Secondary pancreatic involvement by a diffuse large B-cell lymphoma presenting as acute pancreatitis

Diffuse large B-cell lymphoma is the most common type of non-Hodgkin's lymphoma. More than 50% of patients have some site of extra-nodal involvement at diagnosis, including the gastrointestinal tract and bone marrow. However, a diffuse large B-cell lymphoma presenting as acute pancreatitis is rare. A 57-year-old female presented with abdominal pain and matted lymph nodes in her axilla. She was admitted with a diagnosis of acute pancreatitis. Abdominal computed tomography (CT) scan showed diffusely enlarged pancreas due to infiltrative neoplasm and peripancreatic lymphadenopathy. Biopsy of the axillary mass revealed a large B-cell lymphoma. The patient was classified as stage Ⅳ, based on the Ann Arbor Classification, and as having a high-risk lymphoma, based on the International Prognostic Index. She was started on chemotherapy with CHOP (cyclophosphamide, doxorubicin, vincristine and prednisone). Within a week after chemotherapy, the patient’s abdominal pain resolved. Follow-up CT scan of the abdomen revealed a marked decrease in the size of the pancreas and peripancreatic lymphadenopathy. A literature search revealed only seven cases of primary involvement of the pancreas in B-cell lymphoma presenting as acute pancreatitis. However, only one case of secondary pancreatic involvement by B-cell lymphoma presenting as acute pancreatitis has been published. Our case appears to be the second report of such a manifestation. Both cases responded well to chemotherapy.     

Pancreatic tuberculosis in a human immunodeficiency virus positive patient：A case report

Despite the increased incidence of tuberculosis related to human immunodeficiency virus （HIV） in recent decades, pancreatic tuberculosis has rarely been described. We report a case of pancreatic tuberculosis in a 39-year- old African man who presented with progressive dysphagia, vomiting, weight loss and productive cough, accompanied by localized epigastric pain and one episode of melena. HIV-1 testing was positive and lymphocyte subset profile showed CD4 count of 9/mm3. Abdominal computed tomography （CT） scan with contrast revealed a cystic mass in the body of the pancreas, significant portal and retroperitoneal cystic adenopathy, and multiple cystic lesions in the spleen and liver. CT guided cyst aspiration and node biopsy detected Mycobacterium tuberculosis. The patient responded well on antituberculosis and antiretroviral therapy. Tuberculosis rarely involves the pancreas, probably due to the presence of pancreatic enzymes which interfere with the seeding of Mycobacterium tuberculosis. Pancreatic tuberculosis is considered to be the result of dissemination of the infection from nearby lymphatic nodes. Endoscopic ultrasound or CT guided fine needle aspiration for cytology is the recommended diagnostic technique. Although the prognosis is good with anti-tuberculosis treatment, it could be fatal without correct diagnosis and treatment. The clinician’s high index of suspicion of pancreatic tuberculosis and application of FNAB to obtain pathological evidence are extremely important to a correct diagnosis, especially in young HIV positive patients.     

Incidents and adverse events of endoscopic ultrasoundguided fine-needle aspiration for pancreatic cystic lesions

AIM To evaluate the diagnostic value and safety mainly regarding incidents of endoscopic ultrasound-guided fine-needle aspiration(EUS-FNA) for pancreatic cystic lesions(PCLs).METHODS A total of 150 consecutive patients with suspected PCLs were prospectively enrolled from April 2015 to November 2016. We finally enrolled 140 patients undergoing EUS-FNA. We compared the diagnostic accuracy of EUS-FNA and pathological diagnosis, which is regarded as the gold standard, for PCLs. Patients undergoing EUS-FNA at least 1 wk preoperatively were monitored for incidents and adverse events to evaluate its safety.RESULTS There were 88(62.9%) women and 52(37.1%) men among 140 patients, with a mean age of 50.1(± 15.4) years. There were 67 cysts located in the head/uncinate of the pancreas and 67 in the body/tail, and 6 patients had at least 1 cyst in the pancreas. There were 75 patients undergoing surgery and 55 undergoing EUS-FNA with interval at least 1 wk before other operations, with 3 patients undergoing the procedure twice. The accuracy of EUS-FNA in differentiating benign and malignant lesions was 97.3%(73/75), while the accuracy of characterizing PCL subtype was 84.0%(63/75). The incident rate was 37.9%(22/58), whereas only 1 AE was observed in 58 cases.CONCLUSION EUS-FNA is effective and safe for diagnosis of PCLs, however procedure-related incidents are common. Caution should be taken in patients undergoing EUSFNA.     

自身免疫性胰腺炎误诊误治17例临床分析

Objective To summarize the reasons of mis-diagnosis and mis-treatment of autoimmune pancreatitis (AIP). Methods Clinical data of 17 patients with AIP,who were admitted to the hospital from May 2005 to July 2010 and experienced mis-diagnosis and mis-treatment, were retrospectively analyzed. Results The main clinical manifestations included epigastric pain (13 cases),progressive obstructive jaundice (12 cases), fever (6 cases) and weight loss (9 cases). Fifteen patients had extrapancreatic organ involvemnet, including allergic rhinitis, swelling of lymphoglandulae submaxillares, swelling of submaxillary gland, allergic asthma, rheumatoid arthritis, Sjogren syndrome, diabetes mellitus, primary sclerosing cholangitis and autoimmune hepatitis. Of these 17 cases, 11 cases presented with high serum globulin, 14 cases with high serum IgG, 13 cases with high serum γ-globulin, 13 cases with positive anti-nuclear antibody and 2 cases with positive anti-insulin IgG antibody. The abdominal imaging demonstrated that 15 patients had diffuse enlargement of the pancreas with diffuse or segmental narrowing of main pancreatic duct, narrowing of the intrapancreatic common bile duct, dilation of the proximal biliary duct and gallbladder enlargement. Focal enlargement of the pancreas was found in 2 cases. Thirteen cases were misdiagnosed as pancreatic carcinoma. Among them, 4 cases underwent pancreaticoduodenectomy and 7 cases underwent choledochojejunostomy. Two cases were misdiagnosed as end stage of cancer that lost therapeutic chance. Another 4 cases were misdiagnosed as chronic pancreatitis. Steroid therapy was administered in all patients with satisfactory response. All patients were followed-up for 15 months (ranged from 6 months to 45 months), and recurrence was found in 4 cases. Satisfactory response was found in patients treated with steroid for the second time. No pancreatic cancer was found in these patients in the follow up period. Conclusion The main causes of mis-diagnosis and mis-treatment of AIP may be contributed by difficulty in differentiating AIP from pancreatic carcinoma based on clinical manifestations and inadequate knowledge of AIP as well as insufficient attention to AIP in China.     

Cross-modality PET/CT and contrast-enhanced CT imaging for pancreatic cancer

AIM:To explore the diagnostic value of the crossmodality fusion images provided by positron emission tomography/computed tomography(PET/CT) and contrast-enhanced CT(CECT) for pancreatic cancer(PC).METHODS:Data from 70 patients with pancreatic lesions who underwent CECT and PET/CT examinations at our hospital from August 2010 to October 2012were analyzed.PET/CECT for the cross-modality image fusion was obtained using Ture D software.The diagnostic efficiencies of PET/CT,CECT and PET/CECT were calculated and compared with each other using aχ2 test.P0.05 was considered to indicate statistical significance.RESULTS:Of the total 70 patients,50 had PC and 20had benign lesions.The differences in the sensitivity,negative predictive value(NPV),and accuracy between CECT and PET/CECT in detecting PC were statistically significant(P0.05 for each).In 15 of the 31patients with PC who underwent a surgical operation,peripancreatic vessel invasion was verified.The differences in the sensitivity,positive predictive value,NPV,and accuracy of CECT vs PET/CT and PET/CECT vs PET/CT in diagnosing peripancreatic vessel invasionwere statistically significant(P0.05 for each).In 19of the 31 patients with PC who underwent a surgical operation,regional lymph node metastasis was verified by postsurgical histology.There was no statistically significant difference among the three methods in detecting regional lymph node metastasis(P0.05for each).In 17 of the 50 patients with PC confirmed by histology or clinical follow-up,distant metastasis was confirmed.The differences in the sensitivity and NPV between CECT and PET/CECT in detecting distant metastasis were statistically significant(P0.05 for each).CONCLUSION:Cross-modality image fusion of PET/CT and CECT is a convenient and effective method that can be used to diagnose and stage PC,compensating for the defects of PET/CT and CECT when they are conducted individually.     

Primary pancreatic lymphoma： Report of six cases

AIM: To heighten recognition of primary pancreatic lym phoma (PPL) in clinical practice. METHODS: A retrospective review of the clinical presentation, imaging characteristics and pathological features of PPL patients were presented, as well as their diagnosis and treatment, in combination with literature review. RESULTS: Histological diagnosis was made in four patients by surgery and in two patients by EUS-FNA. The six PPL patients (5 males and 1 female; age range, 16-65 years; mean age, 46 years) had the duration of symptoms for two weeks to three months. The primary presenting symptoms, though not characteristic, were abdominal pain, abdominal masses, weight loss, jaundice, nausea and vomiting. One of the patients developed acute pancreatitis. In one patient, the level of serum CA19-9 was 76.3μg/L. Abdominal CT scan showed that three of the six tumors were located in the head of pancreas, two in the body and tail, and one throughout the pancreas. Diameter of the tumors in the pancreas in four cases was more than 6 cm, with homogeneous density and unclear borders. Enhanced CT scan showed that only the tumor edges were slightly enhanced. The pancreatic duct was irregularly narrowed in two cases whose tumors were located in the pancreatic head and body, in which endoscopic retrograde cholangiopancreatography (ERCP) showed that the proximal segment was slightly dilated. Two patients underwent Whipple operation, one patient underwent pancreatectomy, and another patient underwent operative biliary decompression. PPL was in stage I E in 2 patients and in stage II E in 4 patients according to the Ann Arbor classification system. The diagnosis of B-cell non-Hodgkin's lymphoma was made in all patients histopathologically. All six patients underwent systemic chemotherapy, one of whom was also treated with gamma radiometry. One patient died two weeks after diagnosis, two patients lost follow-up, two patients who received chemotherapy survived 49 and 37 mo, and the remaining patient is still alive 21 mo, after diagnosis and treatment. CONCLUSION: PPL is a rare form of extranodal lympho-ma originating from the pancreatic parenchyma. Clinical and imaging findings are otherwise not specific in the differentiation of pancreatic lymphoma and pancreatic cancer, which deserves attention. EUS-guided fine-needle aspiration (EUS-FNA) of the pancreas requires experienced cytopathologists as well as advanced immunohis-tochemical assays to obtain a final diagnosis on a small amount of tissue. Surgery and adjuvant chemotherapy or radiotherapy can produce fairly good outcomes.     

Tumor micrometastases in mesorectal lymph nodes and their clinical significance in patients with rectal caner

AIM:To investigate the number,size,and status of lymph nodes within the mesorectum and to explore the prognostic significance of lymph node micrometastases in patients with rectal cancer. METHODS:Thirty-one patients with rectal cancer undergone total mesorectal excision between October 2001 and October 2002 were included.Mesorectal nodes retrieved from the resected specimens were detected with a combination of haematoxylin and eosin(HE)staining and immunohistoch- emistry(IHC).The relations between lymph node metastases, micrometastases and postoperative recurrence were analyzed. RESULTS:A total of 548 lymph nodes were harvested, with 17.7±8.2 nodes per case.The average number of metastatic nodes in HE-positive patients and micrometastatic nodes in IHC-positive patients was 5.2±5.1 per case and 2.2±1.3 per case,respectively.The mean size of all nodes and metastatic nodes was 4.1±1.8 mm and 5.2±1.7 mm in diameter,respectively.The mean size of micrometastatic nodes was 3.9±1.4 mm in diameter.The size of the majority of mesorectal nodes(66.8%),metastatic nodes(52.6%),and micrometastatic nodes(79.5%)was less than 5 mm in diameter. During a median follow-up period of 24.6±4.7 too,5 patients (16.7%)had recurrence,of them 2 died and 3 survived. Another case died of tumor unrelated cause and was excluded. All 5 recurrent cases had 3 or more nodes involved,and one of them developed only lymph node micrometastases.The mean number of both metastatic and micrometastatic nodes per case differed significantly between the recurrent and non-recurrent groups(P<0.01 and P=0.01,respectively). CONCLUSION:The majority of lymph nodes,metastatic, and micrometastatic lymph nodes within the mesorectum are smaller than 5 mm in diameter.The nodal status and the number of lymph nodes involved with tumor metastases and micrometastases are related to the rapid postoperative recurrence.     

Solid-pseudopapillary tumor of the pancreas： Clinical experience and literature review

AIM: To evaluate the clinical presentations of solid-pseudopapillary tumor of the pancreas (SPT) and examine the diagnosis, treatment, low grade malignant potential of this rare disease. METHODS: We retrospectively reviewed a series of seven patients with SPT managed in our hospital between July 1990 and October 2003. Six females and one male with mean age of 31 years (range 13 to 50 years) were diagnosed with SPT at our institution. RESULTS: Clinical presentation included a palpable abdominal mass in two patients and vague abdominal discomfort in another two. Two patients were asymptomatic; their tumors were found incidentally on abdominal sonographic examination for other reasons. The final patient was admitted with hemoperitoneum secondary to tumor rupture. The mean diameter of the tumors in the seven patients was 10.5 cm (range 5 to 20 cm). The lesions were located in the body and tail in five cases and in the head of the pancreas in two. Surgical procedures included distal pancreatectomy (3), distal pancreatectomy with splenectomy (2), pancreaticoduodenectomy (1) and a pylorus-preserving Whipple procedure (1). There were gross adhesions or histological evidence of infiltration to the adjacent pancreas and/or splenic capsule in four cases. None of the patients received adjuvant therapy. The mean follow up was 7 years (range 0.5 to 14 years). One patient developed multiple liver metastases after 14 years of follow up. CONCLUSION: SPT is a rare tumor that behaves less aggressively than other pancreatic tumor. However, in cases with local invasion, long-term follow up is advisable.     

Diagnosis and management of autoimmune pancreatitis： Experience from China

AIM： To determine the clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities in patients with autoimmune pancreatitis （AIP）. METHODS： In this retrospective study, the data of patients with diagnosed chronic pancreatitis （CP） between 1995 and 2006 in Chinese PLA General Hospital were included to screen for the cases with AIP, according to the following diagnostic criteria： （1） diagnostic histopathologic features, and abound IgG4-positive plasma cells on pancreatic tissues; （2） characteristic imaging on computed tomography and pancreatography, together with increased serum IgG, y-globulin levels or presence of autoantibodies; （3） response to steroid therapy. The clinical, radiographic and pathologic characteristics, diagnostic and treatment modalities, and outcome of AIP cases were reviewed. RESULTS： Twenty-five （22 male, 3 female; mean age 54 years, 36-76 years） out of 510 CP patients were diagnosed as AIP, which accounted for 49% （21/43） of CP population undergoing surgical treatment in the same period. The main clinical manifestations included intermittent or progressive jaundice in 18 cases （72%）, abdominal pain in 11 （44%）, weight loss in 10 （40%）, and 3 cases had no symptoms. The imaging features consisted of pancreatic enlargement, especially in the head of pancreas （18 cases）, strictures of main pancreatic duct and intrapancreatic bile duct. Massive lymphocytes and plasma cells infiltration in pancreatic tissues were showed on pathology, as well as parenchymal fibrosis. Twenty-three patients were misdiagnosed as pancreaticobiliary malignancy, and 21 patients underwent exploratory laparotomy, theremaining 4 patients dramatically responded to steroid therapy. No pancreatic cancer occurred during a mean 46-mo follow-up period. CONCLUSION： AIP patients always are subjected to mistaken diagnosis of pancreatic cancer and an unnecessary surgical exploration, due to its similarity in clinical features with pancreatic cancer. T     

Helicobacter species ribosomal DNA in the pancreas, stomach and duodenum of pancreatic cancer patients

AIM: To determine whether gastric and enteric Helicobacter species are associated with pancreatic cancer. METHODS: Patients with exocrine pancreatic cancer (n = 40), neuroendocrine cancer (n=14), multiple endocrine neoplasia type 1 {n = 8), and chronic pancreatitis (n = 5) were studied. Other benign pancreatic diseases (n = 10) and specimens of normal pancreas (n=7) were included as controls. Pancreatic tissue specimens were analyzed by He/icobacter-specific PCR-assay and products were characterized by denaturing gradient electrophoresis and DNA-sequencing. From a subset of the pancreatic cancer patients, gastric and/or duodenal tissue as well as gallbladder and ductus choledochus tissue were analyzed. Gallbladder and choledochus samples were included as controls. Stomach and duodenum samples were investigated to analyze whether a gastric helicobacter might disseminate to the pancreas in pancreatic cancer patients. Pancreatic specimens were analyzed by Bacteroides-specific PCR for detecting the translocation of indigenous gut microbes to the diseased pancreas. RESULTS: Helicobacter DNA was detected in pancreas (tumor and/or surrounding tissue) of 75% of patients with exocrine cancer, 57% of patients with neuroendocrine cancer, 38% of patients with multiple endocrine neoplasia, and 60% of patients with chronic pancreatitis. All samples from other benign pancreatic diseases and normal pancreas were negative. Thirty-three percent of the patients were helicobacter-positive in gastroduodenal specimens. Surprisingly, H. bilis was identified in 60% of the positive gastro-duodenal samples. All gallbladder and ductus cho-ledochus specimens were negative for helicobacter. Bacteroides PCR-assay was negative for all pancreatic samples. CONCLUSION: Helicobacter DNA commonly detected in pancreatic cancer suggests a possible role of the emerging pathogens in the development of chronic pancreatitis and pancreatic cancer.     

Susceptibility pattern and epidemiology of Mycobacterium tuberculosis in a Saudi Arabian hospital: a 15-year study from 1989 to 2003

OBJECTIVES: The objective of this study was to examine the prevalence and trends of drug resistance of Mycobacterium tuberculosis at the Saudi Aramco Medical Services Organization. METHODS: We retrospectively identified M tuberculosis isolates from January 1989 to December 2003. Antimicrobial susceptibility and clinical data were collected and analyzed. RESULTS: From 1989 to 2003, 276 nonrepetitive culture-positive cases were identified. There were 236 Saudis (84.6%), and the remainder were non-Saudis (15.4%). M tuberculosis isolates were obtained from pulmonary specimens (49%) and extrapulmonary sites (51%). The resistance rates of M tuberculosis to tested first-line agents were as follows: isoniazid, 12.5%; ethambutol, 7.5%; streptomycin; 6.9%; and rifampin, 1.1%. The resistance rate to isoniazid and streptomycin was 1.8%, the rate to isoniazid and rifampin was 0.7%, and the rate to isoniazid and ethambutol was 2.5%. The resistance rate to isoniazid, ethambutol, and streptomycin was 0.7% CONCLUSION: M tuberculosis resistance to isoniazid showed a decreased rate over the study period from 20 to 5.7%. The rate of multidrug-resistant M tuberculosis remained low.     

134例老年肺结核患者痰结核菌耐药情况分析

目的探讨老年肺结核患者痰结核菌的耐药情况。方法采用ＢＡＣＴＥＣ法对１３４例老年痰菌阳性肺结核患者痰结核分支杆菌做耐药性检测。结果老年肺结核患者初始耐药率为３６８％，显著低于获得性耐药率的７５９％（Ｐ＜００１）；耐异烟肼（ＩＮＨ，Ｈ）、利福平（ＲＦＰ，Ｒ）、链霉素（ＳＭ，Ｓ）前者亦明显低于后者（Ｐ＜００１）。初治组耐２和３种药比例为６６％和５３％，与复治组的２２４％和２７７％相比差异有显著性（Ｐ＜００１）。至少耐异烟肼和利福平两种药的比例，初治组为９２％，显著低于复治组的５００％（Ｐ＜００１）。结论老年人肺结核耐药情况严重，尤其是获得性耐药和耐多药比例偏高，应引起足够重视     

Evidence of 'amplifier effect' in pulmonary multidrug-resistant tuberculosis: report of three cases.

INTRODUCTION: A cluster of three related cases of tuberculosis (TB) with primary multidrug resistance was investigated at the Centre Hospitalier Universitaire of Kigali (CHUK) in Rwanda. The patients were HIV-1/2 seronegative. Patients 1 and 2 were hospitalized in the same room of CHUK for one month. Patient 3 was a younger sibling of patient 2. METHODS: Drug susceptibility of two consecutive Mycobacterium tuberculosis isolates from each patient was tested by the BACTEC 460 radiometric method. DNA fingerprinting was performed using spoligotyping and mycobacterial interspersed repetitive units of variable numbers of tandem repeats (MIRU-VNTR) analysis. All patients initially received the World Health Organization category I regimen. RESULTS: The isolates collected during the first TB episode were resistant to isoniazid, rifampin and ethambutol. After subsequent retreatment regimens with rifampin, isoniazid, streptomycin, pyrazinamide (8 months) and rifampin, isoniazid, streptomycin, pyrazinamide, ciprofloxacin (21 months), patients 1 and 2 developed additional resistance to streptomycin and quinolones. Patient 3 received only the category I regimen and consecutive isolates retained the initial drug susceptibility pattern. All isolates were genetically indistinguishable by spoligotyping and MIRU-VNTR, indicating the same origin. CONCLUSIONS: These observations highlight the risk of nosocomial transmission of multidrug-resistant (MDR) TB and the possible selection of secondary resistance to second-line drugs if a single new drug is added at the time of retreatment of MDR TB patients.     

Influence of initial drug resistance on the response to short-course chemotherapy of pulmonary tuberculosis

The response to short-course chemotherapy of patients with pulmonary tuberculosis caused by drug-resistant Mycobacterium tuberculosis was examined in 12 controlled trials carried out during the past decade in Africa, Hong Kong, and Singapore. Among those with initial resistance to isoniazid and/or streptomycin, failures during chemotherapy were encountered in 17% of 23 patients given a 6-month regimen of isoniazid and rifampin and in 12% of 264 patients given rifampin only in an initial 2-month intensive phase of their regimen. The proportion of failures fell as the number of drugs in the regimen and the duration of treatment with rifampin were increased, to reach 2% of 246 patients receiving 4 or 5 drugs including rifampin in 6-month regimens. The sterilizing activity of the regimens, whether these included rifampin or pyrazinamide, was little influenced by initial resistance, because the sputum conversion rate at 2 months was similar to that in patients with initially sensitive bacilli, and the relapse rates after chemotherapy were only a little higher. The response in the 11 patients with initial rifampin resistance was, however, much less good, failure during chemotherapy occurring in 5 and relapse afterwards in a further 3 patients. This review demonstrates the value of rifampin in preventing failure caused by the emergence of resistance during treatment and the greater sterilizing activity of rifampin and pyrazinamide compared with that of isoniazid and streptomycin.     

Endoscopic ultrasound-guided fine-needle aspiration for the diagnosis of peripancreatic tuberculous lymphadenitis

The percentage of patients with atypical extrapulmonary forms of tuberculosis has been increasing. Among extrapulmonary tuberculosis cases, tuberculosis of the pancreas and peripancreatic lymph nodes is a rare clinical entity. Here, we present a case of peripancreatic tuberculous lymphadenitis diagnosed by endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) both cytologically and microbiologically. A 23-year-old man had a 1-week history of epigastralgia and low-grade fever. Subsequently, he was found to have an abnormality on abdominal ultrasound. A computed tomography scan of the abdomen showed a solitary mass consisting of multiple cystic components with rim enhancement in the peripancreatic portion contiguous to the gall bladder. Endoscopic ultrasound-guided fine-needle aspiration was performed to confirm the diagnosis. The cytological examination revealed epithelioid cells with caseous necrosis, indicating tuberculosis. The aspirated fluid was positive by polymerase chain reaction (PCR) analysis and culture for Mycobacterium tuberculosis. Antituberculosis therapy with isoniazid, rifampicin, ethambutol, and pyrazinamide was started based on the PCR and cytology results, and a good response to the treatment was noted. Endoscopic ultrasound-guided fine-needle aspiration cytology with PCR analysis is very useful for the diagnosis of peripancreatic tuberculosis.     

A 62-dose, 6-month therapy for pulmonary and extrapulmonary tuberculosis. A twice-weekly, directly observed, and cost-effective regimen

STUDY OBJECTIVE: To evaluate the efficacy and toxicity of a 62-dose, four-drug, 6-month, and directly observed regimen for treatment of pulmonary and extrapulmonary tuberculosis. DESIGN: An open, nonblinded clinical trial, with intended follow-up of patients for 36 months after the completion of therapy. SETTING: A metropolitan tuberculosis clinic in a public health department. PATIENTS: From March 1981 through April 1989, we enrolled 160 patients with suspected or known tuberculosis; 35 of these patients were excluded from the analysis. INTERVENTIONS: Isoniazid, rifampin, pyrazinamide, and streptomycin were administered daily for 2 weeks; these drugs were then given in higher doses twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 6 weeks, followed by isoniazid and rifampin twice weekly for 18 weeks. A total of 62 doses were administered, and all therapy was directly observed by a nurse or an outreach worker. MEASUREMENTS AND MAIN RESULTS: Of the 125 evaluable patients, 101 (81%) had pulmonary tuberculosis, 7 (6%) had both pulmonary and extrapulmonary involvement, and 17 (13%) had extrapulmonary disease only. Seventy-one (57%) patients had a history of recent alcoholism. There were two relapses (1.6% +/- 2.2%), occurring 6 and 56 months after the completion of therapy. The time at which sputum samples became culture negative in pulmonary patients ranged from 1 to 19 weeks (median, 4.6 weeks); 40% +/- 9.6% of patients were culture-negative after 4 weeks of therapy, 75% +/- 8.5% after 8 weeks, 94% +/- 4.7% after 12 weeks, 97% +/- 3.3% after 16 weeks, and 100% after 20 weeks. Adverse drug reactions included hyperuricemia (greater than 178 mumol/L [3 mg/dL] above normal) secondary to pyrazinamide in 80 patients (64%), twofold or greater elevations of aspartate aminotransferase in 21 patients (17%), 1.5-fold or greater elevations of alkaline phosphatase in 33 patients (27%), cutaneous abnormalities in 8 patients (6%), nausea in five patients (4%), and dizziness in 1 patient (1%). CONCLUSIONS: This 62-dose, largely twice-weekly tuberculosis treatment regimen is efficacious and relatively nontoxic and is especially useful for patients in whom directly observed therapy is indicated.     

Short course intermittent chemotherapy in childhood tuberculosis

Summary A total of 130 children diagnosed as having pulmonary and extrapulmonary tuberculosis who received short course intermittent chemotherapy between 1978–1992 were evaluated retrospectively. One hundred and ten children with tuberculosis were treated with isoniazid (10–15 mg/kg, maximum 400 mg), rifampin (10–15 mg/kg, maximum 600 mg), and streptomycin (30 mg/kg, maximum 1 g) daily, for 15 days. Treatment was completed with similar doses of isoniazid and rifampin twice a week for a period of 9 months. Since 1986, 20 children with tuberculosis were being treated with the same regimen but without streptomycin. The majority of patients in these cases had pulmonary tuberculosis (75%), followed by lymph nodes (9%), pleural (7%), bone and joint (5%), miliary (3%), and abdominal tuberculosis (1%). The clinicoradiologic response to treatment was observed to be excellent. Only one case of relapse was detected, which was the case of a patient with lymph node tuberculosis that occurred 18 months after the completion of treatment. No serious adverse drug reaction was observed in any of the cases mentioned. In conclusion, short-course low-dose intermittent chemotherapy is an effective and economical treatment with minimal side effects for pulmonary and extrapulmonary tuberculosis in childhood.

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Intermittierende Kurzzeit-Chemotherapie bei Tuberkulose im Kindesalter

Zusammenfassung Zwischen 1978 und 1986 wurden in der Abteilung für Pneumologie im Kinderkrankenhaus Hacettepe 110 Patienten mit Tuberkulose 2 Wochen lang täglich mit Isoniazid (10–15 mg/kg, Maximum 400 mg/d), Rifampicin (10–15 mg/kg, Maximum 600 mg/d) und Streptomycin (30 mg/kg, Maximum 1 g/d) behandelt. Danach wurde die Therapie mit Isoniazid und Rifampicin zweimal wöchentlich in der gleichen Dosierung für insgesamt 9 Monate weitergeführt. Ab 1986 wurden 20 Patienten diesmal ohne Streptomycin also nur mit Isoniazid und Rifampicin in der gleichen Weise behandelt. Die Mehrzahl der Patienten hatte Lungentuberkulose (75%), außerdem lagen in 9% der Fälle Lymphknoten-, 7% Pleura-, 5% Gelenk- und Knochentuberkulosen, 3% miliäre und 1% abdominale Tuberkulosen vor. Bei allen Patienten war die Behandlung erfolgreich. Bei der Langzeit-Beobachtung wurde bei einem Patienten mit Lymphknotentuberkulose ein Rückfall festgestellt. Außer einem vorübergehenden Transaminasenanstieg bei einem Patienten wurden keine Nebenwirkungen beobachtet. Die kurzfristige, niedrig dosierte Intermittierende Therapie wird als eine ökonomische Therapie, mit geringen Nebenwirkungen für verschiedene Formen pulmonaler und extrapulmonaler Tuberkulose im Kindesalter vorgeschlagen.

     

Low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid and rifapentine

To understand why once-weekly isoniazid/rifapentine therapy for tuberculosis was less effective than twice-weekly isoniazid/rifampin, we studied human immunodeficiency virus-seronegative patients with either failure (n = 4), relapse (n = 35), or cure (n = 94), recruited from a comparative treatment trial. In multivariate analyses that were adjusted for severity of disease, low plasma concentrations of isoniazid were associated with failure/relapse with once-weekly isoniazid/rifapentine (median isoniazid area under the concentration-time curve for 12 hours after the dose [AUC(0-12)] was 36 microg x hour/ml in failure/relapse versus 56 microg x hour/ml in control cases p = 0.005), but not with twice-weekly isoniazid/rifampin. Furthermore, two patients who relapsed with Mycobacterium tuberculosis monoresistant to rifamycin had very low concentrations of isoniazid. Finally, isoniazid acetylator status determined by N-acetyltransferase type 2 genotype was associated with outcome with once-weekly isoniazid/rifapentine (p = 0.03) but not twice-weekly isoniazid/rifampin. No rifamycin pharmacokinetic parameter was consistently and significantly associated with outcome (p > 0.10). Because low isoniazid concentrations were associated with failure/relapse, a drug with consistently greater area under the concentration-time curve than isoniazid may be needed to achieve highly active once-weekly therapy with rifapentine.     

Utilization of antituberculosis drugs expressed in defined daily doses in Klenovnik Hospital in the period between 1983 and 1987

In this paper the utilization of antituberculosis drugs was analyzed in defined daily doses per 1000 bed-days (DDD/1000 BD) in the Hospital for Pulmonary Diseases and Tuberculosis, Klenovnik, from 1983 to 1987. The utilization of these drugs increased from 894 DDD/1000 BD in 1983 to 1112 DDD/1000 BD in 1984, and then decreased to 1077 DDD/1000 BD in 1986; but in 1987 it again increased to 1270 DDD/1000 BD. During the research period the following drugs were prescribed: ethambutol, rifampin, pyrazinamide, streptomycin, isoniazid, and two combinations of drugs: a combination of isoniazid with pyridoxine and a combination of ethambutol, isoniazid and pyridoxine. For the whole of that period the use of ethambutol, isoniazid with pyridoxine and rifampin made up more than 85% of the general utilization of antituberculosis drugs, while other drugs were prescribed in lesser quantities. The data presented indicate that tuberculosis in Klenovnik hospital was in most cases treated with ethambutol, the combination of isoniazid with pyridoxine, and rifampin.     

新疆喀什地区1307例肺结核患者行利福平和异烟肼耐药性检测的结果分析

目的 分析新疆维吾尔自治区喀什地区结核病患者行利福平和异烟肼耐药性检测的结果。 方法 搜集2019年1月1日至6月30日喀什地区11个市(县)根据《WS 288—2017 肺结核诊断》确诊的1307例患者的痰培养标本及患者信息,利用结核分枝杆菌利福平耐药突变检测试剂盒和结核分枝杆菌异烟肼耐药突变检测试剂盒对利福平和异烟肼进行耐药性检测,对不同年龄组、不同性别、不同治疗史、不同地区患者对两种药品的耐药情况进行统计分析。计数资料组间比较采用χ²检验,以P<0.05为差异有统计学意义。 结果 在1307例患者中,利福平耐药198例,耐药率为15.15%;异烟肼耐药151例,耐药率为11.55%;耐多药63例,耐多药率为4.82%。男性与女性患者利福平耐药率[15.71%(110/700)和14.57%(88/604)]、异烟肼耐药率[10.71%(75/700)和12.42%(75/604)]和耐多药率[4.57%(32/700)和5.13%(31/604)]差异均无统计学意义(χ²=0.330,P=0.566;χ²=0.924,P=0.337;χ²=0.222,P=0.638)。初治和复治患者利福平耐药率[15.46%(160/1035)和16.32%(31/190)]、异烟肼耐药率[11.30%(117/1035)和14.74%(28/190)]和耐多药率[4.73%(49/1035)和6.32%(12/190)]差异均无统计学意义(χ²=0.090,P=0.765;χ²=1.812,P=0.178;χ²=0.849,P=0.357)。60~70岁年龄组耐多药率最高(6.12%,21/343);30~40岁年龄组对利福平和异烟肼耐药率均最高,分别为21.32%(29/136)和14.71%(20/136)。喀什地区11个市(县)中,喀什市耐多药率(10.59%,9/85)、利福平耐药率(25.88%,22/85)和异烟肼耐药率(28.24%,24/85)均为最高。 结论 喀什地区耐药结核病状况较为严重,应加强耐药性筛查力度,及时发现耐药结核病患者,并制订有效的化疗方案。