CONCLUSION: Membrane-covered stents have significantly better palliation than conventional bare metal stents because of decreased rates of tumor ingrowth that necessitate endoscopic reintervention for dysphagia.

Selenio y carcinogénesis mamaria / Selenium and breast carcinogenesis

La relación entre el selenio (Se) y el cáncer comenzó a plantearse en 1943 y desde entonces, aunque algunos estudios epidemiológicos han mostrado un incremento del riego del cáncer de mama ante estados deficitarios de Se, otra proporción similar de trabajos no han encontrado tal asociación. En estu dios experimentales el Se se mostró muy eficaz para inhibir la carcinogénesis mamaria inducida por diferentes noxas en diversos modelos animales. Se cuestiona la utilidad del Se sérico en las enfermas de cáncer de mama como un marcador tumoral.De acuerdo con los datos de la bibliografía revisada y de los hallazgos de nuestro grupo, la disminución del Se sérico en las enfermas con cáncer de mama estaría relacionada con la actividad biológica del tumor, siendo un fenómeno posterior a la aparición del cáncer. También se apuntan nuevas líneas de investigación. (AU)

Tretinoin in pregnancy complicated with acute promyelocytic leukaemia.

Acute promyelocytic leukemia (APL) in pregnancy poses serious danger to both the mother and fetus. Cytotoxic chemotherapy may cause teratogenicity to the fetus. APL is unique because it is usually associated with a coagulopathy that markedly increases the risk for the mother and fetus. A 21 year old lady with APL in her third trimester of pregnancy was treated with oral tretinoin. Tretinoin reversed the coagulopathy and normalised her blood counts without causing cytotoxic damage associated with cancer chemotherapy. Fetal distress occurred at 37 weeks of gestation and an emergency caesarean section was performed without complications and no blood transfusion support was needed as her coagulopathy and thrombocytopenia had resolved. A remission was achieved with only tretinoin induction. She subsequently had consolidation and maintenance chemotherapy. The mother and baby remain well at 4 years from completion of chemotherapy. A total of 10 pregnancies associated with APL have been reported in the current literature. Premature delivery and a fetal arrhythmia were the only complications. Although retinoin is considered teratogenic, its use so far in second and third trimester has been safe.

Fc gamma receptor IIIB-NA gene frequencies in patients with systemic lupus erythematosus and healthy individuals of Malay and Chinese ethnicity.

The neutrophil antigen (NA)1 and 2 is coded by two recognized allelic forms of Fc gamma receptor IIIB (FcgammaRIIIB). FcgammaRIIIb is a low affinity receptor and preferentially removes immune complexes from the circulation. Systemic lupus erythematosus (SLE) is an autoimmune and polygenic disorder characterized by accumulation of autoimmune complexes. The majority of SLE patients in our medical center are of Chinese ethnicity, followed by Malay and Indian. Recently, studies have focussed on the Fc receptors in different ethnic groups and their relation to SLE. We chose to study the gene distribution of this receptor in the Chinese and Malays population in Malaysia. We designed a polymerase chain reaction allele specific primers (PCR-ASP) method to distinguish the two allelic forms. Genomic DNA was isolated from the peripheral blood of 183 Chinese and 55 Malays SLE patients as well as 100 Chinese and 50 Malays healthy controls. Genotyping of Chinese SLE patients revealed that the gene frequencies for FcgammaRIIIB-NA1 and FcgammaRIIIB-NA2 were 0.648 and 0.347, while in the ethnically matched healthy controls they were 0.68 and 0.32, respectively. One out of the 183 Chinese SLE patients was identified as a NA-null due to the absence of PCR product for both alleles. The FcgammaRIIIB-NA1 and FcgammaRIIIB-NA2 allele frequencies for both the Malays SLE and healthy controls were 0.62 and 0.38.

Human Fc gamma receptor IIA (FcgammaRIIA) genotyping and association with systemic lupus erythematosus (SLE) in Chinese and Malays in Malaysia.

SLE is an autoimmune and polygenic disorder characterized by an accumulation and deposition of immune complexes. Several studies have indicated differential impact of FcgammaR polymorphism genotypes in different ethnic groups studied. The Fc receptor for IgG class IIA gene (FcgammaRIIA) occurs in two allelic forms. The allele FcgammaRIIA-H131 encodes a receptor with a histidine at the 131 amino acid position; the other allele FcgammaRIIA-R131 encodes an arginine. This polymorphism is believed to determine the affinity of the receptor for hIgG2 in immune complexes. FcgammaRIIA-H131 has a higher capacity for hIgG2 compared to FcgammaRIIA-R131 as measured by in vitro studies of insoluble immune complex clearance. We have investigated the polymorphism for FcgammaRIIA using a novel polymerase chain reaction-allele specific primer (PCR-ASP) method designed specifically to distinguish the two allelic forms. Our studies were based on 175 Chinese and 50 Malays SLE patients as well as 108 and 50 ethnically matched healthy controls for the respective groups. Analysis of the data (chi2 test with Yates correction factors and odds ratios) revealed that there were no significant differences between SLE patients and controls. We have not found evidence of a protective effect conferred by FcgammaRIIA-H131 in the ethnic groups studied.

Management of occluded biliary Wallstents.

BACKGROUND: Wallstents (Schneider Stent, Inc., USA) used for the palliation of malignant biliary strictures, although associated with prolonged patency, can occlude. There is no consensus regarding the optimal management of Wallstent occlusion. AIMS: To evaluate the efficacy of different endoscopic methods for managing biliary Wallstent occlusion. METHODS: A multicentre retrospective study of patients managed for a biliary Wallstent occlusion. RESULTS: Data were available for 38 patients with 44 Wallstent occlusions, all of which had initial endoscopic management. Twenty four patients had died and 14 were alive after a median follow up of 231 (30-1095) days following Wallstent occlusion. Occlusions were managed by insertion of another Wallstent in 19, insertion of a plastic stent in 20, and mechanical cleaning in five. Endoscopic management was successful in 43 (98%). Following management of the occlusion, bilirubin decreased from 6.0 (0.5-34.3) to 2.1 (0.2-27.7) mg/100 ml (p < 0.05). No complications occurred. The median duration of second stent patency was 75 days (95% confidence interval 43 to 107) after insertion of another Wallstent, 90 days (71 to 109) after insertion of a plastic stent, and 34 days (30 to 38) after mechanical cleaning (NS). The respective median survivals were 70 days (22-118), 98 days (54-142), and 34 days (30-380) (NS). Incremental cost effective analysis showed that plastic stent insertion is the most cost effective option. CONCLUSION: Although all three methods are equally effective in managing an occluded Wallstent, the most cost effective method appears to be plastic stent insertion.

Endoscopic sphincterotomy for stones by experts is safe, even in younger patients with normal ducts.

OBJECTIVE: To provide current information on the risks of endoscopic sphincterotomy for stone. SUMMARY BACKGROUND DATA: In recent years (since the popularity of laparoscopic cholecystectomy), endoscopic sphincterotomy has been used increasingly for the management of bile duct stones in relatively young and healthy patients. The validity of this trend has been questioned using data on short-term complications derived from earlier decades that involved more elderly and high-risk patients. METHODS: Seven academic centers collected data prospectively using a common database. Complications within 30 days of the procedures were documented by standard criteria. RESULTS: Of 1921 patients, 112 (5.8%) developed complications; two thirds of these events were graded as mild (<3 days in hospital). There was no evidence of increased risk in younger patients or in those with smaller bile ducts. There was only one severe complication and there were no fatalities in 238 patients age <60, with bile duct diameters of <9 mm. CONCLUSION: Sphincterotomy for stones can be performed very safely by experienced endoscopists.

Successful treatment of post-cholecystectomy bile leaks using nasobiliary tube drainage and sphincterotomy.

OBJECTIVE: Bile leaks are known complications of cholecystectomy. The combination of sphincterotomy and nasobiliary tube (NBT) drainage is effective for the immediate decompression of bile ducts and provides access for follow-up cholangiography. Our objective was to study, retrospectively, 19 patients who had undergone treatment for bile leaks with this combination between October 1991 and December 1995. METHODS: Nineteen patients (15 F, 4 M) ages 23-83 yr (mean 50 yr) presented with bile leaks secondary to open cholecystectomy (n = 1) and laparoscopic cholecystectomy (n = 18). All patients had sphincterotomy and NBT placement. Symptoms, findings at ERCP, and outcome were reviewed. RESULTS: Patients presented from 0 to 150 days after cholecystectomy (median = 2) with pain (n = 17), fever (n = 8), bile leakage in a surgical drain (n = 4), elevated liver tests (n = 8), and nausea and vomiting (n = 4). Fourteen patients had diagnostic imaging before endoscopic management. ERCP findings included cystic stump leak (n = 12), including one with a colocutaneous biliary fistula, gallbladder fossa leak (n = 3), right hepatic branch leak (n = 1), or no leak (n = 3). Three patients had choledocholithiasis. NBT drainage was used for a mean of 3.9 days (range 1-12 days). Fourteen patients had radiographic evidence of leak closure. One patient ultimately required surgical correction for a chronic colocutaneous biliary fistula. There were no early or late endoscopic complications. CONCLUSIONS: Endoscopic management with nasobiliary drainage and sphincterotomy is effective for acute uncomplicated bile leaks but may not be adequate for chronic fistulas. The advantages over endoprostheses include access for subsequent cholangiography, improved biliary decompression, and catheter removal without further endoscopy.

Adult allogeneic bone marrow transplantation: initial experience in the University Hospital, Kuala Lumpur.

Prior to 1993, bone marrow transplantation for adult patients was not available in Malaysia. Adult allogeneic bone marrow transplantation commenced in Malaysia when the first transplant was conducted at the University Hospital, Kuala Lumpur on 2 November 1993. Up till July 1995, 10 adult bone marrow transplants had been conducted at the University Hospital. Five patients had acute myeloid leukaemia in first remission, 4 had chronic myeloid leukaemia and 1 had acute lymphoblastic leukaemia in first partial remission. The age range of patients at the time of transplant is 16-40 years (mean 25.5 years). All patients engrafted successfully and the survival for the first 100 days post-transplant is 90%. One patient demonstrated haematological relapse post-transplant but achieved remission with donor buffy-coat infusion. The mean drug cost incurred was RM28,269 for the first 100 days. Locally available adult allogeneic bone marrow transplantation is safe, affordable and has comparable results with reputable overseas transplant centres.