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Purpose To clarify the impact of donor and recipient characteristics on the survival of recipients before and after lung transplantation in the Japanese population. Methods Patients’ data were collected for retrospective analysis from all authorized lung transplant centers in Japan. We included 1963 patients listed for lung transplantation by the end of December 2021, comprised of 658 deceased-donor and 270 living-donor lung transplants. Results Primary disease had a significant impact on the mortality of patients waiting for transplantation. The indications for transplant significantly affected the post-transplant survival rate of deceased-donor lung transplant recipients. The recipient’s age also significantly affected the post-transplant survival rate of the deceased-donor and living-donor lung transplant recipients. The recipients of grafts transplanted from donors aged 61 years or older showed a worse post-transplant survival rate (≧60 years old). The survival rate for the combination of a female donor to a male recipient among the deceased-donor lung transplant recipients was the worst among the four combinations. Conclusion The donor and recipient characteristics significantly impacted the survival of recipients after lung transplantation. The underlying mechanism of the negative impact of the gender mismatch of female donor to male recipient on post-transplant survival needs to be investigated further.

The incidence of sublobar resection is increasing because of the rise in the detection of small lung cancers. However, local recurrence needs to be addressed, and several methods are needed for the resection with secure margins of non-visible and non-palpable tumors.We retrospectively reviewed the use of a radiofrequency identification (RFID) system in sublobar resection of adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) at our institute.From June 2020 to June 2022, 39 patients underwent sublobar resection for AIS or MIA. The median age was 69 years (interquartile range, 64-76). Among the 39 patients, 24 were diagnosed with AIS and 15 with MIA. Segmentectomy, subsegmentectomy, and wedge resection were performed in nine, six, and 24 patients, respectively. The median size of the target tumor was 9.0 mm (8.1-12.9) and the median distance between the tag and the tumor was 2.9 mm (0-7.5). The median pathological surgical margin was 15.0 mm (10-17.5). Complete resection of all lesions was performed with a secure surgical margin. The median follow-up duration was 6 months, during which no local recurrence was detected in any of the patients.The RFID marking system accurately informed the surgeons of the tumor location and helped them to perform precise sublobar resection.

Lung transplantation (LTx) is the last resort for patients who fail to respond to drug therapy and progress to advanced idiopathic interstitial pneumonias (IIPs). However, more than one-third of patients registered for LTx face despair because of rapid disease progression and donor shortage. This study aimed to identify the risk factors of waitlist mortality in LTx candidates with IIPs and investigate the association of anti-fibrotic therapy with waitlist mortality.We retrospectively investigated 56 patients with IIPs, including 29 patients with idiopathic pulmonary fibrosis (51.7%) and 11 patients with idiopathic pleuroparenchymal fibroelastosis (19.6%), registered for LTx at Fukuoka University Hospital between January 2006 and June 2020. The risk factors affecting transplantation-censored survival were evaluated.The waitlist mortality rate of patients with nonspecific interstitial pneumonia was significantly lower than that of others. Multivariate survival analysis using Cox's model identified a history of pneumothorax (P = 0.029) and short 6-min walk distance (6MWD) (P = 0.012) to be significant variables affecting waitlist mortality. Patients receiving anti-fibrotic therapy (n = 27, 48.2%) had a lower risk of pneumothorax (P = 0.017) and their 6MWD was longer than that of non-therapy patients (P 0.001). The waitlist mortality rate of patients on anti-fibrotic therapy was significantly lower (P = 0.012).History of pneumothorax and short 6MWD were independent predictors of waitlist mortality in LTx candidates with IIPs. The anti-fibrotic therapy may potentially reduce mortality in patients with IIPs on the waiting list for LTx.

Oral carcinoma cuniculatum (CC) is defined as a rare variant of low-grade, well-differentiated squamous cell carcinoma (SCC). The diagnosis of oral CC has remained very difficult, due to the lack of familiarity of clinicians and pathologists with this pathology. Oral CC is therefore often initially diagnosed as osteomyelitis, dental abscess, or keratocyst. Histopathologically, oral CC is characterized by keratinized tissue lined by epithelium with no or only mild cellular atypia, which invades locally and rapidly into the bone. In the present case, oral CC developed from a state of leukoplakia. A white lesion on the lower gingiva was pathologically diagnosed as epithelial dysplasia without cellular atypia, but kept recurring after repeated local removal. Two years and nine months after the first visit, the lesion showed rapid invasion into alveolar bone, in which richly keratinized tissue was observed. The patient then underwent marginal mandibulectomy and the tumor was pathologically diagnosed as SCC. Based on the clinical follow-up, we suspected the lesion represented oral CC and wide resection with reconstructive surgery was performed. If oral CC can be diagnosed at an earlier stage, the area of resection can be minimized. As oral CC tends to be misdiagnosed because of a lack of evidence of malignant tumor, both clinicians and pathologists should consider oral CC when leukoplakia shows frequent recurrence.

This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF). We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018. There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/m2, respectively; P

BACKGROUND: Early stage non-small cell lung cancer (NSCLC) is good candidate for video-assisted thoracoscopic surgery (VATS). Long-term outcome compared between VATS and open surgery remains unclear. The aim of this study was to assess the long-term outcome of VATS in early stage adenocarcinoma. METHODS: A retrospective study was performed in 546 patients which were operated between January 2006 and December 2010 in our institute and of those, 240 (220 lobectomies, and 20 segmentectomies) were clinical N0 adenocarcinoma. One hundred and thirty-five patients underwent VATS and 105 patients for open surgery. Long-term oncological outcomes were compared in both groups. RESULTS: There were significant differences in age, gender, Blinkman index, clinical T factor and tumor size between two groups. VATS group showed statistically longer operation time (P=0.01), less blood loss (P=0.005), shorter length of stay (P=0.001), and less dissected number of lymph nodes (P

A total number of 1,787 patients have been registered in the Japan Organ Transplantation Network (JOTN), of whom 838 (46.9%) have received cadaveric lung transplantation or living-donor lobar lung transplantation since The Japanese Organ Transplant Law took effect in 1997. Subsequent to four other university hospitals( Tohoku, Kyoto, Osaka and Okayama), Fukuoka University Hospital was authorized to start lung transplantation in 2005. The survival rates after lung transplantation are lower than other solid organ transplantations not only in Japan but also around the world due to complications including infections and rejections. Between December 2005 and June 2021, 129 patients from the Fukuoka University Hospital were registered in the JOTN, and 50 underwent lung transplantation( five living-donor lobar lung transplantations and 45 cadaveric lung transplantations). Herein, we report our single-center experience of lung transplant program and an overview of the observed gastrointestinal complications associated with lung transplantation at our center.

Safety of combination chemotherapy using platinum and fluorouracil has not been evaluated adequately for advanced gastric cancer (AGC) in elderly patients.We initiated a phase II study to evaluate the efficacy and safety of capecitabine plus oxaliplatin (CapeOX) as first-line therapy for patients with AGC aged ≥70 years. Planned assessment of toxicity was made upon recruitment of the first 20 patients.In five out of 20 patients, unacceptable toxicity was observed, including three patients who were unable to complete the initial two courses due to adverse events. Among the other 15 patients, dose reduction due to toxicity were needed in 10 and treatment delay for adverse events also occurred in 12 patients during the first two courses.Early analyses of safety suggest that the CapeOX regimen was not tolerated without dose reduction for elderly patients with AGC in this study.

Bronchopleural fistula (BPF) is a critical complication that may progress to pneumonia and empyema, but optimal treatment remains uncertain. Our purpose was to develop a novel material for bronchial occlusion that can be used to treat BPF by blocking airflow and promoting wound healing.Sponges were prepared in concentrations of 25, 40, and 50 mg/dL of silk-elastin by hydrophobic processing. Five adult Beagle dogs underwent right anterior lobectomy, and 5 underwent left posterior lobectomy. Silk-elastin sponges were placed at bronchial stumps of 8 dogs, and silicone plugs were placed at the stumps of 2 dogs as a control.Postoperative complications were not observed, except in 1 dog in which the silicone plug had been placed and which had massive subcutaneous emphysema at 4 weeks after operation. Histologic examination revealed that stumps were covered with connective tissue and that there was more regeneration of airway epithelium in the silk-elastin sponge group than in the silicone plug group. There were increased numbers of myofibroblasts around the bronchial stump occluded by silk-elastin sponges at 2 weeks after placement, which completely disappeared after 2 months, during which abundant neovascularization occurred.We showed that silk-elastin sponges can manage and promote regeneration of bronchial epithelium. Our results demonstrate that bronchial occlusion with a silk-elastin sponge is a promising option for treatment of BPF.

Purpose FOLFOXIRI plus bevacizumab is regarded as a first-line therapeutic option for selected patients with metastatic colorectal cancer (mCRC). Our aim was to assess the efficacy and safety of induction treatment with FOLFOXIRI plus bevacizumab in patients with untreated mCRC harboring UGT1A1 wild (*1/*1), or single-hetero (*1/*6 or *1/*28) genotypes. Methods Twelve cycles of FOLFOXIRI plus bevacizumab were administered to patients with untreated mCRC. The primary endpoint was the overall response rate (ORR) assessed by central independent reviewers. Secondary endpoints included time to treatment failure (TTF), progression-free survival (PFS), overall survival (OS), relative dose intensity (RDI), R0 resection rate, and safety. The exploratory objectives were early tumor shrinkage (ETS) and depth of response (DoR). Results Of the 47 patients enrolled, 46 and 44 patients were eligible for the safety and efficacy analysis, respectively. The primary endpoint was met. The ORR was 63.6% (95% CI 47.8–77.6). At a median follow-up of 25.4 months, median TTF, PFS, and OS was 8.1, 15.5, and 34.4 months, respectively. The median RDI of 5-fluorouracil, irinotecan, oxaliplatin, and bevacizumab was 72, 69, 62, and 71%, respectively. R0 resection rate was 22.7%. Grade 3 or higher adverse events (≥ 10%) included neutropenia (65.2%), febrile neutropenia (26.1%), leukopenia (23.9%), anorexia (10.9%), nausea (10.9%), and diarrhoea (10.9%). No treatment-related deaths were observed. ETS and DoR were 70.5 and 45.4%, respectively. Conclusions FOLFOXIRI plus bevacizumab induction treatment of Japanese patients was shown to be beneficial and manageable, although caution is required since the treatment causes febrile neutropenia.

Unique right hilar mobilization was performed by pulmonary venous transposition of the right middle and lower lobe veins to the opening of the right upper pulmonary vein to achieve tension-free airway anastomosis after carinal right upper lobectomy for a patient with adenoid cystic carcinoma. The right middle and lower lobes were reconstructed safely thereafter by side-to-end anastomosis between the side of the lower trachea and intermediate bronchus with acceptable suturing tension.

Currently, inhaled nitric oxide (NO) therapy for lung transplantation is not covered by public health insurance in Japan. In this study, we evaluated the perioperative use and safety of inhaled NO therapy for lung transplantation. Data regarding the duration of treatment and adverse events of inhaled NO therapy were collected for all lung transplantations performed from January 1, 2015, to December 31, 2019, at nine lung transplant facilities in Japan. During the study period, lung transplants were performed in 357 patients, among whom inhaled NO therapy was administered to 349 patients (98%). The median initial and median maximum inhaled NO doses were 10 and 20 ppm, respectively. Inhaled NO therapy was introduced during surgery and continued postoperatively in 313 patients (90%) for a median of 4 days. Significant improvements in oxygenation and decreases in pulmonary arterial pressure were observed in patients receiving inhaled NO therapy. Side effects of inhaled NO therapy, such as methemoglobinemia, were observed in 15 patients (4%), with a significant incidence in patients aged

Background Infection is the most common cause of mortality within the first year after lung transplantation (LTx). The management of perioperative antibiotic therapy is a major issue, but little is known about worldwide practices. Methods We sent by email a survey dealing with 5 daily clinical vignettes concerning perioperative antibiotic therapy to 180 LTx centers around the world. The invitation and a weekly reminder were sent to lung transplant specialists for a single consensus answer per center during a 3-month period. Results We received a total of 99 responses from 24 countries, mostly from Western Europe (n = 46) and the USA (n = 34). Systematic screening for bronchial recipient colonization before LTx was mostly performed with sputum samples (72%), regardless of the underlying lung disease. In recipients without colonization, antibiotics with activity against gram-negative bacteria resistant strains (piperacillin / tazobactam, cefepime, ceftazidime, carbapenems) were reported in 72% of the centers, and antibiotics with activity against methicillin-resistant Staphylococcus aureus (mainly vancomycin) were reported in 38% of the centers. For these recipients, the duration of antibiotics reported was 7 days (33%) or less (26%) or stopped when cultures of donor and recipients were reported negatives (12%). In recipients with previous colonization, antibiotics were adapted to the susceptibility of the most resistant strain and given for at least 14 days (67%). Conclusion Practices vary widely around the world, but resistant bacterial strains are mostly targeted even if no colonization occurs. The antibiotic duration reported was longer for colonized recipients.

This study was performed to compare the outcome of lung transplantation (LT) for idiopathic pleuroparenchymal fibroelastosis (IPPFE) with that of LT for idiopathic pulmonary fibrosis (IPF).We reviewed, retrospectively, all adult patients who underwent LT for IPPFE or IPF in Japan between 1998 and 2018.There were 100 patients eligible for this study (31 with IPPFE and 69 with IPF). Patients with IPPFE tended to have a significantly lower body mass index (BMI) than those with IPF (median, 16.7 vs. 22.6 kg/mDespite extrapulmonary problems such as a flat chest, low BMI, and associated restrictive impairment persisting in patients with IPPFE, patient survival after LT for IPPFE or IPF was equivalent.

Left‐unilateral single‐lobe lung transplantation from a living donor was performed in a 4-year-old boy who suffered from severe respiratory failure caused by bronchiolitis obliterans (BO) as a result of graft versus host disease (GVHD) after peripheral blood stem cell transplantation (PBSCT). The patient grew well during his early childhood years, with an excellent lung allograft function. However, severe thoracic scoliosis occurred 7 years after lung transplantation, which ultimately resulted in compression of the lung allograft followed by severe respiratory dysfunction, and the patient became dependent on mechanical ventilation support. Posterior spinal fusion of Th2‐L3 with instrumentation and bone grafting was performed to correct scoliosis in the hope of recovering his thoracic capacity. The left thoracic volume was dramatically improved immediately after spinal fusion surgery, and the patient was ultimately weaned off of mechanical ventilation after a year of pulmonary rehabilitation.

Background A male worker with indium‐tin oxide (ITO)‐induced pneumoconiosis underwent bilateral lung transplantation (LT). Methods Post‐LT histopathological investigations of the isolated lungs and hilar lymph nodes were performed and indium concentration in serum (In‐S) and serum Krebs von den Lungen‐6 (KL‐6) were tracked for 122 weeks. Results He has attained the ultimate treatment goal of > 2‐year survival. The main histopathological characteristics were pan‐lobular emphysematous change, interstitial fibrosis, and lymphocytic infiltration in the peribronchiolar/perivascular portions, and numerous cholesterol clefts and giant cells containing brown particles. These findings support the conclusion that the lung injury was caused by the inhalation of ITO. Metal element mapping and indium in the isolated lungs revealed that inhaled ITO particles in humans migrate to the lymph nodes. In‐S remained at remarkably high levels (≥30 ng/mL) and showed wide fluctuation with bimodality until 46 weeks after LT, but KL‐6 remained in the normal range for almost the entire period. The indium concentration in the donor's resection lung at 10 weeks after LT was 143.5 ng/g wet‐weight, which was only one one‐thousandth of the recipient's lung (161 µg/g wet‐weight). After 48 weeks of LT, the recipient's In‐S had gradually decreased; the biological half‐life was 1.2 years. These results clearly suggest that indium remaining in the recipient's tissues did not adversely influence the transplant donor's lungs. Conclusions The transplanted donor's lungs were not influenced by indium in the recipient's organs. Bilateral LT is thus an effective treatment option in severe indium lung disease cases.

Adenosquamous carcinoma is a high-grade malignant tumor and is known to be more aggressive than conventional squamous cell carcinoma in the head and neck region. Initial precise diagnosis of ASC and consequent appropriate surgical resection of the primary lesion with neck dissections of regional lymph nodes is significantly important to achieve a good prognosis from ASC. Keywords: Adenosquamous carcinoma, Tongue, Differential diagnosis

Background S-1 plus cisplatin is a standard regimen for advanced gastric cancer (AGC) in Asia. The ToGA trial established a fluoropyrimidine plus cisplatin and trastuzumab as a standard treatment for human epidermal growth factor receptor 2 (HER2)-positive AGC. In the HERBIS-1 trial, trastuzumab combined with S-1 plus cisplatin showed promising antitumor activity in patients with HER2-positive AGC. However, cisplatin has several important drawbacks, including vomiting and renal toxicity. These disadvantages of cisplatin are prominent in elderly patients. Therefore, we conducted a prospective phase II study of trastuzumab plus S-1 without cisplatin in elderly patients with HER2-positive AGC. Methods Patients 65 years or older who had HER2-positive AGC received S-1 orally on days 1–28 of a 42-day cycle and trastuzumab intravenously on day 1 of a 21-day cycle. Results A total of 51 patients were enrolled. Two patients were ineligible. The full analysis set thus comprised 49 patients. The median age was 71 years (range 65–85). The confirmed response rate was 40.8% (95% CI 27.1–54.6%), and the null hypothesis was rejected. The median follow-up period was 10.6 months. Median overall survival was 15.8 months. Median progression-free survival was 5.1 months, and time to treatment failure was 4.0 months. Major grade 3 or 4 adverse events included neutropenia (12.0%), anemia (24.0%), diarrhea (10.0%), and anorexia (12.0%). There was one treatment-related death. Conclusions Trastuzumab in combination with S-1 alone demonstrated promising antitumor activity and manageable toxic effects as well as promising survival results in elderly patients with HER2-positive AGC. Clinical trials registration UMIN000007368.

Purpose Idiopathic pleurparenchymal fibroelastosis (IPPFE) is a relatively new disease entity of interstitial pneumonia characterized by upper lobe dominant fibrosis and flat chest. The purpose of this study is to evaluate the outcome of lung transplantation for IPPFE in comparison with idiopathic pulmonary fibrosis (IPF). Methods We retrospectively reviewed patients with IPPFE and those with IPF aged 20 or over who underwent lung transplantation between 1998 and 2018. Data were collected from all nine lung transplant centers in Japan, under the support of Japanese Society of Lung and Heart-Lung Transplantation. Results One hundred patients were eligible, including 31 IPPFE and 69 IPF patients. Patients with IPPFE were more likely to be women (58% vs 28%; P Conclusion The survival of patients with IPPFE after lung transplantation was comparable with those with IPF. However, patients with IPPFE showed longer ICU stay, limited improvement in pulmonary function, and no improvement in low BMI, suggesting systemic or extrapulmonary problems such as stiff chest wall in patients with IPPFE.

We describe a unique technique for pulmonary artery reconstruction using a bovine pericardial conduit after long-segment sleeve resection of the pulmonary artery. In this technique, the conduit tube was not created in advance but was sewn in situ from a bovine pericardial “sheet” step-by-step to form a desirable diameter, length and curve to fit the vascular defect. This is a safe and secure method to create desirable conduit for long and complex pulmonary artery replacement.

Recent clinical studies indicate that the disturbed phosphate metabolism in chronic kidney disease (CKD) may facilitate kidney injury; nonetheless, the causal role of phosphate in CKD progression remains to be elucidated. Here, we show that intestinal phosphate binding by sucroferric oxyhydroxide (SF) ameliorates renal injury in the rat remnant kidney model. Sprague-Dawley rats received 5/6 nephrectomy (RK) and had a normal chow or the same diet containing SF (RK + SF). RK rats showed increased plasma FGF23 and phosphate levels, which were suppressed by SF administration. Of note, albuminuria in RK rats was significantly ameliorated by SF at both 4 and 8 weeks. SF also attenuated glomerulosclerosis and tubulointerstitial injury. Moreover, several different approaches confirmed the protective effects on podocytes, explaining the attenuation of glomerulosclerosis and albuminuria observed in this study. As a possible mechanism, we found that SF attenuated renal inflammation and fibrosis in RK rats. Interestingly, von Kossa staining of the kidney revealed calcium phosphate deposition in neither RK nor RK + SF rats; however, plasma levels of calciprotein particles were significantly reduced by SF. These data indicate that latent positive phosphate balance accelerates CKD progression from early stages, even when overt ectopic calcification is absent.

Purpose Malignancy is one of the leading causes of death after organ transplantation. We conducted a national survey of malignancy after lung transplantation among all lung transplant centers in Japan. Methods All recipients who underwent lung transplantation since October 1998 until December 2017 in Japan were retrospectively reviewed. Results Malignant diseases developed in 41 (6.9%) of 596 lung transplant recipients in 388 brain-dead donor lung transplantation and 208 living donor lobar lung transplantation. Except recurrence of the original malignant diseases (n=4/596, 0.7%) and possible progression after transplantation in cancer-baring recipients (n=5/596, 0.8%), de novo malignancy occurred in 33 patients (5.5%). The most common de novo malignancy was lymphoproliferative disorder (n=16/34, 46%). Compared with the ISHLT registry, we observed far fewer skin cancer (n=1). In terms of the underlying disease for lung transplantation, interstitial pneumonitis (n=13/33, 39%) and lung complication after hematopoietic stem cell transplantation (n=10/33, 30%) were common, suggesting that long-term immunosuppression before and after transplantation has a negative impact on occurrence of de novo malignancy. The average time of occurrence after transplantation was 39 (±38) months. Death due to malignancy occurred in 11/33 (33%). The overall 5-year survival of patients with malignancies after lung transplantation was 49%. Conclusion In Japan, the most common malignancy after lung transplantation was posttransplant lymphoproliferative disorder. Long-term immunosuppression before and after transplantation can have a negative impact on occurrence of de novo malignancy after lung transplantation

134 Background: FOLFOXIRI-Bmab has been recognized as one of the standard first-line treatments for mCRC. We conducted a single arm, multicenter, phase II study to assess the efficacy and safety of FOLFOXIRI-Bmab in pts with untreated mCRC harboring UGT1A1(*6 and *28) wild or single hetero genotype. Methods: Pts received FOLFOXIRI-Bmab (irinotecan 165 mg/m2, oxaliplatin 85 mg/m2, l-leucovorin 200mg/m2, fluorouracil 3200 mg/m2 and Bmab 5mg/kg repeated biweekly) up to a maximum of 12 cycles, followed by the sequential therapy which consisted of the remaining drugs if any of the individual drugs were discontinued at the investigator’s discretion. Protocol therapy was continued until progressive disease, an unacceptable adverse event, tumor resection or consent withdrawal. The primary endpoint was ORR evaluated by central reviewers. Secondary endpoints include TTF, PFS, OS, R0 resection rate, relative dose intensity (RDI) and safety. The exploratory objectives were early tumor shrinkage (ETS), depth of response (DoR). Results: 47 pts were enrolled from 16 centers between April 2015 and May 2017, of whom 1 was excluded for not meeting the inclusion criteria. The full analysis set consisted of 44 pts because 2 had no target lesions that were considered measurable lesion by central reviewers. 46 pts had the following characteristics: median age 58 (29-68), 57% male, 76% PS0, 22% right-sided tumors and 52% UGT1A1 wild. RAS status was 37% wild, 52% mutant, 11% unknown. Primary endpoint was met. The ORR was 63.6% (95% CI, 47.8-77.6). ETS and DoR was 70.5%, 43.9%, respectively. R0 resection rate was 23%. Median PFS was 15.5mo (95% CI, 11.5-23.4). Median TTF was 8.1mo (95% CI, 5.3-10.1). Median OS was 34.4mo (95% CI, 26.4-not reached). The mean RDI of fluorouracil, irinotecan and oxaliplatin were 71%, 67%, and 64%, respectively. Grade 3 or higher adverse events (≥10%) were neutropenia (65.2%), febrile neutropenia (FN) (26.1%), anorexia (10.9%), nausea (10.9%), and diarrhea (10.9%). No treatment-related deaths were observed. Conclusions: Our results of FOLFOXIRI-Bmab in Japanese pts showed to be beneficial and manageable although caution to FN is required. Clinical trial information: NCT02497157.

Giant cell tumor of bone is a rare and osteolytic neoplasm that that usually affecting the epiphyses in long bones of the extremities. They seldom occur in the skull, preferentially affecting the sphenoid and temporal bones. Most pathologically benign, and total removal by surgery was regarded as the first treatment, however, it was very difficult in skull lesion. In 2014 the molecular targeting drug anti-RANKL inhibitor was approved in Japan. We report a case in which an anti-RANKL inhibitor was administered to a skull base bone giant cell tumor that was difficult to remove completely. A 56-year-old man with a sudden right neck pain followed by dysphoria and dysphagia was referred to our hospital. Computed tomography showed 4.4 x 2.0 cm osteolytic lesion involving the right occipital bone and occipital condyle. Magnetic resonance imaging demonstrated an extensive soft-tissue mass occupying. Surgical biopsy was performed and the pathological diagnosis was giant cell tumor. Patient received the anti-RANKL inhibitor (Denosumab®). After 4 weeks, ossification was observed, and neurological symptoms were improved after 12 weeks. Patient has been on good course for 5 years without recurrence and is still following-up.

Background: Regorafenib is an oral multikinase inhibitor with a proven survival benefit for metastatic colorectal cancer patients. The KSCC1402/HGCSG1402 study investigated the prophylactic effect of oral dexamethasone (DEX) on regorafenib-related fatigue and/or malaise. Patients and Methods: Patients who progressed after standard chemotherapy were randomized 1: 1 to a DEX group (2 mg/day; days 1–28) with regorafenib or a placebo group with regorafenib. The primary endpoint was the incidence of fatigue and/or malaise, based on version 4.0 of the National Cancer Institute’s CTCAE (Common Terminology Criteria for Adverse Events). One of the secondary endpoints was the in­cidence of fatigue and/or malaise based on the CTCAE assessed by patient-reported outcome (PRO). Results: The incidence of any grade of fatigue and/or malaise assessed by the investigators was 58.8% in the DEX group and 61.1% in the placebo group (p = 0.8101), and that assessed by PRO was 47.2 and 58.3%, respectively (p = 0.3450). The incidence of grade ≥2 fatigue and/or malaise, as assessed by the investigators, was 19.4% for the DEX group and 38.9% for the placebo group (p = 0.0695), and that assessed by PRO was 27.8 and 52.8%, respectively (p = 0.0306). Conclusion: Our results suggest that prophylactic oral DEX is clinically effective in improving regorafenib-related fatigue and/or malaise.

The aim of the present study was to elucidate the associations between the expression of the vascular endothelial growth factor-C (VEGF-C)/VEGF receptor-3 (VEGFR-3) axis and lymphangiogenesis, regional lymph node metastasis and clinicopathological factors in oral tongue squamous cell carcinoma (OTSCC) using immunohistochemistry. The expression of VEGF-C, VEGFR-3 and podoplanin was immunohistochemically evaluated in specimens obtained from 65 patients with OTSCC (T1-2, N0) who had undergone radical surgery alone. The associations between the expression of VEGF-C, VEGFR-3 and podoplanin, and lymphangiogenesis, regional lymph node metastasis and clinocopathological factors were determined by immunohistochemical analysis. VEGF-C, VEGFR-3 and combined VEGF-C/VEGFR-3 expression was significantly higher in cases with regional recurrence compared with those without lymph node involvement (P, Oncology Letters, 10(4), pp.2027-2034; 2015

Objective: The criteria for T4 staging of carcinoma of the mandibular gingiva are controversial. Oral cancer staged as T4 implies "invasion to an adjacent organ" such as the skin, extrinsic muscles of the tongue, masticator space, or mandibular bone. In this study, we compared different T classifications and retrospectively investigated the correlation between each classification and the prognosis of patients with carcinoma of the mandibular gingiva. Methods: We investigated 81 patients with squamous cell carcinoma of the mandibular gingiva treated at two institutions. Results: There was a significant correlation between soft tissue classification and local recurrence ( P< 0.05) and that the correlation with prognosis is borderline significant ( P= 0.05). Conclusions: Soft tissue classification, which does not consider bone invasion, was the most useful for diagnosis, selecting the appropriate surgical procedure, and assessing the correlation to prognosis. We recommended using this classification to define T4. Because this classification is not new but is based on International Union Against Cancer classification, it could be easily adopted. However, the current study is a retrospective analysis of a small number of patients. A multi-institutional, prospective study is necessary to determine the appropriate criteria for the TNM staging of carcinoma of the mandibular gingiva., Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 27(5), pp.631-636; 2015

Central odontogenic fibromas (COFs) are benign odontogenic tumors derived from the dental mesenchymal tissues. They are rare tumors that account for 0.1–12.8% of all odontogenic tumors [1–8]. The location of COFs and the tumor incidence with respect to sex and age distributions are not well understood. Clinical features of the tumor include an asymptomatic expansion of the cortical plate of the mandible or maxilla and unilocular or multilocular radiolucency. Here, we describe a case of COF in the posterior region of the left mandible in a 3-year-old girl. The mandible was segmentally resected with the tumor and reconstructed with a parietal bone graft. No signs of recurrence or postoperative complications including occlusion were found. The esthetic outcome was satisfactory.

Pleomorphic carcinoma (PC) of the lung is a rare epithelial tumor. The clinicopathological characteristics and prognostic factors of PC are controversial. The information on the ZEB1 gene, which crucially impacts survival of patients with other malignant tumors, is limited for PC.Clinicopathological characteristics of 62 patients with PC were investigated in this study. Associations between immunohistochemical expression of ZEB1 and clinical factors, including patient prognosis, were examined. The patient population consisted of 51 (82.2%) men and 11 (17.8%) women, with a mean age of 65.5 years (range, 31-81 years).The overall survival rate of the 42 patients, for whom follow-up was available, was 68.3% at 5 years. Using TNM criteria, 7 (11.3%), 11 (17.7%), 3 (4.8%), 21 (33.8%), 15 (24.2%), 2 (3.2%), and 3 (4.8%) patients were classified under pathological stage IA, IB, IIA, IIB, IIIA, IIIB and IV carcinomas, respectively. Fifteen (24.1%) patients had tumors consisting entirely of spindle and giant cells (PC component). The other 47 (75.8%) cancers contained additional carcinoma components (i.e., adenocarcinoma (34/62, 54.8%), squamous cell carcinoma (7/62, 11.3%), adenosquamous carcinoma (4/62, 6.5%) and large cell carcinoma (2/62, 3.2%)). Four of 7 (57.1%) stage IA (20mm) tumors consisted only of spindle and giant cells. ZEB1 expression was observed only in the PC component. Diffuse expression of ZEB1, was defined as positive nuclear staining in ≥75% of cancer cells, and was found in the PC component in 12 patients. Multivariate analysis revealed that lymph node metastasis, pleural invasion, and diffuse ZEB1 expression in the PC component predicted poorer disease-specific survival (p=0.007, 0.022, and 0.016, respectively).This is the first report to indicate that ZEB1 may be used as an immunohistochemical prognosticator of PC, which may be useful for histological assessment of PC in biopsy and surgical specimens.

Background: The Geriatric Nutritional Risk Index (GNRI) is a new index recently introduced for predicting the risk of nutrition-related complications. The GNRI has mainly been reported as a simple and accurate tool to assess the nutritional status and prognosis of elderly patients. So far, there have been no reports of the GNRI in patients with gastrointestinal cancer. Our objective was to examine the association between the GNRI and short-term outcomes, especially postoperative complications, in patients with esophageal cancer who underwent esophagectomy and gastric tube reconstruction. Materials and Methods: The present study enrolled 122 consecutive patients with esophageal cancer who underwent esophagectomy and gastric tube reconstruction. The GNRI at admission to the hospital was calculated as follows: (1.489 × albumin in g/l) + (41.7 × present/ideal body weight). The characteristics and short-term outcomes were compared between two groups: the high (GNRI ≥90) and the low (GNRI Results: The mean age of the 122 patients was 63.9 ± 9.1 years (range 43-83). There were no significant differences in either patient or operative characteristics. The low GNRI group had a significantly higher rate of respiratory complications (p = 0.002). A multivariate analysis demonstrated that the GNRI was the only independent significant factor predicting respiratory complications (hazard ratio 3.41, 95% confidence interval 1.19-9.76; p = 0.022). Conclusion: The GNRI is considered to be a clinically useful marker that can be used to assess the nutritional status and predict the development of postoperative respiratory complications in patients with esophageal cancer undergoing esophagectomy and gastric tube reconstruction.

Spontaneous esophageal perforation is relatively uncommon, but carries a high mortality rate if diagnosis or treatment is delayed. We report the case of a 68-year-old man with spontaneous esophageal perforation who was successfully treated over 96 h after onset by thoracic drainage and jejunostomy for enteral nutrition. He vomited after drinking alcohol, soon followed by epigastralgia. Heart failure was suspected on admission to another hospital. Spontaneous esophageal perforation was diagnosed 48 h after admission. Chest tube drainage was performed, but his general condition deteriorated and he was transferred to our hospital. Emergent surgery was performed and esophageal perforation combined with pyothorax and mediastinitis was identified on the left side of the lower esophagus. The left thoracic cavity was rinsed and thoracic drainage was performed. Feeding jejunostomy was performed for postoperative enteral nutrition. Effective drainage and sufficient nutrition management appear extremely valuable in treating spontaneous esophageal perforation.