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Japanese Journal of Clinical Oncology

Japanese Journal of Clinical Oncology - RSS feed of current issue

The Japan Public Health Center-based prospective Study conducted a baseline survey for 140 000 registered residents aged 40–69 years within 11 public health center areas nationwide in 1990–94. Five- and 10-year follow-up surveys were conducted to update information on lifestyle habits and health conditions. In total, 130 000 participants responded to at least one of the three questionnaire surveys, and 78 000 to all three. In addition, 60 000 participants provided blood samples on at least one of the two sampling times, and 23 000 on both. The subjects have been followed for vital status and the occurrence of cancer and other diseases. As of December 2011, 24 000 deaths have been documented, as well as 17 000 cases of cancer, 6000 cases of stroke and 1100 cases of myocardial infarction. We have tested the association between potential causal factors and the incidence of or mortality from cancer and other diseases, and published >250 papers to date. Typical dietary habits in Japan are high consumption of soy/isoflavones, fish/n-3 fatty acids, salt/salted foods and green tea, and low consumption of red meat and saturated fat. This paper briefly summarizes the observed associations of these foods/nutrients with cancer, cardiovascular diseases and diabetes. The Japan Public Health Center-based prospective Study is scheduled to conduct active follow-up for a total of 30 years, and we plan to publish additional evidence on the potential causes of a shorter life and major disease occurrence.


Objective

Overweight and obesity, indicated as increased body mass index, are associated with the risk of some cancers. We carried out a meta-analysis on published cohort and case–control studies to assess the strength of association between body mass index and gastric cancer.

Methods

Relevant studies were identified through PubMed, Web of Science and Medline electronic databases. Adjusted relative risks (odds ratios) with 95% confidence interval were used to assess the strength of association between body mass index and gastric cancer.

Results

Sixteen eligible studies were included in this meta-analysis. Overall, obesity (body mass index ≥30 kg/m2) was associated with an increased risk of gastric cancer (odds ratio = 1.13, 95% confidence interval = 1.03–1.24) compared with normal weight (body mass index = 18.5 to <25 kg/m2), while overweight (body mass index = 18.5 to <30 kg/m2) showed no association (odds ratio = 1.04, 95% confidence interval = 0.96–1.12). Specifically, a stratified analysis showed there were associations between obesity and the increased risk of gastric cancer for males (odds ratio = 1.27, 95% confidence interval = 1.09–1.48), non-Asians (odds ratio = 1.14, 95% confidence interval = 1.02–1.28) and both cohort studies (odds ratio = 1.10, 95% confidence interval = 1.00–1.22) and case–control studies (odds ratio = 1.29, 95% confidence interval = 1.03–1.60). Both overweight (odds ratio = 1.22, 95% confidence interval = 1.05–1.42) and obesity (odds ratio = 1.61, 95% confidence interval = 1.15–2.24) were associated with the increased risk of gastric cardia cancer.

Conclusions

The results indicated that obesity was associated with the risk of gastric cancer, especially for males and among non-Asians. Both overweight and obesity were associated with the risk of gastric cardia cancer.


Objective

Breast, gastric and lung cancers are the most common cancers that cause pulmonary lymphangitis carcinomatosa. However, little is known about the clinical features of pulmonary lymphangitis carcinomatosa in advanced gastric cancer.

Methods

We retrospectively reviewed the data throughout the clinical courses of 33 patients with gastric cancer who developed pulmonary lymphangitis carcinomatosa. Pulmonary lymphangitis carcinomatosa was confirmed by both a pulmonologist and a diagnostic radiologist on the basis of computed tomography findings of interstitial patterns such as thickening or irregularity of interlobular septa and bronchovascular bundles.

Results

The median age of the 33 patients was 55 years old (range, 25–73 years). The percentages of female patients, those with performance status 3 or 4, and those with respiratory symptoms at diagnosis were 70, 36 and 76%, respectively. The histologically diffuse type of gastric cancer accounted for 85% of cases. Mediastinal lymph node, peritoneal and bone metastases were found in 64, 61 and 39% of patients, respectively. Disseminated intravascular coagulation was noted in 21% of patients. The median survival time of the 18 chemotherapy-naïve patients treated with chemotherapy was 5.7 months (range, 0.4–37.0 months). Two patients obtained symptomatic relief, and one patient treated with S-1 + cisplatin + sunitinib survived >3 years.

Conclusions

Pulmonary lymphangitis carcinomatosa caused by gastric cancer has some specific clinicopathological features. While the prognosis of gastric cancer patients with pulmonary lymphangitis carcinomatosa is extremely poor, some patients may have survival benefit from chemotherapy.


Objective

The quality of surgery with D3 resection in randomized controlled clinical trial [Japan Clinical Oncology Group study (JCOG0404)] was assessed by evaluation of the photo documentation of both open and laparoscopic surgeries.

Methods

A multi-institutional randomized-controlled trial (JCOG0404) was conducted to evaluate open and laparoscopic D3 resection (complete mesocolic excision + ligation and dissection at the root of the main vessels) for Stage II/III colon cancer (UMIN-CTR number C000000105). A total of 1057 (open, 528; laparoscopic, 529) eligible patients were enrolled. For quality control, it was ensured that the surgeries were performed by accredited surgeons, and a central committee reviewed each surgery on the basis of the submitted photographs of the resected field, specimen and skin incision.

Results

For right-sided tumors, the rate of D3 resection was 98.5% (131/133) in the open arm and 100% (136/136) in the laparoscopic arm, and for left-sided tumors, they were 97.9% (322/329) and 98.2% (320/326), respectively. Sufficient length of the resected longitudinal margin was ensured in all cases. The skin incisions made in all the cases were <8 cm as defined in the protocol in laparoscopic arm.

Conclusions

Completion of high quality surgery with D3 resection was confirmed in JCOG0404 by central peer review of photographs of the surgical procedures in addition to operator regulations. This study suggests that the central review of the photo documentation is one of the important tools to assure a quality control of surgical technique in the Phase III randomized-controlled study.


Objective

The report presents an 11-year Institutional experience of 203 cases with superior gingivobuccal sulcus tumours receiving surgical intervention at a comprehensive tertiary cancer care centre.

Methods

A retrospective chart review of patients with a confirmed diagnosis of squamous cell carcinoma of superior gingivobuccal sulcus was done and data related to patient demographic profile; details of surgical procedure, follow-up and survival were collected.

Results

Infratemporal fossa clearance was performed in 56 patients. The 10-year overall survival and disease-free survival was observed to be 39 and 52%, respectively, with a median follow-up of 15 months. The overall survival was 40 and 36%, respectively, in cases with and without infratemporal fossa clearance. Similarly, the disease-free survival was found to be 58 and 49%, respectively, in cases with and without infratemporal fossa clearance.

Conclusion

Patients with higher stage tumours who underwent infratemporal fossa clearance showed better overall and disease-free survival than those who did not undergo infratemporal fossa clearance.


Objective

Extra-articular resection is necessary to obtain a wide margin for primary osteosarcomas invading the knee joint, and the limb is often reconstructed using a prosthesis. Here, outcomes of extra-articular and intra-articular procedures were compared.

Methods

Between 1999 and 2012, 14 patients with osteosarcoma underwent extra-articular excision (n = 6; ages 23–65 years; mean follow-up 82.8 months) or intra-articular excision (n = 8; ages 8–58 years; mean follow-up 96.4 months). In the extra-articular group, there was one Enneking Stage IIA case and five Enneking Stage IIB cases. No local recurrences were noted in either group.

Results

Patient outcomes were as follows (extra-articular cases vs. intra-articular cases): continuous disease-free (2 vs. 7), alive with disease (2 vs. 0) and death from disease (1 vs. 1). Average Musculoskeletal Tumor Society functional scores were 69.4% (range 63.3–83.3%) and 88.3% (range 70.0–96.7%) in the extra-articular and intra-articular groups, respectively, constituting a significant difference (P < 0.05). The 5-year oncological overall survival exceeded 80% in both groups. Amputation was necessary for one patient in the extra-articular group. The 5-year event-free prosthesis survival rates in the extra-articular and intra-articular groups were 33.3 and 75.0%, respectively (P < 0.05).

Conclusion

The extra-articular excision group developed more complications than the intra-articular excision group, as a result of extensive bone and muscle excision. The limb survival rates were similar in both groups. Our results suggest that extra-articular resection was a necessary and clinically acceptable procedure.


Objective

The purpose of this study was to examine the relationship between emotional suppression and psychological distress in breast cancer patients after surgery. We examined this relationship using questionnaires at the first visit to the breast cancer outpatient clinic at our hospital and after surgery, as well as interviews after surgery.

Methods

A total of 31 breast cancer patients were asked to complete the Courtauld Emotional Control Scale and the Profile of Mood States at their first visit to the outpatient clinic. Patients were also asked to complete the Profile of Mood States between 1 and 6 months after surgery. Trained clinical psychologists conducted the interviews, asking patients to speak freely about their current anxieties, worries and thoughts. Based on the median Courtauld Emotional Control Scale score of 42 points, participants were divided into emotional suppression and emotional expression groups.

Results

The Total Mood Disturbance score, as well as each of the subscale (except vigor) scores of the Profile of Mood States, were significantly higher in the emotional suppression group than the emotional expression group. The emotional suppression group expressed significantly more negative emotions and fewer positive emotions than the emotional expression group.

Conclusions

Patients with emotional suppression felt and expressed more psychological distress after surgery. This finding highlights the need for medical staff to comprehend the psychological traits of breast cancer patients, including emotional suppression, in the early stages of breast cancer in order to provide adequate psychological support.


Objective

Although the diagnostic yield of guided bronchoscopy for peripheral pulmonary lesions has improved to 70%, it is still low compared with transthoracic needle aspiration. We produced a new bronchoscope with middle-range diameter and large channel (BF-Y0053, Olympus, Japan), and evaluated its diagnostic efficacy for peripheral pulmonary lesions.

Methods

This was a retrospective study on 70 consecutive patients with peripheral pulmonary lesions who underwent diagnostic bronchoscopy using BF-Y0053 combined with endobronchial ultrasound with a guide sheath at the National Cancer Center Hospital from September 2013 to November 2013. Diagnostic performance of the procedure was analyzed and compared among three groups of peripheral pulmonary lesions: ‘peripheral-small’ lesions (≤30 mm and adjacent to visceral pleura), ‘central-small’ lesions (≤30 mm and not adjacent to the visceral pleura), and ‘large’ lesions (>30 mm).

Results

Sixty (85.7%) patients had malignant diseases. Diagnosis was established by bronchoscopy in 61 of 70 patients (87.1%); the respective yields for ‘central-small’ and ‘large’ lesions were significantly higher than that for ‘peripheral-small’ lesions (96.3%, 94.4%, 72%, P = 0.0026). This diagnostic accuracy was achieved regardless of other clinical and procedural factors such as, lesion size, feature ground glass opacity (or solid), endobronchial ultrasound-probe location (within or outside) or operator skill. There were no major post-procedural complications.

Conclusions

A new middle-range diameter bronchoscope with large channel combined with endobronchial ultrasound with a guide sheath can enhance the efficacy of transbronchial sampling to its maximal potential to diagnose peripheral pulmonary lesions safely and accurately, particularly for patients who have tumors away from the visceral pleura.


Objective

Several clinical studies have demonstrated the efficacy and safety of adjuvant chemotherapy in patients with completely resected small cell lung cancer for a selected limited stage. However, it is unclear whether adjuvant chemotherapy is feasible in clinical practice. The objective of this study was to analyze the efficacy and safety of adjuvant chemotherapy for small cell lung cancer patients retrospectively in clinical practice.

Methods

From January 2002 to March 2012, 56 small cell lung cancer patients underwent surgery as initial therapy in our institute. Of these, 26 patients received adjuvant chemotherapy. The clinical data of patients who received adjuvant chemotherapy were retrospectively analyzed.

Results

The chemotherapy regimens were cisplatin and irinotecan in 16 patients, cisplatin and etoposide in 1 and carboplatin and etoposide in 9. Median follow-up time was 44.8 months. Nineteen (73%) patients received the full course of chemotherapy. Median recurrence-free survival was 21.4 months. Median survival time was not reached. There was no treatment-related death.

Conclusion

Adjuvant chemotherapy may be generally safe and efficacious in selected small cell lung cancer patients.


Objective

Endobronchial ultrasound-guided transbronchial needle aspiration is widely used for mediastinal and hilar lesions. Histologic specimens from this procedure are important for specific diagnosis and targeted therapy. Studies on the traditional endobronchial ultrasound-guided transbronchial needle aspiration needles reported yields of only 50–60% for diagnostic histologic specimens. Recently, a new needle has become available in Europe, USA and Asia. The investigators aimed to evaluate the histologic specimen retrieval yields of the two needles.

Methods

Patients who underwent endobronchial ultrasound-guided transbronchial needle aspiration with the new 22 G needle (M group, n = 94) were compared with a historical control group who underwent endobronchial ultrasound-guided transbronchial needle aspiration with the traditional 22 G needle (O group, n = 82). The quality of needle aspirates from both groups was evaluated.

Results

There were no significant differences between the two groups in terms of demographics, lesion characteristics, primary disease and examiner experience. The M group had a significantly shorter procedure time than the O group (P = 0.049). Of the 214 punctures by the M group, 159 (74.3%) were diagnostic, 28 (13.1%) were non-diagnostic and 27 (12.6%) had no histologic specimen. The 235 punctures by the O group were diagnostic in 144 (61.3%), non-diagnostic in 60 (25.5%) and had no histologic specimen in 31 (13.2%). The yield for diagnostic histologic specimens of the M group was significantly higher than the O group (P = 0.0035). There were no major complications observed.

Conclusions

The yield for diagnostic histologic specimens by the new 22 G endobronchial ultrasound-guided transbronchial needle aspiration needle was high. Further technical improvements of histologic sampling yields are very important when selecting targeted therapy.


Objective

Irinotecan is a potent inhibitor of deoxyribonucleic acid topoisomerase 1 and the weekly schedule of 100–125 or 350 mg/m2 administration on Day 1 every 3 weeks is recommended for recurrent small cell lung cancer. However, severe gastrointestinal toxic effects and myelosuppression are often observed in this dose setting. We conducted a retrospective study to evaluate the efficacy and safety of low-dose irinotecan monotherapy (60 mg/m2 on Days 1, 8 and 15 every 4 weeks) as second-line chemotherapy for small cell lung cancer.

Methods

The medical charts of small cell lung cancer patients who had received second-line chemotherapy at the National Cancer Center Hospital East between April 2003 and June 2012 were reviewed. Consecutive 57 patients who were treated with low dose of irinotecan (60 mg/m2 on Days 1, 8 and 15 every 4 weeks) were analyzed in this study.

Results

Median age was 70 years (range, 51–83). Fifty-two (91%) were male, 36 (63%) had an Eastern Cooperative Oncology Group performance status 0–1 and 26 (46%) were sensitive relapse. The median number of chemotherapy cycles was 2. The objective response rate was 32% (95% confidence interval: 20–45%).The median progression-free survival and the median overall survival were 2.9 months (95% confidence interval: 1.9–3.4 months) and 5.3 months (95% confidence interval: 3.6–7.6 months), respectively. The incidence of Grade 3/4 neutropenia, diarrhea and nausea/vomiting was 21, 4 and 5%, respectively.

Conclusions

Low-dose irinotecan monotherapy for recurrent small cell lung cancer might be effective with favorable toxicity. Randomized trial of 60 mg/m2 versus standard dose of irinotecan is warranted.


Objective

To individualize prostate-specific antigen threshold values to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy in elderly men.

Methods

A total of 406 men aged over 70 years old with prostate-specific antigen levels between 4.0 and 20.0 ng/ml, normal digital rectal examination results and diagnosed by transrectal needle biopsy were retrospectively analyzed. The patients were divided into a no/favorable-risk cancer group or an unfavorable-risk cancer group based on their Gleason score and the number of positive cores. Prostate-specific antigen levels, percent free prostate-specific antigen level, prostate transition zone volume and the number of previous biopsies were used to discriminate between the two groups.

The optimal individualized prostate-specific antigen threshold values based on the other variables that gave a sensitivity of 95% for the detection of unfavorable-risk cancer were calculated using a boosting method for maximizing the area under the receiver operating characteristic curve.

Results

A total of 66 men had favorable-risk cancer, and 139 had unfavorable-risk cancer. The area under the receiver operating characteristic curve of the combination model determined by the boosting method for maximizing the area under the receiver operating characteristic curve was 0.852. The sensitivity and specificity of the threshold values for the detection of unfavorable-risk cancer were 95 and 36%, respectively. By using the threshold values, 100 (25%) of the subjects with no/favorable-risk cancer could have avoided undergoing biopsies, with a <5% risk of missing the detection of unfavorable-risk cancer.

Conclusions

These individualized prostate-specific antigen threshold values may be useful for determining an indication of prostate biopsy for elderly men to avoid overdiagnosis of prostate cancer and reduce unnecessary biopsy.


Objective

To clarify the risk factors and develop a refined risk-stratification model to help in the appropriate selection of docetaxel chemotherapy in patients with castration-resistant prostate cancer.

Methods

This study included 97 Japanese patients with castration-resistant prostate cancer who were treated with 70–75 mg/m2 docetaxel and 10 mg prednisone every 3 or 4 weeks from 2008 to 2013. The oncological outcomes and prognostic significance of clinicopathological factors were analyzed, and significant prognostic factors were used to develop a risk-stratification model.

Results

Prostate-specific antigen decline was observed in 75 patients (77.3%), including 43 (44.3%) who achieved a prostate-specific antigen decline of ≥50%. The median progression-free survival and overall survival were 5.1 and 20.8 months, respectively. Univariate analysis identified performance status, alkaline phosphatase value, visceral metastasis, duration from diagnosis, duration from initiation of hormone treatment and prior treatment with estramustine as significant predictors of overall survival. Among these, alkaline phosphatase value, visceral metastasis and duration from initiation of hormone treatment were independent prognostic factors in multivariate analysis. Furthermore, risk classification according to the number of independent risk factors present effectively stratified survival among docetaxel-treated castration-resistant prostate cancer patients.

Conclusions

Oncologic outcomes in Japanese patients with castration-resistant prostate cancer receiving docetaxel chemotherapy were comparable to or slightly better than those in Western populations, and the risk-stratification model developed in this study may help to predict prognosis and contribute to the selection of suitable therapy after castration resistance.


Epithelioid inflammatory myofibroblastic sarcoma is a variant of inflammatory myofibroblastic tumor with aggressive clinical course associated with RANBP2-ALK fusion. The present report describes a case of a 22-year-old Japanese man with a pelvic mesenchymal neoplasm. The feature of the neoplasms, including epithelioid morphology, anaplastic lymphoma kinase staining on the nuclear membrane, and results from the reverse transcriptase-polymerase chain reaction, led to diagnosis of epithelioid inflammatory myofibroblastic sarcoma with RANBP2-ALK fusion. Despite two surgical excision procedures, local recurrence rapidly occurred, and the tumor developed resistance to conventional chemotherapy with doxorubicin. Subsequent administration of crizotinib, an oral anaplastic lymphoma kinase inhibitor, resulted in tumor shrinkage. Distinguishing epithelioid inflammatory myofibroblastic sarcoma from conventional inflammatory myofibroblastic tumor is important, and crizotinib is a promising treatment for this aggressive tumor.


We herein report a case of fatal fulminant hepatitis secondary to crizotinib administration. The patient was 54-year-old female with a history of Hepatitis C infection (not current), dermatomyositis and steroid-induced diabetes mellitus. She was diagnosed with advanced lung adenocarcinoma with anaplastic lymphoma kinase rearrangement. We began 400 mg of crizotinib as first-line therapy. No adverse effects were seen until Day 16. On Day 29, she was admitted to hospital with elevated liver enzymes (aspartate aminotransferase 3236 IU/l, alanine aminotransferase 5201 IU/l) and coagulopathy (prothrombin time <10%), and was diagnosed with crizotinib-induced fulminant hepatitis. We started intensive care, using plasma exchange, continuous hemodiafiltration and high-dose steroid therapy. Unfortunately, she did not respond to therapies, and died on Day 36. The mechanism and risk factors of crizotinib-induced hepatotoxicity are uncertain. Physicians should be aware of possible adverse effects of crizotinib. A systemic survey is imperative to identify possible risk factors of crizotinib-related hepatotoxicity.


Sentinel node biopsy is a standard procedure in clinically node-negative breast cancer patients. It has eliminated unnecessary axillary lymph node dissection in more than half of the early breast cancers. However, one of the unresolved issues in sentinel node biopsy is how to manage axilla surgery for sentinel node-positive patients and clinically node-negative patients. To evaluate the outcome of no axillary lymph node dissection in sentinel node-positive breast cancer, a prospective cohort study registering early breast cancer patients with positive sentinel nodes has been conducted (UMIN 000011782). Patients with 1–3 positive micrometastases or macrometastases in sentinel lymph nodes are eligible for the study. The primary endpoint is the recurrence rate of regional lymph nodes in patients treated with sentinel node biopsy. Patients treated with sentinel node biopsy followed by axillary lymph node dissection are also registered simultaneously to compare the prognosis. The propensity score matching is used to make the distributions of baseline risk factors comparable.