Yuri Ito

Intralesional steroid injection to prevent stricture after endoscopic submucosal dissection for esophageal cancer: a controlled prospective study

BACKGROUND AND STUDY AIMS The frequency of stricture after endoscopic submucosal dissection (ESD) for esophageal squamous cell carcinoma with a mucosal defect involving more than three-quarters of the circumference is 70% - 90%. Stricture decreases quality of life and requires multiple endoscopic balloon dilation (EBD) sessions. We investigated the efficacy and safety of a single session of intralesional steroid injections to prevent post-ESD stricture. PATIENTS AND METHODS We conducted a prospective study on 30 patients with esophageal squamous cell carcinoma treated by ESD, who had a more than three-quarter but less than whole circumferential defect. A single session of intralesional steroid injections was undertaken immediately after ESD. Esophagogastroduodenoscopy was performed whenever patients reported dysphagia and 2 months after ESD in patients without dysphagia. Results were compared with a historical control group of 29 patients who underwent ESD without intralesional steroid injection. The primary endpoint was the post-ESD stricture rate. Secondary endpoints were the number of EBD sessions and the complication rate. RESULTS Compared with the historical control group, the study group had a significantly lower stricture rate (10%, 3/30 patients vs. 66%, 19/29 patients; P < 0.0001) and a lower number of EBD sessions (median 0, range 0 - 2 vs. median 2, range 0 - 15; P < 0.0001). The study group had a complication rate of 7 % (2 /30 patients), comprising a submucosal tear in one patient and bleeding in another, which were not a direct result of EBD. CONCLUSIONS A single session of intralesional steroid injections showed promising results for the prevention of stricture after ESD for esophageal cancer.

Sublobar Resection Provides an Equivalent Survival After Lobectomy in Elderly Patients With Early Lung Cancer

BACKGROUND Sublobar resection is indicated for early-stage non-small cell lung cancer in patients with a perioperative risk associated with impaired medical conditions. This study was conducted to investigate the clinical impact of this procedure in the elderly. METHODS The patients who underwent complete resection for stage IA non-small cell lung cancer from 1990 and 2007 were enrolled (n = 764). Two age groups were defined as elderly (≥75 years) and younger (<75 years) patients. The 5-year survival, recurrence, and postoperative complications after sublobar resection were compared with those after standard lobectomy according to age group. RESULTS There were 133 elderly patients (79 standard lobectomies and 54 sublobar resections) and 631 younger patients (539 standard lobectomies and 92 sublobar resections). While the 5-year survival after sublobar resection was significantly inferior to that after standard lobectomy in the younger group (64.0% and 90.9%, respectively, p < 0.0001), however, no substantial difference was observed in the elderly (67.6% and 74.3%, p = 0.92). Locoregional recurrence rates were higher in patients after sublobar resection than those after standard lobectomy in both the elderly (11.1% vs 1.3%) and the younger (12.0% vs 1.5%) groups. No significant difference in postoperative complications was observed between the types of surgery in the elderly. CONCLUSIONS Sublobar resection for stage IA is considered to be an appropriate treatment in the elderly patients as this procedure provides an equivalent long-term outcome in comparison with lobectomy. A larger scale study with matching patients is necessary to confirm the noninferiority of sublobar resection in comparison with standard lobectomy in this population.

Diagnostic Accuracy of Noninvasive Genotyping of EGFR in Lung Cancer Patients by Deep Sequencing of Plasma Cell-Free DNA

BACKGROUND Genotyping of EGFR (epidermal growth factor receptor) mutations is indispensable for making therapeutic decisions regarding whether to use EGFR tyrosine kinase inhibitors (TKIs) for lung cancer. Because some cases might pose challenges for biopsy, noninvasive genotyping of EGFR in circulating tumor DNA (ctDNA) would be beneficial for lung cancer treatment. METHODS We developed a detection system for EGFR mutations in ctDNA by use of deep sequencing of plasma DNA. Mutations were searched in >100 000 reads obtained from each exon region. Parameters corresponding to the limit of detection and limit of quantification were used as the thresholds for mutation detection. We conducted a multi-institute prospective study to evaluate the detection system, enrolling 288 non-small cell lung cancer (NSCLC) patients. RESULTS In evaluating the performance of the detection system, we used the genotyping results from biopsy samples as a comparator: diagnostic sensitivity for exon 19 deletions, 50.9% (95% CI 37.9%-63.9%); diagnostic specificity for exon 19 deletions, 98.0% (88.5%-100%); sensitivity for the L858R mutation, 51.9% (38.7%-64.9%); and specificity for L858R, 94.1% (83.5%-98.6%). The overall sensitivities were as follows: all cases, 54.4% (44.8%-63.7%); stages IA-IIIA, 22.2% (11.5%-38.3%); and stages IIIB-IV, 72.7% (60.9%-82.1%). CONCLUSIONS Deep sequencing of plasma DNA can be used for genotyping of EGFR in lung cancer patients. In particular, the high specificity of the system may enable a direct recommendation for EGFR-TKI on the basis of positive results with plasma DNA. Because sensitivity was low in early-stage NSCLC, the detection system is preferred for stage IIIB-IV NSCLC.

Trends in Colorectal Cancer Incidence by Subsite in Osaka, Japan

To date, the time trends of left-to-right shift of colorectal cancer incidence have been reported in Western countries. In the present study, we calculated the average annual number of colorectal cancer incidence and the age-adjusted colorectal rates, and examined the change of subsite distribution using the data from the Osaka Cancer Registry between 1974 and 2003. Mucosal carcinoma cases were excluded from the analyses. The proportions of right colon cancer among all colorectal cancer cases were consistently increased; from 21.5% in 1974-78 to 25.6% in 1999-2003 among men, and from 28.2% in 1974-78 to 36.8% in 1999-2003 among women. The age-adjusted incidence rates of right colon cancer among men and women recently levelled off, while the rates of left colon and rectal cancers showed a declining trend. Among women, right colon cancer was more common in the elderly than in the young. The change of subsite distribution seemed to be associated with population aging, changes of life style and the development of total colonoscopy. Careful monitoring is necessary to confirm these findings.

Anatomical versus non-anatomical resection for hepatocellular carcinoma.

The optimal surgical resection method in patients with HCC to minimize the risk of local recurrence has not yet been determined. The aim of this study was to compare the prognosis following anatomical versus non‐anatomical hepatic resection for hepatocellular carcinoma (HCC).

Incidence of metachronous second primary cancers in Osaka, Japan: Update of analyses using population-based cancer registry data

Cancer survivors are at excess risk of developing second primary cancers, but the precise level of risk in Japanese patients is not known. To investigate the risk of survivors developing second primary cancers, we conducted a retrospective cohort study using data from the Osaka Cancer Registry. The study subjects comprised all reported patients aged 0–79 years who were first diagnosed with cancer between 1985 and 2004 in Osaka and who survived for at least 3 months, followed‐up through to December 2005. A metachronous second primary cancer was defined as any invasive second cancer that was diagnosed between 3 months and 10 years after the first cancer diagnosis. The main outcome measures were incidence rates per 100 000 person‐years, cumulative risk and standardized incidence ratios (SIR) of second primary cancer. Metachronous second primary cancers developed in 13 385 of 355 966 survivors (3.8%) after a median follow‐up of 2.5 years. Sex‐specific incidence rates of metachronous second primary cancer per 100 000 person‐years increased with age, and were higher among men than women (except for the 0–49 years age group), but these rates did not differ over the study period. The 10‐year cumulative risk was estimated as 13.0% for those who first developed cancer at 60–69 years of age (16.2% for men, 8.6% for women). The SIR among those with first cancer diagnosed at 0–39 and 40–49 years of age were 2.13 and 1.52, respectively, in both sexes, whereas the SIR among cancers of the mouth/pharynx, esophagus and larynx were much higher than one as for site relationships. We showed that cancer survivors in Osaka, Japan, were at higher risk of second primary cancers compared with the general population. Our findings indicate that second primary cancers should be considered as a commonly encountered major medical problem. Further investigations are required to advance our understanding to enable the development of effective measures against multiple primary cancers. (Cancer Sci 2012; 103: 1111–1120)

Tobacco smoking and the risk of subsequent primary cancer among cancer survivors: a retrospective cohort study

BACKGROUND Smoking is a well-known risk factor for cancer; however, there is little evidence as to whether the smoking status of cancer survivors has any risk for subsequent primary cancer (SPC) incidence, regardless of the first cancer sites. PATIENTS AND METHODS In total, 29,795 eligible patients with a first cancer between 1985 and 2004 were examined for SPC until the end of 2006, using a record linkage between hospital-based and population-based cancer registries. The association between smoking at the time of the first cancer diagnosis and three SPC groups (i.e. specific SPC, smoking-related SPCs, and all SPCs) was calculated by Poisson regression. RESULTS Ever smokers had 59% and 102% higher risk for all SPCs and smoking-related SPCs, respectively, than never smokers. Cancer survivors who had recently stopped smoking had 18% and 26% less risk, respectively, for these SPCs than those who smoked at the diagnosis. We also found that, compared with those who had never smoked, cancer survivors who had ever smoked had a significantly elevated risk of oral/pharyngeal, esophageal, stomach, lung, and hematological SPCs, regardless of the first cancer sites. CONCLUSIONS These findings indicate that smoking increases not only the first cancer but also a second or SPC. Moreover, the results from recent quitters versus current smokers suggest that smoking cessation may decrease the risk for SPC, especially for smoking-related SPCs in cancer survivors. Preventive measures are necessary to reduce not only SPC incidence but also tobacco use.

Trends in cancer incidence and mortality in Osaka, Japan: Evaluation of cancer control activities

It is essential to analyze trends in cancer incidence and mortality in the evaluation of cancer control activities. Previous studies from Japan, however, described trends in cancer incidence and mortality only qualitatively. There have been few studies that evaluated the trends quantitatively. We calculated age‐standardized mortality rates (1968–2006) and incidence rates (1968–2002) for overall cancer sites and for each major site (stomach, colorectal, liver, lung, prostate, breast, and uterus) in Osaka. We applied a joinpoint regression model to the trends in incidence and mortality, in order to identify the joinpoint and estimate annual percentage change. Then, we quantified the contribution of individual cancer sites to the change in overall cancer mortality rate. For the sites that made a major contribution, we estimated the contribution of the incidence reduction to the mortality reduction. In Osaka, the overall cancer mortality started to decrease from 1998. The decrease was largely attributable to the reduction of stomach and liver cancer mortality (73% for men, 53% for women). The reduction of mortality from the two cancer sites could be explained by the decrease in their incidences (more than 80% for stomach, approximately 100% for liver). Female breast cancer incidence and mortality were both increased probably due to lifestyle changes and delayed introduction of an effective screening program among Japanese. In conclusion, the decreased overall cancer mortality in Osaka during the study period was mainly due to natural decreases in the incidence of stomach and liver cancer, which were attributable to the decrease in risk factors. (Cancer Sci 2009: 100: 2390–2395)

Conditional survival for longer-term survivors from 2000–2004 using population-based cancer registry data in Osaka, Japan

BackgroundWe usually report five-year survival from population-based cancer registries in Japan; however these survival estimates may be pessimistic for cancer survivors, because many patients with unfavourable prognosis die shortly after diagnosis. Conditional survival can provide relevant information for cancer survivors, their family and oncologists.MethodsWe used the period approach to estimate the latest 10-year survival of 38,439 patients with stomach, colorectal, lung, breast and prostate cancer diagnosed between 1990 and 2004 and followed-up from 2000–04 in Osaka, Japan. Conditional survival is an estimate, with the pre-condition of having already survived a certain length of time. Conditional five-year relative survival of one to five years after diagnosis was calculated by site, age and stage for survivors under the age of 70.ResultsFive-year relative survival for stomach cancer was 60%. Conditional five-year relative survival was 77% one year after diagnosis and 97% five years after diagnosis. This means that 97% of patients who survive five years after diagnosis can survive a further five years. Conditional five-year relative survival improved successively with each additional year that patients lived after diagnosis for stomach, colorectal and lung cancer. These figures for breast and prostate cancer were stable at high survival. Liver cancer did not show an increase in conditional five-year survival.ConclusionConditional five-year survival is a relevant figure for long-term cancer survivors in Japan. It is important for population-based cancer registries to provide figures which cancer patients and oncologists really need.

Partial Cancer Prevalence in Japan up to 2020: Estimates Based on Incidence and Survival Data from Population-based Cancer Registries

Measuring cancer prevalence in Japan has been difficult because population-based cancer registries have been conducted in limited areas. The purpose of this study was to estimate cancer prevalence in Japan from 1995 to 2020 for 5-year periods based on selected population-based cancer registry data. 1-, 2-3-, 4-5- and 5-year partial prevalence were estimated using incidence and survival data. Incidence and survival were calculated using data from selected cancer registries. We estimated the cancer survival by age group, primary site, and sex using the mixture cure fraction model. Kaplan-Meier estimates were applied to subgroups for which the survival did not converge to the estimated model. We projected that 1-year cancer prevalence for all sites would increase from 209 971 to 367 354 for men and from 164 622 to 275 776 for women, that 2-3-year prevalence would increase from 288 284 to 508 731 for men and from 255 684 to 418 630 for women, that 4-5-year prevalence would increase from 216 834 to 379 461 in men and from 211 764 to 342 031 in women, and that 5-year prevalence would increase from 715 089 to 1 255 546 in men and from 632 070 to 1 036 437 in women. This study is the first estimate of cancer prevalence in the future in Japan.