Laparoscopic sleeve gastrectomy followed by laparoscopic adrenalectomy for patients with obesity and primary aldosteronism: Report of two patients.

INTRODUCTION AND IMPORTANCE: Primary aldosteronism (PA) is the most frequent cause of secondary hypertension. Surgical treatment of unilateral PA usually resolves excessive aldosterone secretion. Obesity is an independent factor for postoperative persistent hypertension for patients with unilateral PA. Laparoscopic sleeve gastrectomy has become popular due to its efficacy in resolving obesity. A specific strategy might to be needed for patients with unilateral PA and obesity. CASE PRESENTATION: Two males with PA and obesity (Body Mass Index: BMIs of 35.9 and 39.0, respectively) were referred for evaluation. Both patients had hypertension caused by PA and obesity. We performed laparoscopic sleeve gastrectomy (LSG) prior to adrenalectomy to avoid persistent postoperative hypertension and perioperative obesity related comorbidities. LSG could lead to decreasing of BMIs to 27.7 and 32.1. Comorbidities associated with obesity were also resolved in both patients. Laparoscopic adrenalectomy was then safely performed in these two patients with PA. CLINICAL DISCUSSIONS: Patients with PA developing resistant hypertension were estimated to be 20 % of those who underwent adrenalectomy. Decreased BMI can be an independent preoperative determinant for successful outcome after adrenalectomy regarding hypertension. We need to review with special care the preoperative BMI and the nature of hypertension before performing surgery on patients with unilateral PA. CONCLUSIONS: A successful strategy was used to treat two obese patients with unilateral PA who underwent laparoscopic adrenalectomy after LSG to minimize complications associated with obesity-related comorbidities.

Correction to: Thoracic and cardiovascular surgery in Japan during 2001 : Annual report by the Japanese Association for Thoracic Surgery.

The original publication of the articles cited above included incorrect values.

Esophageal stenosis and the Glasgow Prognostic Score as independent factors of poor prognosis for patients with locally advanced unresectable esophageal cancer treated with chemoradiotherapy (exploratory analysis of JCOG0303).

BACKGROUND: The aim of this study was to investigate the possible prognostic factors and predictive accuracy of the Glasgow Prognostic Score (GPS) for patients with unresectable locally advanced esophageal squamous cell carcinoma (LAESCC) treated with chemoradiotherapy. METHODS: One hundred forty-two patients were enrolled in JCOG0303 and assigned to the standard cisplatin and 5-fluorouracil (PF)-radiotherapy (RT) group or the low-dose PF-RT group. One hundred thirty-one patients with sufficient data were included in this analysis. A Cox regression model was used to analyze the prognostic factors of patients with unresectable LAESCC treated with PF-RT. The GPS was classified based on the baseline C-reactive protein (CRP) and serum albumin levels. Patients with CRP ≤1.0 mg/dL and albumin ≥3.5 g/dL were classified as GPS0. If only CRP was increased or only albumin was decreased, the patients were classified as GPS1, and the patients with CRP >1.0 mg/dL and albumin <3.5 g/dL were classified as GPS2. RESULTS: The patients' backgrounds were as follows: median age (range), 62 (37-75); male/female, 119/12; ECOG PS 0/1/2, 64/65/2; and clinical stage (UICC 5th) IIB/III/IVA/IVB, 3/75/22/31. Multivariable analyses indicated only esophageal stenosis as a common factor for poor prognosis. In addition, overall survival tended to decrease according to the GPS subgroups (median survival time (months): GPS0/GPS1/GPS2 16.1/14.9/8.7). CONCLUSIONS: Esophageal stenosis was identified as a candidate stratification factor for randomized trials of unresectable LAESCC patients. Furthermore, GPS represents a prognostic factor for LAESCC patients treated with chemoradiotherapy. CLINICAL TRIAL INFORMATION: UMIN000000861.

Risk Factors for Esophageal Fistula Associated With Chemoradiotherapy for Locally Advanced Unresectable Esophageal Cancer: A Supplementary Analysis of JCOG0303.

Esophageal fistula is a critical adverse event in patients treated with chemoradiotherapy (CRT) for locally advanced esophageal cancer. However, risk factors associated with esophageal fistula formation in patients receiving CRT have not yet been elucidated.We retrospectively analyzed data obtained from 140 patients who were enrolled in a phase II/III trial comparing low-dose cisplatin with standard-dose cisplatin administered in combination with 5-flurouracil and concomitant radiotherapy. Inclusion criteria were performance status (PS) 0 to 2 and histologically proven thoracic esophageal cancer clinically diagnosed as T4 and/or unresectable lymph node metastasis for which definitive CRT was applicable. Risk factors for esophageal fistula were examined with univariate analysis using Fisher exact test and multivariate analysis using logistic regression models.Esophageal fistula was observed in 31 patients (22%). Of these, 6 patients developed fistula during CRT. Median time interval between the date of CRT initiation and that of fistula diagnosis was 100 days (inter quartile range, 45-171). Esophageal stenosis was the only significant risk factor for esophageal fistula formation both in univariate (P = 0.026) and in multivariate analyses (odds ratio, 2.59; 95% confidence interval, 1.13-5.92, P = 0.025). Other clinicopathological factors, namely treatment arm, age, sex, PS, primary tumor location, T stage, lymph node invasion to adjacent organs, blood cell count, albumin level, and body mass index, were not risk factors fistula formation.Esophageal stenosis was a significant risk factor for esophageal fistula formation in patients treated with CRT for unresectable locally advanced thoracic esophageal squamous cell carcinoma.

Chylous leakage from a remaining duplicated left-sided thoracic duct after esophagectomy successfully treated by ligation of the left-sided thoracic duct with left-sided video-assisted thoracoscopic surgery with the patient in the prone position.

A 69-year-old man who had undergone an esophagectomy was diagnosed with chylous leakage on postoperative day 2, and his pleural effusion output gradually increased daily. On postoperative day 6, intranodal lymphangiography using lipiodol demonstrated chylous leakage from branches of an incomplete duplicated left-sided thoracic duct; it also indicated successful ligation of the right-sided thoracic duct at initial operation. After lymphangiography, the chylous leakage did not heal and remained uncontrollable. Based on the preoperative lymphangiographic findings, we ligated the left-sided thoracic duct with left-sided video-assisted thoracoscopic surgery, with the patient in the prone position, on postoperative day 9. The patient experienced no other postoperative complications. The use of the prone position with pneumothorax treatment was helpful in providing a wide operative field in the posterior mediastinum, thus allowing for a better chance for a successful postoperative outcome.

Inter-institutional survival heterogeneity in chemoradiation therapy for esophageal cancer: exploratory analysis of the JCOG0303 study.

It is important to examine variation in the treatment effects of patients with esophageal cancer in order to generalize treatment outcomes. We aimed to investigate the range of prognostic differences among hospitals in the treatment of locally advanced esophageal cancer. The JCOG0303 study compared the efficacy of radiotherapy plus low-dose cisplatin and 5-fluorouracil with that of high-dose cisplatin and 5-fluorouracil for unresectable esophageal cancer. Of 32 institutions participating in the JCOG0303 study, the 18 institutions that enrolled three or more patients were included in this study. We predicted the 1-year survival in each institution by using a mixed-effect model. We found that the predicted 1-year survival in the 18 institutions with three or more patients was a median of 60.9%, with a range of 60.9-60.9%. This study is the first to investigated heterogeneity of survival in patients who received definitive chemoradiotherapy for locally advanced esophageal squamous cell carcinoma.

Efficacy of lymph node dissection by node zones according to tumor location for esophageal squamous cell carcinoma.

BACKGROUND: The extent of node dissection in esophageal cancer surgery is usually estimated by the number of resected nodes, irrespective of the area of dissection. The efficacy of lymph node dissection by area was evaluated according to the location of the primary tumor. METHODS: The study group comprised the 3827 patients who underwent R0 esophagectomy with three-field lymph node dissection for squamous cell carcinoma, registered in a nationwide registry in Japan. The areas of lymph node were classified into zones according to AJCC Staging Manual. The Efficacy Index (EI) calculating the frequency and patient survival of metastases to each zone was investigated according to tumor location. RESULTS: The EI was high in supraclavicular and upper mediastinal zones in patients with upper esophageal tumors, highest in upper mediastinal zone followed by supraclavicular and perigastric zones in patients with middle esophageal tumors, and highest in perigastric zone followed by upper and lower mediastinal zones in patients with lower esophageal tumors. In patients with middle and lower esophageal cT1 tumors, the EIs of upper mediastinal and perigastric zones were higher than middle and lower mediastinal zones. CONCLUSION: The EIs of each zone were differed by tumor location. The extent of lymph node dissection should be estimated by the dissected zones and modified by the tumor location. Supraclavicular dissection is indispensable for patients with upper esophageal tumors, and recommended for patients with middle esophageal tumors. Upper mediastinal dissection is recommended for all patients with thoracic esophageal squamous cell carcinoma, irrespective of the location.

Prognostic Factors in Patients Receiving Neoadjuvant 5-Fluorouracil plus Cisplatin for Advanced Esophageal Cancer (JCOG9907).

OBJECTIVE: Neoadjuvant chemotherapy with 5-fluorouracil plus cisplatin and subsequent esophagectomy with two- to three-field lymphadenectomy is a standard treatment for patients with clinical stage II/III squamous cell carcinoma (SCC) of the esophagus. This study investigates the prognostic factors for patients who received neoadjuvant chemotherapy. METHODS: Of 164 patients assigned to receive neoadjuvant chemotherapy in the JCOG9907 trial, multivariate analyses were performed for 159 and 149 patients to evaluate the preoperative and the combined preoperative and postoperative prognostic factors, respectively. RESULTS: The multivariate analyses using preoperative factors showed that clinical stage T3 [vs. cT1-2; hazard ratio (HR) 3.60, p = 0.0007] and serum albumin (Alb) <4.0 g/dl (vs. ≥ 4.0 g/dl; HR 2.29, p = 0.0005) were associated with a poor prognosis. Four independent prognostic factors were identified by multivariate analysis of both preoperative and postoperative factors: pathological curability B (pB; R0 with stage IV or pD < pN) or pC [microscopic or macroscopic residual tumor (R1/R2)] [vs. pA (R0); HR 1.93, p = 0.015], pathological stage N1 (vs. pN0; HR 3.86, p = 0.0012), cT3 (vs. cT1-2; HR 2.80, p = 0.0073), and serum Alb <4.0 g/dl (vs. ≥ 4.0 g/dl; HR 2.03, p = 0.0069). CONCLUSIONS: Preoperative cT stage, Alb, and postoperative pathological findings are independent prognostic factors for patients undergoing neoadjuvant chemotherapy for advanced thoracic esophageal SCC. This analysis may aid in stratification according to individual patient risk.

Randomized study of low-dose versus standard-dose chemoradiotherapy for unresectable esophageal squamous cell carcinoma (JCOG0303).

Low-dose cisplatin and 5-fluorouracil (LDPF) chemotherapy with daily radiotherapy (RT) is used as an alternative chemoradiotherapy regimen for locally advanced esophageal carcinoma. We evaluated whether RT plus LDPF chemotherapy had an advantage in terms of survival and/or toxicity over RT plus standard-dose cisplatin and 5-fluorouracil (SDPF) chemotherapy in this study. This multicenter trial included esophageal cancer patients with clinical T4 disease and/or unresectable regional lymph node metastasis. Patients were randomly assigned to receive RT (2 Gy/fraction, total dose of 60 Gy) with SDPF (arm A) or LDPF (arm B) chemotherapy. The primary endpoint was overall survival (OS). A total of 142 patients (arm A/B, 71/71) from 41 institutions were enrolled between April 2004 and September 2009. The OS hazard ratio in arm B versus arm A was 1.05 (80% confidence interval, 0.78-1.41). There were no differences in toxicities in either arm. Arm B was judged as not promising for further evaluation in the phase III setting. Thus, the Data and Safety Monitoring Committee recommended that the study be terminated. In the updated analyses, median OS and 3-year OS were 13.1 months and 25.9%, respectively, for arm A and 14.4 months and 25.7%, respectively, for arm B. Daily RT plus LDPF chemotherapy did not qualify for further evaluation as a new treatment option for patients with locally advanced unresectable esophageal cancer. This study was registered at the UMIN Clinical Trials Registry as UMIN000000861.

Curative resection of esophageal cancer with a double aortic arch.

Thoracic esophageal cancer with a double aortic arch is extremely rare. We herein report the case of a 63-year-old man with a double aortic arch who underwent an esophagectomy with a three-field lymphadenectomy for cancer in the lower thoracic esophagus. In such cases, it is important to recognize the relationship between the right and left aortic arches and the bilateral recurrent laryngeal nerves (RLNs). We were able to accurately understand the anatomical position of the RLNs using a precedent cervical procedure with partial resection of the manubrium to remove the nodes along the bilateral RLNs.

Supraclavicular node metastasis from thoracic esophageal carcinoma: A surgical series from a Japanese multi-institutional nationwide registry of esophageal cancer.

OBJECTIVES: In the present TNM classification, involvement of supraclavicular nodes is defined as distant metastases. However, the therapeutic value of supraclavicular node dissection remains controversial. The purpose of this study was to evaluate the survival benefit of dissection of metastases to the supraclavicular lymph nodes in patients with thoracic esophageal carcinoma by using a large nationwide registry of esophageal cancer maintained by the Japanese Esophageal Society. METHODS: The study group comprised 1309 patients with thoracic esophageal carcinoma treated in 2001, 2002, and 2003, who underwent esophagectomy with 3-field dissection for curative intent, and in whom the locations of pathologic metastatic lymph nodes and outcome evaluations were available. RESULTS: Of 1309 patients, 559 (42.7%) had no nodal metastases, 560 (42.8%) had at least 1 positive node but were supraclavicular node-negative, and 190 (14.5%) had supraclavicular node metastases. The 5-year survival was 73.7% for patients with N0, 40.4% for node-positive patients without supraclavicular node disease, and 24.1% for patients with supraclavicular node metastasis. In a multivariate analysis, male sex (P<.001), deeper T category (P<.001), and more positive nodes (P<.001) retained statistical significance as adverse prognostic factors for overall survival. Supraclavicular node metastasis was not significant (P=.062). CONCLUSIONS: The survival benefit of dissection of metastases to the supraclavicular lymph nodes was indicated in patients with thoracic esophageal carcinoma. Supraclavicular nodes appear to be regional nodes similar to other regional nodes.

Coffee and green tea consumption is associated with upper aerodigestive tract cancer in Japan.

The impact of coffee and green tea consumption on upper aerodigestive tract (UADT) cancer risk has not been established. Evaluation of the possible anticarcinogenic properties of their ingredients is confounded by the potential increase in risk owing to the high temperatures at which these beverages are generally consumed. We conducted a case-control study to evaluate the association between coffee and tea consumption and the risk of UADT cancer. The study enrolled 961 patients with UADT cancer and 2,883 noncancer outpatients who visited Aichi Cancer Center between 2001 and 2005. Information on coffee and green tea consumption and other lifestyle factors was collected via a self-administered questionnaire. Consumption of three or more cups of coffee per day had a significant inverse association with UADT cancer [odds ratio (OR) 0.73, 95% confidence interval (CI) 0.55-0.96]. In contrast, consumption of three or more cups of green tea per day had a significant positive association with UADT cancer (OR 1.39, 95% CI 1.13-1.70). These associations were evident for head and neck cancer but not for esophageal cancer. The association of coffee consumption with head and neck cancer was observed only among never smokers and alcohol drinkers. Similarly, the association of green tea consumption was observed among never smokers and never alcohol drinkers. No change in these associations was seen on stratification by each confounding factors. These findings suggest that consumption of coffee might be associated with a decreased risk of UADT cancer, whereas that of green tea might be associated with an increased risk.

Time to first cigarette and upper aerodigestive tract cancer risk in Japan.

BACKGROUND: Cigarette smoking is the major cause for upper aerodigestive tract (UADT) cancers. The time to first cigarette (TTFC) of the day is a distinct indicator of nicotine dependence, but scanty information is available on its possible relation with UADT cancers (oral, oropharyngeal, hypopharyngeal, laryngeal, nasopharyngeal, and esophageal cancers). METHODS: This case-control study includes a total of 1,009 incident UADT cancer cases and 3,027 age- and sex-matched noncancer controls admitted to the Aichi Cancer Center (Nagoya, Japan) between 2001 and 2005. We estimated OR and 95% confidence intervals (CI) for TTFC using logistic regression models after adjustment for several potential confounders. RESULTS: TTFC was inversely related to the risk of UADT cancer, and this association was consistent across subtypes of head and neck cancer and esophageal cancer. For all UADT cancers considered among ever smokers and after accurate allowance for smoking quantity and duration, besides other relevant covariates, compared with TTFC more than 60 minutes, the adjusted ORs were 1.40 (95% CI: 0.93-2.11) for 31 to 60 minutes, 1.76 (95% CI: 1.20-2.58) for 6 to 30 minutes, and 2.43 (95% CI: 1.64-3.61) for within 5 minutes. No significant heterogeneity was found in strata of sex, age, alcohol consumption, fruit and vegetable intake, and occupation for overall and site-specific analysis. CONCLUSION: Nicotine dependence, as indicated by the TTFC, is associated with increased risk of UADT cancers and is therefore an independent marker of exposure to smoking. IMPACT: Our result indicates more detailed risk evaluation of UADT cancers that is enabled by the TTFC.

Inverse association between yoghurt intake and upper aerodigestive tract cancer risk in a Japanese population.

Although the combination of tobacco smoking and alcohol drinking account for approximately 80% of upper aerodigestive tract (UADT) cancer risk, the role of dietary factors, including dairy products, in the risk of these cancers remains controversial. We aimed to evaluate the association between dairy product intake and UADT cancer risk in a Japanese population. We conducted a case-control study in 959 patients with UADT cancer and 2877 sex- and age-matched noncancer control subjects who visited the Aichi Cancer Center in Nagoya, Japan. Data on lifestyle factors, including diet, were obtained by self-administered questionnaire. Associations were assessed by multivariate logistic regression models that considered potential confounders. We found a significant inverse association between yoghurt intake and UADT cancer risk with multivariate-adjusted odds ratios and 95% confidence intervals for <1 time/week, ≥ 1 time/week and <1 time/day, and ≥ 1 time/day consumption of yoghurt of 0.70 (95% confidence interval: 0.54-0.91), 0.67 (0.54-0.84), and 0.73 (0.55-0.95) relative to nonconsumers (P trend=0.005). When stratified by primary tumor site, this association was significant among patients with hypopharyngeal, laryngeal, and esophageal cancer. However, we saw no significant association between milk or butter intake and UADT cancer risk. In this study, we found that a high intake of yoghurt may lower the risk of developing UADT cancer in a Japanese population. Further investigation of this association is warranted.

A randomized trial comparing postoperative adjuvant chemotherapy with cisplatin and 5-fluorouracil versus preoperative chemotherapy for localized advanced squamous cell carcinoma of the thoracic esophagus (JCOG9907).

BACKGROUND: Patients with esophageal carcinoma receiving postoperative chemotherapy showed superior disease-free survival than those receiving surgery alone in a Japan Clinical Oncology Group trial (JCOG9204). The purpose of this study was to evaluate optimal perioperative timing-that is, before or after surgery-for providing chemotherapy in patients with locally advanced esophageal squamous cell carcinoma. METHODS: Eligible patients with clinical stage II or III, excluding T4, squamous cell carcinoma were randomized to undergo surgery followed (group 1) or preceded (group 2) by chemotherapy consisting of two courses of cisplatin plus 5-fluorouracil. The primary end point was progression-free survival. RESULTS: We randomized 330 patients, with 166 assigned to group 1 and 164 to group 2, between May 2000 and May 2006. The planned interim analysis was conducted after completion of patient accrual. Progression-free survival did not reach the stopping boundary, but overall survival in group 2 was superior to that of group 1 (P = 0.01). Therefore, the Data and Safety Monitoring Committee recommended early publication. Updated analyses showed the 5-year overall survival to be 43% in group 1 and 55% in group 2 (hazard ratio 0.73, 95% confidence interval 0.54-0.99, P = 0.04), where the median follow-up of censored patients was 61.6 months. Concerning operative morbidity, renal dysfunction after surgery in group 2 was slightly higher than in group 1. CONCLUSIONS: Preoperative chemotherapy with cisplatin plus 5-fluorouracil can be regarded as standard treatment for patients with stage II/III squamous cell carcinoma.

Radiotherapy quality assurance review for a multi-center randomized trial of locally advanced esophageal cancer: the Japan Clinical Oncology Group (JCOG) trial 0303.

BACKGROUND AND PURPOSE: The purpose of this study was to evaluate the radiotherapy (RT) quality assurance (QA) for JCOG 0303. METHODS AND MATERIALS: JCOG 0303 was a multi-center phase II/III trial that compared two types of chemotherapy administered concomitantly with RT for locally advanced esophageal cancer. RT requirements included a total dose of 60 Gy in 30 fractions and CTV with a 2-cm margin cranio-caudally to the primary tumor. The QA assessment was given as per protocol (PP), deviation acceptable (DA), violation unacceptable (VU), and incomplete/not evaluable following predefined criteria for quality parameters. RESULTS: A total of 142 cases were accrued. After excluding 36 incomplete/not evaluable, 106 (75%) were fully evaluable for RT quality review. Of these 106, there were 4 VU (4%) and overall RT compliance (PP + DA) was 96%. Comparing the incidence of VU based on the numbers enrolled by institution, the highest quarter of enrollment (≥7 cases) had no VU, while all VU (4; 11%) were from institutions enrolling <7 patients. CONCLUSIONS: The results of the RTQA assessment for JCOG 0303 were sufficient to provide reliable results. Additional improvements will be needed for institutions with low accrual rates.

Docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer.

BACKGROUND: This study aimed to evaluate the efficacy of docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy for locally advanced borderline-resectable T4 esophageal cancer. PATIENTS AND METHODS: We retrospectively analyzed data regarding thirty patients with borderline-resectable T4 tumor who received either DCF or cisplatin plus 5-fluorouracil (FP) as induction chemotherapy. RESULTS: The overall response rate was significantly better for the DCF group than the FP group. In the DCF group, 6/16 patients achieved a grade 2 histological post-chemotherapeutic effect after treatment, compared to 1/14 in FP group. Except for myelotoxicity, no other significant differences in toxicity were observed during induction chemotherapy between groups. The DCF regimen did not result in increased postoperative complications compared to the FP regimen. Postoperative recurrence or distant metastasis was observed in 7/10 of FP patients and 5/12 of DCF patients. CONCLUSION: DCF induction chemotherapy may be an option for conversion therapy of initially unresectable, locally advanced esophageal cancer.

Inverse association between toothbrushing and upper aerodigestive tract cancer risk in a Japanese population.

BACKGROUND: Oral hygiene is attracting increasing attention as a potential risk factor for cancers. To investigate the association between toothbrushing frequency and upper aerodigestive tract (UADT) cancer, the authors conducted a large-scale case-control study. METHODS: A total of 856 UADT cancer case participants and 2696 age- and sex-matched control subjects without cancer were included. Edentulous or participants with unknown frequency of toothbrushing or number of remaining teeth were excluded. Associations were assessed by odds ratios and 95% confidence intervals in logistic regression models with adjustment for potential confounders. RESULTS: Compared with toothbrushing once per day, the adjusted odds ratio for brushing twice or more was 0.82 (95% confidence interval: 0.68, 0.99) whereas that for not brushing was 1.79 (0.79, 4.05). This association was observed especially in subjects who had a history of heavy smoking or drinking. CONCLUSIONS: The authors suggest that toothbrushing could have a protective effect for UADT cancer.

The benchmark analysis of gastric, colorectal and rectal cancer pathways: toward establishing standardized clinical pathway in the cancer care.

Most clinical pathways in treating cancers in Japan are based on individual physician's personal experiences rather than on an empirical analysis of clinical data such as benchmark comparison with other hospitals. Therefore, these pathways are far from being standardized. By comparing detailed clinical data from five cancer centers, we have observed various differences among hospitals. By conducting benchmark analyses, providing detailed feedback to the participating hospitals and by repeating the benchmark a year later, we strive to develop more standardized clinical pathways for the treatment of cancers. The Cancer Quality Initiative was launched in 2007 by five cancer centers. Using diagnosis procedure combination data, the member hospitals benchmarked their pre-operative and post-operative length of stays, the duration of antibiotics administrations and the post-operative fasting duration for gastric, colon and rectal cancers. The benchmark was conducted by disclosing hospital identities and performed using 2007 and 2008 data. In the 2007 benchmark, substantial differences were shown among five hospitals in the treatment of gastric, colon and rectal cancers. After providing the 2007 results to the participating hospitals and organizing several brainstorming discussions, significant improvements were observed in the 2008 data study. The benchmark analysis of clinical data is extremely useful in promoting more standardized care and, thus in improving the quality of cancer treatment in Japan. By repeating the benchmark analyses, we can offer truly clinical evidence-based higher quality standardized cancer treatment to our patients.