Cost-effectiveness of primary prophylaxis of febrile neutropenia with pegfilgrastim in docetaxel, cisplatin and 5-fluorouracil therapy for esophageal cancer.

Objective: The efficacy of docetaxel, cisplatin, and 5-fluorouracil (DCF) therapy in treating esophageal cancer has been reported. However, febrile neutropenia (FN) is a potentially serious adverse event of DCF therapy with an incidence of 10 to 40%. Pegfilgrastim, a granulocyte colony-stimulating factor (G-CSF), has been shown to have a primary prophylactic role in FN. However, it has been suggested that excessive use of expensive G-CSF should be avoided. Therefore, we performed a cost-utility analysis of primary prophylaxis with pegfilgrastim. Design: Cost-effectiveness analysis using decision tree modelling. Methods: We used a decision tree analysis model based on the report of primary prophylaxis with pegfilgrastim. Based on a previous study, the FN incidence rate was set at 40.0% (95% confidence interval (CI): 11.9-68.1) for the pegfilgrastim group and 43.5% (95%CI: 21.6-65.4) for the no pegfilgrastim group. The FN treatment cost was US$726.63, and the duration of FN was 3.65±1.20 days. The utility value of patients who received DCF therapy was 0.643, and the change in utility value at FN onset was -0.15. Expected cost, quality-adjusted life year (QALY), and incremental cost-effectiveness ratio (ICER) were calculated, and cost-utility analysis was performed. Results: The ICER of pegfilgrastim was 184,976.75 USD/QALY. As a result of sensitivity analysis, the utility of FN had the greatest impact on the cost-effectiveness analysis, followed by the drug cost of pegfilgrastim. Conclusion: Primary prophylaxis of FN with pegfilgrastim might not be cost-effectiveness. In determining whether to administer pegfilgrastim it is necessary to consider patient factors, not just the incidence of FN.

Intraoperative radiotherapy for esophageal carcinoma--significance of IORT dose for the incidence of fatal tracheal complication.

PURPOSE: The feasibility of intraoperative radiotherapy (IORT) combined with modified regional lymphatic dissection (plus esophagectomy) for advanced esophageal carcinoma was tested. The quality of life in the patients was expected to improve by modified surgery, securing a good local control by additional IORT. METHODS AND MATERIALS: Total esophagectomy plus modified three-regional lymphatic dissection with upper mediastinal IORT followed by postoperative external beam irradiation was systematically given to 62 patients between August 1989 and June 1992. Sixty-five percent of the patients were age over 60, and 76% (47/62) of the patients were Stage III or IV by pTNM. Several techniques for the IORT were developed and used throughout this period, including a temporary collapse of the right lung by unilateral tracheal incubation (for the insertion of IORT applicator) and an in vivo dosimetry to know the appropriate range (energy) of electron beam. The method of surgical treatment, the dose of external beam irradiation were kept standardized, and only the dose of IORT was randomized either to 20 or 25 Gy. IORT-related complications and the pattern of failures were carefully monitored. RESULTS: (a) Most prominent IORT-related complication was the late tracheal damage, which occurred 6 of 44 patients who were at risk for more than a year. (b) The incidence of IORT-induced tracheal damage was sharply dependent on the dose of IORT; 6 out of 21 patients who received single dose of 25 Gy, and none out of 33 who were given 20 Gy or less. (c) 2-year cause-specific survival and actuarial 2-year survival were 75.0 +/- 14.5% and 62.5 +/- 13.2%, respectively. No loco-regional recurrence has been detected at the time of analysis. CONCLUSION: IORT in combination with modified total esophagectomy is an effective and safe method to obtain a local control in advanced esophageal carcinomas, if the dose of IORT does not exceed 20 Gy.

A resected case of Mycobacterium szulgai pulmonary disease.

We present the first reported case of Mycobacterium szulgai pulmonary disease that needed surgical resection due to unsuccessful antimycobacterial chemotherapy. The patient was a non-immunocompromised 48-year-old male who presented with hemoptysis and whose sputum cultures repeatedly yielded M. szulgai. Antimycobacterial chemotherapy with isoniazid (INH) and rifampin (RMP)/ethambutol (EMB) for three years had been unsuccessful, and subsequent chemotherapy with RMP, EMB, ethionamide and kanamycin had to be discontinued due to liver dysfunction. Surgical resection was finally performed, and resulted in a favorable outcome. Although M. szulgai pulmonary disease is usually well controlled by antimycobacterial chemotherapy alone, surgical treatment may be necessary in some cases.

Translamino-pedicular screw fixation with bone grafting for symptomatic isthmic lumbar spondylolysis.

Anterior or posterolateral spondylodesis has been reported and used widely as a surgical treatment for lumbar spondylolysis or spondylolisthesis. Although spinal fusion is necessary when there is extensive vertebral slippage or spinal instability, the direct repair of the defect is thought to be anatomical, logical, and less invasive as a surgical treatment for symptomatic lumbar spondylolysis or a minimal degree of spondylolisthesis. This operation, with a few modifications, has been performed since 1985 in our clinic. The results, using Henderson's criteria, were excellent in 64.5% and good in 25.8% of the patients thus treated. For younger patients with symptomatic lumbar spondylolysis, direct repair of the defect using translamino-pedicular instrumentation with bone grafting is recommended, as degenerative changes have not usually occurred in the vertebral discs.

Perianal mucinous carcinoma successfully treated with a combination of external beam radiotherapy and high dose rate interstitial brachytherapy.

The case of an 84-year-old man with perianal mucinous carcinoma is presented. The tumour was 6 cm in diameter and extended into the surrounding tissues. Taking the patient's advanced age and disease into account, rectosigmoidectomy and colostomy were carried out without resection of most of the tumour. Radiotherapy consisted of pre-operative external beam radiotherapy (EBRT) of 40 Gy in 20 fractions, post-operative EBRT of 24 Gy in 12 fractions, and high dose rate interstitial brachytherapy of 12 Gy in a single fraction. The patient tolerated the entire course of radiotherapy well. The patient is doing well without regrowth or complications 7 years after radiotherapy. To our knowledge, there have been no reports on the successful outcome of radiotherapy for perianal mucinous carcinoma. This case suggests that a combination of EBRT plus interstitial brachytherapy boost may play a role in the definitive treatment of perianal mucinous carcinoma.

De novo formation characteristics of dioxins in the dry zone of an iron ore sintering bed.

The objectives of this work are to understand the details of the mechanism of dioxin formation in the part of a sintering bed termed the dry zone, and to obtain ideas on how to prevent their formation. Sinter mixtures of various composition types were heated in a packed bed reactor, and dioxins in the outlet gas and in the sinter mixture residue were measured. The dioxin formation potential of a simple sinter mixture composed of iron ore, coke and limestone was markedly lower than that of fly ash from a municipal solid waste incinerator (MSWI). In consideration of this result, a series of experiments were conducted using a sinter mixture impregnated with CuCl2. Experimental results showed that dioxin formation was temperature-dependent in the range of 300-550 degrees C, with the maximum observed at around 300 degrees C, which was quite similar to that of fly ash from the MSWI. The homologue distribution of PCDD/Fs in gas and solid reflected the possible difference in carbonaceous materials in coke and activated coke. Gaseous hydrogen chloride acted as a chlorinating reagent for dioxin formation.

Rapid improvement of osteomalacia by treatment in a case with Sjögren's syndrome, rheumatoid arthritis and renal tubular acidosis type 1.

We present here a case of Sjögren's syndrome (SjS) with osteomalacia based on renal tubular acidosis type 1 (RTA-1). A 53-year-old woman, diagnosed as having rheumatoid arthritis (RA) at the age of 33, was admitted to our hospital because of sicca complex, fatigability and worsening general aching. The activity of RA had been low, but it was complicated by SjS, RTA-1 and remarkable osteomalacia. Acidosis was corrected by alkali supplement therapy. By treatment with a regimen consisting of alfacalcidol, calcium L-aspartate, elcatonin and ipriflavone, her bone mineral density (BMD) was remarkably improved within months and the generalized aching gradually diminished.

[Immunotherapy by polyvalent bacterial antigen (Broncasma Berna) in the prevention of pneumonia in the elderly].

Pneumonia in the elderly often occurs repeatedly, and the mortality rate from pneumonia continues to remain high today despite the usual use of antibacterial chemotherapy. Therefore, we conducted immunotherapy using a polyvalent bacterial vaccine (broncasma Berna). We treated 54 elderly patients with Broncasma Berna, containing chief bacterial pathogens responsible for pneumonia in the elderly. Clinical results obtained during 2 years were compared with those of 18 subjects not treated with Broncasma Berna. The survival rate was 64.8% for the group treated with Broncasma Berna and 50% for the group not treated. The frequency of contraction of pneumonia decreased significantly in the group treated. Clinical efficacy was obtained in 63% of the group treated to prevent pneumonia. The death rate from pneumonia was 17.6% for the group treated and 44.4% for the group not treated. Immunologically, reinforcement in humoral and cellular immunities was indicated by immunoglobulin values, positive tuberculin skin tests, and an increase in lymphocyte stimulation index values for Broncasma Berna. Significant pathogens in sputum disappeared or decreased in 6 (54.6%) out of 11 patients. Side effects such as pain or redness at the site of injection were observed in 6 patients. From the above results, it may be concluded that Broncasma Berna can be considered to be effective as a long-term immunoprophylactic agent in the prevention of pneumonia in the elderly.

[A case of non-herpetic acute encephalitis presenting high intensity lesion at unilateral temparal cortex on MR FLAIR image].

We reported a case of non-herpetic acute encephalitis with unilateral temporal cortex lesion revealed by MR imaging and SPECT study. The patient was an eighteen years old woman who developed tonic-clonic seizure after common cold symptom. She was healthy before this episode. Neurological abnormality was only a single convulsion at onset and there was no other abnormal physical and neurological signs except for low grade fever. Electroencephalogram showed spike and slow wave complex of 2 Hz focused on a right posteriotemporal point (T 6) and an MR FLAIR (fluid-attenuated inversion recovery) image revealed a high signal intensity area at right temporal cortex. There was a decrease of cerebral blood flow in the same portion on SPECT study. This lesion was obscure on T1 and T2 MR images. Cerebrospinal fluid showed pleocytosis with normal glucose level and protein concentration. Bacterial and fungal cultures of CSF were negative and a detection of tubercule bacillus by PCR hybridization method was also negative. Although CSF findings suggested viral infection of CNS, virological study could not demonstrate infections of herpes simplex virus type 1, type 2, varicella-zoster virus, cytomegalovirus, measles virus, mumps virus, Japanese encephalitis virus, and influenza virus type A and B. After infusion of acyclovir and antibiotics, the patient was discharged from our hospital without sequelae of encephalitis. EEG was normal at this point and a high intensity area of MR FLAIR image disappeared two months later. SPECT findings were normalized six months later. The encephalitis presenting unilateral temporal cortex lesion without the infection of herpes simplex virus is thought to be very rare. Our case was distinguished from non-herpetic acute limbic encephalitis by an extent of the lesion and clinical manifestations. MR FLAIR image was useful for the detection of the lesion in this case.

[Clinical research on transfer of cefpiramide to the blood and large intestinal tissue in patients with cancer of the large bowel].

Cefpiramide (CPM) shows antibacterial activity against Staphylococci, Enterococci, Pseudomonas aeruginosa and anaerobic Bacteroides spp. CPM is a cephalosporin antibiotic which also exhibits antibacterial activity against Klebsiella and intestinal bacteria including Escherichia coli. Concentrations in blood of CPM which has antibacterial activity against main bacterial species detected during gastrointestinal surgeries and concentration transferred to the large intestinal tissue were measured in patients with cancer of the large intestine. Eighteen patients who were hospitalized and underwent large intestinal surgery from December, 1985 to March, 1987 were examined as subjects. CPM was administered at a dose 1 g each of 11 cases and 2 g to each of 7 cases. Concentrations in blood after administration of 1 g of CPM were in a range of 81.56-212.6 micrograms/ml between 25 minutes and 2 hours 20 minutes after administration, and concentrations in the large intestinal tissue were in a 14.17-66.95 micrograms/g range. Ratios of the tissue to the blood concentrations were 0.08-0.49, averaging 0.24 +/- 0.05. Concentrations in blood after administration of 2 g of CPM were 128.4-253.5 micrograms/ml between 1 hour 10 minutes and 3 hours 50 minutes after administration. Tissue concentrations were 48.33-116.5 micrograms/g between 1 hour 10 minutes and 5 hours 15 minutes after administration. Ratios of the tissue to the blood concentrations were 0.21-0.55, averaging 0.42 +/- 0.05 between 1 hour 10 minutes and 3 hours 5 minutes.(ABSTRACT TRUNCATED AT 250 WORDS)

[Clinical study of cefmenoxime in the field of abdominal surgery].

The effect of cefmenoxime (CMX) was evaluated in the abdominal surgery at 18 hospitals on the prevention and the treatment of postoperative infections. The results were summarized as follows. In 179 patients with prophylactic use of 2-4 g of CMX a day, no postoperative infection was observed in 94.4%. Using fever index to judge the effect of CMX in prevention of postoperative infections, the value of fever index was higher in the infected group than in the non-infected group. A significant difference was also observed in mean fever index value between the groups given CMX in 2 g and 4 g daily, being 15.4 degree hours and 1.7 degree hours. The incidence of postoperative infections was higher in cases with intraoperative bleeding of more than 500 ml than in cases with less bleeding. Postoperative infection and peritonitis subsided after the administration of 2-4 g of CMX/day for more than 8 days in 77.1% of cases. Very few side effects were noted due to CMX. These results suggest that CMX is safe and effective in the field of abdominal surgery for the prevention of postoperative infections and in the treatment of postoperative infections.

[Asymptomatic multiple intracranial tuberculous nodules detected in a case of miliary tuberculosis].

A case of multiple intracranial tuberculous nodule following miliary tuberculosis was reported. The case was a 19-year-old woman visited a general practitioner, because of fever. Chest x-ray film on the first visit showed diffuse granular shadows in her both lungs with pleural effusion in the left side. The case was diagnosed as bacterial pneumonia, and was treated with antibiotics. She had been getting worse, and the doctor finally examined her sputum, and tubercle bacilli were seen in her sputum (Gaffky 4) by the Ziehl Neelsen's staining. She was introduced to our hospital. Chest x-ray film on admission showed diffuse granular shadows in her both lungs and she was diagnosed her as miliary tuberculosis, and anti-tuberculous therapy was quickly started. She didn't complain of any neurological disorders, but her brain CT showed several nodules in the left cerebral cortex enhanced with contrast medium. T1 weighted MRI enhanced by Gd-DTPA revealed abnormal enhancements in the cerebrum, the cerebellum, and the midbrain. She was treated with anti-epileptic drugs, but after 65 days, she started to suffer from epileptic stroke. Six months later, her brain lesions have improved by the use of anti-tuberculosis drugs and anti-epileptic drugs. The incidence of tuberculosis has decreased in Japan, and, many doctors did not show concern on, thus, a doctor's delay is a serious problem in Japan. Advocary should be made to doctors to detect tuberculous patients as early as possible.

[Primary hyperparathyroidism in cases of urinary stone].

During the 5-year period from October, 1978 to September, 1983, primary hyperparathyroidism has been found at our clinic in 16 out of 395 cases of urinary stones (4.1%) and in 12.6% of the recurrent or multiple stone-forming patients. Plasma-ionized calcium level and rapid rapid calcium load test were most valuable in the diagnosis of primary hyperparathyroidism. It has been proved that neck surgery for primary hyperparathyroidism prevents recurrence of urinary tract stones.

[Treatment of stress incontinence by percutaneous bladder neck stabilization (Vesica)].

We experienced 9 cases of percutaneous bladder neck stabilization (Vesica) for patients with urinary incontinence who were diagnosed with stress incontinence from December 1995 to June 1998. None of the patients were able to control continence with any drugs. Chain cystography was performed on all of the patients before and after surgery. The posterior urethro-vesical angle before surgery was over 130 degrees in all of the patients, and it improved after the operation. Moreover, the mean volume of the pad test greatly decreased from 47 g to 1 g. All of the patients were treated with epidural anesthesia. The operation time was less than 60 minutes. The subjective and objective findings were satisfactory. We conclude that percutaneous bladder neck stabilization is a very useful surgical treatment for stress incontinence.

[Usefulness of magnetic resonance imaging for the diagnosis of superior lumbar hernia: a case report].

A 48-year-old man consulted us with the chief complaints of right flank mass. On examination, there was a soft bulge on the right superior lumbar area. Since computed tomographic scanning showed subcutaneous fatty tissue, we suspected a superior lumbar hernia. The diagnosis was confirmed by magnetic resonance imaging (MRI) that revealed a lumbar muscle defect and prolapsed fatty tissue around the kidney. During the operation, a small hernia hiatus, 2 cm in width, opened in the superior lumbar triangle. The herniated fatty tissue was excised, and the defect of fascia was closed by overlapping the adjacent fascial structure. No signs of recurrence were found at 3 months postoperatively. The usefulness of MRI for the diagnosis is discussed and previous literature is reviewed.

[Cystolithotripsy for bladder stones: comparison of holmium:YAG laser with Lithoclast as a lithotripsy device].

From March 1995 to March 1999, endoscopic lithotripsy of bladder stones was done for 33 patients. We used Holmium:YAG laser for the initial 23 patients, and the Swiss Lithoclast for the recent 10 patients. We compared the safety and efficacy of the two modalities. Both lithotriptors were safe and effective to fragment the bladder stones. All the patients became stone-free at one session. However, we needed to use the Holmium:YAG laser in one patient to disintegrate the larger fragments after Lithoclast. For a big stone, Holmium:YAG laser is preferable.

[Urological complications after renal transplantation].

Urological complications occurred in 17.5% of the 80 patients who had received renal transplantations in our clinic between March, 1975 and May, 1984. Urinary fistulas occurred in 3 patients, urolithiasis occurred in 6 patients, ureteral stenosis occurred in 1 patient and urinary tract bleeding occurred in 4 patients. Graft loss was observed in 1 patient, but there were no patients whose death was directly attributable to urological complications. Urological complications can be avoided by careful procedures in donor nephrectomy and urinary tract reconstruction.

[Clinical studies on cefoperazone in renal transplantation].

Two grams of Cefoperazone was intravenously administered twice a day for 5 days by drip infusion to 10 donors and 9 recipients after renal transplantation. The concentration of cefoperazone in the blood after administration in both donors and recipients did not show any accumulation tendency. The urinary recovery rate of cefoperazone for 24 hours in donors was 8.8% and that in recipients was 8.1%. There was no change in the renal function in donors after administration of cefoperazone. No change was observed in blood examination, BUN or creatinine, but S-GOT and S-GPT showed a temporary increase in 1 donor and 1 recipient. It is considered that Cefoperazone is a very useful drug for prophylactic chemotherapy after renal transplantation.

[Prophylaxis of recurrence of superficial bladder tumor by intravesical chemotherapy].

During the past 10 years, we have experienced 110 bladder tumor cases. Among them, 70 patients were diagnosed superficial bladder tumor. Of these 70 cases, 30 were treated with intravesical adriamycin (ADR) and peplomycin (PEP), 13 with ADR only and one case with PEP and remaining 26 with TUR and hydrostatic pressure technique. We studied the efficacy of combination intravesical chemotherapy with ADR and PEP and other treatments in the prevention of recurrence in the superficial bladder tumor cases. The recurrence rate during 3 years of each group, was 25% in the group treated with ADR and PEP, 35% with ADR and 55% in remaining group. 3 years recurrence rate in the group treated with ADR and PEP was significantly low than that in the group tread with TUR and hydrostatic pressure technique alone (Wilcoxon test). Side effects was pollakisuria, pain after micturition and others. Anaphylactic shock appeared in one case. From these results we concluded that intravesical chemotherapy with combined agents is more effective than that with a single one or no treatment after TUR.