Drug-resistant pulmonary tuberculosis in a tertiary referral hospital in Korea

OBJECTIVES: To estimate the resistance rate and to correlate the clinical characteristics of resistant tuberculosis with the patients of pulmonary tuberculosis who were referred to the university hospital. METHODS: We prospectively performed sensitivity tests for all patients who were diagnosed as active tuberculosis by sputum smear or sputum culture from January, 1995 to June, 1996. Patients profile, previous treatment history, patterns of drug resistance, initial chest films and other clinical findings were analysed. RESULTS: Overall, 24(26.0%) of the 92 patients had resistance to at least one drug and 8(8.6%) had resistance to isoniazid(INH) and rifampin(RFP). Among the 66 patients without previous tuberculosis therapy, 11(16.6%) were drug-resistant and 2(3.0%) were multi-drug resistant. Among the 26 patients with previous therapy, 13(50.0%) were drug-resistant and 6(23.0%) were multi-drug resistant. For all 92, resistance to INH was most common (19.5%), followed by RFP (9.7%) and ethambutol (9.7%). Drug resistance was significantly high in previously treated patients and in cavity-positive patients. Treatment failure was also high in previously treated patients with resistant tuberculosis. In patients with primary resistance, treatment failure was not observed. CONCLUSION: Sensitivity tests are strongly recommended in all culture positive patients with previous therapy but, in patients with primary resistance, sensitivity tests are not required. Proper combination chemotherapy should be given under careful surveillance.

Prospective Study for Treatment Method of Cervical Tuberculous Lymphadenitis / 결핵

BACKGROUND: Tuberculous cervical lymphadenitis is one of the common causes of cervical mass in adult (espe cially in woman) in korea. Sometimes it appears to be difficult in defining the role of surgery and duration of antituberculous chemotherapy. METHOD: To clarify the proper duration and/or combination of regimens, we analyzed the clinical data of 31 patient with cervical lymphadenitis diagnosed at Chungnam National University Hospital from March 1996 to December 1996 and all patients were prospectively randomized into two groups(2HREZ/4HRE and 6HREZ) by treatment method. RESULT: Prevalent age, male to female ratio, association with pulmonary tuberculosis and history of previous antituberculous medication were not statiscally different between two groups. The average size of the largest lymph node before teatment was 2.43+/-0.98cm and 3.15+/-1.74cm, respectively and was 0.63cm and 0.6cm after treatment, respectively. In both groups, 2 patients have engrowing node or not changed node during tratment and no recurrence was found during follow up period upto 12 months. In both groups, no significant side reaction resulting in discotinuation or changing the regimens was noticed. CONCLUSION: Short course antituberculosis therapy(2HREZ/4HRE) could be recommanded as effective standard therapy for superficial lymph node tuberculosis. Longterm follow up at least 36 months to observe recurrence might be needed to confirm this conclusion.

A Clinical Study on Tuberculous Cervical Lymphadenitis / 대한내과학회지

OBJECTIVES: Tuberculous cervical lymphadenitis is one of the common cause of cervical mass in young adult in Korea. Sometimes it appears to be difficult in defining the role of surgery and duration of antituberculous treatment. To clarify the duration of medical treatment and to define the cause of prolonged treatment duration METHODS: we analyzed the clinical data of 62 patients with tuberculous cervical lymphadenitis diagnosed at the Chungnam National University Hospital from Jan. 1994 to July 1996 and all patients were divided into two groups (standard and prolonged) by treatment duration. RESULTS: The most prevalent age group was 20 to 39 years old (67%) and male to female ratio was 1:2.6. The most common physical finding was painless swelling on neck, standard group was 52%, prolonged group was 42%. The average size of lymph node was 2.7cm and 3.2cm, respectively (p<0.05). In prolonged group, incidence of associated pulmonary tuberculosis and previous antituberculous treatment history were higher than that in standard group (27%, 35% respectively). The most common affected site was right side of neck , whereas 19% of prolonged regimen group were involved in both side of neck. Bacteriological study from node aspirates showed relatively higher positivity in prolonged group (27%) than in standarded group (5%). The causes of prolonged treatment were increased mass(27%) or remnant mass(23%) and the develoment of new node formation and existing nodes after completion of treatment were found in both groups(10% of standard group , 19% of prolonged group). CONCLUSION: A new, prospective trial for proper regimens or duration of antituberculosis treatment is strongly needed.

Delayed Diagnosis of Primary Lung Cancer / 결핵

BACKGROUND: Lung cancer is an important public health problem because of rapidly increasing malignancy in both sexes in relation with high smoking rate in Korea. Despite advances in therapeutic modalities and supportive cares, 5-year survival rate has improved only marginally during the past 2 decades. Therefore, the early detection of lung cancer is strongly needed for batter prognosis and we conducted this study to review the clinical factors resulting in delayed diagnosis of lung cancer. METHOD: The clinical data such as presenting symptoms duration for diagnosis disease entities causing misdiagnosis or delayed diagnosis, were analyzed retrospectively in 154 patients with primary lung cancer diagnosed at Chungnam National university hospital from January to December in 1995. RESULTS: 63 patients(40.9%) out of 154 patients were delayed diagnosed with the duration of 6.3 months compared with 3.6 months in patients diagnosed without delay. In delayed diagnosed group, Cough & sputum and dyspnea as presenting symptom were more critical than hemoptysis and chest pain, and doctor's delay was more critical than patient's delay. Tuberculosis(30/63) was most frequent disease entity causing delayed diagnosis, followed by pneumonia(9/63), COPD(6/63), heart diseases(5/63), etc.. CONCLUISON: It should be emphasized that any respiratory symptom be checked with chest X-ray to differentiate lung cancer and periodic check of chest X-ray be also needed for the longterm patients with any disease, especially with high risk group.

Immunohistochemical Detection of p53, erbB-2 and CEA Oncoprotein in Lung Cancer Clinical Correlations / 결핵

BACKGROUND: The prognosis of patients with lung cancer is still poor. Lung cancer exhibits a variable clinical outcome, even in those patients with same stage Numerous reports suggest that oncogene expression night play a role in explaining the variability of response and survival But many of these reports are still under debete. So we studied the clinical relevance of oncogene expression in Korean lung cancer patients. lmmunohistochemistry of p53, erbB-2, CEA expression was performed. METHOD: From March, 1992 until March, 1997, 120 patients with lung cancer were reviewed. p53, erbB-2, and CEA expression were detected on paraffin-embedded tumor blocks with the use of monoclonal antibodies. The survival arid response has correlated with the expressibility of p53, erbE-2, arid CEA oncoprotein. RESULTS: Overall, the expression rates of p53 erbB-2, and CEA were 33.7%, 59.3%, and 32.6% respectively. Expression rates were not con-elated to cell type or stage. Compared with response to chemotherapy, no correlation was found. The expression of p53, erbB-2, or CEA was not correlated with 2-year survival. With simultaneous applications of p53. erbB-2, and CEA, patients with 2 or more expressions also did not show poor response to chemotherapy. CONCLUISON: We conclude the p53, erbB-2, and CEA expression are clinically less useful in predicting response to chemotherapy or survival.

The Study of Combined Treatment in Locally Advanced Non - Small Cell Lung Cancer / 대한내과학회지

BACKGROUND: The majority of patients with locally advanced, unresectable, non-small cell lung cancer(NSCLC) were treated with conventional thoracic radiation therapy Throcic radiation therapy produces tumor regression in most patients but few cures and dismal 5-year survival rate. Several randomized studies have demonstrated that systemic chemotherapy controls micrometastasis and improve survival ratNes for patients who have locally advanced NSCI.C. Hut the optimal frequency of chemotherapy and sequence for chemotherapy and radiotherapy are yet to be determined. In this study, we analyzed response rate, median survival time, side effects and prognostic variables according to the frequency of chemotheray in locally advanced NSCLC patients. METHODS: We separated locally advanced, unresectable, NSCLC patients into two groups according to given number of chemotherapy cycles. Among 28 patients evaluated, eleven patients were classified to group A, receiving above 3 cycled chemotherapy and seventeen patients, classified to group B, receiving 3 cycled chemotherapy. In both groups, thoracic irradiation of 5940 cGy was given to all patients after chemotherapy. RESULTS: 1) Median survival time was 12.9 months for group A, 12.8 months for group B but there was no statistically significant difference(P>0.05), 2) Overall response rates were not significantly different between two groups(P>0.05). 3) Frequency rate of local failure and distant metastasis were not significantly different between two groups (P>0.05). 4) The grade and frequency of toxicities during treatment were not significantly different between two groups (P>0.05). 5) Clinical stage was the only major prognostic factor for overall survival (P<0.05). CONCLUSION: Median survival time, response rate, toxicities and frequency of local failure and distant metastasis were not significantly different between two groups. So, when we treat locally advanced, unresectable, NSCLC patients in sequential combined treatement, we should consider planned therapy(limiting chemotherapy cycles given), because planned therapy reduces many troubles of patients, that is, economic loss and time consuming, psychiatric anxiety etc, during treatment period. The optimal frequency of chemotherapy is remained to be validated in large scale study in the future in the setting of combined treatment.

The effects according to the timing of thoracic radiotherapyin limited stage small cell lung cancer / 결핵

Background: Combination chemotherapy is now considered to be the cornerstone of small cell lung cancer (SCLC). management but the optimal management of limited SCLC is not well defined. The role of thoracic radiotherapy (TRT) is less well established. Recent meta-analyses reports revealed that TRT combined with chemotherapy produce "good" local control and prolonged survival. But other reports that survival was not changed. The timing, dose, volume and fractionation for TRT with the combined chemotherapy of SCLC remains unsettled. In this study, we analyzed the effects according to the timing of thoracic radiotherapy in limited SCLC. Method: All fifty one patients received cytoxan, adriamycin and vincristine(CAV) alternating with etoposide and cisplatin(VPP) every 3 weeks for 6 cycles were randomized prospectively into two groups: concurrent and sequential. 27 patients received 4500cGy in 30 fractions(twice daily 150cGy fractional dose) over 3 weeks to the primary site concurrent with the first cycle of VPP(concurrent gorup). 24 patients received 4000 to 5000cGy over 5 or 6 weeks after completion of sixth cycles of chemotherapy(sequential group). Results: 1. Response rates and response duration: Response rates were not significantly different between two groups(p=0.13). But response duration was superior in the concurrent group(p=0.03). 2. Survival duration was not different between two groups(p=0.33). 3. Local control rate was superior in the concurrent group(p=0.00). 4. Side effects and toxicities: Hematologic toxicides, especially leukopenia, infection and frequency of radiation esophagitis were higher in the concurrent group(p=0.00, 0.03, 0.03). Conclusion: The concurrent use of TRT with chemotherapy failed to improve the survival of limited stage SCLC patients compared with the sequential use of TRT but response duration and local control rate were superior in the concurrent group. Frequency of radiation esophagitis, life threatening hematologic toxicities and infection were more frequent in the concurrent group than sequential group. So, the selection of an optimal schedule of chemotherapy combined with TRT that would lead to a major increase in survival with minimal toxicity is remained to be validated in large scale study in the future.

Endobronchial Tuberculosis in Patients with Pulmonary Tuberculosis / 결핵

BACKGROUND: Known as a kind of complication or a specific form of pulmonary tuberculosis, endobronchial tuberculosis caused several kinds of problems in diagnosis and managements. But the frequency of this disease are is widely variable, generally reported from as low as 10 - 20% to as high as 40 - 50%. We prospectively performed bronchoscopy in patients diagnosed as pulmonary tuberculosis to evaluate the frequency of endobronchial tuberculosis and its related findings. METHOD: From March, 1995 to February, 1996, we prospectively performed bronchoscopy in patients newly diagnosed as pulmonary tuberculosis and evaluated the frequency of endobronchial tuberculosis, its clinical features and laboratory findings including raiologic, microbiologic and physiologic aspects. RESULTS: Number of patients diagnosed as pulmonary tuberculosis was 103 and 55 patients(53.4%) were found to have endobronchial tuberculosis. But the frequency were 43.8% in male and 76.7% in female, respectively. Frequently noted symtoms were nonspecific including cough, sputum, fever, weight loss in the order of frequency but cough was more frequent than in pulmonary tuberculosis. Physical examination showed rale,decreased breathing sound and wheezing and wheezing was more frequent than in pulmonary tuberculosis. All 7 subtypes were noted bronchoscopically and edema-hyperemia (stenotic without fibrosis) type was most frequently(32.7%) noted, and followed by chronic nonspecific bronchitis type stenotic with fibrosis type and actively caseating type in the order of frequency. The relationship between subtypes of endobronchial tuberculosis and radiologic findings was insignificant. Right lung was involved more frequently than left lung and left upper lobe was most commonly involved site, and followed by right upper lobe and trachea. Acid-fast bacilli(AFB) positivity in sputum and / or bronchial washing fluid was 73% and suggested high risk of infectivity. CONCLUSION: The frequency of endobronchial tuberculosis in patients with pulmonary tuberculosis was higher than known and also suggested bronchoscopic examination to detect endobronchial involvement should be recommanded and careful management is also needed to prevent complications.

Comparison of Single vs Combined Modality Treatment inLocally Advanced Non-Small Cell Lung Cancer / 결핵

BACKGROUND: One quarter to one third of patients with NSCLC present with primary tumors that although confined to the thorax are too extensive for surgical resection. Until resently standard treatment for these patients had been thoracic radiation, which produces tumor regression in most patients but few cures and dismal 5-year survival rate. The fact that death for most patients with stage III tumors is caused by distant metastases has promped a reevaluation of combined modality treatment approaches that include systemic chemotherapy. Therefore, we report the results observed in a study to evaluate the effect of multimodality treatment in locally advanced non-small cell lung cancer from 1/91 to 8/93 in CNUH. METHOD: We grouped the patients according to the treatment modalities and evaluated response rate, median survival and the effect of prognostic variables. Among 67 patients evaluated, twenty seven patients classified with group A, received cisplatin and etoposide containing combination chemotherapy alone, eighteen patients, classified with group B, received chemotherapy and radiotherapy, fifteen patients, group C, received neoadjuvant or adjuvant chemotherapy and surgery with/without radiation therapy, seven patients, group D, received only supportive care. RESULT: The major response rate for group A and B was 37% and 61% respectively. There was no statistically significant difference in response rate between A and B groups(p=0.97). The analysis of prognostic factors showed that differences of age, sex, pathology, blood type, smoking year, stage and ECOG performance did not related to improvement in survival. Median survival time was 8.6 months for group A, 13.4 months for group B, 19.2 months for group C, and 5.4 months for group D, respectively and there was statistically significant difference(p=0.003), suggesting that multimodality therapy was associated with signigicant improvement in survival. Subset survival analysis showed a significant therapeutic effect for earlier stage and good performance state(p=0.007, 0.009, respectively). A possible survival advantages were observed for major response groups. CONCLUSION: It was suggested that multimodality therapy for the management of patients who had stage III disease, has yielded good median survival and long survival for seleted patients. But, it is necessory to validate above result with further investigation in large scale and in prospective randomized trials.