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Japanese Journal of Clinical Oncology

Japanese Journal of Clinical Oncology - RSS feed of current issue

Most T1 bladder cancers are high grade and have the potential to progress to muscle invasion and extravesical dissemination. Many studies reported that ~50% of patients displayed residual tumors when a second transurethral resection was performed 2–6 weeks after the initial resection for patients who were diagnosed with T1 bladder cancer. Furthermore, muscle-invasive disease was detected by the second transurethral resection in 10–25% of those patients. Therefore, a second transurethral resection is strongly recommended for patients newly diagnosed with high-grade T1 bladder cancer in various guidelines. T1 bladder cancers are heterogeneous in terms of progression and prognosis after the second transurethral resection. Optimal management and treatment should be considered for patients with T1 bladder cancer based on the pathological findings for the second transurethral resection specimen. If the second transurethral resection reveals residual tumors, aggressive treatments based on the pathological findings should be performed. Conversely, overtreatment with respect to the tumor status should be avoided. Since the evidence of pathological diagnosis at the second transurethral resection is insufficient and many retrospective studies were carried out before the second transurethral resection era, prospective randomized studies should be conducted.


Non-randomized controlled trials, cohort studies and database studies are appealing study designs when there are urgent needs for safety data, outcomes of interest are rare, generalizability is a matter of concern, or randomization is not feasible. This paper reviews four typical case studies from methodological viewpoints and clarifies how to minimize bias in observational studies in oncology. In summary, researchers planning observational studies should be cautious of selection of appropriate databases, validity of algorithms for identifying outcomes, comparison with incident users or self-control, rigorous collection of information on potential confounders and reporting details of subject selection. Further, a careful study protocol and statistical analysis plan are also necessary.


Objective

As neuroendocrine carcinomas in the head and neck region are extremely rare, their clinicopathological characteristics remain largely unknown. Moreover, the 2005 World Health Organization classification criteria for head and neck carcinomas with neuroendocrine features have numerous limitations. Therefore, the clinicopathological features and patient outcomes of these tumors must be clarified.

Methods

Between 2007 and 2012, we encountered nine cases of head and neck cancer involving a neuroendocrine carcinoma component. We investigated these tumors according to the 2010 World Health Organization classification criteria for neuroendocrine tumors, and their clinicopathological characteristics and clinical outcomes were examined.

Results

Carcinomas with neuroendocrine features were found to have an aggressive clinical course, which corresponded with the Ki-67 index and mitotic count.

Conclusions

Owing to the difficulty in appropriately diagnosing head and neck carcinomas with neuroendocrine features using the current classification system, a new classification system should be developed for use in these cases.


Objective

Sorafenib is a recommended treatment for advanced hepatocellular carcinoma. The study is to evaluate the efficacy of sorafenib plus cyproheptadine compared with sorafenib alone in patients with advanced hepatocellular carcinoma.

Methods

A retrospective cohort study reviewed all consecutive advanced hepatocellular carcinoma cases with Child-Pugh Class A disease starting sorafenib treatment at our hospital from August 2012 to March 2013. They were followed up until 31 December 2013. A total of 52 patients were enrolled: 32 patients in the combination (sorafenib–cyproheptadine) group and 20 patients in the control (sorafenib alone) group. The response to treatment, overall survival and progression-free survival were compared.

Results

The median overall survival was 11.0 months (95% confidence interval: 6.8–15.1 months) in the combination group compared with 4.8 months (95% confidence interval: 3.1–6.6 months) in the control group (crude hazard ratio = 0.45, 95% confidence interval: 0.22–0.82). The median progression-free survival time was 7.5 months (95% confidence interval: 5.1–10.0 months) in the combination group compared with 1.7 months (95% confidence interval: 1.4–2.1 months) in the control group (crude hazard ratio = 0.43, 95% confidence interval: 0.22–0.86). Kaplan–Meier survival analysis revealed that both overall survival and progression-free survival in the combination group were significantly longer than that in the control group. The multivariate model found patients in the combination group were 76% less likely to die (adjusted hazard ratio = 0.24, 95% confidence interval: 0.10–0.58) and 82% less likely to have progression (adjusted hazard ratio = 0.18, 95% confidence interval: 0.08–0.44) during the 17 months of follow-up.

Conclusion

Cyproheptadine may significantly improve survival outcomes of sorafenib-treated advanced hepatocellular carcinoma patients.


Objective

Although pre-operative chemoradiotherapy appears to be a promising treatment for patients with pancreatic ductal adenocarcinoma, there have been no reports of the feasibility of pre-operative chemoradiotherapy in pancreatic ductal adenocarcinoma patients with renal impairment. The aim of this study was to evaluate retrospectively the feasibility of pre-operative chemoradiotherapy in pancreatic ductal adenocarcinoma patients with renal impairment.

Methods

Twelve patients with resectable pancreatic ductal adenocarcinoma and a creatinine clearance of <60 ml/min were enrolled in this study. Gemcitabine-based pre-operative chemoradiotherapy was performed, followed by surgery. The feasibility of the treatment was evaluated in terms of clinical outcome and adverse events in the patients.

Results

All 12 patients completed gemcitabine-based pre-operative chemoradiotherapy without worsening of renal function. Restaging after the therapy revealed radiologically unresectable disease in two patients. Among the remaining 10 patients who underwent laparotomy, curative resection was performed in eight patients. After curative resection, five patients out of the eight completed post-operative adjuvant therapy. The 1- and 3-year survival rates after the start of chemoradiotherapy in the 12 patients were 80.8 and 36.9%, respectively.

Conclusions

Our findings suggest that gemcitabine-based pre-operative chemoradiotherapy may be a safe and effective treatment for pancreatic ductal adenocarcinoma in patients with renal impairment.


Objective

This study aims to explore the characteristics of a good death for children with cancer.

Methods

A total of 10 pediatric cancer survivors, 10 bereaved family members and 20 medical professionals participated in in-depth interviews. Qualitative content analysis was performed on the transcribed data obtained from semi-structured interviews.

Results

Thirteen characteristics including unique and specific for children of a good death were identified: (i) sufficient opportunities to play freely, (ii) peer supporters, (iii) continued access to the patient's usual activities and relationships, (iv) assurance of privacy, (v) respect for the patient's decisions and preferences, (vi) a sense that others acknowledge and respect the patient's childhood, (vii) comfort care to minimize distressing symptoms, (viii) hope, (ix) not aware of the patient's own impending death, (x) constant dignity, (xi) strong family relationships, (xii) no sense of being a burden to family members and (xiii) good relationships with medical staffs.

Conclusions

This study identifies important characteristics of a good death for children with cancer. These findings may help medical staffs provide optimal care for children with cancer and their families, enabling them to achieve a good death.


Objective

This Phase II study was conducted to evaluate the efficacy and safety of S-1 and irinotecan combination therapy as a second-line treatment in patients with advanced non-small cell lung cancer.

Methods

Irinotecan was administered at 60 mg/m2 on Days 1 and 8. Oral S-1 was administered on Days 1–14 every 3 weeks at 80 mg/day for patients with a body surface area of <1.25 m2, 100 mg/day for patients with a body surface area of 1.25–1.5 m2 and 120 mg/day for patients with a body surface area of >1.5 m2. The primary endpoint was response rate, while the secondary endpoints were progression-free survival, overall survival and safety.

Results

Thirty-one patients were enrolled in this study. The response and disease control rates were 6.5 and 58.1%, respectively. Progression-free survival and median survival time were 2.8 and 12.6 months, respectively. Grade 3–4 adverse events were reported for 29.0% of the patients. Hematological toxicities of Grade 3 or 4 included leukopenia (9.7%), neutropenia (9.7%), febrile neutropenia (3.2%), thrombopenia (3.2%) and anemia (6.5%). Non-hematological toxicities of Grade 3 or 4 included pneumonitis (6.5%), diarrhea, colitis, dyspnea, rash, oral mucositis, anorexia and pulmonary thromboembolism/deep vein thrombosis (3.2% each).

Conclusions

S-1 and irinotecan combination therapy at the present dose and schedule exhibited only modest efficacy with mild toxicities in previously treated patients with non-small cell lung cancer. No further clinical investigation with current dose and schedules is warranted for patients with non-small cell lung cancer who failed first-line platinum-based doublet chemotherapy.


Objective

Endobronchial ultrasound with a guide sheath has been a widely used diagnostic procedure for peripheral pulmonary lesions. After sequential sampling with the usual devices, small portions of the collected specimen remain in the guide sheath and these can potentially contribute to diagnosis. We assessed the diagnostic value of each histological and cytological sample, especially the guide sheath flush, for pulmonary malignancies.

Methods

The medical records of patients who were diagnosed to have peripheral lung cancer by endobronchial ultrasound with a guide sheath in our hospital between January 2014 and May 2014 were reviewed. Separate samples from forceps biopsy, bronchial brushing, device wash, guide sheath flush and bronchial lavage were compared and analyzed.

Results

A total of 106 consecutive patients (54 men, 52 women, median age 69.0 years) were included. The median long axis size of the lesions was 26.0 mm. A definitive diagnosis was made in 90.6% of forceps biopsy samples and in 85.8% of all cytology samples combined. Individual yields were 61.3% from brushing, 77.4% from device wash, 72.6% from guide sheath flush and 32.1% from bronchial lavage. The diagnosis yield from forceps biopsy was significantly higher than each cytological sampling method (P < 0.05). Among the cytological sampling methods, yield from bronchial lavage was significantly the lowest (P < 0.001).

Conclusions

Forceps biopsy is an important sampling method during endobronchial ultrasound with a guide sheath for peripheral pulmonary lesions. In the collection of diagnostic liquid samples, guide sheath flush is more advantageous than bronchial lavage and provides specimen that may be adequate for molecular testing.


Objective

Small pulmonary nodules are often followed up. This study aimed to establish radiographic criteria with which to accurately and reproducibly predict indolent cancers including adenocarcinoma in situ.

Methods

We examined correlations between pre-operative factors and surgical outcomes, including pathological findings and prognosis among 609 patients with clinical Stage IA lung adenocarcinoma that had been completely resected at multiple institutions. Indolent cancers were defined as tumors without lymphatic, blood vessel, pleural invasion or lymph node involvement (LY0V0PL0N0) regardless of stromal invasion.

Results

Pathological assessments of specimens of 35 of 85 (41%) pure ground glass opacity tumors including 3 (23%) of 13 pure ground glass opacity tumors ≤1 cm, revealed partially invasive components. Receiver operating characteristic curves for LY0V0PL0N0 revealed solid tumor size ≤6 mm on high-resolution computed tomography or maximum standardized uptake values ≤0.6 on 2-[18F]fluoro-2-deoxy-d-glucose positron emission tomography/computed tomography as radiographic indolent tumor criteria for predicting indolent tumors. Among 216 (35.5%) of 609 patients who met these criteria, none developed recurrence over a median follow-up of 41.6 months.

Conclusions

Pure ground glass opacity lesions on high-resolution computed tomography could pathologically include invasive components and would not correspond to adenocarcinoma in situ. Solid tumor size on high-resolution computed tomography and maximum standardized uptake values on positron emission tomography/computed tomography can predict indolent LY0V0PL0N0 lung tumors that can be followed up.


Objective

In a previous study, we described the relationship between operating time and obesity, particularly visceral obesity, in laparoscopic surgery. Operating time in laparoscopic surgery is affected by the experience and technique of the surgeon. Here, we investigated whether a difference in the surgeon's experience affects the operating time for laparoscopic radical nephrectomy in patients with visceral obesity.

Methods

From January 2006 to February 2012, 167 laparoscopic radical nephrectomies were performed at our institution. Visceral fat area was measured at the level of the umbilicus using computed tomography. A visceral fat area ≥ 100 cm2 was used as the definition of visceral obesity. All laparoscopic radical nephrectomies were performed by six surgeons. Two of the six surgeons perform 50 cases or more laparoscopic surgeries every year and they were defined as the expert group. We analyzed the relationships between clinical findings, methods, surgeon experience, body mass index or visceral fat area and operating time.

Results

The expert and non-expert surgeons performed 77 and 90 laparoscopic radical nephrectomies, respectively, and the median operating time was 167.0 ± 44.0 and 227.5 ± 60.6 min. Twenty-five patients underwent laparoendoscopic single-site nephrectomy by the expert surgeons. For all surgeons, visceral obesity was a significant factor for prolonged operating time. Multivariate analysis showed that visceral obesity and clinical T stage were independent risk factors for prolonged operating time for the non-expert surgeons [P = 0.004, hazard ratio (HR): 5.15, P = 0.037, HR:10.41]. However, for the expert surgeons, clinical T stage was the only independent risk factor for prolonged operating time (P = 0.039, HR: 4.33).

Conclusion

Visceral obesity was a factor of prolonged operating time in laparoscopic radical nephrectomy. The non-expert surgeons were particularly affected by visceral obesity.


A case of advanced parotid cancer in which long-term control was achieved by superselective intra-arterial cisplatin infusion with concomitant radiotherapy is reported. A 63-year-old woman with parotid squamous cell carcinoma was referred to our hospital. Magnetic resonance images revealed extraparotid extension of the tumor, indicating that complete resection would be difficult. Consequently, intra-arterial cisplatin infusion with concomitant radiotherapy was planned as an alternative therapy. Superselective intra-arterial infusion of cisplatin (100 mg/m2) was performed six times, at intervals of 7–9 days. The arteries chosen for superselective infusion were the posterior auricular artery, the transverse facial artery and the intrinsic parotid artery originating directly from the external carotid artery. Concurrently, external radiotherapy of a total of 50 Gy in 25 fractions was also performed. The patient achieved a complete response and has remained free of disease recurrence 5 years after treatment. Intra-arterial cisplatin infusion with concomitant radiotherapy can be a practical option for patients with unresectable parotid squamous cell carcinoma.


Recently, new drugs targeting the immune system have been introduced to the standard care of metastatic malignant melanoma. One of these immunomodulatory drugs is ipilimumab, a fully human monoclonal antibody that blocks cytotoxic T-lymphocyte antigen-4. The following case reports on a 54-year-old man with metastatic melanoma, who developed Grade 4 thrombocytopenia during treatment with ipilimumab already after first dose. Bone marrow examination confirmed a diagnosis of drug-induced, immune-mediated thrombocytopenia. Isolated thrombocytopenia has rarely been associated with ipilimumab and there is no standard treatment algorithm of such complication. This case demonstrates the importance of monitoring full blood count in all patients receiving ipilimumab and suggests a possible treatment algorithm.


A randomized Phase II/III trial commenced in May 2014. Endoscopic balloon dilation with steroid injection is the current standard treatment for patients with refractory anastomotic stricture after esophagectomy. The purpose of this study is to confirm the superiority of radial incision and cutting with steroid injection in terms of both restricture-free survival and number of dilations within 24 weeks compared with endoscopic balloon dilation with steroid injection for these patients. A total of 130 patients will be accrued from 30 Japanese institutions over 3 years. The primary endpoint in the Phase II part is proportion of Grade 3/4 intraoperative hemorrhages, post-operative esophageal perforations, esophageal hemorrhages, pneumothorax, lung or mediastinum infections or other unexpected adverse events. Co-primary endpoints in the Phase III part are restricture-free survival and number of dilations within 24 weeks after treatment. Secondary endpoints are proportion of patients with anastomotic diameter >10 mm at 8 weeks after treatment, proportion of adverse events, proportion of patients experiencing improvement of dysphagia score at 2, 4, 8 and 24 weeks after treatment and proportion of patients with dysphagia score ≤1 at 24 weeks after treatment. This trial has been registered in the UMIN Clinical Trials Registry as UMIN000014017 [http://www.umin.ac.jp/ctr/index.htm].


The analysis of cancer trends in Japan requires periodic updating. Herein, we present a comprehensive report on the trends in cancer incidence and mortality in Japan using recent population-based data. National cancer mortality data between 1958 and 2013 were obtained from published vital statistics. Cancer incidence data between 1985 and 2010 were obtained from high-quality population-based cancer registries of three prefectures (Yamagata, Fukui and Nagasaki). Joinpoint regression analysis was performed to examine the trends in age-standardized rates of cancer incidence and mortality. All-cancer mortality decreased from the mid-1990s, with an annual percent change of –1.3% (95% confidence interval [CI]: –1.4, –1.3). During the most recent 10 years, over 60% of the decrease in cancer mortality was accounted for by a decrease in stomach and liver cancers (63% for males and 66% for females). The long-term increase in female breast cancer mortality, beginning in the 1960s, plateaued in 2008. All-cancer incidence continuously increased, with annual percent changes of 0.6% (95% CI: 0.5, 0.8) between 1985 and 2005, and 1.8% (95% CI: 0.6, 2.9) between 2005 and 2010. During the most recent 10 years, almost half of the increase in cancer incidence was accounted for by an increase in prostate cancer (60%) in males and breast cancer (46%) in females. The cancer registry quality indices also began to increase from ~2005. Decreases in stomach and liver cancers observed for incidence and mortality reflect the reduced attribution of infection-related factors (i.e. Helicobacter pylori and hepatitis virus). However, it should be noted that cervical cancer incidence and mortality rates began to increase from ~1990.