Incidence and risk factors associated with the development of hypothyroidism after postoperative chemoradiotherapy for head and neck cancer patients with high-risk features: Supplementary analysis of JCOG1008.

BACKGROUND AND PURPOSE: Hypothyroidism is a recognized late adverse event following radiotherapy for head and neck cancer (HNC). In the JCOG1008 trial, we treated patients with high-risk HNC with postoperative chemoradiotherapy. We aimed to elucidate factors associated with hypothyroidism by analyzing the JCOG1008 data. MATERIALS AND METHODS: In 2012-2018, 261 patients from 28 institutions were enrolled in JCOG1008. Thyroid function tests were conducted to assess hypothyroidism, including free thyroxine (FT4) and thyroid-stimulating hormone assays. Hypothyroidism was defined as Grade 2 or higher in CTCAE v4.0. Various clinical and dosimetric parameters were analyzed. In radiotherapy, there were no dose constraints for the thyroid. Multivariable analysis was conducted on these variables to identify predictive factors for hypothyroidism. RESULTS: The analysis included 162 patients (57 with 3D-CRT and 105 with IMRT), with a median follow-up of 4.7 years (0.3-9.3 years). Among these, 27 (16.7 %) developed hypothyroidism within 2 years after radiotherapy. In a multivariable analysis, the weekly cisplatin [OR=7.700 (CI: 1.632-36.343, p = 0.010)] and baseline FT4 [OR=0.009 (CI: <0.001-0.313, p = 0.010)] were significantly associated with hypothyroidism in the IMRT group. Regarding dosimetric characteristics, V60Gy [OR=1.069 (CI: 0.999-1.143, p = 0.054)] was potentially associated with the development of hypothyroidism. CONCLUSION: The study revealed that the incidence of hypothyroidism within 2 years after postoperative chemoradiotherapy for high-risk HNC was 16.7 % based on analytical results from prospective clinical trials.

Extent of thyroidectomy and paratracheal lymph node dissection in total pharyngolaryngectomy for pyriform sinus cancer, and recurrence, survival, and postoperative hypoparathyroidism: A multicenter retrospective study.

BACKGROUND: Total pharyngolaryngectomy (TPL) is standard treatment for hypopharyngeal cancer. However, extensive thyroidectomy and paratracheal nodal dissection (PTND) can cause hypoparathyroidism. We sought to determine the optimum extent of resection. METHODS: We analyzed the clinicopathological information of 161 pyriform sinus cancer patients undergoing TPL from 25 Japanese institutions. Rates of recurrence and risk factors for hypoparathyroidism, as well as incidence of pathological contralateral level VI nodal metastasis and stomal recurrence, were investigated. RESULTS: The extent of thyroidectomy and nodal dissection were not independent risk factors for recurrence. Incidences of contralateral level VI nodal involvement and stomal recurrence were 1.8% and 1.2%, respectively. Patients undergoing hemithyroidectomy/ipsilateral PTND did not develop stomal recurrence and had the lowest incidence of hypoparathyroidism. Prognosis in patients without tracheostomy prior to hemithyroidectomy/ipsilateral PTND was comparable to that with more extensive resections. CONCLUSIONS: Hemithyroidectomy/ipsilateral PTND may be sufficient for pyriform sinus cancer cases without tracheostomy.

Dose-Finding and Efficacy Confirmation Trial of the Superselective Intra-arterial Infusion of Cisplatin and Concomitant Radiation Therapy for Locally Advanced Maxillary Sinus Cancer (JCOG1212): Results of the Efficacy Confirmation Phase in Patients with T4aN0M0.

PURPOSE: Locally advanced maxillary sinus cancers require radical surgery as a standard treatment, but this often results in significant disfigurement and impairment of function. JCOG1212 seeks to evaluate the safety and efficacy of the superselective intra-arterial infusion of cisplatin and concomitant radiation therapy (RADPLAT) for T4aN0M0 and T4bN0M0 maxillary sinus squamous cell carcinomas. We herein report the results of the efficacy confirmation phase in the T4a cohort. METHODS AND MATERIALS: Patients received 100 mg/m2 cisplatin intra-arterially weekly for 7 weeks with concomitant radiation therapy (total 70 Gy) as determined by the results of the preceding dose-finding phase. The trial aimed to evaluate the primary endpoint of 3-year overall survival (OS), comparing RADPLAT with the historical control for 3-year OS in surgery (80%). RESULTS: From April 2014 to August 2018, 65 patients were registered in the T4a cohort from 18 institutions, consisting of 54 men and 11 women with a median age of 64 years (range, 40-78 years) and Eastern Cooperative Oncology Group performance status 0/1 (58/7). After excluding 1 ineligible patient, 64 patients were included in the primary analysis of efficacy and safety. The median follow-up was 4.5 years in all eligible patients, and the primary endpoint for 3-year OS was 82.8% (90% CI, 73.4%-89.2%). With regard to acute adverse events, mucositis (grade ≥3), neutropenia (grade ≥3), increased creatinine (grade ≥2), hearing impairment (grade ≥2), and stroke (grade ≥2) were observed in 20.3%, 14.1%, 3.1%, 3.1%, and 1.6% of patients, respectively. One treatment-related death due to a thromboembolic event was reported. CONCLUSIONS: We demonstrated that RADPLAT showed favorable results for patients with T4aN0M0 maxillary sinus squamous cell carcinomas compared with the historical control for 3-year OS in surgery, which was from an earlier period, and showed some specific toxicities. Therefore, RADPLAT, as well as surgery, can be regarded as a possible treatment option for these patients.

Evaluation of usefulness of tongue pressure measurement device for dysphagia associated with treatment of patients with head and neck cancer (ELEVATE).

INTRODUCTION: Dysphagia is often caused by radiotherapy (RT) in patients with head and neck cancer (HNC), and reduced tongue pressure (TP) is often associated with swallowing dysfunction in the oral stage. However, the evaluation of dysphagia by measuring TP has not yet been established in HNC patients. Herein, we conducted a clinical trial to evaluate the usefulness of TP measurement using a TP-measuring device as an objective indicator of dysphagia induced by RT in HNC patients. METHODS AND ANALYSIS: This ELEVATE trial is a prospective, single-center, single-arm, non-blind, non-randomized trial to evaluate the usefulness of a TP measurement device for dysphagia associated with the treatment of HNC. Eligible participants include patients with oropharyngeal or hypopharyngeal cancer (HPC) undergoing RT or chemoradiotherapy (CRT). The TP measurements are conducted before, during, and after RT. The primary endpoint is the change in the maximum TP values from before RT to 3 months after RT. Moreover, as secondary endpoints, the correlation between the maximum TP value and the findings of video-endoscopic and video-fluoroscopic examinations of swallowing will be analyzed at each evaluation point, as well as changes in the maximum TP value from before RT to during RT and at 0, 1, and 6 months after RT. DISCUSSION: This trial aimed to investigate the usefulness of evaluation by measuring TP for dysphagia associated with HNC treatment. We expect that an easier evaluation for dysphagia will improve rehabilitation programs for dysphagia. Overall, we expect this trial to contribute to the improvement of patients' quality of life (QOL).

Risk factors for the lateral cervical lymph node metastasis of papillary thyroid carcinoma: A clinical study.

Currently, there is a lack of evidence-based risk factors for the lateral cervical lymph node metastasis of papillary thyroid carcinoma (PTC). Thus, the risk factors and recurrence rate of lateral cervical lymph node metastasis were investigated in the present study for patients with PTC who underwent initial radical surgery. The data of 274 patients with PTC who underwent initial radical surgery over a 10-year period from January, 2009 to December, 2018 were retrospectively analyzed. By applying univariate analysis, lymphovascular invasion, venous invasion, extrathyroidal infiltration, paratracheal lymph node metastasis and tumor size were designated as significant risk factors for lateral cervical lymph node metastasis. As regards multivariate analysis, paratracheal lymph node metastasis and tumor size were identified as independent risk factors. The recurrence rate was higher in patients presenting with lateral cervical lymph node metastasis, and the disease-free survival rate was significantly lower in the patient group presenting with lateral cervical lymph node metastasis. On the whole, the present study demonstrated that paratracheal lymph node metastasis and tumor size were independent risk factors for lateral cervical lymph node metastasis.

An extremely rare case of interdigitating dendritic cell sarcoma of the parotid gland with a 40­month disease­free survival time after only surgery: A case report.

Interdigitating dendritic cell sarcoma (IDCS) is an extremely rare neoplasm arising from dendritic cells and is mainly located in the lymph nodes. To the best of our knowledge, no treatment strategy has yet been established for IDCS, despite its aggressive clinical features. The present study presents the case of a patient with IDCS who experienced a 40-month disease-free survival time after surgery alone. The patient, a 29-year-old woman, presented with a painful right subaural swelling. Diagnostic MRI and 18F-fludeoxyglucose positron emission tomography/computed tomography revealed a right parotid gland tumour and ipsilateral cervical lymph node. The patient underwent surgical resection, and histological examination of the resected tissue specimens confirmed IDCS diagnosis. To the best of our knowledge, this is only the fifth report of an IDCS located in the parotid gland, with the longest follow-up period among cases of IDCS reported in this region. The positive outcome of this patient suggests that surgical resection may be an effective treatment option for local IDCS. Nonetheless, further studies are required to establish a definitive diagnosis and treatment strategy for IDCS.

Clinical Study on the Risk Factors for the Recurrence of Papillary Thyroid Carcinoma.

INTRODUCTION: Papillary thyroid carcinoma is the most common endocrine malignancy and the most common type of thyroid cancer, accounting for approximately 85% of all thyroid cancer cases. It usually has a favorable course, with the 10-year survival rate exceeding 90%. However, the literature reports a recurrence rate of 7-23% after initial surgical treatment. It is important to consider medical treatment policies for this recurrence. METHODS: In this study, we examined the risk factors for the recurrence of papillary thyroid carcinoma. We treated 274 patients with thyroid papillary carcinoma at our hospital between 2009 and 2018. RESULTS: Recurrence occurred in 20 cases (7.3%). Lympho-vascular invasion and lateral cervical lymph node metastasis made significant independent contributions. CONCLUSION: The selection of the surgical mode should be based on the recurrence and after comprehensive consideration of the clinical features.

Resection of brachial plexus schwannomas while monitoring transcranial motor evoked potentials: report of two cases.

A schwannoma is a benign nerve sheath tumor treated by enucleation, which carries the risk of intraoperative nerve injury that is observed after awakening. Transcranial motor evoked potential (TcMEP) monitoring has been established as an effective method to predict and prevent intraoperative neurological complications during brain and spinal surgery. However, there have been few reports on its application in head and neck surgeries. We performed enucleation to relieve the symptoms due to schwannomas in the neck of two women, aged 25 years and 70 years. Both women presented with a left cervical mass, paresthesia of the left upper limb, and a Tinel-like sign without muscle weakness. TcMEPs were recorded before beginning surgery, during surgery, and immediately before completing surgery. The dissecting lines were decided using the stimulator attached to the dissecting instrument, which helped warn the surgeon regarding risky areas. Histopathological examinations confirmed the diagnosis of schwannoma. There was no significant difference in the pre- and postoperative TcMEP recordings, and no postoperative motor deficits were identified. Intraoperative TcMEP monitoring is expected to be useful in preventing operative complications while treating head and neck schwannomas.

Head and neck small-cell carcinoma: A multicenter study of 39 cases from 10 institutions.

Objective: Basal information of head and neck small-cell carcinoma (HNSmCC) including epidemiology, primary site, treatment, and prognosis remains sparse due to its rarity. We report here a multicenter retrospective study on the diagnosis, treatment, and outcomes of patients with HNSmCC. Materials and methods: This study involved 47 patients with HNSmCC from 10 participating institutions. Eight patients were excluded for whom no pathological specimens were available (n = 2) and for discrepant central pathological judgements (n = 6). The remaining 39 patients were processed for data analysis. Results: As pretreatment examinations, computed tomography (CT) was performed for the brain (n = 8), neck (n = 39), and chest (n = 32), magnetic resonance imaging (MRI) for the brain (n = 4) and neck (n = 23), positron emission tomography-CT (PET-CT) in 23 patients, bone scintigraphy in 4, neck ultrasonography in 9, and tumor markers in 25. Primary sites were oral cavity (n = 1), nasal cavity/paranasal sinuses (n = 16), nasopharynx (n = 2), oropharynx (n = 4), hypopharynx (n = 2), larynx (n = 6), salivary gland (n = 3), thyroid (n = 2), and others (n = 3). Stages were II/III/IV-A/IV-B/IV-C/Not determined = 3/5/16/6/5/4; stage IV comprised 69%. No patient had brain metastases. First-line treatments were divided into 3 groups: the chemoradiotherapy (CRT) group (n = 27), non-CRT group (n = 8), and best supportive care group (n = 4). The CRT group included concurrent CRT (CCRT) (n = 17), chemotherapy (Chemo) followed by radiotherapy (RT) (n = 5), and surgery (Surg) followed by CCRT (n = 5). The non-CRT group included Surg followed by RT (n = 2), Surg followed by Chemo (n = 1), RT alone (n = 2), and Chemo alone (n = 3). The 1-year/2-year overall survival (OS) of all 39 patients was 65.3/53.3%. The 1-year OS of the CRT group (77.6%) was significantly better compared with the non-CRT group (31.3%). There were no significant differences in adverse events between the CCRT group (n = 22) and the Chemo without concurrent RT group (n = 9). Conclusion: Neck and chest CT, neck MRI, and PET-CT would be necessary and sufficient examinations in the diagnostic set up for HNSmCC. CCRT may be recommended as the first-line treatment. The 1-year/2-year OS was 65.3%/53.3%. This study would provide basal data for a proposing the diagnostic and treatment algorithms for HNSmCC.

Intraoperative Transcranial Motor-Evoked Potential Monitoring During Head and Neck Surgeries: A Case of Cervical Vagus Nerve Schwannoma With Laryngeal Paralysis.

Intraoperative transcranial motor-evoked potential (TcMEP) monitoring can effectively prevent neurological complications by enabling the evaluation of neurological deficits in all pathways from the motor cortex to the periphery. However, studies regarding its applicability in head and neck surgery are insufficient. This case report discusses a patient who was intraoperatively diagnosed with a right cervical vagus nerve schwannoma previously at another hospital. The patient then developed right laryngeal paralysis after the surgery without neuromonitoring. No significant recovery of the paralysis was observed, and after eight months of being referred to our institution, the patient opted for surgical retreatment following tumor growth and accompanying symptoms such as cervical swelling and discomfort. The patient was examined to evaluate the nerve damage in his previous surgery TcMEP monitoring as well as direct stimulation (DS). The right vagus nerve (RVN) showed no response on TcMEP monitoring throughout the surgery despite a significant response to DS at the tumor site. These findings suggest that the RVN had been damaged medial to the tumor site, and the damage occurred because of traction and ischemia during the previous surgery. Thus, contrary to our belief, medial nerve damage may be present even when local and peripheral nerve preservation is observed through peripheral neuromonitoring. This suggests that DS alone during neuromonitoring in head and neck surgery is insufficient. A multimodal evaluation approach, including TcMEP monitoring, is effective in not only preventing neurological complications but also in evaluating neurological deficits in all pathways from the motor cortex to the periphery.

A survey of feeding and swallowing function after free jejunal flap reconstruction in cases of head and neck cancer.

Reconstructive surgery using the free jejunum flap for locally advanced head and neck cancer is effective in preserving the swallowing function; however, it does not allow normal oral intake in all patients. A total of 47 patients underwent surgery at Nara Medical University between Jan 2010 and Dec 2019. The patients' ages ranged from 48 to 86 years. Sites were the hypopharynx (33 cases), larynx and cervical esophagus (5 cases each) and oropharynx (4 cases). Swallowing function was assessed using videofluorography, from the start of oral intake to discharge, as well as meal form at discharge. Lateral-retropharyngeal-lymph node dissection (LRPLND), preoperative radiation therapy, extended resection to the nasopharynx and incidence of stenosis in the jejuno-esophageal anastomosis were examined. Significant differences were revealed in the scores of pharyngeal residues of contrast medium and pharyngeal contraction, with and without preoperative radiotherapy. LRPLND did not affect swallowing function; dissection group cases had lower scores for soft palate elevation. Overall, resection extended to the nasopharynx, and the anastomosis method did not affect scores of swallowing function.

Four cases of medullary thyroid carcinomas associated with multiple endocrine neoplasia 2B with rearranged during transfection codon M918T mutation in the same family.

Multiple endocrine neoplasia (MEN) with medullary thyroid carcinoma (MTC) is associated with rearranged during transfection (RET) mutations. The authors encountered four cases of MTC-related MEN type 2B (MEN2B) with RET codon M918T mutation in one family. Case 1 included a 19 year-old male diagnosed with MTC with lung metastases. Genetic testing revealed an RET codon M918T mutation, which indicated MEN2B. The patient responded partially to vandetanib and the disease has shown no progression in 25 months. Case 2 involved the mother of the patient in Case 1. She underwent total thyroidectomy (TT) when diagnosed with MTC-related MEN2B at 12 years of age, but was not counseled adequately. Cases 3 and 4 involved the sisters of the Case 1 patient and were assessed after Case 1 was diagnosed. Genetic testing revealed the same mutation. Case 3 was diagnosed with MTC and underwent TT. Case 4 was asymptomatic but underwent prophylactic TT; histopathologic examination revealed MTC tissue. Prophylactic TT prevented MTC from being detected at an advanced state. Genetic counseling is essential in treating MEN2B. The mother was uninformed about the genetic characteristics of MEN2B, delaying the detection of MTC in her children. The present study reaffirms the importance of family history and screening.

Distribution pattern and pathologic analysis of metastatic sentinel and non-sentinel lymph nodes in lymphatic basin dissection for clinical T2/T3 oral cancer with clinical N0 status.

OBJECTIVE: The localization pattern of metastatic sentinel lymph node (SN) and non-SNs and pathologic analysis of metastatic lymph nodes in SN lymphatic basin dissection (SLBD) were investigated in patients with cT2/T3cN0 oral squamous cell carcinoma (OSCC). METHODS: This prospective multicenter trial involved 10 institutions nationwide in Japan. A total of 57 patients were enrolled. The lateral neck was divided into 5 lymphatic basins. The lymphatic basin containing SNs was defined as the SN lymphatic basin. All patients underwent SLBD with backup selective neck dissection (I-III) combined with primary tumor removal. When SNs were found outside of levels I-III, including in the contralateral neck, SLBD was performed by removing the compartments containing SNs separately. SN metastasis was classified as isolated tumor cells (ITCs), micrometastasis, or macrometastasis. ITCs are defined as a lesion no larger than 0.2 mm in largest dimension and are classified as pN0. RESULTS: SN metastasis was observed in 22 cases. All metastatic lymph nodes, including false-negative cases, were detected in the SN lymphatic basin. Isolated tumor cells in the SNs did not affect prognosis, whereas micrometastasis tended to have poor prognosis. After adjusting for other risk factors, a positive SN remained a significant predictor of poor 5-year overall survival in pT2-4 OSCC. CONCLUSION: SLBD for intraoperative SN biopsy is a sufficient therapeutic procedure and is valuable for determining pathologic nodal stage in OSCC. SN positivity was demonstrated to be an independent predictor of poor prognosis in patients with pT2-4 disease undergoing SLBD with backup selective neck dissection (I-III).

Anaplastic thyroid cancer with long-term survival with lenvatinib therapy and preservation of laryngeal function after one-stage reconstruction: A case report.

Laryngotracheal reconstruction is performed to treat locally advanced thyroid carcinoma invading the larynx and/or trachea. The reconstructive technique varies. The present report describes the case of a 71-year-old female patient who underwent surgery for thyroid carcinoma involving the larynx. Reconstructive surgical techniques were employed to maintain laryngeal structure and function. An anterolateral thigh flap with free rib cartilage grafts was used to compensate for laryngeal defects. Although a temporary tracheal stoma was constructed, it closed spontaneously after decannulation. Therefore, one-stage laryngeal reconstruction was accomplished. Post-operative histopathological examination revealed focal anaplastic changes in the lesion, which mainly consisted of papillary components. Post-operative positron emission tomography/computed tomography indicated early recurrence in the left side of the neck. Therefore, lenvatinib was started as adjuvant therapy. Complete response was observed with lenvatinib therapy. The patient was alive and had good laryngeal function 26 months after the operation. One-stage laryngeal reconstruction can reduce burden and improve quality of life in patients with thyroid carcinoma involving the larynx. Lenvatinib may be useful for treating early recurrence of anaplastic thyroid carcinoma after reconstructive surgery with a free flap.

A study of 24 cases of salivary gland carcinoma with distant metastasis.

Salivary gland carcinoma is a relatively rare disease of the head and neck. Although it frequently presents with distant metastases, few reports have been published on this subject. The present study investigated the prognosis of patients with distant metastases from salivary gland cancer. A total of 24 cases of salivary gland carcinoma with distant metastasis who were initially treated at the Department of Otolaryngology-Head and Neck Surgery of Nara Medical University during a 16-year period from August 2004 to July 2020 were included. The histopathological types included salivary duct carcinoma (8 cases), adenoid cystic carcinoma (6 cases), myoepithelial carcinoma (3 cases), Squamous cell carcinoma (2 cases), adenocarcinoma (2 cases), acinic cell carcinoma (2 cases) and mucoepidermoid carcinoma (1 case). A total of 18 patients had stage IV carcinoma, which represented the majority. Of all patients, ~80% developed distant metastases within 2 years of initial diagnosis. Survival rates after the appearance of distant metastases were 43.5% at 5 years and 14.5% at 10 years. The results of the current study revealed that no factors significantly influenced long-term prognosis after the development of distant metastases. In future, it may be necessary to re-examine these results in a larger sample size and standardise treatment methods as a result.

Neck Dissections Based on Sentinel Lymph Node Navigation Versus Elective Neck Dissections in Early Oral Cancers: A Randomized, Multicenter, and Noninferiority Trial.

PURPOSE: This study aimed to compare patients with early oral cavity squamous cell carcinoma (OCSCC) (tumor category [T] 1-2, node-negative, and no distant metastasis) treated with traditional elective neck dissection (ND) with those managed by sentinel lymph node biopsy (SLNB) using survival and neck function and complications as end points. METHODS: Sixteen institutions in Japan participated in the study (trial registration number: UMIN000006510). Patients of age ≥ 18 years with histologically confirmed, previously untreated OCSCC (Union for International Cancer Control TNM Classification of Malignant Tumors 7th edition T1-2, node-negative no distant metastasis), with ≥ 4 mm (T1) depth of invasion, were randomly assigned to undergo standard selective ND (ND group; n = 137) or SLNB-navigated ND (SLNB group; n = 134). The primary end point was the 3-year overall survival rate, with a 12% noninferiority margin; secondary end points included postoperative neck functionality and complications and 3-year disease-free survival. Sentinel lymph nodes underwent intraoperative multislice frozen section analyses for the diagnosis. Patients with positive sentinel lymph nodes underwent either one-stage or second-look ND. RESULTS: Pathologic metastasis-positive nodes were observed in 24.8% (34 of 137) and 33.6% (46 of 134) of patients in the ND and SLNB groups, respectively (P = .190). The 3-year overall survival in the SLNB group (87.9%; lower limit of one-sided 95% CI, 82.4) was noninferior to that in the ND group (86.6%; lower limit 95% CI, 80.9; P for noninferiority < .001). The 3-year disease-free survival rate was 78.7% (lower limit 95% CI, 72.1) and 81.3% (75.0) in the SLNB and ND groups, respectively (P for noninferiority < .001). The scores of neck functionality in the SLNB group were significantly better than those in the ND group. CONCLUSION: SLNB-navigated ND may replace elective ND without a survival disadvantage and reduce postoperative neck disability in patients with early-stage OCSCC.

Surgical technique for the prevention of tracheal necrosis following total pharyngolaryngectomy.

Total pharyngolaryngectomy with cervical esophagectomy (TPLCE) is an invasive procedure with various post-operative complications. Tracheal necrosis (TRN) is a fatal complication of TPLCE. The present study aimed to identify a surgical technique which may be used to prevent TRN. The post-operative complications of 48 patients who underwent TPLCE from January, 2010 to December, 2019 were retrospectively investigated. The incidence of TRN was examined and measures against TRN were reviewed. The results revealed that 3 patients (6%) experienced TRN within 1 week following surgery. In addition, 2 patients required the surgical debridement of the necrotic tissue and tracheoplasty. The other patient underwent conservative treatment. Stomal recurrence developed in 1 patient (2%). On the whole, the present study demonstrates that the incidence of TRN following TPLCE is lower than that observed in previous reports, and only one stomal recurrence was reported. Preserving the blood supply to the trachea is essential for the prevention of TRN. The eight surgical processes used herein effectively preserved the blood supply. Further investigations however, are necessary in order to confirm the present findings and to ensure effective measures are found with which to prevent TRN following TPLCE.

Impact of PSCA Polymorphisms on the Risk of Duodenal Ulcer.

BACKGROUND: While duodenal ulcer (DU) and gastric cancer (GC) are both H. pylori infection-related diseases, individuals with DU are known to have lower risk for GC. Many epidemiological studies have identified the PSCA rs2294008 T-allele as a risk factor of GC, while others have found an association between the rs2294008 C-allele and risk of DU and gastric ulcer (GU). Following these initial reports, however, few studies have since validated these associations. Here, we aimed to validate the association between variations in PSCA and the risk of DU/GU and evaluate its interaction with environmental factors in a Japanese population. METHODS: Six PSCA SNPs were genotyped in 584 DU cases, 925 GU cases, and 8,105 controls from the Japan Multi-Institutional Collaborative Cohort (J-MICC). Unconditional logistic regression models were applied to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for the association between the SNPs and risk of DU/GU. RESULTS: PSCA rs2294008 C-allele was associated with per allele OR of 1.34 (95% CI, 1.18-1.51; P = 2.28 × 10-6) for the risk of DU. This association was independent of age, sex, study site, smoking habit, drinking habit, and H. pylori status. On the other hand, we did not observe an association between the risk of GU and PSCA SNPs. CONCLUSIONS: Our study confirms an association between the PSCA rs2294008 C-allele and the risk of DU in a Japanese population.

Study Profile of the Japan Multi-institutional Collaborative Cohort (J-MICC) Study.

BACKGROUND: The Japan Multi-institutional Collaborative Cohort (J-MICC) study was launched in 2005 to examine gene-environment interactions in lifestyle-related diseases, including cancers, among the Japanese. This report describes the study design and baseline profile of the study participants. METHODS: The participants of the J-MICC Study were individuals aged 35 to 69 years enrolled from respondents to study announcements in specified regions, inhabitants attending health checkup examinations provided by local governments, visitors at health checkup centers, and first-visit patients at a cancer hospital in Japan. At the time of the baseline survey, from 2005 to 2014, we obtained comprehensive information regarding demographics, education, alcohol consumption, smoking, sleeping, exercise, food intake frequency, medication and supplement use, personal and family disease history, psychological stress, and female reproductive history and collected peripheral blood samples. RESULTS: The baseline survey included 92,610 adults (mean age: 55.2 [standard deviation, 9.4] years, 44.1% men) from 14 study regions in 12 prefectures. The participation rate was 33.5%, with participation ranging from 19.7% to 69.8% in different study regions. The largest number of participants was in the age groups of 65-69 years for men and 60-64 years for women. There were differences in body mass index, educational attainment, alcohol consumption, smoking, and sleep duration between men and women. CONCLUSIONS: The J-MICC Study collected lifestyle and clinical data and biospecimens from over 90,000 participants. This cohort is expected to be a valuable resource for the national and international scientific community in providing evidence to support longer healthy lives.