Impact of tumor growth rate during preceding treatment on tumor response to nivolumab or irinotecan in advanced gastric cancer.

BACKGROUND: Nivolumab (NIVO) and irinotecan (IRI) are standard treatments for refractory advanced gastric cancer (AGC); however, it is unclear which drug should be administered first or in which cases. The tumor growth rate (TGR) during preceding treatment is reported to be associated with tumor response in metastatic colorectal cancer patients treated with regorafenib or trifluridine/tipiracil, suggesting that TGR may be useful for drug selection. Therefore, we evaluated the association between TGR during preceding treatment and the tumor response to NIVO or IRI. PATIENTS AND METHODS: We retrospectively evaluated consecutive AGC patients treated with NIVO or IRI and divided them into slow-growing (Slow) and rapid-growing (Rapid) groups according to TGR and the presence or absence of new lesions (NL+/NL-, respectively) during preceding treatment (Slow group: NL- with low TGR <0.30%/day; Rapid group: NL+ or high TGR ≥0.30%/day). RESULTS: A total of 117 patients (Rapid/Slow groups, 72/45; NIVO/IRI groups, 32/85) were eligible. All baseline characteristics except peritoneal metastases were similar between patients treated with NIVO and IRI in the Rapid and Slow groups. The response rate was significantly higher in patients treated with NIVO compared with IRI [31%/3%; odds ratio (OR), 13.8; P = 0.01; adjusted OR, 52; P = 0.002] in the Slow group, but there was no difference between patients treated with NIVO and IRI (5%/8%; OR, 0.68; P = 0.73; adjusted OR, 0.94; P = 0.96) in the Rapid group. Disease control rate, progression-free survival, and overall survival were consistent with these results. CONCLUSIONS: Our findings suggest that NIVO treatment is a more favorable option for patients with slow-growing tumors, and NIVO and IRI are similarly recommended for patients with rapid-growing tumors in refractory AGC. TGR and NL emergence during preceding treatment may be helpful for drug selection and warrant further investigation.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of oesophageal cancer was published in 2016, and covered the management and treatment of local/locoregional disease, limited disease, locally advanced disease and the management of advanced/metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and the Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic oesophageal cancer in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic oesophageal cancer representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence, and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic gastric cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS.

The most recent version of the European Society for Medical Oncology (ESMO) Clinical Practice Guidelines for the diagnosis, treatment and follow-up of gastric cancer (GC) was published in 2016, and covered the management and treatment of local, locoregional, locally advanced and metastatic disease. At the ESMO Asia Meeting in November 2017 it was decided by both ESMO and The Japanese Society of Medical Oncology (JSMO) to convene a special guidelines meeting immediately after the JSMO Annual Meeting in 2018. The aim was to adapt the ESMO 2016 guidelines to take into account the ethnic differences associated with the treatment of metastatic GC in Asian patients. These guidelines represent the consensus opinions reached by experts in the treatment of patients with metastatic GC representing the oncological societies of Japan (JSMO), China (CSCO), Korea (KSMO), Malaysia (MOS), Singapore (SSO) and Taiwan (TOS). The voting was based on scientific evidence and was independent of both the current treatment practices and the drug availability and reimbursement situations in the individual participating Asian countries.

Propagation and some physiological effects of Citrus bark cracking viroid and Apple fruit crinkle viroid in multiple infected hop (Humulus lupulus L.).

The hop metabolome important for the brewing industry and for medical purposes is endangered worldwide due to multiple viroid infections affecting hop physiology. Combinatorial biolistic hop inoculation with Citrus bark cracking viroid (CBCVd), Apple fruit crinkle viroid (AFCVd), Hop latent viroid, and Hop stunt viroid (HSVd) showed a low CBCVd compatibility with HSVd, while all other viroid combinations were highly compatible. Unlike to other viroids, single CBCVd propagation showed a significant excess of (-) over (+) strands in hop, tomato, and Nicotiana benthamiana, but not in citruses. Inoculation of hop with all viroids led to multiple infections with unstable viroid levels in individual plants in the pre- and post-dormancy periods, and to high plant mortality and morphological disorders. Hop isolates of CBCVd and AFCVd were highly stable, only minor quasispecies were detected. CBCVd caused a strong suppression of some crucial mRNAs related to the hop prenylflavonoid biosynthesis pathway, while AFCVd-caused effects were moderate. According to mRNA degradome analysis, this suppression was not caused by a direct viroid-specific small RNA-mediated degradation. CBCVd infection led to a strong induction of two hop transcription factors from WRKY family and to a disbalance of WRKY/WDR1 complexes important for activation of lupulin genes.

Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5-year overall surgery, 57.5%; P = 0.167). Patients who underwent R0 resection showed significantly longer OS than did those who underwent R1, R2, or no resection (P = 0.001). In multivariate analysis using age, perioperative chemotherapy, depth of invasion, LN metastasis, surgical radicality, postoperative pneumonia, and anastomotic leakage as covariates, LN metastasis [cN2: hazard ratio (HR), 1.389; P = 0.309; cN3: HR, 16.019; P = 0.012] and surgical radicality (R1: HR, 3.949; P = 0.009; R2 or no resection: HR, 2.912; P = 0.022) were shown to be significant independent prognostic factors. In clinical stage III ESCC patients, no significant difference in OS was observed between NAC and upfront surgery. Although potential patient selection bias might be a factor in this retrospective analysis, the noncurative resection rate was higher after NAC than after upfront surgery. The survival benefit of more intensive NAC needs to be further evaluated.

Randomized phase III study of bevacizumab plus FOLFIRI and bevacizumab plus mFOLFOX6 as first-line treatment for patients with metastatic colorectal cancer (WJOG4407G).

BACKGROUND: FOLFIRI and FOLFOX have shown equivalent efficacy for metastatic colorectal cancer (mCRC), but their comparative effectiveness is unknown when combined with bevacizumab. PATIENTS AND METHODS: WJOG4407G was a randomized, open-label, phase III trial conducted in Japan. Patients with previously untreated mCRC were randomized 1:1 to receive either FOLFIRI plus bevacizumab (FOLFIRI + Bev) or mFOLFOX6 plus bevacizumab (mFOLFOX6 + Bev), stratified by institution, adjuvant chemotherapy, and liver-limited disease. The primary end point was non-inferiority of FOLFIRI + Bev to mFOLFOX6 + Bev in progression-free survival (PFS), with an expected hazard ratio (HR) of 0.9 and non-inferiority margin of 1.25 (power 0.85, one-sided α-error 0.025). The secondary end points were response rate (RR), overall survival (OS), safety, and quality of life (QoL) during 18 months. This trial is registered to the University Hospital Medical Information Network, number UMIN000001396. RESULTS: Among 402 patients enrolled from September 2008 to January 2012, 395 patients were eligible for efficacy analysis. The median PFS for FOLFIRI + Bev (n = 197) and mFOLFOX6 + Bev (n = 198) were 12.1 and 10.7 months, respectively [HR, 0.905; 95% confidence interval (CI) 0.723-1.133; P = 0.003 for non-inferiority]. The median OS for FOLFIRI + Bev and mFOLFOX6 + Bev were 31.4 and 30.1 months, respectively (HR, 0.990; 95% CI 0.785-1.249). The best overall RRs were 64% for FOLFIRI + Bev and 62% for mFOLFOX6 + Bev. The common grade 3 or higher adverse events were leukopenia (11% in FOLFIRI + Bev/5% in mFOLFOX6 + Bev), neutropenia (46%/35%), diarrhea (9%/5%), febrile neutropenia (5%/2%), peripheral neuropathy (0%/22%), and venous thromboembolism (6%/2%). The QoL assessed by FACT-C (TOI-PFC) and FACT/GOG-Ntx was favorable for FOLFIRI + Bev during 18 months. CONCLUSION: FOLFIRI plus bevacizumab was non-inferior for PFS, compared with mFOLFOX6 plus bevacizumab, as the first-line systemic treatment for mCRC. CLINICAL TRIALS NUMBER: UMIN000001396.

New method for quantitative assessment of airway calibre using a stereovision fibreoptic bronchoscope.

BACKGROUND: We have developed a new bronchoscopy system with two independent lenses at the tip of the device. This enables measurement of object size using the principle of triangulation. This study was performed to assess the accuracy of this system. METHODS: The accuracy of the bronchoscopy system was confirmed by measuring the diameters of four plastic tubes and 36 airway calibres in 12 surgical patients under general anaesthesia. The measured diameters of the tubes and airway tracts were compared with the manufactured diameters of tubes and those measured by high-resolution computed tomography (HRCT)-based virtual bronchoscopy, respectively. RESULTS: Using the new bronchoscope system, tube diameters, 9, 12, 15, and 19 mm, were measured as 9.9 (0.7), 12.8 (1.4), 16.3 (1.6), and 20.1 (2.0) mm, respectively. Airway calibres obtained by a stereovision bronchoscopy and HRCT-based virtual bronchoscopy were 8.66 (4.31) and 9.38 (5.09) mm, respectively. There is a significant correlation between airway calibres with the two measurement methods (r=0.975, P<0.01). CONCLUSIONS: We have confirmed that this new bronchoscopy system could provide relatively accurate quantitative data. This new system may be useful in the clinic to measure airway dimension and lesion sizes such as tumours.

[Three primary cancers of pulmonary cancer, malignant melanoma and esophageal cancer; report of a case].

A 61-year-old man, who had medical history of hepatitis type C, surgery for malignant melanoma of the lower limb, endoscopic mucosal resection for esophageal cancer, was pointed out a pulmonary nodule in the right middle lobe by surveillance computed tomography after 5 years of surgery for melanoma. Pathology of esophageal cancer was squamous cell carcinoma limited in mucosa without lymphatic nor venous invasion. The nodule gradually enlarged and respiratory endoscopic examination could not establish pathological diagnosis. Thoracoscopy-assisted pulmonary biopsy revealed squamous cell carcinoma, and right middle lobectomy with mediastinal node dissection was performed. Histological examination showed moderately differentiated squamous cell carcinoma without lymph node involvement. The stage of lung cancer was T1N0M0, stage IA. Although 9 months have passed since surgery for lung cancer, recurrence of each malignancy has not been detected.

[Assessment of surgical treatment for lung cancer with pericardial or left atrial invasion].

We evaluated surgical results for the patients who underwent pulmonary resection combined with pericardial or left atrial resection due to locally advanced non-small cell lung cancer (NSCLC). Seven patients who underwent pericardial resection (T3 group) and 4 patients who underwent resection of the left atrium (T4 group) were included in this study, and clinical findings and prognosis were evaluated. Eight patients underwent pneumonectomy, and others underwent lobectomy or bilobectomy. Histology of the cancer was squamous cell carcinoma in all patinets. As for pathological node involvement, N0/N1 disease was 72.7% and N2 disease was 27.3%. Induction chemotherapy was performed in 75.0% of T4 group. Adjuvant chemotheraphy was performed in 71.4% of T3 group and 75.0% of T4 group. Five-year-survival was 57.1% in T3 group and 25.0% in T4 group. Five-year-survival was 62.5% in N0/N1 disease and 0% in N2 disease. Statistical significance in prognosis was seen in lymph node status (p = 0.0317). Extended resection of pericardium or left atrium for patients with N2 disease of NSCLC is not recommended. When invasion to pericardium or left atrium is diagnosed during surgery, extended resection should be indicated in patient without N2 metastasis.

[Pleuroperitoneal communication at the beginning of continuous ambulatory peritoneal dialysis; report of a case].

A 46-years-old woman admitted for induction of continuous ambulatory peritoneal dialysis (CAPD). When peritoneal functional test was performed, dyspnea was occurred. Chest X-ray and chest computed tomography (CT) scan revealed massive right hydrothorax. Technetium-99m macroaggregated albumin scintigraphy showed communication between abdominal cavity and thoracic cavity. The thoracoscopic diaphragmal repair was performed. After CAPD was started, right hydrothorax occurred again. Re-repair of the diaphragm was performed in small thoracotomy and small hole was revealed. The hole was sutured and diaphragm was coverd by fibrin glue and polyglycolacid (PGA) felt all over. Since then, CAPD was continued successfully. Thoracoscopic surgery is less invasive and appropriate therapy for this case. It is important that the diaphragm will be covered all over by fibrin glue and PGA sheet because even pin-hole makes recurrence. For detect of the communicative portion, use of indigocarmin and examination of glucose concentration in the pleural effusion were effective.

[Thymic carcinoid tumor with Cushing syndrome].

A case of a 71-year-old male with ectopic adrenocorticotropic polypeptide (ACTH)-producing thymic carcinoid tumor presenting Cushing's syndrome was reported. This patient had symptoms of fatigue and a polyposia for 2 years before a mediastinal tumor was detected. Chest computed tomography (CT) scan demonstrated an anterior mediastinal mass, and serum ACTH and cortisol level revealed very high. Secretion of cortisol was not inhibited in an 8-mg dexamethazone suppression test. We diagnosed ectopic ACTH-producing tumor, and performed complete excision of the thymus including thymic tumor. Histologically, the tumor demonstrated typical carcinoid with the positivity of ACTH immunostaining. After the operation, ACTH and cortisol levels were reduced and the clinical symptoms were improved rapidly. We have concluded that it is important to control serum perioperative cortisol level for the prevension of morbidity.

Akt activation and localisation correlate with tumour invasion and oncogene expression in thyroid cancer.

INTRODUCTION: Akt activation is involved in the pathogenesis of inherited thyroid cancer in Cowden's syndrome and in sporadic thyroid cancers. In cell culture, Akt regulates thyroid cell growth and survival; but recent data suggest that Akt also regulates cell motility in non-thyroid cell lines. We therefore sought to evaluate the role of Akt in thyroid cancer progression. METHODS: We evaluated 46 thyroid cancer, 20 thyroid follicular adenoma, and adjacent normal tissues samples by immunohistochemistry for activated Akt (pAkt), Akt 1, 2, and 3, and p27 expression. Immunoblots were performed in 14 samples. RESULTS: Akt activation was identified in 10/10 follicular cancers, 26/26 papillary cancers, and 2/10 follicular variant of papillary cancers, but in only 4/66 normal tissue samples and 2/10 typical benign follicular adenomas. Immunoactive pAkt was greatest in regions of capsular invasion; and was localised to the nucleus in follicular cancers and the cytoplasm in papillary cancers, except for invasive regions of papillary cancers where it localised to both compartments. Immunoactive Akt 1, but not Akt 2 or Akt 3, correlated with pAkt localisation, and nuclear pAkt was associated with cytoplasmic expression of p27. In vitro studies using human thyroid cancer cells demonstrated that nuclear translocation of Akt 1 and pAkt were associated with cytoplasmic p27 and cell invasion and migration. Cell migration and the localisation of Akt 1, pAkt, and p27 were inhibited by PI3 kinase, but not MEK inhibition. DISCUSSION: These data suggest an important role for nuclear activation of Akt 1 in thyroid cancer progression.

[Congenital esophagobronchial fistula treated with thoracoscopic assisted surgery].

A case of congenital esophagobronchial fistula in a 58-year-old woman was described. The patient had presented with repeated attacks of pulmonary infection from her childhood and had a history of recurrent cough after eating or drinking. Preoperative examinations including esophagogram by barium swallow revealed existence of a fistula between the upper thoracic esophagus and the right B3 bronchus. The fistula was recognized as type I of Braimbridge classification. Thoracoscopic assisted fistulectomy and diverticulectomy for esophagobronchial fistula with esophageal diverticulum were performed. The neck of the diverticulum and the fistula were divided with endo-stapling technique. Intraoperative esophagoscopy was found to be useful for the definite localization and complete excision of the fistula and the diverticulum and the avoidance of stenosis of the esophagus. Postoperative course was uneventful. It is to be considered that the present thoracoscopic assisted procedure with intraoperative esophagoscopy can be used as a standard operative procedure for esophagobronchial fistula with esophageal diverticulum.

A prospective and randomized study of primary hormonal therapy for patients with localized or locally advanced prostate cancer unsuitable for radical prostatectomy: results of the 5-year follow-up.

OBJECTIVE: To evaluate the effect of primary hormonal therapy for patients with localized and locally advanced prostate cancer. PATIENTS AND METHODS: Patients with stage T1b-T3 prostate cancer who were not scheduled for radical prostatectomy were allocated into two groups: group 1 (73 men) received luteinizing hormone-releasing hormone (LHRH) agonist monotherapy and group 2 (78 men) received LHRH agonist and chlormadinone acetate. Patients were followed using serum prostate specific antigen levels, prostate size and the detection of distant metastasis for 5 years. RESULTS: The median (range) follow-up was 78 (63-87) months. The 5-year progression-free survival rate was significantly higher in group 2 (68%) than in group 1 (47%). However, the overall and cause-specific survival rate at 5 years were similar in both groups, at 72% and 93% in group 1, and 64% and 89% in group 2, respectively. CONCLUSION: The overall survival rates of the both groups were no different from that of the normal Japanese population of the same age group. Although this study did not include an untreated group, i.e. watchful waiting, these results might indicate the usefulness of primary hormonal therapy in controlling localized and locally advanced prostate cancer. The 5-year observation period is still short and the study is continuing to determine the 10-year survival.

[An adult case of Bochdalek hernia without an obvious cause; report of a case].

A 72-year-old female was transported by ambulance to our department to undergo transthoracic surgery. She had previously undergone transabdominal surgery under a diagnosis of adult Bochdalek hernia, but the restoration was believed to have been incomplete. During the transthoracic procedure, a dorsolateral defect of the diaphragm was detected and reinforcement with a Gore-Tex patch was performed. The patient's postoperative course was uneventful. Adult Bochdalek hernia is rare, but it requires immediate surgical intervention. Although transabdominal surgery is generally considered the first line treatment approach to restore Bochdalek hernia, restoration of the diaphragm is occasionally difficult. On the other hand, a transthoracic approach is thought to be effective as it allows for observation of the lung and diaphragm, and easy closure of the diaphragmatic defect. As complete restoration through early surgical intervention is important, a transthoracic approach in conjunction with transabdominal surgery should be considered whenever necessary.

Orthotopic neobladder reconstruction in elderly bladder cancer patients.

BACKGROUND: We compared the clinical results of orthotopic neobladder reconstruction in elderly patients and those in younger patients retrospectively in order to verify whether age is a critical factor in selecting a method of urinary diversion. METHODS: Following radical cystectomy for bladder cancer, 12 patients aged 75 or older and 17 patients under 75 who underwent orthotopic neobladder reconstruction between January 1992 and May 1999 were investigated in this study. The authors TS and BS were among the surgeons who performed operations for all cases. Of the 12 elderly patients, orthotopic neobladders were constructed according to Hautmann's method in nine cases, Studer's method in one case and Reddy's method in two cases. Of the 17 younger patients, these methods were employed in 12, one and four cases, respectively. Operative procedure, early and late complications, prognosis, continence and voiding pattern were investigated in these patients. RESULTS: The follow-up periods for elderly and younger groups ranged from 21.3 to 82.7 months and from 8.8 to 94.2 months, respectively. No difference in operation time, amount of bleeding or postoperative length of hospitalization was observed between elderly and younger patients. The rates of early complications in elderly and younger patients were 41.7% and 35.3%, respectively. Late complication rates were 33.3% and 47.1%, respectively. The difference in these complication rates was not statistically significant. One of the elderly and two of the younger patients had local recurrence and metastasis postoperatively. Those three patients had died of their bladder cancer. No statistically significant difference between groups was recognized in either cause-specific survival or overall survival, nor was there such a difference in relation to micturition/continence. CONCLUSION: Based on these results, we believe that because age is not a critical factor in the selection of urinary diversion method, neobladder reconstruction following cystectomy for bladder cancer is indicated in elderly patients. As stoma management is difficult for the patients, we consider orthotopic neobladder reconstruction to be the method of choice if the patients' general physical condition allows.

Severe thyrotoxicosis induced by thyroid metastasis of lung adenocarcinoma: a case report and review of the literature.

A 50-year-old woman who had undergone lung lobectomy because of lung adenocarcinoma presented with thyrotoxicosis, neck swelling, and cervical lymphadenopathy one month after the operation. The total serum triiodothyronine (T3) and thyroxine (T4) levels were markedly elevated to 514 ng/dL and 26.4 microg/dL, respectively, and serum thyrotropin (TSH) was suppressed to less than 0.005 microU/mL. Although the thyroid gland had been normal before surgery, chest computed tomography (CT) scan revealed a markedly enlarged thyroid gland only 1 month after surgery. 123I uptake for 24 hours was suppressed to 4% in the thyroid gland with no uptake elsewhere including the lung. Fine-needle aspiration cytology (FNAC) of the thyroid showed invasion of poorly differentiated adenocarcinoma cells, cytologically identical to the cells obtained from sputum and those infiltrating the resected sections of the lung adenocarcinoma. Immunohistochemical studies of resected lung tissues did not show positive staining for thyroglobulin, carcinoembryonic antigen (CEA), or surfactant protein A. Clinically, the thyrotoxicosis had spontaneously improved, followed by a hypothyroid state with shrinkage of the thyroid gland after chemotherapy. Despite repeated chemotherapy and the administration of thyroxine for hypothyroidism, the patient died of respiratory failure 9 months after the onset of thyrotoxicosis. From these findings and the clinical course, thyroid metastasis, developing subacutely from lung adenocarcinoma, was diagnosed. We speculate that aggressive invasion of tumor cells into the thyroid gland resulted in highly destructive thyrotoxicosis.

The prevalence of renal cell carcinoma: a nation-wide survey in Japan in 1997.

BACKGROUND: The present study was conducted to investigate the incidence of renal cell carcinoma by sex, age group and different regions in Japan. METHODS: The survey was conducted from the beginning of January 1997 to the end of December 1997. A total of 1306 Institutions in all 47 prefectures throughout Japan were requested to register cases. RESULTS: There were 6358 persons with renal cell carcinoma, consisting of 4372 men and 1986 women. The age-specific incidence rates showed a peak in the age group of 65-70 years in both men and women. The crude incidence rates per 100 000 population for men and women were 7.1 and 3.1, respectively, and age-standardized incidence rates per 100 000 population for men and women were 4.9 and 1.8, respectively. The incidence rates in the Hokkaido region were significantly higher than in other regions (P < 0.05), among which there was no significant difference in incidence rates. CONCLUSIONS: The present study showed that the incidence rates of renal cell carcinoma in Japan were approximately the same as among Japanese in Los Angeles. The rates were, however, lower than North American and European countries, but higher than China, Central or South American countries and African countries. The reasons for the high incidence of renal cancer in the Hokkaido region are not entirely clear. Further epidemiologic research is required.

Postoperative plasma cortisol levels predict long-term outcome in patients with Cushing's disease and determine which patients should be treated with pituitary irradiation after surgery.

Transsphenoidal surgery is the treatment of choice for ACTH-producing pituitary adenoma (Cushing's disease) and pituitary irradiation is widely considered the most appropriate treatment for patients with Cushing's disease for whom transsphenoidal surgery has been unsuccessful. We studied 49 consecutive patients who underwent transsphenoidal surgery for the treatment of Cushing's disease at Tokyo Women's Medical University from 1977-1997 with a mean follow-up duration of 87.6 months (range, 24-253 months). We examined the relationship between postoperative endocrinological data, assessed between 3 and 8 weeks after surgery, and long-term outcome and efficacy of pituitary irradiation after surgery. Long-term remission was defined as the regression of the symptom and signs of Cushing's syndrome, and restoration of normal levels of plasma ACTH, cortisol and urinary free cortisol, together with adequate suppression of morning plasma cortisol levels following the administration of low dose (1 mg) of dexamethasone. Thirty patients had no additional treatment after pituitary surgery. Only 1 of 25 patients (4%) whose postoperative plasma cortisol level was less than 2 microg/dl developed recurrent disease whereas 3 out of 5 patients with postoperative plasma cortisol levels higher than 2 microg/dl relapsed. Postoperative external pituitary radiation was used to treat the remaining 19 patients. Four patients who received radiation therapy had a low or undetectable postoperative plasma cortisol level (<2 microg/dl, 56 nmol/L) and all of these patients developed hypopituitarism whereas 5 patients with subnormal plasma cortisol levels (2.0-10.0 microg/dl) remained in remission. Among 10 patients with persistent disease after surgery, 6 entered remission 6-47 months after irradiation but one of them subsequently relapsed after 108 months. These results suggest that 1) additional therapy should be avoided in patients with a postoperative plasma cortisol less than 2 microg/dl because relapse is very rare and radiotherapy will frequently induce hypopituitarism, 2) patients with a subnormal cortisol level following surgery should be treated with pituitary irradiation, because the relapse rate is reportedly high and radiotherapy is effective in preventing relapse, 3) radiotherapy in patients with persistent disease after surgery is effective only in 50% (5/10) of the patients.

Treatment of androgen-independent prostate cancer with dexamethasone: a prospective study in stage D2 patients.

PURPOSE: In order to evaluate the efficacy of dexamethasone in the treatment of Japanese men with androgen-independent prostate cancer, a prospective study was conducted using prostate-specific antigen (PSA) as a primary end-point. METHODS: Nineteen Japanese men with stage D2 androgen-independent prostate cancer were registered and treatment was started. After ruling out anti-androgen withdrawal syndrome, they were treated with dexamethasone (1.5 mg daily). Patients were monitored for PSA, symptoms, radiologic response, survival rate, time to disease progression, time to treatment failure and complications. RESULTS: Prostate-specific antigen levels decreased in nine patients (50.0%); five (27.8%) showed a 50% or greater decrease and two (11.1%) showed an 80% or greater decrease. For the nine patients, the mean duration of PSA response was 7.3 months and the median duration was 2.1 months (range, 1.2-27.5+). Bone pain, which was noted in 13 patients at study entry, improved in seven patients (53.8%). Of nine patients who had serial radiographic examinations with bone scan, three (33%) showed partial response, two (22%) were stable and four (44%) showed disease progression. Treatment was well tolerated, except for one patient who suffered a severe pulmonary infection. CONCLUSION: Dexamethasone decreased PSA levels and produced subjective symptomatic improvement in the patients with stage D2 androgen-independent prostate cancer.