Adjuvant S-1 compared with observation in resected biliary tract cancer (JCOG1202, ASCOT): a multicentre, open-label, randomised, controlled, phase 3 trial.

BACKGROUND: S-1 has shown promising efficacy with a mild toxicity profile in patients with advanced biliary tract cancer. The aim of this study was to evaluate whether adjuvant S-1 improved overall survival compared with observation for resected biliary tract cancer. METHODS: This open-label, multicentre, randomised phase 3 trial was conducted in 38 Japanese hospitals. Patients aged 20-80 years who had histologically confirmed extrahepatic cholangiocarcinoma, gallbladder carcinoma, ampullary carcinoma, or intrahepatic cholangiocarcinoma in a resected specimen and had undergone no local residual tumour resection or microscopic residual tumour resection were randomly assigned (1:1) to undergo observation or to receive S-1 (ie, 40 mg, 50 mg, or 60 mg according to body surface area, orally administered twice daily for 4 weeks, followed by 2 weeks of rest for four cycles). Randomisation was performed by the minimisation method, using institution, primary tumour site, and lymph node metastasis as adjustment factors. The primary endpoint was overall survival and was assessed for all randomly assigned patients on an intention-to-treat basis. Safety was assessed in all eligible patients. For the S-1 group, all patients who began the protocol treatment were eligible for a safety assessment. This trial is registered with the University hospital Medical Information Network Clinical Trials Registry (UMIN000011688). FINDINGS: Between Sept 9, 2013, and June 22, 2018, 440 patients were enrolled (observation group n=222 and S-1 group n=218). The data cutoff date was June 23, 2021. Median duration of follow-up was 45·4 months. In the primary analysis, the 3-year overall survival was 67·6% (95% CI 61·0-73·3%) in the observation group compared with 77·1% (70·9-82·1%) in the S-1 group (adjusted hazard ratio [HR] 0·69, 95% CI 0·51-0·94; one-sided p=0·0080). The 3-year relapse-free survival was 50·9% (95% CI 44·1-57·2%) in the observation group compared with 62·4% (55·6-68·4%) in the S-1 group (HR 0·80, 95% CI 0·61-1·04; two-sided p=0·088). The main grade 3-4 adverse events in the S-1 group were decreased neutrophil count (29 [14%]) and biliary tract infection (15 [7%]). INTERPRETATION: Although long-term clinical benefit would be needed for a definitive conclusion, a significant improvement in survival suggested adjuvant S-1 could be considered a standard of care for resected biliary tract cancer in Asian patients. FUNDING: The National Cancer Center Research and the Ministry of Health, Labour, and Welfare of Japan.

Videofluoroscopic analysis of the laryngeal movement of older adults in swallowing.

Even without diseases that cause dysphagia, physiological swallowing function declines with age, increasing the risk of aspiration. This study analyzed age-related changes in laryngeal movement in older adults. The study population consisted of 10 volunteers in their 80s and six in their 20s. A videofluoroscopic study of 3 and 10 mL barium swallows was performed laterally using a digital fluorographic. The recorded images were retrieved to a personal computer and analyzed frame-by-frame using video analysis software. The movement of the larynx during swallowing, barium's pharyngeal transit time (PTT), and laryngeal elevation delay time (LEDT) were analyzed. Results were compared between the 20s and 80s age groups using statistical analyses. The PTT was shorter in the 20s than in the 80s age group. The PTT was significantly longer in the 80s group than in the 20s for both 3 and 10 mL barium swallows. LEDT in the 80s was statistically significantly longer than that in the 20s for the 10 ml barium. No statistically significant differences were found; however, there was a tendency for the 80s group to have more types of laryngeal movement velocity peaks. In this study, LEDT was prolonged in the 80s with 10 ml barium swallowing than in the 20s. Two peak patterns of laryngeal elevation during swallowing were observed. The velocity peaks showed a two-peak pattern when the patients were in their 80s and when the barium volume was tested at 10 mL. Our results suggest that aging's effect on swallowing relates to laryngeal elevation.

Cone-beam computed tomography-based investigation of pre-eruptive intracoronal resorption prevalence.

This retrospective study aimed to investigate the prevalence of pre-eruptive intracoronal resorption (PEIR) using cone-beam computed tomography (CBCT) and to explore the mechanism and characteristics of PEIR development. CBCT images of patients aged ≤ 20 years with unerupted teeth at Hiroshima University Hospital were collected. We examined 1530 patients with 10,576 unerupted teeth. Teeth with PEIR were identified for the detailed location and size of the PEIR in the crown using multiplanar reconstruction. The subject and tooth prevalence rates of PEIR were 1.96% and 0.31%, respectively. The teeth that were the most commonly affected by PEIR were mandibular third molars (3.09%). The prevalence of PEIR was significantly higher in females than in males, and higher in the mandible than in the maxilla. No significant difference between in the position of PEIR within the crown was observed. Moreover, CBCT imaging revealed the onset of PEIR in one case. This study demonstrated the prevalence of PEIR and identified statistically significant sex- and location-based differences. Furthermore, one case of CBCT imaging supports the hypothesis that the onset of PEIR was due to resorption after completion of the crown.

Can oral diadochokinesis be used as an assessment tool of oral function in older adults requiring care in nursing home?

BACKGROUND: Oral diadochokinesis (OD) test is an articulation test that analyses fine movements of the lips, cheeks and tongue. It is difficult to perform the test accurately in older people with reduced physical and cognitive functions. OBJECTIVES: This study aimed to investigate the number of older adults who could not be tested for OD and to investigate their characteristics. METHODS: The participants included 145 older residents of an aged care nursing home. They were divided into two groups: those who could be tested for OD and those who could not, and their characteristics were compared. The degree of requiring long-term care was classified into five levels. The degree of dementia was classified into five levels. Those having difficulty in performing daily activities alone and having degree III or higher dementia were considered to have severe dementia. RESULTS: The participants included 41 men and 104 women with a median age of 89 years (range, 64-105 years). Sixty-eight participants failed the OD test (46.9%). In univariate and multivariate analyses, degree of dementia and oral care (among other characteristics in univariate analysis) showed statistically significant differences between the two groups. Cut-off values for older adults who could not perform OD test were level 4 or higher in need of care and degree III or higher in dementia. CONCLUSION: This study suggests that additional assessment tools for oral function should be considered for older adults requiring a nursing care level of 4 or higher and a dementia degree of III or higher.

Relationships between physical and immunological tumor microenvironment in pancreatic ductal adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is physically palpated as a hard tumor with an unfavorable prognosis. Assessing physical features and their association with pathological features could help to elucidate the mechanism of physical abnormalities in cancer tissues. A total of 93 patients who underwent radical surgery for pancreatic and bile duct cancers at a single center hospital during a 28-month period were recruited for this study that aimed to estimate the stiffness of PDAC tissues compared to the other neoplasms and assess relationships between tumor stiffness and pathological features. Physical alterations and pathological features of PDAC, with or without preoperative therapy, were analyzed. The immunological tumor microenvironment was evaluated using multiplexed fluorescent immunohistochemistry. The stiffness of PDAC correlated with the ratio of Azan-Mallory staining, α-smooth muscle actin, and collagen I-positive areas of the tumors. Densities of CD8+ T cells and CD204+ macrophages were associated with tumor stiffness in cases without preoperative therapy. Pancreatic ductal adenocarcinoma treated with preoperative therapy was softer than that without, and the association between tumor stiffness and immune cell infiltration was not shown after preoperative therapy. We observed the relationship between tumor stiffness and immunological features in human PDAC for the first time. Immune cell densities in the tumor center were smaller in hard tumors than in soft tumors without preoperative therapies. Preoperative therapy could alter physical and immunological aspects, warranting further study. Understanding of the correlations between physical and immunological aspects could lead to the development of new therapies.

A Multicenter Survey on Eligibility for a Randomized Phase III Trial of Adjuvant Chemotherapy for Resected Biliary Tract Cancer (JCOG1202, ASCOT).

BACKGROUND: The Adjuvant S-1 for Cholangiocarcinoma Trial (JCOG1202, [ASCOT]) was a multicenter, randomized controlled trial aimed at investigating the efficacy and safety of adjuvant chemotherapy (AC) with S-1 for resected biliary tract cancer (BTC). This trial reported that overall survival was prolonged with AC compared with observation. METHODS: With the aim of increasing enrollment, the present survey biannually recorded the number of patients eligible for enrollment into ASCOT and reasons for ineligibility among patients who had undergone surgery for BTC from April 2015 to September 2017 at 36 institutions participating in ASCOT. RESULTS: Of 2039 patients who underwent surgery for BTC, 211 (10.3%) were already enrolled, 166 (8.1%) were eligible but had not been enrolled, and 1662 (81.5%) were ineligible. Among ineligible patients, the predominant reasons for ineligibility were patient refusal (n = 332, 20.0%), pathologic stage (pT1N0; n = 248, 14.9%), age (≥ 81 years; n = 196, 11.8%), and prolonged postoperative complications (n = 176, 10.6%). CONCLUSIONS: Patients undergoing surgery for BTC are a heterogeneous cohort comprising patients with earlier pathologic stage, advanced age, and prolonged postoperative complications. These factors should be considered during the design of future clinical trials of perioperative treatments for resectable BTC.

Ghost cell odontogenic carcinoma arising in dentinogenic ghost cell tumor, peripheral: A case report.

Ghost cell odontogenic carcinoma (GCOC) is an extremely rare intraosseous malignant odontogenic tumor with prominent ghost cell keratinization and dentinoid formation. Here, we present the first case of GCOC arising in dentinogenic ghost cell tumor (DGCT), peripheral. The patient was a man in his 60s with an exophytic mass in the anterior part of lower gingiva. The resected tumor measured 4.5 cm in maximum diameter. Histologically, the nonencapsulated tumor proliferated in the gingiva without bone invasion. It was predominantly composed of ameloblastoma-like nests and islands of basaloid cells with ghost cells and dentinoid in the mature connective tissue, suggesting DGCT, peripheral. As minor components, sheets of atypical basaloid cells and ameloblastic carcinoma-like nests with pleomorphism and high proliferative activity (Ki-67 labeling index up to 40%) consistent with malignancy were identified. CTNNB1 mutation and ß-catenin nuclear translocation were observed in both benign and malignant components. Final diagnosis was GCOC arising in DGCT, peripheral. GCOC shows similar histological features to DGCT. In this unique case without invasion, the cytological atypia and high proliferative activity supports the diagnosis of malignant transformation from DGCT.

Liver functional assessment using time-associated change in the liver-to-spleen signal intensity ratio on enhanced magnetic resonance imaging: a retrospective study.

BACKGROUND: Liver-to-spleen signal intensity ratio (LSR) is evaluated by magnetic resonance imaging (MRI) in the hepatobiliary phase and has been reported as a useful radiological assessment of regional liver function. However, LSR is a passive (non-time-associated) assessment of liver function, not a dynamic (time-associated) assessment. Moreover, LSR shows limitations such as a dose bias of contrast medium and a timing bias of imaging. Previous studies have reported the advantages of time-associated liver functional assessment as a precise assessment of liver function. For instance, the indocyanine green (ICG) disappearance rate, which is calculated from serum ICG concentrations at multiple time points, reflects a precise preoperative liver function for predicting post-hepatectomy liver failure without the dose bias of ICG or the timing bias of blood sampling. The aim of this study was to develop a novel time-associated radiological liver functional assessment and verify its correlation with traditional liver functional parameters. METHODS: A total of 279 pancreatic cancer patients were evaluated to clarify fundamental time-associated changes to LSR in normal liver. We defined the time-associated radiological assessment of liver function, calculated using information on LSR from four time points, as the "LSR increasing rate" (LSRi). We then investigated correlations between LSRi and previous liver functional parameters. Furthermore, we evaluated how timing bias and protocol bias affect LSRi. RESULTS: Significant correlations were observed between LSRi and previous liver functional parameters such as total bilirubin, Child-Pugh grade, and albumin-bilirubin grade (P < 0.001 each). Moreover, considerably high correlations were observed between LSRi calculated using four time points and that calculated using three time points (r > 0.973 each), indicating that the timing bias of imaging was minimal. CONCLUSIONS: This study propose a novel time-associated radiological assessment, and revealed that the LSRi correlated significantly with traditional liver functional parameters. Changes in LSR over time may provide a superior preoperative assessment of regional liver function that is better for predicting post-hepatectomy liver failure than LSR using the hepatobiliary phase alone.

Head and neck cancer patients show poor oral health as compared to those with other types of cancer.

PURPOSE: Several studies have found associations between periodontitis and various types of cancer. Since the site of head and neck cancer (HNC) has contiguity or proximity to the oral cavity, it may be particularly influenced by oral inflammation. This study aimed to determine whether HNC patients have poor oral health as compared to those with other types of cancer. METHODS: This study retrospectively examined oral environmental factors including periodontal inflamed surface area (PISA), a new periodontal inflammatory parameter. A total of 1030 cancer patients were divided into the HNC (n = 142) and other cancer (n = 888) groups. Furthermore, the HNC group was divided into high (n = 71) and low (n = 71) PISA subgroups, and independent risk factors affecting a high PISA value were investigated. RESULTS: Multivariate logistic regression analysis showed that number of missing teeth (odds ratio 1.72, 95% CI 1.15-2.56, P < 0.01), PISA (odds ratio 1.06, 95% CI 1.03-1.06, P < 0.05), and oral bacterial count (odds ratio 1.02, 95% CI 1.01-1.03, P < 0.01) were independent factors related to HNC. In addition, multivariate logistic regression analysis indicated that current smoker (odds ratio 7.51, 95% CI 1.63-34.71, P < 0.01) and presence of untreated dental caries (odds ratio 3.33, 95% CI 1.23-9.00, P < 0.05) were independent risk factors affecting high PISA values in HNC patients. CONCLUSION: HNC patients have higher levels of gingival inflammation and poor oral health as compared to patients with other types of cancer, indicating that prompt oral assessment and an effective oral hygiene management plan are needed at the time of HNC diagnosis.

Neoadjuvant S-1 With Concurrent Radiotherapy Followed by Surgery for Borderline Resectable Pancreatic Cancer: A Phase II Open-label Multicenter Prospective Trial (JASPAC05).

OBJECTIVE: This study assessed whether neoadjuvant chemoradiotherapy (CRT) with S-1 increases the R0 resection rate in BRPC. SUMMARY OF BACKGROUND DATA: Although a multidisciplinary approach that includes neoadjuvant treatment has been shown to be a better strategy for BRPC than upfront resection, a standard treatment for BRPC has not been established. METHODS: A multicenter, single-arm, phase II study was performed. Patients who fulfilled the criteria for BRPC received S-1 (40 mg/m 2 bid) and concurrent radiotherapy (50.4 Gy in 28 fractions) before surgery. The primary endpoint was the R0 resection rate. At least 40 patients were required, with a 1-sided α = 0.05 and ß = 0.05 and expected and threshold values for the primary endpoint of 30% and 10%, respectively. RESULTS: Fifty-two patients were eligible, and 41 were confirmed to have definitive BRPC by a central review. CRT was completed in 50 (96%) patients and was well tolerated. The rate of grade 3/4 toxicity with CRT was 43%. The R0 resection rate was 52% among the 52 eligible patients and 63% among the 41 patients who were centrally confirmed to have BRPC. Postoperative grade III/IV adverse events according to the Clavien-Dindo classification were observed in 7.5%. Among the 41 centrally confirmed BRPC patients, the 2-year overall survival rate and median overall survival duration were 58% and 30.8 months, respectively. CONCLUSIONS: S-1 and concurrent radiotherapy seem to be feasible and effective at increasing the R0 resection rate and improving survival in patients with BRPC. TRIAL REGISTRATION: UMIN000009172.

Early postoperative decrease of skeletal muscle mass predicts recurrence and poor survival after surgical resection for perihilar cholangiocarcinoma.

BACKGROUND: Preoperative sarcopenia is a predictor of poor survival in cancer patients. We hypothesized that sarcopenia could progress as occult metastasis arose, especially after highly invasive surgery for highly aggressive malignancy. This study aimed to evaluate the associations of postoperative changes in skeletal muscle mass volume with survival outcomes in patients who underwent surgery for perihilar cholangiocarcinoma. METHODS: Fifty-six patients who underwent major hepatectomy with extrahepatic bile duct resection for perihilar cholangiocarcinoma were studied. The skeletal muscle index (SMI) at the third lumbar vertebra was calculated from axial computed tomography images taken preoperatively and 3-6 months postoperatively (early postoperative period). The associations of clinicopathological variables, including changes of SMI after surgery, with overall survival and recurrence-free survival were evaluated. Moreover, the associations of decreased SMI and elevated serum carbohydrate antigen 19-9 level with early recurrence and poor survival was compared. RESULTS: Among 56 patients, 26 (46%) had sarcopenia preoperatively and SMI decreased in 29 (52%) in the early postoperative period. During the median follow-up of 57.9 months, 35 patients (63%) developed recurrence and 29 (50%) died. Decreased SMI in the early postoperative period was independently associated with a shorter overall survival (hazard ratio, 2.39; 95% confidence interval, 1.00-6.18; P = 0.049) and a shorter recurrence-free survival (hazard ratio, 2.14; 95% confidence interval, 1.04-4.57; P = 0.039), whereas elevated carbohydrate antigen 19-9 level was not. CONCLUSIONS: Decreased SMI in the early postoperative period may be used as a predictor for recurrence and poor survival in patients undergoing surgery for perihilar cholangiocarcinoma.

Laparoscopic liver resection can be performed safely without intraoperative drain placement.

BACKGROUND: Laparoscopic liver resection (LLR) has become a standardized procedure with advances in surgical techniques and perioperative management in the last decade; however, the necessity of routine drain placement in LLR has not been fully investigated. This study aimed to evaluate the need for intraoperative drain placement (IDP) in LLR. METHODS: A total of 607 patients who underwent LLR for liver tumor at our institution between January 2015 and August 2021 were studied. Clinicopathological data, including intraoperative factors and postoperative outcomes, were compared between patients with and without IDP before and after propensity score matching. Variables shown to be different between the two groups were used for matching. Then, risk analysis for additional drainage procedure after surgery was performed in the original and matched cohorts. RESULTS: Of the 607 patients, 4 (0.7%) and 14 (2.3%) developed incisional and organ/space surgical site infections, respectively, and 9 (1.5%) required additional drainage procedure after surgery. Ninety-three patients (15.3%) underwent IDP. The incidence and severity of postoperative complications were similar between patients with and without IDP in both the original and matched cohorts. In the matched cohort, simultaneous colectomy (odds ratio, 14.051, 95% confidence interval, 1.103-178.987; P = 0.042), rather than IDP (odds ratio, 1.836, 95% confidence interval, 0.157-21.509; P = 0.629), was independently associated with the risk of additional drainage procedure after surgery. CONCLUSIONS: This study demonstrated that LLR could be performed safely without IDP.

Sarcomatoid hepatocellular carcinoma is distinct from ordinary hepatocellular carcinoma: Clinicopathologic, transcriptomic and immunologic analyses.

Sarcomatoid hepatocellular carcinoma (SHCC), which was a rare histological subtype of hepatocellular carcinoma (HCC), is currently subclassified as poorly differentiated HCC because of insufficient evidence to define SHCC as a subtype of HCC. We aimed to assess the feasibility of classifying SHCC as a histological subtype of HCC by comprehensively identifying novel and distinct characteristics of SHCC compared to ordinary HCC (OHCC). Fifteen SHCCs (1.4%) defined as HCC with at least a 10% sarcomatous component, 15 randomly disease-stage-matched OHCCs and 163 consecutive OHCCs were extracted from 1106 HCCs in the Pathology Database (1997-2019) of our hospital. SHCC patients showed poor prognosis, and the tumors could be histologically subclassified into the pleomorphic, spindle and giant cell types according to the subtype of carcinomas with sarcomatoid or undifferentiated morphology in other organs. The transcriptomic analysis revealed distinct characteristics of SHCC featuring the upregulation of genes associated with epithelial-to-mesenchymal transition and inflammatory responses. The fluorescent multiplex immunohistochemistry results revealed prominent programmed death-ligand 1 (PD-L1) expression on sarcomatoid tumor cells and higher infiltration of CD4+ and CD8+ T cells in SHCCs compared to OHCCs. The density of CD8+ T cells in the nonsarcomatous component of SHCCs was also higher than that in OHCCs. In conclusion, the comprehensive analyses in our study demonstrated that SHCC is distinct from OHCC in terms of clinicopathologic, transcriptomic and immunologic characteristics. Therefore, it is reasonable to consider SHCC as a histological subtype of HCC.

Drain Placement After Uncomplicated Hepatic Resection Increases Severe Postoperative Complication Rate: A Japanese Multi-institutional Randomized Controlled Trial (ND-trial).

OBJECTIVE: To assess the clinical impact of a no-drain policy after hepatic resection. SUMMARY OF BACKGROUND DATA: Previous randomized controlled trials addressing no-drain policy after hepatic resection seem inconclusive because they did not adopt appropriate study design to validate its true clinical impact. METHODS: This unblinded, randomized controlled trial was done at 7 Japanese institutions. Patients undergoing hepatic resection without biliary reconstruction were randomized to either D group or ND group. When the risk of postoperative bile leakage or hemorrhage were considered high, the patients were excluded during the operation. Primary endpoint was the postoperative complication of C-D grade 3 or higher within 90 postoperative days. A noninferiority of ND group to D group was assessed, and if it was confirmed, a superiority was assessed. RESULTS: Between May 2015 and July 2017, a total of 400 patients were finally included in the per-protocol set analysis: 199 patients in D group and 201 patients in ND group. Intraoperatively, 37 patients were excluded from the final enrollment because of high risk of bile leakage or hemorrhage. Postoperative complication rate of C-D grade 3 or higher was 8.0% (16/199) in the D group and 2.5% (5/201) in the ND group. The risk difference was -5.5% (95% confidence interval: -9.9% to -1.2%) and fulfilled the prescribed noninferiority margin of 4%. No postoperative mortality was experienced in both groups. Bile leakage was diagnosed in 8.0% (16/199) of the D group and none in the ND group (P < 0.001). In none of the subgroups classified based on 8 potentially relevant factors, drain placement was favored in terms of C-D grade 3 or higher complication. CONCLUSIONS: Drains should not be placed after uncomplicated hepatic resections.

Impact of Preoperative Circulating Tumor DNA Status on Survival Outcomes After Hepatectomy for Resectable Colorectal Liver Metastases.

BACKGROUND: The optimal perioperative management of patients who undergo hepatectomy for resectable colorectal liver metastases (CRLM) remains unclear due to the lack of reliable methods to stratify the risk of recurrence. METHODS: A single-center retrospective study was performed to investigate the impact of preoperative circulating tumor DNA (ctDNA) on survival outcomes of patients who underwent initial hepatectomy for solitary resectable CRLM between January 2005 and December 2017 using the comprehensive genotyping platform Guardant360®. RESULTS: Of 212 patients who underwent initial hepatectomy for solitary resectable CRLM, 40 patients for whom pre-hepatectomy plasma was available underwent ctDNA analysis. Among them, 32 (80%) had at least 1 somatic alteration in their ctDNA, while the other 8 (20%) had no detectable ctDNA. Among the patients with undetectable ctDNA, only one had recurrence and none died during a median follow-up period of 39.0 months. The recurrence-free survival was significantly shorter in patients who were positive for ctDNA than in those who were negative for ctDNA [median, 12.5 months vs not reached (NR); HR, 7.6; P = 0.02]. The overall survival also tended to be shorter in patients who were positive for ctDNA than those who were negative for ctDNA (median, 78.1 months vs NR; P = 0.14; HR not available). CONCLUSIONS: In patients undergoing hepatectomy for solitary resectable CRLM, the absence of detectable preoperative ctDNA identified patients with a high chance for a cure. Risk stratification according to preoperative ctDNA analysis may be an effective tool that can improve the perioperative management of these patients.

Effects of perioperative oral care on postoperative inflammation following heart valve surgery.

OBJECTIVE: Whether oral health care during the perioperative period can lead to a better outcome after heart valve surgery has not been adequately elucidated. We examined the effects of perioperative oral care on postoperative inflammation response in patients who underwent heart valve surgery. MATERIALS AND METHODS: In this retrospective cohort study, 223 patients scheduled for single valve heart surgery were divided into the oral care, who underwent professional teeth cleaning or scaling within 3 days prior to surgery, and also following surgery at least twice a week (n = 111), and non-oral care (n = 112) groups. After propensity score matching, records of both groups (80:80) were examined after surgery to evaluate inflammation markers (white blood cell count [WBC], neutrophil/white blood cell ratio [NWR], C-reactive protein [CRP] level, body temperature [BT]). RESULTS: WBC, NWR, CRP level, and BT were increased in both groups the day following surgery. Thereafter, CRP level, WBC, NWR, and BT on various days after surgery in the oral care group showed greater decreases as compared to the non-oral care group. CONCLUSIONS: Perioperative oral health care can decrease postoperative inflammation in patients undergoing heart valve surgery and may be important to ensure a better outcome in those patients.

Intraoral Ultrasonographic Features of Tongue Cancer and the Incidence of Cervical Lymph Node Metastasis.

PURPOSE: The purpose of this study was to investigate the relationship between the visual characteristics of tongue lesion images obtained through intraoral ultrasonographic examination and the occurrence of late cervical lymph node metastasis in patients with tongue cancer. PATIENTS AND METHODS: This study investigated patients with primary tongue cancer who were examined using intraoral ultrasonography at Hiroshima University Hospital between January 2014 and December 2017. The inclusion criteria were squamous cell carcinoma, curative treatment administration, lateral side of tongue, surgery or brachytherapy alone, no cervical lymph node or distant metastasis as primary treatment, and treatment in our hospital. The exclusion criteria were carcinoma in situ, palliative treatment, dorsum of tongue, and multiple primary cancers. The follow-up period was more than 1 year. The primary endpoint was the occurrence of late cervical lymph node metastasis, and the primary predictor variables were age, gender, longest diameter, thickness, margin or border shapes of the lesion, and treatment methods. The relationship between the occurrence of late cervical lymph node metastasis and the longest diameter, thickness, margin types, and border types as evaluated through intraoral ultrasonography were assessed. The data were collected through a retrospective chart review. RESULTS: Fifty-four patients were included in this study. The analysis indicated that irregular lesion margins were significantly associated with the occurrence of late cervical lymph node metastasis (P < .0001). The cutoff value for late cervical lymph node metastasis was 21.2 mm for the longest diameter and 3.9 mm for the thickness. CONCLUSIONS: The results of this study indicates that the irregular lesion margin assessed using intraoral ultrasonography may serve as an effective predictor of late cervical lymph node metastasis in N0 cases.

Relationship between oral and nutritional status of older residents with severe dementia in an aged care nursing home.

OBJECTIVE: The aim of this study was to investigate the relationships between the oral and nutritional status of older residents with dementia in an aged care nursing home. BACKGROUND: Insufficient oral evaluation and care due to refusal of treatment in older people with dementia may cause deterioration in oral and nutritional status. MATERIALS AND METHODS: The subjects were 123 older residents with dementia who had been admitted to an aged care nursing home. Oral condition and body mass index (BMI) as a measure of nutritional status were investigated, and the results for the mild and severe dementia groups were compared. BMI was compared by the food consistency between the mild and severe dementia groups. RESULTS: In the severe dementia group, fewer older adults had removable dentures and many had no molar occlusion. The rate of subjects who had refused oral care by the caregivers was significantly higher in the severe dementia group than in the mild dementia group. In the severe dementia group, the BMI of those having texture-modified foods was significantly lower than those having a normal diet. The BMI of subjects without molar occlusion and with a history of cerebrovascular disease was significantly lower in the severe dementia group. CONCLUSIONS: The BMI of subjects in the severe dementia group having texture-modified food was significantly lower than that of those with a normal diet. The BMI of subjects in the severe dementia group without molar occlusion was significantly lower than those with molar occlusion.

Peptide vaccine as an adjuvant therapy for glypican-3-positive hepatocellular carcinoma induces peptide-specific CTLs and improves long prognosis.

There is no established postoperative adjuvant therapy for hepatocellular carcinoma (HCC), and improvement of patient prognosis has been limited. We conducted long-term monitoring of patients within a phase II trial that targeted a cancer antigen, glypican-3 (GPC3), specifically expressed in HCC. We sought to determine if the GPC3 peptide vaccine was an effective adjuvant therapy by monitoring disease-free survival and overall survival. We also tracked GPC3 immunohistochemical (IHC) staining, CTL induction, and postoperative plasma GPC3 for a patient group that was administered the vaccine (n = 35) and an unvaccinated patient group that underwent surgery only (n = 33). The 1-y recurrence rate after surgery was reduced by approximately 15%, and the 5-y and 8-y survival rates were improved by approximately 10% and 30%, respectively, in the vaccinated group compared with the unvaccinated group. Patients who were positive for GPC3 IHC staining were more likely to have induced CTLs, and 60% survived beyond 5 y. Vaccine efficacy had a positive relationship with plasma concentration of GPC3; high concentrations increased the 5-y survival rate to 75%. We thus expect GPC3 vaccination in patients with HCC, who are positive for GPC3 IHC staining and/or plasma GPC3 to induce CTL and have significantly improved long-term prognosis.

Plasma and tumoral glypican-3 levels are correlated in patients with hepatitis C virus-related hepatocellular carcinoma.

Glypican-3 (GPC3) is a cancer antigen expressed in approximately 80% of hepatocellular carcinomas (HCC) and is secreted into the blood. To confirm the effectiveness of GPC3 as a biomarker in HCC, we analyzed the relationship between GPC3 expression levels in cancer cells and in blood in 56 patients with HCC. Preoperative plasma GPC3 levels were determined with an immunoassay, and expression of GPC3 in resected tumors was analyzed by immunohistochemical staining. Median plasma GPC3 level in all HCC cases was 4.6 pg/mL, and tended to be higher in patients with hepatitis C virus (HCV)-related HCC (HCV group) (9.9 pg/mL) than in patients with hepatitis B virus (HBV)-related HCC (HBV group) (2.6 pg/mL) or in those without virus infection (None group) (3.0 pg/mL), suggesting that the virus type most likely influences GPC3 secretion. Median percentage of GPC3+ cells in tumors was also higher in the HCV (26.2%) and HBV (11.1%) groups than in the None group (4.2%). In the HCV group, there was a positive correlation between the two parameters (r = 0.66, P < .01). Moreover, receiver operating characteristic analysis predicted >10% GPC3+ cells in a tumor if the cut-off value was 6.8 pg/mL (sensitivity 80%, specificity 100%; area under the curve 0.875, 95% confidence interval 0.726-1) in the HCV group. Plasma concentration of GPC3 could be a predictive marker of tumoral GPC3 expression in patients with HCV-related HCC, suggesting a useful biomarker for immunotherapies targeting GPC3, although larger-scale validations are needed.