A case report of carcinoma of the papilla of Vater associated with a hyperplasia-dysplasia-carcinoma sequence by pancreaticobiliary maljunction.

BACKGROUND: Pancreaticobiliary maljunction (PBM) is a known risk factor for biliary tract cancer. However, its association with carcinoma of the papilla of Vater (PVca) remains unknown. We report a case with PVca that was thought to be caused by the hyperplasia-dysplasia-carcinoma sequence, which is considered a mechanism underlying PBM-induced biliary tract cancer. CASE PRESENTATION: A 70-year-old woman presented with white stool and had a history of cholecystectomy for the diagnosis of a non-dilated biliary tract with PBM. Esophagogastroduodenoscopy revealed a tumor in the papilla of Vater, and PVca was histologically proven by biopsy. We finally diagnosed her with PVca concurrent with non-biliary dilated PBM (cT1aN0M0, cStage IA, according to the Union for International Cancer Control, 8th edition), and subsequently performed subtotal stomach-preserving pancreaticoduodenectomy. Pathological findings of the resected specimen revealed no adenomas and dysplastic and hyperplastic mucosae in the common channel slightly upstream of the main tumor, suggesting a PBM related carcinogenic pathway with hyperplasia-dysplasia-carcinoma sequence. Immunostaining revealed positivity for CEA. CK7 positivity, CK20 negativity, and MUC2 negativity indicated that this PVca was of the pancreatobiliary type. Genetic mutations were exclusively detected in tumors and not in normal tissues, and bile ducts from formalin-fixed paraffin-embedded samples included mutated-ERBB2 (Mutant allele frequency, 81.95%). Moreover, of the cell-free deoxyribonucleic acid (cfDNA) extracted from liquid biopsy mutated-ERBB2 was considered the circulating-tumor deoxyribonucleic acid (ctDNA) of this tumor. CONCLUSIONS: Herein, we report the first case of PVca with PBM potentially caused by a "hyperplasia-dysplasia-carcinoma sequence" detected using immunostaining and next-generation sequencing. Careful follow-up is required if pancreaticobiliary reflux persists, considering the possible development of PVca.

The association of oral frailty with fall risk in community-dwelling older adults: a cross-sectional, observational study.

PURPOSE: This cross-sectional study examined the direct association of oral frailty with falls in community-dwelling older adults, controlling for the effects of sarcopenia and physical performance. METHODS: The participants were 237 community-dwelling older people (age: 76.0 ± 5.7 years, male: 23.6%). Oral frailty was assessed using the Oral Frailty Index-8. History of falls, timed up and go test (TUG), and sarcopenia were also assessed. The association between oral frailty and fall incidence was analyzed using multivariate logistic regression analysis adjusted for TUG and sarcopenia. RESULTS: Forty-six (19.4%) participants fell, and 130 (54.9%) had a risk of oral frailty. On multivariate logistic regression analysis, oral frailty was significantly associated with fall incidence (odds ratio = 2.38, 95% confidence interval 1.11-5.07), even after adjusting for TUG and sarcopenia. CONCLUSION: Oral frailty is a possible fall risk factor, independent of sarcopenia and physical performance, in community-dwelling older people.

Reconsidering resectable oncological conditions in pancreatic tail cancer: A multicenter retrospective study on prognostic factors in pancreatic tail cancer after resection (HOPS Pt-01).

BACKGROUND: Pancreatic tail cancer (Pt-PC) is generally considered resectable when metastasis is absent, but doubts persist in clinical practice due to the variability in local tumor extent. We conducted a multicenter retrospective study to comprehensively identify prognostic factors associated with Pt-PC after resection. METHODS: We enrolled 100 patients that underwent distal pancreatectomy. The optimal combination of factors influencing relapse-free survival (RFS) was determined using the maximum likelihood method (MLM) and corrected Akaike and Bayesian information criteria (AICc and BIC). Prognostic elements were then validated to predict oncological outcomes. RESULTS: Therapeutic interventions included neoadjuvant treatment in 16 patients and concomitant visceral resection (CVR) in 37 patients; 89 patients achieved R0. Median RFS and OS after surgery were 23.1 and 37.1 months, respectively. AICc/BIC were minimized in the model with ASA-PS (≥2), CA19-9 (≥112 U/mL at baseline, non-normalized postoperatively), need for CVR, 6 pathological items (tumor diameter ≥19.5 mm, histology G1, invasion of the anterior pancreatic border, splenic vein invasion, splenic artery invasion, lymph node metastasis), and completed adjuvant treatment (cAT) for RFS. Regarding the predictive value of these 11 factors, area under the curve was 0.842 for 5-year RFS. Multivariate analysis of these 11 factors showed that predictors of RFS include CVR (hazard ratio, 2.13; 95 % confidence interval, 1.08-4.19; p = 0.028) and cAT (0.38, 0.19-0.76; p = 0.006). CONCLUSIONS: The MLM identified certain Pt-PC cases warranting consideration beyond resectable during clinical management. Particular attention should be paid to conditions requiring CVR, even though immortal time bias remains unresolved with adjuvant treatment.

The Combination of Hearing Impairment and Frailty Is Associated with Cognitive Decline among Community-Dwelling Elderly in Japan.

Hearing impairment and frailty are associated with cognitive decline in older people. This study aimed to investigate the effect of the interaction between hearing impairment and frailty on cognitive decline in community-dwelling older people. A mail survey of community-dwelling, older people (age ≥ 65 years) who lived independently was conducted. Cognitive decline was defined using the self-administered dementia checklist (≥18 out of 40 points). Hearing impairment was assessed using a validated self-rated questionnaire. Furthermore, frailty was assessed using the Kihon checklist, and robust, pre-frailty, and frailty groups were identified. Multivariate logistic regression analysis, adjusted for potential confounding factors, was performed to determine the association of the interaction between hearing impairment and frailty with cognitive decline. Data obtained from 464 participants were analyzed. Hearing impairment was independently associated with cognitive decline. Additionally, the interaction term of hearing impairment and frailty was significantly related to cognitive decline. For participants in the robust group, hearing impairment was not associated with cognitive decline. In contrast, for participants in the pre-frailty or frailty groups, hearing impairment was associated with cognitive decline. The association between hearing impairment and cognitive decline was affected by frailty status in community-dwelling, older people.

Tumor-Informed Approach Improved ctDNA Detection Rate in Resected Pancreatic Cancer.

Pancreatic cancer is one of the cancers with very poor prognosis; there is an urgent need to identify novel biomarkers to improve its clinical outcomes. Circulating tumor DNA (ctDNA) from liquid biopsy has arisen as a promising biomarker for cancer detection and surveillance. However, it is known that the ctDNA detection rate in resected pancreatic cancer is low compared with other types of cancer. In this study, we collected paired tumor and plasma samples from 145 pancreatic cancer patients. Plasma samples were collected from 71 patients of treatment-naïve status and from 74 patients after neoadjuvant therapy (NAT). Genomic profiling of tumor DNA and plasma samples was conducted using targeted next-generation sequencing (NGS). Somatic mutations were detected in 85% (123/145) of tumors. ctDNA was detected in 39% (28/71) and 31% (23/74) of treatment-naïve and after-NAT groups, respectively, without referring to the information of tumor profiles. With a tumor-informed approach (TIA), ctDNA detection rate improved to 56% (40/71) and 36% (27/74) in treatment-naïve and after-NAT groups, respectively, with the detection rate significantly improved (p = 0.0165) among the treatment-naïve group compared to the after-NAT group. Cases who had detectable plasma ctDNA concordant to the corresponding tumor showed significantly shorter recurrence-free survival (RFS) (p = 0.0010). We demonstrated that TIA improves ctDNA detection rate in pancreatic cancer, and that ctDNA could be a potential prognostic biomarker for recurrence risk prediction.

Appropriate Lymph Node Dissection Sites for Cancer in the Body and Tail of the Pancreas: A Multicenter Retrospective Study.

Distal pancreatectomy (DP) with lymphadenectomy is the standard surgery for pancreatic body-tail cancer. However, the optimal lymph node (LN) dissection area for DP remains controversial. Thus, we evaluated the frequency and patterns of LN metastasis based on the tumor site. In this multicenter retrospective study, we examined 235 patients who underwent DP for pancreatic cancer. Tumor sites were classified as confined to the pancreatic body (Pb) or pancreatic tail (Pt). The efficacy index (EI) was calculated by multiplying the frequency of metastasis to each LN station by the five-year survival rate of patients with metastasis to that station. LN metastasis occurred in 132/235 (56.2%) of the patients. Patients with Pb tumors showed no metastasis to the splenic hilum LN. Distal splenic artery LNs and anterosuperior/posterior common hepatic artery LNs did not benefit from dissection for Pb and Pt tumors, respectively. In multivariate analysis, splenic artery LN metastasis was identified as an independent predictor of poor overall survival in patients with pancreatic body-tail cancer. In conclusion, differences in metastatic LN sites were evident in pancreatic body-tail cancers confined to the Pb or Pt. Spleen-preserving pancreatectomy might be feasible for Pb cancer.

Postpartum regression of human papillomavirus-related vulvar cancer: A case report.

We report a case of a 23-year-old pregnant woman (gravida 2 para 0, pregnancy 33 weeks and 3 days) with a history of laser ablation for cervical intraepithelial neoplasia-3 at 22 years. At initial visit, a 2 × 2 × 1-cm elevated mass was found on right labia majora. Biopsy results revealed squamous cell carcinoma of right labia; immunostaining revealed p16 positivity. Patient was diagnosed with human papillomavirus-related vulvar cancer. Selective cesarean section was performed at 36 weeks and 4 days of gestation. Postoperative histopathological diagnosis of squamous cell carcinoma, and 1.7-mm deep infiltrations led to vulvar cancer stage IB diagnosis. Reduction operation was performed, and postoperative follow-up of 1 year and 8 months revealed no recurrence. These results emphasize that small vulvar tumors during pregnancy should not be underestimated and histological examinations should be performed without hesitation. Careful observation and evaluation of tumors is necessary during pregnancy and after delivery because they may shrink postdelivery.

Association between tongue pressure and skeletal muscle mass and muscle function in community-dwelling older people without sarcopenia.

PURPOSE: This study aimed to cross-sectionally investigate relationships between maximum tongue pressure (MTP) and whole-body muscle mass and strength for non-sarcopenic older adults. METHODS: Study participants comprised 341 adults (105 men, 236 women) ≥ 65 years old (mean age, 72.7 ± 4.8 years). Participants were measured for MTP, grip strength, five-time chair stand test (FCST), gait speed, and skeletal muscle mass index (SMI). Multiple regression analysis adjusted for confounding factors was used to analyze relationships between MTP and each other variable. RESULTS: MTP was significantly related to SMI (r = 0.15, p < 0.001), grip strength (r = 0.12, p < 0.05), FCST (r = - 0.14, p < 0.05), and age (r = 0.25, p < 0.001). Multiple regression analysis showed a positive association between MTP and SMI, even after accounting for the influence of age, sex, physical performance, and other potential confounding factors. CONCLUSION: Whole-body muscle mass was suggested to be decreasing with tongue pressure decline before sarcopenia diagnosis in community-dwelling older adults.

Association Between Physical Function and Neighborhood Environment in Healthy, Older Adults: An Exploratory Study Using Regression Tree Analysis.

The aim of this study was to perform an exploratory investigation of the individual characteristics of older adults that affect the relationships between physical function and neighborhood environment. A total of 624 community-dwelling older adults living independently, aged ≥65 years, participated in this cross-sectional study. Physical function was assessed by muscle strength (grip strength and knee extension strength) and physical performance (5-m walking time and Timed Up and Go Test). The neighborhood environment was assessed using the International Physical Activity Questionnaire Environmental Module. The individual characteristics that affect the association between both were analyzed using multiple regression analysis and Classification and Regression tree (CaRT) analysis. In both older men and women, multiple regression analysis showed that neighborhood environment was significantly associated with physical function. On the other hand, on CaRT analyses, older men ≤80 years of age without low back pain and depressive symptoms and perceived good access to recreational facilities had the shortest 5-m walking time. However, CaRT analyses found no relationship between physical function and neighborhood environment in older women. The relationships between physical function and neighborhood environment may be altered by sex, age, and physical and mental health conditions.

Laparoscopic low anterior resection for rectal cancer wherein the inferior mesenteric artery arose from the superior mesenteric artery: a case report.

BACKGROUND: Few cases have been reported of colorectal cancer with inferior mesenteric artery (IMA) branching abnormalities; therefore, the lymphatic flow in such cases remains unknown. We report the first case of locally advanced rectal cancer in which the IMA arose from the superior mesenteric artery (SMA) in which we achieved to visualize the lymphatic flow. CASE PRESENTATION: A 65-year-old woman complaining of bloody stools was investigated in our hospital and suspected with rectal cancer. Colonoscopy and abdominal enhanced computed tomography (CT) revealed a circumscribed, localized ulcerative tumor in the rectum. 3-Dimensional contrast-enhanced computed tomography (3D-CT) showed that the IMA arose from the SMA. The patient was diagnosed with rectal cancer (cT3N0M0, cStage IIa) and laparoscopic low anterior resection was performed. The sigmoid colon was resected using the medial approach. Only the plexus of the colic branch of the lumbar splanchnic nerve was observed at the site where the root of the IMA usually exists and showed interruption of the indocyanine green (ICG) fluorescence-illuminated lymphatics. The root of the IMA was ligated, and Japanese D3 lymphadenectomy was performed, preserving the accessory middle colic artery. All fluorescent lymph nodes were resected. The pathological diagnosis was pT4aN1aM0 stage IIIb. The patient's postoperative course was uneventful. Adjuvant chemotherapy was administered, and the patient was recurrence-free at 1.5 years after surgery. CONCLUSIONS: We were able to perform safe and appropriate surgery oncologically, despite abnormal vascular anatomy, due to preoperative identification using 3D-CT and intraoperative navigation using ICG administration.

Tracheal Mucoepidermoid Carcinoma Mimicking Deteriorated Bronchial Asthma during Pregnancy.

Primary bronchial tumors are extremely rare. However, symptoms, such as coughing and wheezing, are not specific to this disease, and primary bronchial tumors are often misdiagnosed as bronchial asthma. This report describes the case of a pregnant patient with a bronchial tumor that mimicked deteriorating bronchial asthma. A 37-year-old female patient suffered from repeated episodes of pneumonia since 26 weeks of gestation. Despite treatment, she suffered from another episode of pneumonia at 28 weeks of gestation. This was considered as deteriorating asthma. Bronchoscopy performed at 34 weeks of gestation showed a tumor in the left main lung bronchus, obstructing nearly 100% of the trachea. After cesarean delivery at 34 weeks, she underwent endoscopic bronchial tumor resection. Because of recurrent bronchial obstruction and the possibility of malignant disease, subsequent left main lung bronchial resection and bronchoplasty were performed. The pathological diagnosis was low-grade mucoepidermoid carcinoma. In conclusion, if pneumonia develops repeatedly during pregnancy, the possibility of bronchial tumor should be considered.

Perioperative Predictors of Early Recurrence for Resectable and Borderline-Resectable Pancreatic Cancer.

We aimed to identify the perioperative predictors of the early recurrence (ER) of resectable and borderline-resectable pancreatic ductal adenocarcinomas (PDACs). After surgery for a PDAC, most patients develop a recurrence. Predictive factors may therefore guide therapeutic decision-making. Patients (n = 234) who underwent a pancreatectomy for a PDAC between 2006 and 2019 were included. The postrecurrence survival (PRS) was estimated using Kaplan-Meier curves. Predictive factors for an ER were assessed using logistic regression analyses; 93 patients (39.7%) were recurrence-free at the last follow-up. Patients with an ER (n = 85, 36.3%), defined as a recurrence within the first 12 months after surgery, had 1- and 2-year PRS rates of 38.7% and 9.5%, respectively, compared with 66.9% and 37.2% for those with a late recurrence (n = 56, 23.9%; both p < 0.001). The most common site of an ER was the liver (55.3%) with a significantly shorter median overall survival time than that with either a local or a lung recurrence (14.5 months; p < 0.001). Preoperative and postoperative risk factors for an ER included a tumor size >3.0 cm (odds ratio (OR): 3.11, 95% confidence interval (CI): 1.35-7.14) and preoperative carbohydrate antigen 19-9 (CA19-9) levels >52 U/mL (OR: 3.25, 95% CI: 1.67-6.30) and a pathological tumor size >3.0 cm (OR: 2.00, 95% CI: 1.03-3.90) and postoperative carbohydrate antigen 19-9 levels >37 U/mL (OR: 2.11, 95% CI: 1.02-4.36), respectively. Preoperatively (>52 U/mL) and postoperatively (>37 U/mL) elevated CA19-9 and a tumor size >3.0 cm were independent predictors for an ER after a pancreatectomy for a PDAC.

Survival benefit of conversion surgery after intensive chemotherapy for unresectable metastatic gastric cancer: a propensity score-matching analysis.

PURPOSE: The clinical benefit of conversion surgery (CS) for unresectable gastric cancer (GC), whereby unresectable GC responds to chemotherapy and subsequently receives curative-intent surgery, remains unclear. Here, we aimed to clarify the clinical value of CS. METHODS: In this retrospective cohort study, we analyzed 175 unresectable GC, who received triple combined chemotherapy between 2004 and 2019. We divided patients into two groups: those who underwent CS and those receiving chemotherapy only (CS and C groups, respectively). Propensity score matching was used to minimize confounding bias. RESULTS: Of 175 cases, 61 (34.9%) underwent CS. R0 resection was obtained in 85.2%. After matching, 44 pairs were selected; there were no significant differences in baseline covariants. Group CS had a significantly better median overall survival (OS) (18.8 vs. 46.0 months, p < 0.001), and prolonged progression-free survival (7.4 vs. 25.8 months, p < 0.001). Subgroup analysis of OS showed a favorable trend for CS for almost all subgroups. Multivariate analysis revealed that good ECOG performance status and CS were associated with a longer OS. CONCLUSION: The survival benefit of CS was consistently demonstrated in the univariate and multivariate analysis, even in the matched cohort. Additional large-scale trials are needed for further validation.

Arteriovenous malformation in the pancreatic head initially mimicking a hypervascular mass treated with duodenum-preserving pancreatic head resection: a case report.

BACKGROUND: The mainstay treatment for arteriovenous malformation in the pancreatic head (Ph-AVM) is standard pancreatectomy, especially pancreaticoduodenectomy (PD), or interventional endovascular treatment. We report the first case of Ph-AVM treated with duodenum-preserving pancreatic head resection (DPPHR) performed to preserve the periampullary organs. CASE PRESENTATION: A 59-year-old man presenting with back pain underwent contrast-enhanced computed tomography followed by angiography of the anterior superior pancreaticoduodenal artery. He was diagnosed with Ph-AVM and indicated for DPPHR with preservation of the periampullary organs; Ph-AVM's benign nature seldom requires lymph node dissection. During the operation, the right colon was mobilized and the omental bursa was released to expose the periampullary structures. The pancreas was transected just above the superior mesenteric vein. The inferior pancreaticoduodenal artery and papillary arteries branching from the posterior superior pancreaticoduodenal artery were carefully preserved to maintain the blood flow to the lower bile duct and papilla of Vater. The remnant pancreas was reconstructed with pancreaticogastrostomy using the modified Blumgart method. Pathological examination of the resected specimen revealed an irregular course of the arteries and veins concomitant with marked dilation throughout the pancreatic head. The patient was pathologically diagnosed with Ph-AVM. He developed hematemesis caused by a rupture of the pseudoaneurysm on postoperative day 20 and underwent coil embolization. A bilio-enteric fistula and stenosis of the common bile duct were found and treated by placement of an endoscopic biliary stent. At the 8-month follow-up, the Ph-AVM had not recurred. CONCLUSIONS: Compared to PD, DPPHR confers the clinical benefit of preserving the periampullary organs, although further studies are needed to confirm this. Therefore, the choice of this procedure should be based on the surgical morbidities and long-term outcome of the patient.

Clinical usefulness of saphenous vein graft in major arterial reconstruction during extended pancreatectomy.

PURPOSE: Extended pancreatectomy for locally advanced pancreatobiliary malignancy often involves combined major arterial resection (AR) and reconstruction (ARc). By limiting candidate inflow for ARc after combined resection of the celiac arterial system over a long distance, we evaluated whether great saphenous vein graft (GSVG) is an alternative conduit for obtaining non-anatomical arterial inflow. METHODS: ARc with GSVG conduit was undertaken prior to resection. GSVG was harvested and anastomosed end-to-side with the reconstructing artery and then mostly passed via the retroperitoneal para-inferior vena cava route. Side-to-end anastomosis of GSVG inflow was established with the right common iliac artery or abdominal aorta. RESULTS: Among 468 consecutive pancreatobiliary surgeries, ARc with GSVG was undertaken in seven cases. Primary cancers were in the pancreas in six patients and distal bile duct in one. Radical surgery was performed with pancreaticoduodenectomy in six patients and total pancreatectomy in one. Hepatic artery (HA) was concomitantly resected and reconstructed by GSVG in six patients or by the jejunal artery in one patient. Median operative time and intraoperative blood loss were 763 min and 350 ml, respectively. Serum level of AST, ALT, and LDH in patients with HA reconstruction by GSVG peaked by the second postoperative day and promptly normalized. Postoperative morbidity (CD ≥ III) was encountered in one patient. No surgical mortality was observed. Postoperative serum liver enzymes promptly decreased in ARc patients with GSVG to HA. CONCLUSION: Arterial reconstruction with GSVG prior to resection was performed securely and might help to reduce postoperative liver dysfunction.

Endobronchial metastasis of ovarian cancer rescued by tumor ablation and a self-expanding hybrid stent: A case report and review of the literature.

Tracheal stenosis caused by malignancy is a life-threatening complication. Herein, we performed tumor ablation and airway stenting using a hybrid stent on a patient with upper tracheal stenosis caused by endobronchial metastasis of ovarian cancer. To date, only 9 cases of endobronchial metastasis of ovarian cancer have been reported. This is the first reported case of endobronchial metastasis in the upper part of the trachea, which had a favorable outcome after tumor ablation as a sequential treatment and use of a hybrid stent. In addition, 10 cases of endobronchial metastasis of ovarian cancer, including ours and other case reports, were reviewed.

Effectiveness of Lee Silverman Voice Treatment® LOUD on Japanese-Speaking Patients with Parkinson's Disease.

Background. Lee Silverman Voice Treatment® LOUD (LSVT®) is an intensive program devised in the United States to train patients with Parkinson's disease (PD) to speak louder, at normal intensity, while keeping a good voice quality. Four weeks of LSVT® has been shown to increase vocal loudness and improve intelligibility among Japanese-speaking PD patients. However, the long-term effects of LSVT® have not been examined in these patients. Objective. This study aimed to investigate the long-term effects of LSVT® on Japanese-speaking PD patients. Methods. Twenty-one Japanese PD patients underwent a standardized course (four sessions over four consecutive days, for four weeks) of LSVT® at our hospital. Vocal loudness and intelligibility were assessed at the following three time-points: pretreatment (baseline), immediately after treatment, and at the end of the 12 month follow-up (12FU). Sound pressure levels (dB SPL) were measured during the following tasks: sustained phonation of /a/, reading a standardized text, and delivery of a monologue. Three experienced speech-language pathologists, who were blinded to patients' identities and assessment points, assessed speech intelligibility based on recorded audio samples of each participant during the reading and monologue tasks. Results. Fourteen patients were evaluated at 12FU. Changes in dB SPL from baseline to immediately after treatment were +6.5 dB, +4.2 dB, and +2.8 dB, and those from baseline until 12FU were +4.7 dB, +3.5 dB, and +2.5 dB in sustained phonation of /a/, reading a passage, and delivery of a monologue, respectively. These changes were significant (p < 0.025) in both the baseline-to-immediately-after-treatment and baseline-to-12FU intervals. Intelligibility relative to baseline was significantly improved immediately after treatment, but not at 12FU. Conclusions. LSVT® had a long-term effect on the vocal loudness of Japanese-speaking PD patients. A short-term effect was seen in intelligibility, however, there was no significant long-term effect.

[A Case of Gastric Cancer with Necrotic Lymph Node Perforation in the Stomach during Chemotherapy].

A 63-year-old man was diagnosed with gastric cancer. Distal gastrectomywas performed in November 2011. The pathologic finding was pT3N2M0, Stage ⅢA. S-1 was administered as adjuvant chemotherapy. However, in August 2012, computed tomographyrevealed a tumor measuring 3 cm in size in the dorsal pancreas. Based on endoscopic ultrasound-guided fine- needle aspiration, he was diagnosed with lymph node recurrence of gastric cancer. Injection chemotherapy of CDDP/CPT-11 was initiated in November 2012. In January 2013, the patient developed fever owing to a ruptured abscess from the posterior wall in the stomach. In the 6 years since, although the patient has not undergone chemotherapy, recurrence has not been observed.

The radiobiological effects of He, C and Ne ions as a function of LET on various glioblastoma cell lines.

The effects of the charged ion species 4He, 12C and 20Ne on glioblastoma multiforme (GBM) T98G, U87 and LN18 cell lines were compared with the effects of 200 kVp X-rays (1.7 keV/µm). These cell lines have different genetic profiles. Individual GBM relative biological effectiveness (RBE) was estimated in two ways: the RBE10 at 10% survival fraction and the RBE2Gy after 2 Gy doses. The linear quadratic model radiosensitivity parameters α and ß and the α/ß ratio of each ion type were determined as a function of LET. Mono-energetic 4He, 12C and 20Ne ions were generated by the Heavy Ion Medical Accelerator at the National Institute of Radiological Sciences in Chiba, Japan. Colony-formation assays were used to evaluate the survival fractions. The LET of the various ions used ranged from 2.3 to 100 keV/µm (covering the depth-dose plateau region to clinically relevant LET at the Bragg peak). For U87 and LN18, the RBE10 increased with LET and peaked at 85 keV/µm, whereas T98G peaked at 100 keV/µm. All three GBM α parameters peaked at 100 keV/µm. There is a statistically significant difference between the three GBM RBE10 values, except at 100 keV/µm (P < 0.01), and a statistically significant difference between the α values of the GBM cell lines, except at 85 and 100 keV/µm. The biological response varied depending on the GBM cell lines and on the ions used.