The number of patients treated by proton beam therapy in Japan since 2000 has increased; in 2016, 11 proton facilities were available to treat patients. Notably, proton beam therapy is very useful for pediatric cancer; since the pediatric radiation dose to normal tissues should be reduced as much as possible because of the effect of radiation on growth, intellectual development, endocrine organ function and secondary cancer development. Hepatocellular carcinoma is common in Asia, and most of the studies of proton beam therapy for liver cancer have been reported by Japanese investigators. Proton beam therapy is also a standard treatment for nasal and paranasal lesions and lesions at the base of the skull, because the radiation dose to critical organs such as the eyes, optic nerves and central nervous system can be reduced with proton beam therapy. For prostate cancer, comparative studies that address adverse effects, safety, patient quality of life and socioeconomic issues should be performed to determine the appropriate use of proton beam therapy for prostate cancer. Regarding new proton beam therapy applications, experience with proton beam therapy combined with chemotherapy is limited, although favorable outcomes have been recently reported for locally advanced lung cancer, esophageal cancer and pancreatic cancer. Therefore, ‘chemoproton’ therapy appears to be a very attractive field for further clinical investigations. In conclusion, there are cost issues and considerations regarding national insurance for the use of proton beam therapy in Japan. Further studies and discussions are needed to address the use of proton beam therapy for several types of cancers, and for maintaining the quality of life of patients while retaining a high cure rate.
Previous studies have revealed the association of multidrug resistance with histone deacetylases inhibitors treatment in cancer cells. But little data were available for the correlation of histone deacetylases and drug-resistant-related proteins in breast cancer tissue. This study aimed to exploring the association of histone deacetylases expression with clinicopathological features, drug-resistant-related proteins, prognosis and therapeutic responses in breast cancer patients.
We performed immunohistochemistry to study the expression of HDAC1 and HDAC2 in 226 breast cancer and 34 breast fibroadenoma patients, and the expression of breast cancer resistance protein, P-glycoprotein, lung resistance protein and multidrug resistance protein in 226 breast cancer.
In breast cancer, HDAC2 expression was significantly increased than in fibroadenoma (P = 0.015), and correlated with lymph node metastasis (P = 0.002), advanced clinical stages (P = 0.016) and high histological grade (P = 0.001). Significant positive correlations were found between HDAC2 and Ki67, HDAC1 and multidrug resistance protein, HDAC2 and breast cancer resistance protein, HDAC2 and multidrug resistance protein. HDAC2 positive expression was associated with shorter overall survival (P = 0.035) of breast cancer patients. In addition, HDAC2-positive expression was significantly associated with shorter overall survival in multidrug resistance protein-positive patients (P = 0.034), but not in multidrug resistance protein-negative patients (P = 0.530). HDAC2-positive expression was associated with shorter survival in patients who received chemotherapy containing anthracyclines (overall survival, P = 0.041; disease-free survival, P = 0.084), but not in patients who received chemotherapy without anthracyclines (overall survival, P = 0.679; disease-free survival, P = 0.708).
HDAC2 overexpression correlated with the metastasis, progression and the increased Ki67, multidrug resistance protein expression in breast cancer, and HDAC2 could be a prognostic factor of breast cancer patients, especially the patients who received anthracyclines therapy.
We investigated the efficacy and safety of concurrent chemoradiotherapy using weekly low-dose docetaxel and cisplatin in patients with locally advanced nasopharyngeal carcinoma.
This was a retrospective analysis of 31 patients who were treated with this regimen from 2001 to 2014. Concurrent chemoradiotherapy consisted of radiotherapy with a total dose of 59.4–70.2 Gy plus weekly administration of docetaxel (5–10 mg/m2) and cisplatin (20 mg/m2), up to six cycles. At least two cycles of platinum-based adjuvant chemotherapy were prescribed for Stage IV and Stage III patients with partial response or stable disease after concurrent chemoradiotherapy.
Of the 31 patients, 28 (90%) completed concurrent chemoradiotherapy as planned. The overall complete response and partial response rates were 42% and 52%, respectively. Seventeen of the 21 patients who were prescribed adjuvant chemotherapy underwent it. After a median follow-up of 39.1 months for the 23 surviving patients, 9 (29%) developed locoregional recurrence or progression and 6 patients (19%) developed distant metastasis. The 3-year overall survival and progression-free survival rates were 76% and 56%, respectively. Univariate analyses revealed that clinical stage was a significant predictor of complete response, overall survival and progression-free survival. The most serious adverse events were mucositis during concurrent chemoradiotherapy and neutropenia during adjuvant chemotherapy.
This concurrent chemoradiotherapy protocol showed practical efficacy with high feasibility and acceptable toxicity. To improve the progression-free survival of patients with Stage IV disease who are treated by this protocol, changes to their treatment strategy should be considered.
To evaluate the impact of p16 expression as a surrogate marker of human papillomavirus status in oropharyngeal squamous cell carcinoma patients underwent surgery followed by postoperative radiotherapy.
We identified 126 consecutive patients with histologically confirmed, newly diagnosed oropharyngeal squamous cell carcinoma who received surgery followed by radiotherapy and had p16 expression data available. All patients were treated between 2001 and 2011. Patients with high-risk factors (positive surgical margin and/or extracapsular extension) or other risk factors (multiple positive lymph nodes, perineural/lymphovascular invasion) were offered postoperative radiotherapy with or without concurrent chemotherapy.
One hundred and four (82.5%) patients were p16-positive (p16 (+)) and 22 (17.5%) were p16-negative (p16 (–)). With a median follow-up of 56 months, patients with p16 (+) oropharyngeal squamous cell carcinoma exhibited a significantly better 5-year disease-free survival (80.7% vs. 57.6%, P < 0.001) and overall survival (84.9% vs. 59.1%, P < 0.001) than those with p16 (–) tumors. The p16 (+) oropharyngeal squamous cell carcinoma with high-risk factors (n = 64) showed no difference in disease-free survival (79.7% vs. 68.3%; P = 0.531) and overall survival (82.1% vs. 76.2%; P = 0.964) between postoperative radiotherapy and postoperative radiotherapy with concurrent chemotherapy.
Expression of p16 is a strong independent prognostic factor of survival in the postoperative setting of oropharyngeal squamous cell carcinoma. The favorable prognosis of p16 (+) oropharyngeal squamous cell carcinoma suggests a need to re-examine traditional risk stratification for determining optimal adjuvant treatment.
To evaluate the feasibility of postoperative intensity-modulated radiotherapy for head and neck cancer by investigating the patterns of failure after this therapy.
A retrospective chart review was performed.
Between March 2006 and December 2013, 122 consecutive patients with head and neck squamous cell carcinoma were treated by surgery followed by postoperative intensity-modulated radiotherapy. In regard to the site of the primary tumor, 59 (48%) patients had cancer of the oral cavity, 31 (26%) patients had cancer of the hypopharynx, 14 (11%) patients had cancer of the oropharynx, 10 (8%) patients had cancer of the larynx and 8 (7%) patients had cancer of unknown primary. The median follow-up period of the surviving patients was 54 months (range, 25–115). Concurrent chemotherapy was administered in 76 patients (62%). The median prescribed radiation dose was 66 Gy. The 3-year overall survival, progression-free survival, distant metastasis free survival and loco-regional control rates were 59%, 48%, 52.4% and 71%, respectively. Of the 122 patients, 32 developed loco-regional recurrence as the initial recurrence, including in-field recurrence in 26 patients, marginal recurrence in five patients and out-field recurrence in seven patients. Of the five patients with marginal recurrence, four have had two or more surgeries before the intensity-modulated radiotherapy and three had oral cavity cancer. Severe adverse events were not frequent, occurring at a frequency of <5%, except for mucositis. No severe toxicities associated with the flap reconstruction were observed either.
Postoperative intensity-modulated radiotherapy appears to be effective and feasible for patients with head and neck squamous cell carcinoma.
Surgical resection is employed in patients with resectable non-small cell lung cancer. Despite complete resection, recurrence is sometimes observed. Oncogenic mutations promote initiation and progression of lung cancer, and mutation status predicts treatment outcome of advanced non-small cell lung cancer; however, their impact on the recurrence patterns remains poorly understood.
We retrospectively studied 401 patients showing recurrence after complete resection of non-small cell lung cancer. Clinicopathological factors were reviewed for time to recurrence, and recurrence patterns were compared according to oncogenic status and examined according to EGFR mutational subtype.
Among 401 patients, 185 with EGFR mutation, 46 with KRAS mutation, 15 with ALK rearrangement and 155 with triple-negative mutation were identified. Multivariate analysis following univariate analyses showed that younger age, well–moderately-differentiated histology, earlier pathologic stage and presence of EGFR or ALK mutation were favorable prognostic factors for time to recurrence. Locoregional recurrence was observed in 53.3% of ALK-positive patients, being significantly common in these patients than in EGFR- and KRAS-positive patients. EGFR-positive patients mostly experienced pleural recurrence, the incidence of which was significantly higher in triple-negative mutation patients. Adrenal recurrence was observed in 7.2% of triple-negative mutation patients, but it was rarely identified in EGFR-positive patients. Among EGFR-positive patients, the incidence of brain metastases was significantly higher in L858R cohort than in Del Ex19 cohort.
In resected non-small cell lung cancer, younger age, well–moderately-differentiated histology, earlier pathologic stage and presence of EGFR or ALK mutation were favorable factors for TTR, and distinct recurrence patterns were revealed according to oncogenic mutation status and mutational EGFR subtype. Our results may provide suggestions for developing a strategy for follow-up and adjuvant therapies after resection.
Programmed death-ligand 1 is an immune modulator that promotes immunosuppression by binding to programmed death-1 of T-lymphocytes. Whereas programmed death-ligand 1 expression has been shown to be associated with the clinical response to anti-programmed death-ligand 1 antibody, the association of tumor programmed death-ligand 1 expression with clinicopathological/molecular features and with prognosis remains inconclusive in lung adenocarcinoma. We therefore examined the association of programmed death-ligand 1 expression with the clinicopathological/molecular features and prognosis of lung adenocarcinoma.
Using tissue microarrays of 268 consecutive cases of lung adenocarcinoma, we evaluated programmed death-ligand 1 expression by immunohistochemistry. We examined the association of programmed death-ligand 1 expression with clinicopathological and molecular features. We also examined the prognostic association of programmed death-ligand 1 expression, using the log-rank test as well as Cox proportional hazards regression models to compute the mortality hazard ratio (HR).
Programmed death-ligand 1 immunoreactivity (at least 5% of the tumor cells) was observed in 43 (16%) of 268 cases of lung adenocarcinoma. Programmed death-ligand 1 positivity was associated with less tumor differentiation (P < 0.0001) and EGFR wild-type status (P = 0.0008). In a multivariable logistic regression analysis, less tumor differentiation was independently associated with programmed death-ligand 1 positivity (multivariable odds ratio, 6.54; 95% confidence interval [CI], 2.37–23.3; P = 0.0001). Programmed death-ligand 1 positivity was associated with a poor prognosis for lung cancer-specific survival (log-rank, P = 0.019; HR, 1.73; 95% CI, 1.06–2.72; P = 0.030) and overall survival (log-rank, P = 0.0014; HR, 1.88; 95% CI, 1.25–2.74).
Our study demonstrated that programmed death-ligand 1 positivity in lung adenocarcinoma was associated with less tumor differentiation and EGFR wild-type status, as well as a poor prognosis.
Systematic evaluation of the association between secondhand smoke exposure and lung cancer in Japan has yet to be conducted. Here, we performed a systematic review and meta-analysis of the relationship between secondhand smoke and lung cancer in Japanese non-smokers.
Relevant studies were collected from the MEDLINE and Ichushi Web databases using a combination of search terms and Medical Subject Headings. Eligible studies were identified, and relative risks or odds ratios were extracted to calculate pooled risk estimates. This procedure was performed independently by at least two authors. Stratified analyses were carried out according to study design, publication year, and whether or not potential confounding variables were accounted for. The presence of publication bias was assessed via funnel plots.
We identified four cohort studies and five case-control studies. Quantitative synthesis was conducted only for secondhand smoke exposure in the home during adulthood. Of the 12 populations included in meta-analysis, positive secondhand smoke exposure-lung cancer associations were observed in 11, whereas an inverse association was found in the remaining 1. The pooled relative risk of lung cancer associated with secondhand smoke exposure was 1.28 (95% confidence interval: 1.10–1.48). We found no evidence of publication bias, and a significant association remained even when potentially missing studies were included (pooled relative risk: 1.26; 95% confidence interval: 1.09–1.46). The results were stable across different subgroup analyses, including by study design, publication year, and when adjusting for confounding variables.
Secondhand smoke exposure in the home during adulthood results in a statistically significant increase in the risk of lung cancer.
Although it is well known that radiotherapy for prostate cancer increases comorbid rate of secondary bladder cancer, the effect of aging and smoking with radiotherapy on incidence rate of secondary bladder cancer remains unknown. Then, this study investigated the combinational effect of external beam radiotherapy for prostate cancer and aging or smoking on comorbid rate of secondary bladder cancer.
This study included 754 Japanese patients with prostate cancer treated with radiotherapy (n = 319) and radical prostatectomy (n = 435) from 2000 through 2013. The relationship between therapeutic modality for prostate cancer as well as age or smoking status and comorbid rate of secondary bladder cancer was examined.
During the median follow-up period of 4.3 and 3.1 years, secondary bladder cancer occurred in 11 (3.4%) and 5 (1.1%) of patients with prostate cancer treated with external beam radiotherapy and radical prostatectomy, respectively. The 5-year bladder cancer-free survival rate was 97.3% in the external beam radiotherapy group and 99.4% in the radical prostatectomy group. Age (hazard ratio = 1.15, P = 0.027) and ever smoking (hazard ratio = 5.65, P = 0.011) were significant predictive factors of secondary bladder cancer incidence in the external beam radiotherapy cohort, but not in the radical prostatectomy cohort. Inversely, among men with ever smoking, but not among older men, external beam radiotherapy (hazard ratio = 9.64, P = 0.0052) was a significant risk factor of secondary bladder cancer.
Taken together, these findings suggest that smoking history might be one of criteria to choose radical prostatectomy than external beam radiotherapy for prostate cancer, and that age would not be a criterion for therapeutic selection in terms of secondary bladder cancer.
Our aim was 2-fold: first, to assess the safety of short hydration treatment for urothelial cancer; and second, to assess the resultant quality of life of patients who received the treatment.
We assessed 61 patients including 31 outpatients and 30 inpatients, who received a combination of gemcitabine and cisplatin chemotherapy with short hydration. The serum creatinine (Cr) level and the estimated glomerular filtration rate were measured to assess renal function using linear mixed model analysis. To assess quality of life, the patients were asked to respond to the Functional Assessment of Cancer Therapy-General questionnaire. The responses were then analyzed using the paired t-test.
Patients who received short hydration chemotherapy showed no significant change in serum Cr level (P = 0.423) or estimated glomerular filtration rate (P = 0.582). There was also no significant change in serum Cr level or estimated glomerular filtration rate between patients who received short hydration chemotherapy and those who received consecutive hydration chemotherapy (P = 0.154 and 0.311, respectively). In every patient, the Functional Assessment of Cancer Therapy-General total score and subscale scores both improved as a result of outpatient chemotherapy with short hydration (P < 0.01).
The short hydration gemcitabine and cisplatin regimen for patients with urothelial cancer was safe. Further, the outpatient chemotherapy was found not only to be safe, but also to have improved the patients’ quality of life.
The aim of this study was to identify the clinical predictors related to the risk of high-grade bladder cancer before first-time transurethral resection of the bladder tumor (TUR-Bt) and to externally validate the accuracy of Shapur's nomogram predicting the risk of high-grade bladder cancer in Japanese patients. As a result, episode of gross hematuria (odds ratio: 2.68, P = 0.02), larger tumor size (odds ratio: 1.89, P < 0.01) and positive urinary cytology (odds ratio: 8.34, P < 0.01) were found to be significant predictors for high-grade bladder cancer. Furthermore, the nomogram showed a high predictive accuracy in our Japanese population (area under the curve: 0.79). Clinicians will be able to predict high-grade bladder cancer using the common factors in Shapur's study and ours, such as tumor size and urinary cytology, and gross hematuria as the additional factor first identified here to decide priorities for the treatment of patients diagnosed with bladder cancer.
Although cancer diagnoses during pregnancy are rare, they have been increasing with the rise in maternal age and are now a topic of international concern. In some cases, the administration of chemotherapy is unavoidable, though there is a relative paucity of evidence regarding the administration of anticancer drugs during pregnancy. As more cases have gradually accumulated and further research has been conducted, we are beginning to elucidate the appropriate timing for the administration of chemotherapy, the regimens that can be administered with relative safety, various drug options and the effects of these drugs on both the mother and fetus. However, new challenges have arisen, such as the effects of novel anticancer drugs and the desire to bear children during chemotherapy. In this review, we outline the effects of administering cytotoxic anticancer drugs and molecular targeted drugs to pregnant women on both the mother and fetus, as well as the issues regarding patients who desire to bear children while being treated with anticancer drugs.
Chemoradiotherapy has been clinically indicated for patients with resectable esophageal squamous cell carcinoma who refuse surgical resection and in locally advanced unresectable esophageal squamous cell carcinoma patients. Concurrent chemoradiotherapy prolongs survival than radiation therapy alone when given as definitive treatment. Therefore, chemoradiotherapy is recognized as the standard non-invasive treatment for patients with localized esophageal cancer who opt for non-surgical treatment. JCOG9906 showed promising outcomes for stage II/III ESCC patients. But there are some problems about chemoradiotherapy for esophageal squamous cell carcinoma. Late toxicities are sometimes lethal for patients who achieved complete response even after years. Salvage treatment for residual or recurrent disease is unestablished. Modified Radiation Therapy Oncology Group regimen at the dose of 50.4 Gy reduced late toxicities without reducing efficacy. Optimal timings and procedure of salvage surgery and endoscopic therapy is evaluated in JCOG0909. Strategy including salvage therapy after chemoradiotherapy should be considered at the time of starting the treatment. Targeted therapy has not shown adding effect for chemoradiotherapy for esophageal squamous cell carcinoma yet. New agents, such as immune checkpoint inhibitors, are expected to show synergistic effect with chemoradiotherapy for esophageal squamous cell carcinoma. Further investigation is needed.
Previously, we identified six miRNAs that are differentially expressed in colorectal cancer compared with healthy controls. Here, we tested them in gastric cancer GC.
We performed quantitative RT-PCR on serum samples from 92 patients with gastric cancer and 89 controls for the six miRNAs, and analyzed their risk scores to evaluate the diagnostic value of the serum miRNA profiling system.
After a two-phase selection and validation process, five miRNAs were found to significantly differ in expression between gastric cancer samples and control samples, including miR-21, miR-31, miR-92a, miR-181b, and miR-203. Risk score analysis showed that this miRNA panel could distinguish gastric cancer cases from controls with high sensitivity and specificity. Under receiver operating characteristic curves, areas under the curve for tumor identification were 0.933 (95% confidence interval [CI]: 0.86–1.007) for the training set and 0.919 (95% CI: 0.863–0.975) for the validation set—markedly higher than those of carcinoembryonic antigen (0.624) and carbohydrate antigen 19-9 (0.603).
The signature of these five miRNAs is a novel and noninvasive biomarker for gastric cancer, and could facilitate and simplify its diagnosis.
Colorectal cancer is a major cause of death in patients with familial adenomatous polyposis. Despite evidence for prophylactic colectomy, there is no ideal therapy for patients with coexisting familial adenomatous polyposis and colorectal cancer. We evaluated the correlation between surgery for familial adenomatous polyposis and multimodal treatment for colorectal cancer, and clarified prognosis of Japanese patients with familial adenomatous polyposis and colorectal cancer.
We retrospectively reviewed data from 303 patients who underwent colorectal surgery for familial adenomatous polyposis between 2000 and 2012.
Overall, 172 patients had colorectal cancer. The most common procedure for familial adenomatous polyposis was restorative proctocolectomy with ileal pouch anal anastomosis, irrespective of colorectal cancer. Partial colectomy was more frequent in patients with than without colorectal cancer (8.7% and 0%, respectively). Ileal pouch anal anastomosis was frequently (60.6%) performed in patients with Stage I–III colorectal cancer. Overall, 12 of 20 patients with Stage IV colorectal cancer underwent metastasectomy; six patients simultaneously and six metachronously. There were fewer cases of ileal pouch anal anastomosis, but more total colectomy with ileorectal anastomosis was performed metachronously, compared with simultaneous metastasectomy (P = 0.006). More cytotoxic (P = 0.006) and molecular (P = 0.03) agents were administered to the ileorectal anastomosis/partial colectomy patients, compared with total proctocolectomy/ileal pouch anal anastomosis patients. A 5-year overall survival was 100% in Stage 0/I, 89.8% in Stage II, 87.9% in Stage III and 48.4% in Stage IV.
In patients with familial adenomatous polyposis and colorectal cancer, primary surgery, metastasectomy and chemotherapy could be compatible with standard surgical approaches for familial adenomatous polyposis . However, modifying surgical procedures for familial adenomatous polyposis might help multimodality therapy for Stage IV colorectal cancer to prolong survival.
We conducted a retrospective analysis to evaluate the efficacy and safety of cetuximab plus radiation with or without prophylactic percutaneous endoscopic gastrectomy in locally advanced squamous cell carcinoma of the head and neck patients who were not suitable to receive platinum.
We reviewed the case records of 27 locally advanced squamous cell carcinoma of the head and neck patients treated with cetuximab plus radiation (RT) between January 2013 and July 2014. No patient was able to receive platinum because of renal dysfunction or other contraindications. Patients received an initial dose of cetuximab of 400 mg/m2, followed by weekly doses of 250 mg/m2. The total dose of radiotherapy was 66–70 Gy in five daily fractions of 2–2.12 Gy per week.
The incidence of leukopenia was significantly higher in patients without percutaneous endoscopic gastrectomy placement than in those with (67.5% vs. 7%, P = 0.002). The incidence of Grade 3 or 4 mucositis tended to be higher in patients without percutaneous endoscopic gastrectomy placement than in those with (83% vs. 47%, P = 0.058). Five of twelve patients without percutaneous endoscopic gastrectomy placement required interruption of treatment. More patients without percutaneous endoscopic gastrectomy placement had significantly >10% weight loss than patients with (75% vs. 27%, P = 0.013). The overall response rate was 56% in all patients. The 1-year progression-free survival rate was 30.6% in all patients.
Prophylactic percutaneous endoscopic gastrectomy-feeding tube placement could reduce the incidence of severe toxicities, including mucositis and weight loss, and avoid RT interruption. These results require confirmation in a larger study.
To evaluate the outcomes and prognostic factors in patients with parotid gland cancers treated with adjuvant radiotherapy with or without chemotherapy.
Eighty-five patients with parotid gland cancers were identified between October 2001 and September 2011. The median radiation dose was 66 Gy (range, 9–76 Gy). The outcomes assessment included overall survival, locoregional control, distant metastasis-free survival and disease-free survival.
The stage distribution was 20 patients (23.5%) in stage I, 28 (32.9%) stage II, 14 (16.5%) stage III and 23 (27.1%) stage IV. Fifty-five patients (64.7%) had positive margins and 23 patients (27.1%) had close margins (<0.5 cm). Lymph node extracapsular spreading occurred in nine patients. The adjuvant therapy included radiotherapy alone in 47 patients (55.3%) and concurrent chemoradiotherapy in 38 patients (44.7%). With a median follow-up of 4.5 years (range, 0.4–11 years), the 5-year overall survival, locoregional control, distant metastasis-free survival and disease-free survival were 82.0, 88.4, 82.4 and 77.5%, respectively. Based on multivariate analysis, N1/N2 was a significant negative prognostic factor for distant metastasis-free survival, disease-free survival and overall survival. Perineural invasion was a significant negative prognostic factor for locoregional control, distant metastasis-free survival and disease-free survival. Patients 50 years or older had significantly worse distant metastasis-free survival, disease-free survival and overall survival.
Surgery and radiotherapy treatment could achieve excellent outcomes in a modern cohort. However, N1/N2, perineural invasion and age ≥50 years, but not positive margins, are significant factors associated with a worse prognosis.
This study investigates whether changes in arterial enhancement of hepatocellular carcinoma (HCC) on contrast-enhanced CT in patients treated with Sorafenib predicts overall survival.
Thirty-seven HCC patients treated with Sorafenib were identified retrospectively. Up to two target liver lesions were measured on baseline and follow-up contrast-enhanced CT scans. Patients were stratified by whether arterial enhancement decreased by at least 15% and hazard ratio was calculated for all-cause mortality. Patients were then classified as progressive disease, stable disease or partial response using both the modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria and a novel system of enhancement-based response criteria we modeled on mRECIST, but substituting change in arterial enhancement for longest enhancing diameter as the primary measure of tumor response. This response stratification was assessed using survival analysis.
Patients with a 15% decrease in arterial enhancement on follow-up contrast-enhanced CT had median overall survival of 1022 days versus 189 days in those without; this corresponded to a significant decrease in risk of all-cause mortality (hazard ratio 0.34; P = 0.04). Response groups created using the enhancement-based criteria showed significant differences in overall survival (P < 0.001) and all response groups were significantly separated from each other on a pair-wise basis.
Decrease in arterial tumor enhancement on follow-up contrast-enhanced CT by at least 15% was associated with improved overall survival in this small sample of HCC patients treated with Sorafenib and shows promise as a possible clinical measure of tumor response in this population.
To elucidate the clinical benefit and safety of low-dose chemotherapy using methotrexate and vinblastine in patients (mostly adults) with progressive and/or symptomatic fibromatosis.
Patients were enrolled if they were treated with methotrexate and vinblastine chemotherapy for recurrences after surgical excision or newly diagnosed aggressive fibromatosis that was not amenable to surgical resection at the Korea University Medical Center from May 2008 to February 2016.
Twenty-two patients were treated with this regimen, and 21 were eligible for safety and efficacy analysis. Eleven (52%) of 21 patients showed a documented partial response (PR), and 11 showed stable disease (SD) by the end of treatment. All the patients who achieved PR reported a significant reduction in pain and improvement in the function of the affected lesions. Median progression-free survival was not reached at the time of analysis. The most common adverse event was abnormalities of the liver transaminases (overall 84.2%). The most common grade 3 or higher toxicity was neutropenia (36.8%), but no febrile neutropenic event was observed. The elevated levels of transaminases were normalized by reducing the dose of methotrexate or delaying treatment.
Low-dose chemotherapy with methotrexate and vinblastine for 1 year was effective and well tolerated by adult patients with aggressive, recurrent fibromatosis.
We conducted this study to examine the rate of suicide in patients with gastric cancer and to identify factors associated with increased risk of suicide using the Surveillance, Epidemiology, and End Results database.
The database was queried for patients who were diagnosed with gastric cancer from 1998 to 2011. The rate of suicide and standardized mortality ratio were calculated. Multivariable analyses were conducted to identify factors associated with increased risk of suicide.
A total of 65 535 patients with 109 597 person-years of follow-up were included. A total of 68 patients died of suicide. The age-adjusted rate of suicide was 34.6 per 100 000 person-years (standardized mortality ratios, 4.07; 95% confidence interval, 3.18–5.13). The rate of suicide was highest within the first 3 months after cancer diagnosis (standardized mortality ratios, 67.67; 95% confidence interval, 40.74–106.15). Results of multivariable analyses showed that male sex (incidence rate ratio, 7.15; 95% confidence interval, 3.05–16.78; P < 0.0001), White race (incidence rate ratio, 3.23; 95% confidence interval, 1.00–10.35; P = 0.0491), unmarried status (incidence rate ratio, 2.01; 95% confidence interval, 1.22–3.30; P = 0.0060) and distant stage disease (incidence rate ratio, 2.90; 95% confidence interval, 1.72–4.92; P < 0.0001) were significantly associated with increased risk of suicide.
Patients with gastric cancer have an ~4-fold higher risk of suicide compared with the general US population. The suicide risk is highest within the first 3 months after diagnosis. Male sex, White race, unmarried status and distant stage disease are significantly associated with increased risk of suicide.
Ifosfamide (IFO) is considered an essential drug for the treatment of pediatric, adolescent and young adult patients with solid tumors. Hemorrhagic cystitis (HC) is one of the dose-limiting toxicity of IFO. However, there are insufficient evidence for risk factor and supportive care of IFO-induced HC.
In this retrospective study, patients (<30-year-old) with malignant solid tumors who had been treated with IFO-based chemotherapy, were categorized according to the presence or absence of HC, and were analyzed possible risk factors for IFO-induced HC. In our institution, continuous hydration to increase urine output and intravenous 2-mercaptethane sulfonate (mesna) are used for prophylaxis of IFO-induced HC. Increased hydration and dosage of mesna are administered to patients who develop IFO-induced HC; they also receive 24-h continuous infusion of mesna in subsequent treatment cycles.
Nine treatment regimens were used in the 70 study patients. The range of daily IFO dosage was 1.2–3.0 g/m2. HC occurred in 14/425 IFO-based chemotherapy cycles (3.3%). The daily IFO dosages (mean ± SD) in patients with or without HC were 2.23 ± 0.58 g/m2 and 1.85 ± 0.50 g/m2, respectively (P = 0.006). Only one of the nine patients who developed IFO-induced HC had experienced this complication in a subsequent cycle of treatment.
The incidence of IFO-induced HC may be associated with the dosage of IFO. When administering IFO higher than 2.0 g/m2/day, the volume of hydration, dosage of mesna and duration of mesna infusion should be increased to prevent HC.
The aim of the study was to assess pain levels and perceptions concerning pain by both children and their parents during hospitalization, as well as the impact of that pain upon parents’ quality of life.
The sample of the study consisted of 92 pediatric cancer patients, 159 pediatric patients with musculoskeletal problems and one of their parents. The study was performed between November 2010 and May 2011. The Pediatric Pain Questionnaire (Parent Version) and the PedsQL-Family Impact Module were used for pain assessment and the quality of life by the parents. Young patients completed the pediatric version of the Pediatric Pain Questionnaire for the evaluation of pediatric pain. Pain was measured by using the Wong–Baker facial pain scale, included in both parent and child version of the Pediatric Pain Questionnaire. This rating scale is recommended for children 3 years and older.
Young patients reported higher acute pain scores than their parents (z = –2.5, P = 0.011; 99% confidence interval: 0.008–0.013). Young patients with orthopedic disorders had higher acute and chronic pain scores in comparison to their parents’ reports (z = –3.4, P = 0.001; 99% confidence interval: 0.000–0.001 and z = –2.3, P = 0.021; 99% confidence interval: 0.017–0.025, respectively). Girls reported higher pain scores than boys (z = –2.0, P = 0.047; 99% CI: 0.041–0.052).
Parental reports tended to underestimated children's pain, especially acute pain. The sex of children, the age and the marital status affect the perceptions of both children and their parents about pain. The parental quality of life is affected especially when the pain is caused by life-threatening diseases such as cancer. However, it improves as the treatment of their children is completed with no complications.
Although sedation with fentanyl and midazolam during bronchoscopic examination is widely accepted in the USA and Europe, it is not routine practice in Japan. The objective of the present study was to evaluate sedation with fentanyl and midazolam during bronchoscopy.
Thirty-seven patients were enrolled prospectively between November 2014 and July 2015 at Okayama University Hospital. Fentanyl (20 μg) was administered to the patients just before the examination, and fentanyl (10 μg) and midazolam (1 mg) were added as needed during the procedure. A questionnaire was administered 2 hours after the examination. In the questionnaire, patient satisfaction was scored using a visual analog scale as follows: great (1 point), good (2 points), normal (3 points), uncomfortable (4 points) and very uncomfortable (5 points). An additional question (‘Do you remember the bronchoscopic examination?’) was also used. Predefined matters for investigation (e.g. blood pressure, heart rate, oxygen saturation and complications) were recorded.
The enrolled patients included 13 males and 24 females; the median age was 67 (range: 31–87) years. The patients received a median dose of fentanyl of 45.4 μg (range: 30–100 μg) and midazolam of 2.56 mg (range: 1–10 mg). Twenty-six patients (70.2%) agreed to undergo a second bronchoscopic examination, and the average levels of discomfort and re-examination were 2.02 points for each. Only 37.8% of the patients remembered the bronchoscopic examination. No severe complications were reported.
Sedation with fentanyl and midazolam during bronchoscopic examination should be recommended for use in Japan.
Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain–Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain–Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain–Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.
This is a randomized, multi-center, open-label, phase III study to evaluate the efficacy of professional oral care in preventing oral mucositis induced by everolimus in postmenopausal estrogen receptor-positive metastatic breast cancer. Patients will be randomized into professional oral care and control groups (1:1 ratio). All patients will receive everolimus with exemestane and will continue everolimus until disease progression. In the professional oral care group, patients will receive teeth surface cleaning, scaling and tongue cleaning before starting everolimus, and will continue to receive professional oral care weekly from oral surgeons throughout the 8 week treatment. In the control group, patients will brush their own teeth and gargle with 0.9% sodium chloride solution or water. The primary endpoint is the incidence of all grades of oral mucositis. Target accrual is 200 patients with a two-sided type I error rate of 5% and 80% power to detect 25% risk reduction.
Discussion of fertility-sparing treatment is an important part of pretreatment counseling for young patients with early epithelial ovarian cancer. As a result of late childbearing nowadays, fertility preservation has become a major issue in ovarian cancer patients. The purpose of this review is to update current knowledge on fertility-sparing treatment for early stage epithelial ovarian cancer, which may be useful for pretreatment counseling for reproductive-age patients. The multicenter study data on the fertility-sparing treatment published by Japan Clinical Oncology Group in 2010 confirmed that fertility-sparing surgery is a safe treatment for Stage IA patients with non-clear cell histology and Grade 1 or 2 and suggested that Stage IA patients with clear cell histology and Stage IC patients with non-clear cell histology and Grade 1 or 2 can be candidates for fertility-sparing surgery followed by adjuvant chemotherapy. In the current review, we added the recent case series and review, and discussed the fertility-sparing treatment on young patients with early epithelial ovarian cancer. We need not to change the proposal by the Japan Clinical Oncology Group study, but we should wait for the results of an ongoing prospective study to strongly recommend the proposal of the Japan Clinical Oncology Group study.
The prognostic significance of positive peritoneal cytology in patients with early-stage endometrial cancer (Stage 1 or 2) is controversial and perhaps depends on the presence of other factors. The relationship of other prognostic factors with positive peritoneal cytology remains unclear. This study aimed to investigate the association between positive peritoneal cytology and prognostic factors and the influence of positive peritoneal cytology on survival in patients with early-stage endometrial cancer.
We identified 351 articles on the PubMed, Cochrane and Embase databases using a combination of the following search terms: endometrial cancer, endometrial carcinoma, positive peritoneal cytology and positive peritoneal washing. When filtered for studies comparing positive peritoneal cytology with negative peritoneal cytology in early-stage endometrial cancer, 11 retrospective studies met the selection criteria. Meta-analyses were performed using Review Manager 5.3 software.
In patients with surgical stage 1 or 2 early-stage endometrial cancer, the incidence of Grade 3 was higher and 5-year overall survival was worse in patients with positive peritoneal cytology compared with negative peritoneal cytology. However, the incidence of Grade 1 was lower in those with positive peritoneal cytology compared with negative peritoneal cytology. In patients with surgical stage 1 early-stage endometrial cancer, the incidence of myometrial invasion ≥1/2 tended to be higher and 5-year progression-free survival was worse in the positive peritoneal cytology group than the negative peritoneal cytology group. However, the incidence of myometrial invasion <1/2 was lower in the positive peritoneal cytology group than the negative peritoneal cytology group.
This study demonstrates that positive peritoneal cytology in patients with early-stage endometrial cancer is significantly associated with other prognostic factors and survival, suggesting its potential as a prognostic factor.
Our objective was to perform a meta-analysis examining the effectiveness of lymphadenectomy in patients with ovarian cancer.
PubMed and CENTRAL databases were searched on 15 November 2015 using the terms ‘lymphadenectomy’, ‘ovarian cancer’, ‘dissection’, ‘para-aortic’, ‘pelvic’ and survival. Prospective and retrospective studies comparing the outcomes of surgery with or without lymphadenectomy were included. Outcomes were 5-year overall survival, progression-free survival and recurrence rate.
Of the 556 studies identified, 3 randomized controlled trials and 11 retrospective studies were included. Lymphadenectomy was associated with greater 5-year overall survival than no lymphadenectomy (pooled odds ratio = 1.58, 95% confidence interval: 1.41–1.77, p < 0.001). There was no difference in progression-free survival between the groups (pooled overall survival = 1.62, 95% confidence interval: 0.82–3.21, p = 0.168). Lymphadenectomy was associated with greater progression-free survival in randomized clinical trials (pooled overall survival = 1.57, 95% confidence interval: 1.11–2.21, p = 0.010), but not in retrospective studies. Lymphadenectomy was associated with a significantly lower recurrence rate (pooled overall survival = 0.51, 95% confidence interval: 0.30–0.85, p = 0.011). Lymphadenectomy was associated with greater 5-year overall survival in patients with both early and advanced stage cancer, but was associated with greater progression-free survival and lower recurrence rate only in patients with advanced stage cancer.
Lymphadenectomy is associated with greater 5-year overall survival in patients with early and advanced stage ovarian cancer, but an effect on progression-free survival and recurrence rate was only found in patients with advanced stage ovarian cancer.
This study aimed to investigate the efficacy of induction chemotherapy followed by concurrent chemotherapy and helical tomotherapy in patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus in regard to orbital organ preservation and quality of life.
Clinical data of 28 cases of patients with orbital involvement of T4b squamous cell carcinoma of the nasal cavity and paranasal sinus who received multimodal treatment for orbital organ preservation between May 2008 and September 2015 were retrospectively analysed. The treatment efficacy and side effects were assessed. The study included 18 male and 10 female patients. All patients were treated with induction chemotherapy followed by concurrent chemoradiotherapy and/or epidermal growth factor receptor inhibitor. Helical tomotherapy was applied as radiotherapy. Adverse reactions to the chemotherapy were assessed according to Common Terminology Criteria for Adverse Events, Version 4. The overall survival rate, local control rate and rate of effective orbital preservation were calculated using the Kaplan–Meier method.
All patients completed the planned chemotherapy, and 27 (96.4%) of the patients completed the planned radiotherapy cycle. After the multimodal treatment, the 3-year overall survival, local control rate and rate of effective orbital preservation of the patients were 59.2%, 80.2% and 77.8%, respectively.
Multimodal treatment could preserve the orbital organs of patients with T4b squamous cell carcinoma of the nasal cavity and paranasal sinus, achieve relatively ideal organ protection and survival rates and improve the quality of life of patients with advanced squamous cell carcinoma of the nasal cavity and paranasal sinus, thus providing a new treatment option for these patients.
We perform reconstruction using frozen tumor bone treated by liquid nitrogen after excision of malignant bone tumors. To prevent post-operative infection, we use iodine-coated implants that we developed. The purpose of this study is to compare the outcome of reconstruction using frozen autograft with non-coated implants (group N) and iodine-coated implants (group I).
Sixty-two patients were included in group N. The mean age was 31.9 ± 2.3 years. A total of 20 patients died and two were lost to follow-up, averaging 20.0 ± 2.9 months post-operatively, leaving 40 patients available for an assessment at a mean of 79.1 ± 5.8 months post-operatively. There were 38 patients in group I. The mean age was 29.8 ± 3.9 years. The mean follow-up period was 32.1 ± 3.0 months. All patients were alive at the latest follow-up. Survival of frozen bone was determined by Kaplan-Meier analysis.
In group N, survival of frozen bone was 80.7 ± 6.0% and 57.4 ± 10.2% at 5 and 10 years, respectively. Complications were encountered in 31 of 62 patients (50.0%), including deep infection in 10 (16.1%), fracture in 11 (17.7%), local soft-tissue recurrence in 6 (9.7%) and bone absorption in 4 (6.5%). In group I, survival of frozen bone was 86.7 ± 6.3% at 5 years. Complications were encountered in 8 of 38 patients (21.1%), including deep infection in one (2.6%), fracture in four (10.5%), local soft-tissue recurrence in two (5.3%) and bone absorption in one (2.6%). There was a significantly lower infection rate in group I (P = 0.032).
Reconstruction using frozen autograft combined with iodine-coated implants for patients with malignant bone tumor is very useful method in which good limb function can be gained with minimized risk of infection.
The aim of this multicenter study was to determine the appropriate administration schedule for S-1, an oral fluoropyrimidine, for adjuvant chemotherapy in patients with completely resected pathological-Stage IA (tumor diameter, 2–3 cm) non–small-cell lung cancer.
Patients were randomly assigned to receive adjuvant chemotherapy consisting of either the 4-week oral administration of S-1 (80–120 mg/body/day) followed by a 2-week rest (Group A), or the 2-week oral administration of S-1 (80–120 mg/body/day) followed by a 1-week rest (Group B). The duration of adjuvant chemotherapy was 1 year in both arms. The primary endpoint was compliance, namely drug discontinuation-free survival, which was calculated using the Kaplan–Meier method with log-rank test.
Eighty patients were enrolled in this study, and 76 patients actually received S-1 treatment. The drug discontinuation-free survival rates at 1 year were 49.1% in Group A and 52.7% in Group B (P = 0.373). The means of the relative dose intensities were 55.3% in Group A and 64.6% in Group B (P = 0.237). There were no treatment-related deaths. Patients with grade 3/4 toxicities were significantly more frequent in Group A (40.5%) than in Group B (15.4%, P = 0.021). The 2-year relapse-free survival rates were 97.5% in Group A and 92.5% in Group B, and the 2-year overall survival rates were 100% in both groups.
The feasibility showed no significant difference between the two groups among patients with completely resected Stage IA (tumor diameter, 2–3 cm) non–small-cell lung cancer.
No randomized controlled trials comparing stereotactic body radiotherapy and lobectomy for operable early-stage non–small-cell lung cancer have been successfully conducted. This study compared survival outcomes in two multi-institutional clinical trials for stereotactic body radiotherapy (Japan Clinical Oncology Group JCOG0403) and lobectomy (Japan Clinical Oncology Group JCOG0201) with propensity score analysis.
Inclusion criteria were operable, cT1N0M0 and adenocarcinoma diagnosed prior to registration of each trial. Forty of 169 patients from JCOG0403 and 219 of 811 patients from JCOG0201 were included. The primary endpoint was overall survival adjusted with propensity score analysis. The patient selection factors included in the logistic model to estimate the propensity score were age, sex, tumor diameter and consolidation/tumor ratio.
Among patient selection factors, age distribution was quite different with little overlap: the median was 79 (interquartile range: 74.5–83.5) in stereotactic body radiotherapy and 62 (interquartile range: 55–68) in lobectomy. In propensity score analysis, 21 patients from each group were matched and the hazard ratio for stereotactic body radiotherapy over lobectomy was 9.00 (95% confidence interval: 1.14–71.04). In the post hoc subgroup analysis with propensity score analysis of inverse probability of treatment weighting, patients were limited to be aged 75 or younger because JCOG0201 only included them when aged 75 or younger. Thirteen patients for stereotactic body radiotherapy and 219 for lobectomy were compared, and the hazard ratio for stereotactic body radiotherapy over lobectomy was 1.19 (95% confidence interval: 0.38–3.73).
The point estimates of hazard ratio favored lobectomy over stereotactic body radiotherapy in the limited number of patients. A randomized controlled study is needed for valid comparison.
To date, there are few reliable markers to distinguish tumors with aggressive characteristics in upper tract urothelial carcinoma. The purpose of this study was to identify a biomarker related to genetic instability (chromosomal instability or microsatellite instability) with prognostic value, in patients with upper tract urothelial carcinoma.
Expression of chromosomal instability-related markers (BUBR1, p53, polo-like kinase 1) and microsatellite instability-related markers (mismatch repair proteins, MLH1 and MSH2) were assessed by immunohistochemistry in 100 patients who had radical nephroureterectomy for upper tract urothelial carcinoma. Numerical aberrations of chromosomes 7, 9 and 17 were evaluated by fluorescence in situ hybridization, which allowed an estimation of the degree of chromosomal instability. BUB1B copy number was examined by array-based comparative genomic hybridization in 32 patients with upper tract urothelial carcinoma.
BUBR1 status was most significantly correlated with chromosomal instability-related and low mismatch repair parameters, according to the molecular biomarkers examined. Overexpression of BUBR1 is frequently detected in tumors with higher histological grade (P < 0.0001) and is significantly associated with chromosomal instability (P = 0.0071). Array-based comparative genomic hybridization revealed that no tumors (0%) showed BUB1B amplification and gain, indicating that overexpression of BUBR1 was independent of BUB1B copy number. For disease-specific survival, BUBR1 overexpression, lymphovascular invasion, pathological tumor stage, pathological lymph node involvement and low MSH2 expression were significant prognostic factors in univariate analyses. In multivariate analyses, BUBR1 overexpression was an independent prognostic factor for disease-specific survival (P = 0.0483, risk ratio 3.76, 95% confidence interval: 1.01–18.43).
BUBR1 may have significant potential as a biomarker for estimating disease-specific survival in patients with upper tract urothelial carcinoma treated by radical nephroureterectomy.
High-risk clinically localized prostate cancer is seen in a highly heterogeneous population with a wide variation of clinical aggressiveness and a novel subclassification for the better prediction of clinical outcomes is needed. The aim of this study is to validate a modified D’Amico risk criteria for substratification of high-risk prostate cancer with regard to the prediction of biochemical recurrence, clinical progression-free survival or prostate cancer–specific mortality after radical prostatectomy.
We conducted a retrospective multicenter cohort study including 461 clinically organ-confined (cT1-2), D’Amico high-risk prostate cancer patients who underwent radical prostatectomy with pelvic lymph node dissection. The modified criteria subclassified D’Amico high-risk patients into high-risk (n = 189, single high-risk parameter and two low-risk parameters) and very high–risk (n = 272, at least one more intermediate or high-risk parameter in addition to the qualifying high-risk parameter) groups. Biochemical recurrence-free survival, clinical progression-free survival, prostate cancer–specific mortality and overall survival were analyzed.
The very high–risk group, compared with high-risk group, had significantly poorer biochemical recurrence (5- and 10-year biochemical recurrence-free rates: 52.8 vs 73.9% and 42.1 vs 61.7%, respectively, P < 0.0001), clinical progression-free survival (5- and 10-year survivals: 91.8 vs 98.2% and 80.5 vs 98.2%, respectively, P = 0.0013) and prostate cancer–specific mortality (5- and 10-year mortalities: 2.5 vs 0.0% and 6.7 vs 0.0%, respectively, P = 0.0124).
D’Amico high-risk patients can achieve very favorable outcomes unless they are classified as very high risk. Our novel subclassification method is very simple and useful for better patient counseling and decision-making in the pretreatment setting.
A comprehensive survey has not yet been conducted to investigate care patterns by urologists for the management of upper tract urothelial carcinoma.
We conducted a nationwide survey for urologists treating upper tract urothelial carcinoma patients. The questionnaire was approved by the Japanese Urological Association and sent by mail in February 2014 to 1119 institutes in Japan. We identified 627 responders for this study.
Our survey demonstrated that (i) the mean number of radical nephroureterectomy cases per institution in 2013 was 7.6, (ii) the main detecting tool for upper tract urothelial carcinoma is contrast-enhanced computed tomography, (iii) the need for ureteroscopic evaluations is highly dependent on voiding urine cytology results, (iv) 67% of urologists always or often perform radical nephroureterectomy by laparoscopic surgery, (v) more than half of the urologists do not aggressively perform lymph node dissection, (vi) 75% of the urologists perform bladder cuff incision through an extravesical approach, (vii) urologists perform kidney-sparing surgery following various indications, (viii) 59% of the urologists always perform adjuvant systemic chemotherapy for high-risk upper tract urothelial carcinoma patients, (ix) the combination of gemcitabine and cisplatin is the most frequent chemo-regimen for metastatic upper tract urothelial carcinoma, and gemcitabine and cisplatin with dose reductions is also the first choice even in patients with impaired renal function and (x) 10.5% of urologists always or sometimes perform single intravesical chemotherapy immediately after radical nephroureterectomy.
The management strategy for upper tract urothelial carcinoma has changed with the introduction of new devices and development of instruments. The lack of clear evidence for relatively uncommon upper tract urothelial carcinoma affects the consistency of its treatment strategies.
Cisplatin-based chemotherapy has been commonly used as the first-line chemotherapy for metastatic urothelial carcinoma. However, after failure of the first-line cisplatin-based chemotherapy, there is no established standard second-line chemotherapy. Starting in 2006, paclitaxel, ifosfamide and nedaplatin chemotherapy has been performed as the second-line chemotherapy in our institution. Here, we report the treatment results of paclitaxel, ifosfamide and nedaplatin chemotherapy.
From 2006 to 2015, 33 patients with metastatic urothelial carcinoma were treated with paclitaxel, ifosfamide and nedaplatin chemotherapy after failure of first-line cisplatin-based chemotherapy in our institution. We retrospectively examined the treatment outcome and predictive factors for therapeutic effects of paclitaxel, ifosfamide and nedaplatin. The median age, treatment cycle and follow-up period were 62.5 years, 3 cycles and 10.4 months, respectively.
The median overall survival and progression-free survival were 10.4 and 3.5 months, respectively. Complete and partial responses were found in 3 and 7 patients, respectively, with an overall response rate of 30%. All patients developed grade 3–4 neutropenia, but there was no treatment-related death. In multivariate analysis, the only prognostic factor for progression-free survival was 24-hour urinary creatinine clearance.
A paclitaxel, ifosfamide and nedaplatin regimen as second-line chemotherapy for metastatic urothelial carcinoma was effective and tolerable. Moreover, paclitaxel, ifosfamide and nedaplatin chemotherapy may be more effective in patients with satisfactory renal function.
It remains unclear whether coffee drinking is associated with colorectal cancer risk. We performed a systematic review and meta-analysis of epidemiologic studies on this issue among the Japanese population.
Original data were obtained from MEDLINE searches using PubMed or from searches of the ‘Ichushi’ database, complemented with manual searches. Meta-analysis was performed by using the random effects model to estimate the summary relative risk with 95% confidence interval according to the study design. The final judgment was made based on a consensus of the research group members with consideration for both epidemiological evidence and biological plausibility.
We identified five cohort studies and nine case–control studies. Of these, one cohort study reported a strong inverse association (in women only), whereas three case–control studies reported a strong inverse association with colon or rectal cancer. In meta-analysis, high consumption of coffee was not appreciably associated with colorectal cancer risk among cohort studies, whereas it was associated with significantly lower risk of colorectal or colon cancer among case–control studies. The summary relative risk/odds ratio (95% confidence interval) for the highest versus lowest categories of coffee consumption was 0.95 (0.77–1.17) and 0.78 (0.65–0.95) for cohort and case–control studies, respectively.
The evidence is insufficient to support that coffee drinking increases or decreases the risk of colorectal cancer among the Japanese population.