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The aim of this study was to evaluate the efficacy of preoperative chemotherapy for stage II-III esophageal squamous cell carcinoma based on an objective computed tomography method.A total of 82 patients who underwent preoperative chemotherapy followed by surgery for advanced esophageal squamous cell carcinoma from January 2006 to June 2019 were included. Treatment effect was evaluated by measuring the esophageal wall thickness before and after neoadjuvant chemotherapy using contrast-enhanced thoracoabdominal computed tomography. The percentage decrease in esophageal wall thickness was calculated using the following formula: reduction (%)=(wall thickness before preoperative chemotherapy - wall thickness after preoperative chemotherapy)/(wall thickness before preoperative chemotherapy)×100. We demonstrated the efficacy of this measurement method and then analyzed which patient factors might affect the treatment effect.Receiver operating characteristic analysis showed the percentage tumor reduction to be a good predictor of histological therapeutic effect (grade ≥2) (area under the curve=0.727). In the multivariate analysis, tumor location (lower versus upper esophagus) was identified as an independent factor associated with tumor reduction (odds ratio=0.15; 95% confidence interval=0.03-0.79; p=0.025).We demonstrated an association between the reduction of esophageal wall thickness in the tumoral area and the histological therapeutic effect of chemotherapy. Secondary analysis showed poorer tumor reduction in patients with lower esophageal cancer than in those with upper esophageal cancer.

Introduction: The Japan Lung Cancer Society (JLCS) and the Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma (JLCS-JSCC system). Prior to the proposal, the Papanicolaou Society of Cytopathology (PSC) had proposed a revised reporting system (PSC system), which comprises the “neoplastic, benign neoplasm, and low-grade carcinoma” category (N-B-LG category), in addition to the 4 categories of the JLCS-JSCC system. This study aimed to evaluate the interobserver agreement of the JLCS-JSCC system with an additional dataset with more benign lesions in comparison with the PSC system. Methods: We analyzed 167 cytological samples, which included 17 benign lesions, obtained from the respiratory system. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the JLCS-JSCC system and PSC system. Results: The interobserver agreement was moderate in the JLCS-JSCC (k = 0.499) and PSC (k = 0.485) systems. Of the 167 samples, 17 samples were benign lesions: 7 pulmonary hamartomas, 5 sclerosing pneumocytomas, 2 squamous papillomas, one solitary fibrous tumor, one meningioma, and one lymphocytic proliferation. There were diverse sample types as follows: 11 touch smears, 3 brushing smears, 2 aspirations, and one sputum sample. Fourteen samples (82.3%) were categorized into “negative” or “atypical” by more than half of the observers in the JLCS-JSCC system. Conversely, 3 samples were categorized as “suspicious” or “malignant” by more than half of the observers in the JLCS-JSCC system. On the other hand, 11 samples (64.7%) were categorized into the N-B-LG category by more than half of the observers in the PSC system. Conclusions: The concordance rate in the JLCS-JSCC system was slightly higher than that in the PSC system; however, the interobserver agreement was moderate in both the JLCS-JSCC and PSC systems. These results indicate that both the JLCS-JSCC and PSC systems are clinically useful. Therefore, both systems are expected to have clinical applications. It may be important to integrate the 2 systems and construct a universal system that can be used more widely in clinical practice.

Alcohol consumption is a major risk factor for esophageal cancer. In Asia, heavy drinkers are considered to have a higher risk of esophageal cancer than nondrinkers and light drinkers. However, no study has shown an association between alcohol reduction and the morbidity of esophageal cancer in Asian heavy drinkers. Therefore, this study investigated the significance of reducing alcohol consumption to prevent esophageal cancer in Asian heavy drinkers by conducting a systematic review and meta-analysis. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 1995 to December 2020. The hazard ratio (HR) and 95% confidence interval (CI) were calculated using a random-effects model. I2 statistics were used to detect heterogeneity. This study included 21 articles in the qualitative synthesis. Light drinkers and heavy drinkers were categorized based on alcohol consumption amount as ≤ 25 ethanol g/day and ≥ 66 ethanol g/day, respectively, as described in many previous studies, and five cohort studies were eligible for this meta-analysis. The HR of esophageal cancer among heavy drinkers versus nondrinkers was 4.18 (95% CI 2.34–7.47, I2 = 74%). On the other hand, the HR of esophageal cancer among light drinkers was 1.82 compared with nondrinkers (95% CI 1.57–2.10, I2 = 0%). Heavy drinkers have a higher esophageal cancer incidence than light drinkers and nondrinker. It is possible that alcohol reduction may decrease the risk of esophageal cancer in Asian heavy drinkers.

Background Mutations in driver genes such as IDH and BRAF have been identified in gliomas. Meanwhile, dysregulations in the p53, RB1, and MAPK and/or PI3K pathways are involved in the molecular pathogenesis of glioblastoma. RAS family genes activate MAPK through activation of RAF and PI3K to promote cell proliferation. RAS mutations are a well-known driver of mutation in many types of cancers, but knowledge of their significance for glioma is insufficient. The purpose of this study was to reveal the frequency and the clinical phenotype of RAS mutant in gliomas. Methods This study analysed RAS mutations and their clinical significance in 242 gliomas that were stored as unfixed or cryopreserved specimens removed at Kyoto University and Osaka National Hospital between May 2006 and October 2017. The hot spots mutation of IDH1/2, H3F3A, HIST1H3B, and TERT promoter and exon 2 and exon 3 of KRAS, HRAS, and NRAS were analysed with Sanger sequencing method, and 1p/19q codeletion was analysed with multiplex ligation-dependent probe amplification. DNA methylation array was performed in some RAS mutant tumours to improve accuracy of diagnosis. Results RAS mutations were identified in four gliomas with three KRAS mutations and one NRAS mutation in one anaplastic oligodendroglioma, two anaplastic astrocytomas (IDH wild-type in each), and one ganglioglioma. RAS-mutant gliomas were identified with various types of glioma histology. Conclusion RAS mutation appears infrequent, and it is not associated with any specific histological phenotype of glioma.

Although the standard treatment for intramucosal esophageal cancer without lymph node metastasis is endoscopic submucosal dissection (ESD), we sometimes encounter patients who are not able to undergo a transoral endoscopic examination. Here, we report a surgical procedure consisting of transgastric retrograde ESD to treat early esophageal cancer (T1a-EP, N0, M0) because of a stricture after hypopharyngeal cancer surgery. This retrograde ESD procedure can be a safe and effective treatment option for early esophageal cancer. This is the first report of a surgical retrograde ESD method for esophageal cancer.

Rechallenge of immune checkpoint inhibitors has been reported for neoplasms other than breast cancer. Reported here is a case of a 55-year old woman diagnosed as having triple-negative right breast cancer with multiple metastases including lung. Atezolizumab and nab-paclitaxel were administered followed by epirubicin–cyclophosphamide. With subsequent eribulin, the overall best response was progressive disease, and curative surgical resection was performed. Three months after surgery (1.5 years after initial response of lung metastasis), right lung metastasis emerged at a site different from baseline. Based on the microsatellite instability-high status, pembrolizumab was administered and showed a good response. The patient has been treated with pembrolizumab, maintaining partial response, for over 9 months, which suggests the benefit of immune checkpoint inhibitors rechallenge in breast cancer.

A metachronous neoplasm can develop in a gastric conduit used for reconstruction after esophagectomy for thoracic esophageal cancer. Surgical resection is sometimes necessary to treat this neoplasm. We report a method for performing minimally invasive gastrectomy with preservation of the proximal residual stomach through laparotomy for cancer in the distal side of gastric conduit after Ivor-Lewis esophagectomy. Furthermore, Roux-en-Y reconstruction was performed after gastrectomy. This minimally invasive partial gastrectomy for early gastric conduit cancer and followed Roux-en-Y reconstruction may lead to a favorable clinical outcome.

Lymph node (LN) recurrence is frequently encountered in esophageal cancer. The aim of this study was to determine the effects of various factors, including loco-regional treatment of LN-only recurrence, on the survival rate. Among 941 patients who underwent curative resection for esophageal squamous cell carcinoma in 2003–2016, we retrospectively reviewed 117 patients (12.4%) who developed LN-only recurrence. One, 2, 3, and 4 or more metastatic LNs were found in 72, 22, 6, and 17 patients, respectively, after a median disease-free interval of 8.4 months (range 1.1–62.0). Among all cases, recurrence was out of the surgical field in 53 cases (45.3%). Recurrent LNs were controlled by loco-regional treatment in 29 (43.9%) and by chemotherapy alone in 3 patients (7.0%). The 3-year survival rates of patients who did and did not achieve local control were 53.2% and 5.2%, respectively. Univariate analysis showed significant relationships between post-recurrence survival rate and pStage I–II at initial surgery, no history of radiotherapy, recurrence in ≤ 2 LN, and loco-regional treatment of LN recurrence. Multivariate analysis identified recurrence in ≤ 2 LN (HR 0.3169, 95% CI 0.1023–0.5314, p = 0.0038) and loco-regional treatment (HR 0.1973, 95% CI 0.0075–0.3871, p = 0.0416) as the only two significant and independent prognostic factors of survival. Recurrence limited to ≤ 2 LN and loco-regional treatment (chemoradiotheapy or surgery) for LN recurrence were associated with favorable survival of patients with history of radical esophagectomy followed by LN recurrence. Our results emphasize the importance of local control of LN recurrence regardless of location.

The aim of this study was to clarify whether ghrelin infusion is useful for suppressing inflammatory responses after esophagectomy. A phase I study of ghrelin administration after esophagectomy was performed in 20 patients with esophageal cancer. The anti-inflammatory effect of ghrelin was compared with 20 consecutive patients who did not receive ghrelin infusion. Additionally, 10 patients with intermittent infusion for 10 days were compared with 10 patients with continuous infusion for 5 days. The primary endpoint was the duration of systemic inflammatory response syndrome (SIRS). Secondary endpoints included postoperative complications, serum C-reactive protein (CRP), interleukin-6 (IL-6), and growth hormone (GH) levels. No adverse events of ghrelin administration occurred. Patients with ghrelin infusion had higher plasma ghrelin levels on postoperative day (POD) 3 (p = 0.003) and shorter SIRS duration (p = 0.007) than patients without ghrelin infusion. Although SIRS duration was similar (p = 0.19), patients with continuous ghrelin infusion had significantly higher plasma ghrelin (p

Aim To evaluate the association between 11C-methionine positron-emission tomography (11C-methionine PET) findings, isocitrate dehydrogenase (IDH) gene mutation, and O6-methylguanine-DNA methyltransferase (MGMT) promoter methylation in patients with grade II and III gliomas. Materials and methods Data were collected from 40 patients with grade II and III gliomas who underwent both magnetic resonance imaging (MRI) and 11C-methionine PET as part of their pre-surgical examination. IDH mutation was examined via DNA sequencing, and MGMT promoter methylation via quantitative methylation-specific polymerase chain reaction (PCR). Results A threshold of MGMT promoter methylation of 1% was significantly associated with tumour/normal tissue (T/N) ratio. The T/N ratio in samples with MGMT promoter methylation ≥1% was higher than that in samples with MGMT promoter methylation Conclusion 11C-methionine PET parameters can predict MGMT promoter methylation but not IDH mutation status. 11C-methionine uptake may have limited potential to reflect DNA methylation processes in grade II and III gliomas.

Endoscopic diagnosis of the invasion depth of superficial esophageal squamous cell carcinoma (ESCC) is an important determinant of the treatment strategy. The three endoscopic imaging modalities commonly used to predict the invasion depth of superficial ESCC in Japan are non-magnifying endoscopy (non-ME), magnifying endoscopy (ME), and endoscopic ultrasonography (EUS). However, which of these three modalities is most effective remains unclear. We performed a systematic review of the literature to compare the diagnostic accuracy of the three modalities for prediction of the invasion depth of superficial ESCC. We used Medical Subject Heading terms and free keywords to search the PubMed, Cochrane Central, and Ichushi databases to identify direct comparison studies published from January 2000 to August 2020. The results of direct comparison studies were used to compare the diagnostic accuracy of each modality. The primary outcome was defined as the proportion of overdiagnosis of pT1b-SM2/3 cancers, and the main secondary outcome was the proportion of underdiagnosis of pT1b-SM2/3 cancers. Other secondary outcomes were the sensitivity and specificity values of the modalities. Four articles were finally selected for qualitative evaluation. Although ME showed no significant advantages over non-ME in terms of sensitivity and specificity, it had a slightly lower proportion of overdiagnosis. EUS had sensitivity and specificity similar to those of non-ME and ME, but EUS had a higher proportion of overdiagnosis. Non-ME and ME are useful for the diagnosis of cancer invasion depth. EUS may increase overdiagnosis, and caution is required in determining its indications.

Congenital absence of the portal vein (CAPV) is a rare malformation in which intestinal and splenic venous blood bypasses the liver and drains into systemic veins. CAPV is classified into two types based on the absence (type I) or presence (type II) of portal venous flow into the hepatic parenchyma and is associated with multiple other anomalies such as usually benign hepatic tumors. There have been only two case reports describing hepatocellular carcinoma (HCC) in patients with CAPV type II to date. We report the third such patient. A 50‐year‐old woman was referred to our hospital for management of a giant hepatic tumor. Contrast‐enhanced computed tomography (CECT) indicated a huge mass occupying the right lobe of the liver; the radiological diagnosis was HCC. CECT also demonstrated that the superior mesenteric vein (SMV) and the splenic vein (SpV) joined to form a shunt draining into the left renal vein and that a hypoplastic portal vein branched from the confluence of the SMV and SpV and drained into the liver, indicating that the CAPV was type II. Liver resection was successfully performed to treat the HCC, and the pathological diagnosis was well‐differentiated HCC. Seven months after the operation, a recurrent small HCC was detected and treated with radiofrequency ablation without complications. The patient has been carefully followed for 6 months to date without any evidence of further recurrence. Patients with CAPV are predisposed to developing HCC and require close surveillance., A 50‐year‐old woman was diagnosed with a giant hepatocellular carcinoma (HCC) that was associated with congenital absence of the portal vein (CAPV) type II. Patients with CAPV type II are predisposed to developing HCC and require close surveillance.

Extramammary Paget’s disease (EMPD) is a rare form of neoplasm. Metastasis of EMPD to locations other than lymph nodes and intra-epithelial regions is rare; there are a limited number of case reports of metastases to the liver, lung, bone, and brain. We present a rare case of EMPD that metastasized to the brain and was treated with surgical resection. A 66-year-old man presented with a small palpable mass in the scrotum. After 5 years of observation, he was diagnosed with EMPD that metastasized to the lymph nodes and lung. Tumor resection and postoperative chemotherapy were performed. Six months after the last chemotherapy treatment, he presented with a right temporal lobe tumor and underwent surgical resection. Histopathological analysis revealed brain metastasis of EMPD. Three months after surgery, magnetic resonance imaging (MRI) showed local tumor recurrence, and intensity modulated radiation therapy (IMRT) (45 Gy/15 Fr) was performed. Although the metastatic brain tumor was well controlled, the primary tumor progressed. He was provided best supportive care and died 5 months after brain tumor resection. In this report, we present a rare case of brain metastasis of EMPD, treated with surgical resection, and histopathologically confirmed to be metastatic EMPD.

Introduction: The classification of lung carcinoma is based on small biopsies and/or cytology in 80% of patients with non-small cell carcinoma. However, there is no widely accepted classification system for respiratory cytology. The Japan Lung Cancer Society (JLCS) and Japanese Society of Clinical Cytology (JSCC) have proposed a new four-tiered cytology reporting system for lung carcinoma with the following categories: (1) “negative for malignancy,” (2) “atypical cells,” (3) “suspicious for malignancy,” and (4) “malignancy.” Objective: The aim of this work was to perform an interobserver reproducibility study to confirm the utility of the four-tiered reporting system on respiratory cytological samples. Methods: We analyzed 90 cytological samples obtained with bronchoscopy. Seven observers classified these cases into each category by reviewing one Papanicolaou-stained slide per case according to the three-, four-, and five-tiered reporting systems. Results: The interobserver agreement was fair in the three- (κ = 0.50), four- (κ = 0.45), and five-tiered (κ = 0.45) reporting systems. However, the four-tiered reporting system provided more precise information than the three-tiered reporting system in patient management. The risk of malignancy in the four-tiered reporting system was also stratified well: 19.3% for “negative for malignancy,” 45.6% for “atypical cells,” 74.7% for “suspicious for malignancy,” and 88.1% for “malignancy.” Conclusions: The reporting system proposed by the JLCS and JSCC was designed to enhance the communication between clinicians and pathologists and among different institutions. It is simple and applicable to cytological diagnosis of any respiratory diseases. We propose establishing an international classification for respiratory cytology, harmonizing the reporting systems proposed by different countries.

Metastasis of rectal cancer to the breast is an extremely rare clinical event. We report the case of a 67-year-old woman with a metastatic breast tumor derived from a BRAF V600E mutant rectal carcinoma that was diagnosed and resected curatively 1 year previously. Computed tomography showed a left breast mass and multiple lung nodules suspected to be indicative of recurrent rectal cancer. The ultrasonography examination demonstrated a 10 × 10-mm hypoechoic solid lesion in the left breast with an elevation in the serum carcinoembryonic antigen level and serum carbohydrate antigen 19-9 level. Core needle biopsy was performed, and histopathologic examination showed Cytokeratin 20 and CDX-2 positivity, compatible with rectal cancer. To our knowledge, this is the first case of a metastatic breast tumor arising from rectal carcinoma with BRAF mutation. Although breast metastasis is very rare event, the possibility of breast metastasis from extra mammary sites should be considered when the breast tumor is found in cancer treatment.

The consumption of fruit and vegetables was reported to be associated with a reduced risk of esophageal cancer (EC) in many studies of esophageal adenocarcinoma (EAC) and esophageal squamous cell carcinoma (ESCC) from different regions worldwide. Therefore, to provide precise information to reduce the risk of EC in Asia, we performed a systematic review and meta-analysis of studies conducted in the Asian region about fruit and vegetable consumption and the risk of EC. We searched the MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases from January 2010 to December 2020. The summary relative risk (SRR) and 95% CI were calculated using a random-effects model. In addition, I

A 60-year-old man was referred to our hospital for the evaluation and treatment of general malaise. Contrast-enhanced computed tomography detected sigmoid colon cancer that had invaded the bladder, multiple liver metastases, and a small intestinal tumor. Hartmann's procedure was performed, with partial bladder and small bowel resection. A pathological examination revealed that the patient had sigmoid colon cancer and a gastrointestinal stromal tumor. The biopsy findings of a tumor in segment 8 of the liver indicated the presence of adenocarcinoma, thereby indicating the origin of multiple liver metastases from sigmoid colon cancer. On chemotherapy, the tumors in liver segments 2/3 and 8 shrank. However, the tumor in segment 6 enlarged. Since radical resection of all metastatic liver tumors was possible, hepatectomy was performed 10 months after the initial surgery. A pathological examination revealed that the tumors in segments 2/3, 4, and 8 were adenocarcinomas and the tumors in segments 4, 6, and 7 had originated from the gastrointestinal stromal tumor. This suggested the coexistence of liver metastases from sigmoid colon cancer and the gastrointestinal stromal tumor. In cases involving multiple primary tumors, it is necessary to consider the possible coexistence of multiple metastases from different primary tumors.

Long-term proliferating tumorsphere-forming glioma derived cells (LTP-TS-GDCs) and patient derived xenografts (PDXs) are essential tools for translational research for glioma. However, only small subsets of glioma samples are established as LTP-TS and/or PDXs and little is known about the genetics and molecular properties of LTP-TS -forming GDCs and PDX. In this study, we aim to analyze the characteristics of LTP-TS -forming GDCs and PDXs. We tried primary sphere cultures from 56 glioma patient-derived samples and established 11 LTP-TS-GDCs out of 45 glioblastoma samples and no long-term sphere culture was isolated from grade3 and grade 2 gliomas. LTP-TS-GDCs had self-renewal ability and possessed certain multipotency. However, they significantly less expressed SOX1 FOXG1 and TUBB3, whereas they expressed LGALS1 and EN1 significantly higher than normal neural stem/progenitor cells. In addition, we found that LTP-TS-GDCs shared the same genetic profiles with original patients’ tumors. Furthermore, we investigated the genetic differences between the glioma tissues which were successfully established as LTP-TS-GDCs and those which were not. We found that glioma tissues with TERT promotor mutations and triple copy number alteration (CNA) [EGFR, CDKN2A, and PTEN loci] are significantly established as LTP-TS-GDCs. Lastly, we next investigated in vivo characteristics of glioma PDXs. We have injected glioma PDXs lines into immunodeficient mice brains and histopathologically analyzed the characteristics of xenografts. Each xenograft well recapitulated histological features of original patients’ tumors and tumor cells remarkably invade through subventricular zone. In conclusion, each LTP-TS-GDCs and PDXs had various gene expression profiles, reflecting intratumoral and interpatient heterogeneities of glioma. In addition, TERT promotor mutations and triple CNA significantly correlated with success rate of LTP-TS-GDCs. These findings will be of use and advance the preclinical and translational researches of glioma.

We elucidated clinicopathological characteristics of giant cell tumor of bone (GCTB) in Japan, and significant clinicopathological factors for predicting local recurrence. Clinicopathological profiles of 213 patients with GCTB (100 male, 113 female) involving extra‐craniofacial bones were retrieved. Pathological slides obtained at the initial surgery were reviewed. Fourteen pathological and five clinical features were statistically analyzed to disclose prognostic significance. Patient age ranged from 12–80 years (Average 38.7). Long bones were most frequently affected (86.4%), especially around the knee (62.9%). Histological features are basically similar to those previously reported. Within a follow‐up period (24–316 months, average 106.1 months), the local recurrence rate is 29.1%. Metastasis has occurred in 9 patients. Cox regression analysis of representative clinicopathological features shows that younger age, higher mitotic count, smaller zones of stromal hemorrhage, considerable vascular invasion and absence of ischemic necrosis are significant predictors for local recurrence. Initial operative method (curettage) is a significant risk factor in univariate analysis but not by multivariate analysis (P = 0.053). Denosumab administration increases risk but not significantly (P = 0.053). Histone 3.3 G34W immunopositivity is not significant for predicting local recurrence.

A metachronous neoplasm can develop in a gastric conduit used for reconstruction after esophagectomy for thoracic esophageal cancer. Surgical resection is sometimes necessary to treat this neoplasm. We report a method for performing minimally invasive gastrectomy with preservation of the proximal residual stomach through laparotomy for cancer in the distal side of gastric conduit after Ivor-Lewis esophagectomy. Furthermore, Roux-en-Y reconstruction was performed after gastrectomy. This minimally invasive partial gastrectomy for early gastric conduit cancer and followed Roux-en-Y reconstruction may lead to a favorable clinical outcome.

Sitting ability during the acute phase after stroke is a useful indicator of functional outcomes; however, factors that affect this ability have not been evaluated. Therefore, this study aimed to identify and evaluate factors that affect sitting ability in the acute phase after stroke.This multicenter prospective cohort study included hemispheric stroke patients who underwent an inpatient rehabilitation program after acute stroke from five acute care hospitals. The effect of age, sex, lesion side, etiology, consciousness disorder, stroke and dementia history, stroke-related complications, National Institutes of Health Stroke Scale score, hemiparalysis, turn-over movement from the supine position and sit-up movement, and Scale for Contraversive Pushing on the "remain sitting" item in the revised version of the Ability of Basic Movement Scale at the time of acute hospital discharge were investigated. Factors affecting sitting ability were identified using binomial logistic regression analysis.We included 293 stroke patients. Age (odds ratio: 0.943, 95% confidence interval: 0.910-0.977, p=0.001), National Institutes of Health Stroke Scale score (odds ratio: 0.862, 95% confidence interval: 0.811-0.916, p0.001), and Scale for Contraversive Pushing score (odds ratio: 0.543, 95% confidence interval: 0.419-0.705, p0.001) were identified as independent predictors of sitting ability at the time of hospital discharge (median; 23.0 days).Older patients and those with high Scale for Contraversive Pushing and National Institutes of Health Stroke Scale scores experienced difficulties in regaining sitting ability. These results may guide physical therapy for patients with impaired sitting ability due to hemispheric stroke.

Medulloblastoma is the second-most common malignant tumor in children. Medulloblastoma has been categorized into four distinct molecular subgroups: WNT, sonic hedgehog (SHH), group 3, and group 4. We report on a male child with medulloblastoma, in whom an enlarged ventricle was diagnosed in utero. Magnetic resonance imaging showed cyst formation in the cerebellar hemisphere initially, with tumor growth being indicated later. Tumor resection was performed when the boy was 12 months old. The histological findings showed extensive nodularity. Further genetic analysis revealed the tumor to be SHH type. This is the first description of a medulloblastoma observed from the fetal stage. Our findings in this case indicate that cyst formation may be the pre-neoplastic lesion of SHH-subtype medulloblastomas.

A 62-year-old woman was diagnosed with gastric cancer, Type 4, cT4b(LN, mesentery of transverse colon), N1 M1H0P1CY1, cStage ⅣB. S-1 and L-OHP(SOX)were administered for 4 courses and clinical response was SD. She interrupted the treatment because of practicing folk therapy. She had an emergency hospitalization due to pyloric stenosis, vomiting, and an umbilical tumor with pain. She was treated with 1 course of mFOLFOX6(5-FU, L-OHP, l-LV)followed by palliative surgery(laparoscopy assisted distal gastrectomy, Roux-en-Y reconstruction, resection of umbilical tumor, and bypass for transverse colon stenosis due to dissemination). The pathological diagnosis was L, Circ, Type 4, 126×89 mm, porsig, pT4b(SI, mesentery of transverse colon), pN3a(12/13), H0P1CY1, pStageⅣ, and metastatic umbilical tumor. Following surgery, oral administration of mFOLFOX6 is continued. Umbilical metastasis(Sister Mary Joseph's nodule)is associated with poor prognosis, however, appropriate management including symptom control by palliative surgery and continuation of chemotherapy may lead a better prognosis.

Long-term proliferating tumorsphere (LTP-TS)-forming glioma derived cells (GDCs) and patient derived xenografts (PDXs) are essential tools for translational research for glioma. However, only small subsets of glioma samples are established as LTP-TS and/or PDXs and little is known about the genetics and molecular properties of LTP-TS -forming GDCs and PDX. In this study, we aim to analyze the characteristics of LTP-TS -forming GDCs and PDXs. We tried primary sphere cultures from 56 glioma patient-derived samples and established 14 LTP-TS -forming GDCs out of 48 glioblastoma samples and no long-term sphere culture was isolated from grade3 and grade 2 gliomas. LTP-TS -forming GDCs had self-renewal ability and possessed certain multipotency. However, they significantly less expressed SOX1 FOXG1 and TUBB3, whereas they expressed LGALS1 significantly higher than normal neural stem/progenitor cells. In addition, we found that LTP-TS -forming GDCs shared the same genetic profiles with original patients’ tumors. Furthermore, we investigated the genetic differences between the glioma tissues which were successfully established as LTP-TS -forming GDCs and those which were not. We found that glioma tissues with TERT promotor mutations and triple CNA (EGFR, CDKN2A, and PTEN loci) are significantly established as LTP-TS -forming GDCs. Lastly, we next investigated in vivo characteristics of glioma PDXs. We have injected glioma PDXs lines into immunodeficient mice and histopathologically analyzed the characteristics of xenografts. Each xenograft well recapitulated histological features of original patients’ tumors and tumor cells remarkably invade through subventricular zone. In conclusion, each LTP-TS -forming GDCs and PDXs had various gene expression profiles, reflecting intratumoral and interpatient heterogeneities of glioma. In addition, TERT promotor mutations and triple CNA significantly correlated with success rate of LTP-TS -forming GDCs. These findings will be of use and advance the preclinical and translational researches of glioma.

Background/Aims: Since the risk of cancer cells seeding the peritoneum after perforation during endoscopic submucosal dissection (ESD) is unclear, we retrospectively examined peritoneal relapse after gastric perforation during ESD for gastric cancer at a single institution. Methods: Of 876 patients who underwent ESD for early gastric cancer between January 2002 and December 2015, 22 patients (2.5%) experienced gastric perforation during ESD at the Osaka National Hospital in Osaka, Japan. Clinical data from these 22 patients were reviewed for information on pathology, clinical course, and evidence of peritoneal dissemination. Results: Patients were followed for a median of 55 (range 2–108) months. Two patients had peritoneal seeding following perforation during ESD. Multivariate analysis to explore the influence of clinical factors on the peritoneal seeding revealed that an intra-abdominal fluid collection on the CT imaging just after ESD, tumor location at the upper lesion of stomach, and pathologically marginal invasion were independently associated with an incidence of peritoneal relapse. Conclusion: Although rare, we should recognize the possibility of cancer cells seeding the peritoneum after perforation during gastric ESD.

We elucidated clinicopathological characteristics of chondroblastoma (CB) in Japan, and reliable clinicopathologic parameters predicting local recurrence and/or metastasis. Clinicopathological profiles of 103 CB (80 male, 23 female) in extra-craniofacial bones were retrieved. Numerical scoring of nine pathological and five radiological features was statistically analyzed to determine prognostic significance. Age ranged 8–61 years (average 19.6 years). Frequently involved sites were femur, tibia, calcaneus, patella and humerus. Radiologically, tumors were 2–80 mm (average 31.1 mm) in size. Marginal sclerosis and calcification were common. Histologically, pink cartilage, mitoses, and chicken-wire calcification were often seen. Within a follow-up period [2–260 months (average 53.5 months)], the local recurrence rate was 15.5%. No patient had metastasis. Recurrence was most frequently observed at the femur. By log-rank analysis, only cyst formation in images was significant for predicting recurrence free survival (RFS). By Cox hazard analysis with representative clinico-radiological and pathological features, only age (≥16 years) and cyst formation were significant predictors for RFS. Pathological features were not significant in both uni- and multivariate analyses.

Summary Small invasion into ductal carcinoma in situ (DCIS) can easily be overlooked in resected breast specimens. To disclose useful markers predictive of invasive foci within preoperatively diagnosed DCIS lesions, a retrospective histopathological comparison was made between postoperatively diagnosed invasive ductal carcinoma with a predominant intraductal component (IDCPIC) (n = 43) and pure DCIS (n = 82). Through a multivariate logistic regression analysis model, 5 variables (DCIS grade, “tumor thickness,” extent of retraction cleft, presence of lymph node metastasis, and HER2 score) were found to be significantly associated with the presence of invasive foci within DCIS; with a cutoff point of 0.315, sensitivity, specificity, positive predictive value, and negative predictive value were 0.93, 0.77, 0.68, and 0.95, respectively. No statistically significant difference was observed in recurrence-free survival between IDCPIC and pure DCIS, whereas the IDCPIC curve showed a slightly earlier decline than the DCIS one. In general, preoperative detection of lymph node metastasis in DCIS patients is elusive because of the extremely tiny metastatic size in most cases; thus, a 4-variable model, without lymph node metastasis, would be the actual working model. Furthermore, tumor “thickness” was found to be the most significant parameter predictive of invasive foci within DCIS. Although IDCPIC and pure DCIS showed similar recurrence-free survival curves, prediction of invasive foci within DCIS necessitates postoperative pathological analysis of surgically resected lesions.

Recent intensive genomic and molecular biological analyses have made a consensus that medulloblastomas (MBs) are at least classified into four core subgroups, and the new 2016 WHO brain tumor classification has introduced the classification of MBs genetically defined in addition to classical histopathological diagnosis. To establish a nationwide network of a molecular diagnosis system for pediatric brain tumors, the JPMNG co-organized by the Japan Society for Neuro-Oncology and the Japanese Society for Pediatric Neurosurgery have started the clinical researches in 2012, and we have summarized results of molecular analysis of Japanese MBs. Total 236 primary MBs have been subclassified by gene expression profile using the NanoString nCounter system or DNA methylation array, and their single nucleotide mutations and copy number aberrations have been also examined. Mean follow up time was 68.9 months. Proportion of four core subgroups were WNT (16.9%), SHH (25.4%), Group 3 (17.4%) and Group 4 (40.3%), respectively. In cases of less than 3 years old, no WNT have been found and 63.2% cases were SHH. In cases between 3 to 17 years old, Group 4 is the most (47%), and these trends is almost consistent with published references. TP53 mutations were identified in 23.3% of SHH, and they were significantly poor prognosis. Metastatic or MYC gain Group 3 MBs were poor prognosis, while Group 4 MBs with loss of chromosome 11 or whole chromosomal aberration were good prognosis. These findings reveal molecular properties of Japanese MBs and will contribute to develop new therapeutic strategies.

Aging is a known negative prognostic factor in glioblastomas (GBM). Whether particular genetic backgrounds are a factor in poor outcomes of elderly patients with GBM warrants investigation. We aim to elucidate any differences between older and younger adult patients with IDH-wildtype GBM regarding both molecular characteristics and clinical outcomes. We collected adult cases diagnosed with IDH-wildtype GBM from the Kansai Network. Clinical and pathological characteristics were analyzed retrospectively and compared between older (≥ 70 years) and younger (≤ 50 years) cases. Included were 92 older vs. 33 younger cases. The older group included more patients with preoperative Karnofsky performance status score

Identification of genotypes is crucial for treatment of glioma. Here, we developed a method to predict tumor genotypes using a pretrained convolutional neural network (CNN) from magnetic resonance (MR) images and compared the accuracy to that of a diagnosis based on conventional radiomic features and patient age. Multisite preoperative MR images of 164 patients with grade II/III glioma were grouped by IDH and TERT promoter (pTERT) mutations as follows: (1) IDH wild type, (2) IDH and pTERT co-mutations, (3) IDH mutant and pTERT wild type. We applied a CNN (AlexNet) to four types of MR sequence and obtained the CNN texture features to classify the groups with a linear support vector machine. The classification was also performed using conventional radiomic features and/or patient age. Using all features, we succeeded in classifying patients with an accuracy of 63.1%, which was significantly higher than the accuracy obtained from using either the radiomic features or patient age alone. In particular, prediction of the pTERT mutation was significantly improved by the CNN texture features. In conclusion, the pretrained CNN texture features capture the information of IDH and TERT genotypes in grade II/III gliomas better than the conventional radiomic features.

Objectives Inflammation-associated microsatellite alterations (also known as elevated microsatellite alterations at selected tetranucleotide repeats [EMAST]) result from IL-6-induced nuclear-to-cytosolic displacement of the DNA mismatch repair (MMR) protein MSH3, allowing frameshifts of dinucleotide or longer microsatellites within DNA. MSH3 also engages homologous recombination to repair double-strand breaks (DSBs), making MSH3 deficiency contributory to both EMAST and DSBs. EMAST is observed in cancers, but given its genesis by cytokines, it may be present in non-neoplastic inflammatory conditions. We examined ulcerative colitis (UC), a preneoplastic condition from prolonged inflammatory duration. Methods We assessed 70 UC colons without neoplasia, 5 UC specimens with dysplasia, 14 UC-derived colorectal cancers (CRCs), and 19 early-stage sporadic CRCs for microsatellite instability (MSI) via multiplexed polymerase chain reaction capable of simultaneous detection of MSI-H, MSI-L, and EMAST. We evaluated UC specimens for MSH3 expression via immunohistochemistry. Results UC, UC with dysplasia, and UC-derived CRCs demonstrated dinucleotide or longer microsatellite frameshifts, with UC showing coincident reduction of nuclear MSH3 expression. No UC specimen, with or without neoplasia, demonstrated mononucleotide frameshifts. EMAST frequency was higher in UC-derived CRCs than UC (71.4% vs 31.4%, P = 0.0045) and higher than early-stage sporadic CRCs (66.7% vs 26.3%, P = 0.0426). EMAST frequency was higher with UC duration >8 years compared with ≤8 years (40% vs 16%, P = 0.0459). Discussion Inflammation-associated microsatellite alterations/EMAST are prevalent in UC and signify genomic mutations in the absence of neoplasia. Duration of disease and advancement to neoplasia increases frequency of EMAST. MSH3 dysfunction is a potential contributory pathway toward neoplasia in UC that could be targeted by therapeutic intervention.

We attempted to establish a magnetic resonance imaging (MRI)-based radiomic model for stratifying prognostic subgroups of newly diagnosed glioblastoma (GBM) patients and predicting O (6)-methylguanine-DNA methyltransferase promotor methylation (pMGMT-met) status of the tumor. Preoperative MRI scans from 201 newly diagnosed GBM patients were included in this study. A total of 489 texture features including the first-order feature, second-order features from 162 datasets, and location data from 182 datasets were collected. Supervised principal component analysis was used for prognostication and predictive modeling for pMGMT-met status was performed based on least absolute shrinkage and selection operator regression. 22 radiomic features that were correlated with prognosis were used to successfully stratify patients into high-risk and low-risk groups (p = 0.004, Log-rank test). The radiomic high- and low-risk stratification and pMGMT status were independent prognostic factors. As a matter of fact, predictive accuracy of the pMGMT methylation status was 67% when modeled by two significant radiomic features. A significant survival difference was observed among the combined high-risk group, combined intermediate-risk group (this group consists of radiomic low risk and pMGMT-unmet or radiomic high risk and pMGMT-met), and combined low-risk group (p = 0.0003, Log-rank test). Radiomics can be used to build a prognostic score for stratifying high- and low-risk GBM, which was an independent prognostic factor from pMGMT methylation status. On the other hand, predictive accuracy of the pMGMT methylation status by radiomic analysis was insufficient for practical use.