Field carcinogenesis and biological significance of the potential of the bystander effect: carcinogenesis, therapeutic response, and tissue regeneration.

The "bystander effect" is a transmission phenomenon mediating communication from target to non-target cells, as well as cell-to-cell interactions between neighboring and distantly located cells. In this narrative review, we describe the fundamental and clinical significance of the bystander effect with respect to cell-to-cell interactions in carcinogenesis, therapeutic response, and tissue regeneration. In carcinogenesis, the bystander effect mediates communications between tumor microenvironments and non-malignant epithelial cells and has been suggested to impact heterogeneous tumorigenic cells in tumors and cancerized fields. In therapeutic response, the bystander effect mediates communications between drug-sensitive and drug-resistant cells and may transmit both drug efficacy and resistance. Therefore, control of therapeutic response transmission via the bystander effect might offer a promising future cancer treatment. Finally, in tissue regeneration, circulating cells and stromal cells may differentiate into various cells for the purpose of tissue regeneration under direction of the bystander effect arising from surrounding cells in a defective space. We hope that the findings we present will promote the development of innovative cancer therapies and tissue regeneration methodologies from the viewpoint of cell-to-cell interactions through the bystander effect.

HLA Class I Expression Is Associated with DNA Damage and Immune Cell Infiltration into Dysplastic and Neoplastic Lesions in Ulcerative Colitis.

Human leukocyte antigen class I (HLA-I) is considered a genetic pathogen for ulcerative colitis (UC). This study aimed to investigate the significance of DNA damage and HLA-I expression in infiltrating immune cells and immune checkpoint protein PD-L1 expression in dysplasia/colitic cancer (CC) and sporadic colorectal cancer (SCRC). We performed immunohistochemical staining for HLA-I, PD-L1, γH2AX (DNA damage marker), and immune cell markers such as CD8, FOXP3, CD68, and CD163 (in surgically resected specimens from 17 SCRC patients with 12 adjacent normal mucosa (NM) and 9 UC patients with 18 dysplasia/CC tumors. The ratio of membrane HLA-I-positive epithelial cells in UC and dysplasia/CC tissues was significantly higher than that in NM and SCRC. High HLA-I expression in dysplasia/CC was associated with high positivity of γH2AX and PD-L1 expression compared to SCRC. The infiltration of CD8-positive T cells and CD68-positive macrophages in HLA-I-high dysplasia/CC was significantly higher than in UC and SCRC. Dysplasia/CC specimens with DNA damage exhibited high levels of HLA-I-positive epithelial cells with high CD8- and CD68-positive immune cell infiltration compared to UC and SCRC specimens. Targeting DNA damage in UC may regulate immune cell infiltration, immune checkpoint proteins, and carcinogenesis by modulating DNA damage-induced HLA-I antigen presentation.

Comprehensive registry of esophageal cancer in Japan, 2015.

BACKGROUND: The registration committee for esophageal cancer in the Japan Esophageal Society (JES) has collected the patients' characteristics, treatment, and outcomes of patients who underwent any treatment during 2015 in Japan. METHODS: We analyzed patients' data who had visited the participating hospitals in 2015. We collected the data using the National Clinical Database with a web-based data collection system. We used the Japanese Classification of Esophageal Cancer 10th edition by JES and the TNM classification by the Union of International Cancer Control (UICC) for cancer staging. RESULTS: A total of 9368 cases were registered from 355 institutions in Japan. Squamous cell carcinoma and adenocarcinoma accounted for 86.7% and 7.4%, respectively. The 5-year survival rates of patients treated by endoscopic resection, concurrent chemoradiotherapy, radiotherapy alone, and esophagectomy were 87.2%, 33.5%, 24.2%, and 59.9%, respectively. Esophagectomy was performed in 5172 cases. Minimally invasive approaches were selected for 60.6%, and 54.4% underwent thoracoscopic esophagectomy. The operative mortality (within 30 days after surgery) was 0.79% and the hospital mortality was 2.3%. The survival curves showed an excellent discriminatory ability both in the clinical and pathologic stages by the JES system. The survival of pStage IV was better than IIIC in the UICC system because pStage IV included the patients with supraclavicular lymph node metastasis (M1 LYM). CONCLUSION: We hope this report improves all aspects of diagnosing and treating esophageal cancer in Japan.

Concurrent chemoradiotherapy using proton beams can reduce cardiopulmonary morbidity in esophageal cancer patients: a systematic review.

This systematic review was performed to investigate the superiority of proton beam therapy (PBT) to photon-based radiotherapy (RT) in treating esophageal cancer patients, especially those with poor cardiopulmonary function. The MEDLINE (PubMed) and ICHUSHI (Japana Centra Revuo Medicina) databases were searched from January 2000 to August 2020 for studies evaluating one end point at least as follows; overall survival, progression-free survival, grade ≥ 3 cardiopulmonary toxicities, dose-volume histograms, or lymphopenia or absolute lymphocyte counts (ALCs) in esophageal cancer patients treated with PBT or photon-based RT. Of 286 selected studies, 23 including 1 randomized control study, 2 propensity matched analyses, and 20 cohort studies were eligible for qualitative review. Overall survival and progression-free survival were better after PBT than after photon-based RT, but the difference was significant in only one of seven studies. The rate of grade 3 cardiopulmonary toxicities was lower after PBT (0-13%) than after photon-based RT (7.1-30.3%). Dose-volume histograms revealed better results for PBT than photon-based RT. Three of four reports evaluating the ALC demonstrated a significantly higher ALC after PBT than after photon-based RT. Our review found that PBT resulted in a favorable trend in the survival rate and had an excellent dose distribution, contributing to reduced cardiopulmonary toxicities and a maintained number of lymphocytes. These results warrant novel prospective trials to validate the clinical evidence.

Decreased numbers of gastric, colorectal, lung, and breast cancer surgeries performed in 17 cancer-designated hospitals in Gunma Prefecture of Japan during the COVID-19 pandemic.

PURPOSE: This study aims to clarify the influence of the COVID-19 pandemic on cancer surgery in Gunma Prefecture. METHODS: A total of 9839 cases (1406 gastric cancer, 3569 colorectal cancer, 1614 lung cancer, and 3250 breast cancer) from 17 hospitals in Gunma Prefecture were investigated. We compared the number of surgical cases, proportion of cases found by screening, and cStage at the time of the first visit by month in 2020 and 2021 with those in 2019. RESULTS: The rate of decline in cancer surgery was 8.9% in 2020 compared with 2019 (p = 0.0052). Compared with the same month of 2019, in some months of 2020 and 2021, significant decreases were observed in the number of surgeries for gastric and colorectal cancer, the percentage of surgical cases detected by screening in all four cancers, and the proportion of cancers with a relatively early cStage in gastric and breast cancer. CONCLUSIONS: The number of surgical cases of the four cancer types detected by cancer screening decreased in Gunma Prefecture owing to the influence of the COVID-19 pandemic. Furthermore, for some cancer types, the number of operations performed in patients with early-stage cancer is also decreased.

Coolant Wetting Simulation on Simplified Stator Coil Model by the Phase-Field Lattice Boltzmann Method.

Stator coils of automobiles in operation generate heat and are cooled by coolant poured from above. The flow characteristic of the coolant depends on the coil structure, flow condition, solid-fluid interaction, and fluid property, which has not been clarified due to its complexities. Since straight coils are aligned and layered with an angle at the coolant-touchdown region, the coil structure is simplified to a horizontal square rod array referring to an actual coil size. To obtain the flow and wetting characteristics, two-phase fluid flow simulations are conducted by using the phase-field lattice Boltzmann method. First, the flow onto the single-layered rod array is discussed. The wetting area is affected both by the rod gap and the wettability, which is normalized by the gap and the averaged boundary layer thickness. Then, the flow onto the multi-layered rod arrays is investigated with different rod gaps. The top layer wetting becomes longitudinal due to the reduction of the flow advection by the second layer. The wetting area jumps up at the second layer and increases proportionally to the below layers. These become remarkable at the narrow rod gap case, and finally, the dimensionless wetting area is discussed at each layer.

Current status of surgical treatment of Boerhaave's syndrome.

BACKGROUND: Surgical treatment is usually required for Boerhaave's syndrome (post-emetic esophageal perforation), and the technique should be chosen based on the local infection status and patient's general condition. This study was performed to examine the current status of surgical treatment of Boerhaave's syndrome in Japan. METHODS: Ninety-five patients with Boerhaave's syndrome who underwent surgical treatment from January 2010 to December 2015, obtained from a national survey were retrospectively analyzed. The details of each surgical treatment and the type of treatment performed according to the patients' characteristics were examined. RESULTS: Primary closure was performed in 75 (78.9%) patients, T-tube insertion in 15 (15.8%), and esophagectomy in 5 (5.3%). The length of the postoperative stay was significantly shorter in patients who underwent primary closure (p = 0.0011). Esophagectomy tended to be performed more often in patients with a long perforation and was performed significantly more often in patients with a high C-reactive protein concentration (p = 0.0118). The postoperative hospital stay was significantly longer in patients with leakage of the primary closure site (p < 0.0001). As a result, leakage of the primary closure site was significantly correlated with a long duration from symptom onset to patient presentation (p = 0.042), diagnostic imaging of the intrathoracic perforation (p = 0.013), and abscess formation in the mediastinal cavity (p = 0.006). CONCLUSIONS: Selection of an appropriate surgical procedure may contribute to reduced mortality rates in patients with esophageal rupture. With regard to primary closure, it is necessary to understand that leaks are likely to occur in patients with a long duration from symptom onset to presentation or with severe intrathoracic/mediastinal inflammation, and to select an appropriate surgical procedure in consideration of the degree of invasiveness and QOL.

Endoscopic imaging modalities for diagnosing the invasion depth of superficial esophageal squamous cell carcinoma: a systematic review.

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.

The potential for reducing alcohol consumption to prevent esophageal cancer morbidity in Asian heavy drinkers: a systematic review and meta-analysis.

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.

Fruit and vegetable consumption and risk of esophageal cancer in the Asian region: a systematic review and meta-analysis.

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, I2 statistics were used to detect heterogeneity. Twenty-two studies were eligible for meta-analysis (16 case-control studies and 6 cohort studies). The SRR for the lowest versus highest fruit consumption was 0.64 (95% CI 0.53-0.77, I2 = 82%). That for the lowest versus highest vegetable consumption was 0.61 (95% CI 0.50-0.74, I2 = 81%). Based on subgroup analysis, a validated Food Frequency Questionnaire (FFQ) was significantly associated (SRR for fruit: 0.54; 95% CI 0.40-0.74, SRR for vegetable: 0.60; 95% CI 0.48-0.76) with low heterogeneity (I2 = 48% for fruit, I2 = 0% for vegetables). Egger's funnel plot asymmetry test demonstrated publication bias (P < 0.001 for fruit, P = 0.009 for vegetables). Fruit and vegetable consumption might be associated with a lower risk of EC in the Asian region. However, further substantial prospective studies with a validated FFQ and well-controlled important confounding factors are required to confirm the association.

Diagnostic Immunostaining and Tumor Markers Predict the Prognosis of Esophageal Neuroendocrine Cell Carcinoma Patients.

BACKGROUND: Esophageal neuroendocrine carcinoma (ENEC) has a poor prognosis, and predicting the prognosis by examining various markers may contribute to the determination of treatment strategies. Therefore, a multiple-institution retrospective study was performed to identify biomarkers using diagnostic immunohistochemistry and serum tumor markers that predict the prognosis of patients with ENEC. METHODS: The results of immunohistochemical examination and serum tumor markers were extracted from the data of 141 ENEC patients at 39 institutions certified by the Japan Esophageal Society. The study then examined correlations between these data and prognosis or treatment effects. RESULTS: The ENEC patients with positively for all expression of synaptophysin (Syn), chromogranin A (CgA), and CD56 had a significantly worse prognosis than the patients with other expression patterns. Additionally, surgery and chemoradiotherapy were significantly more effective treatments than chemotherapy for the patients who were not positive for all expressions of Syn, CgA, and CD56. In terms of serum tumor markers, the patients with a high neuron-specific enolase (NSE) value had a significantly worse prognosis than the patients with a normal NSE value, and complete response (CR) cases treated with chemotherapy were significantly fewer in the high-NSE group. The results of multivariate analysis demonstrated that high NSE levels were an independent poor prognostic factor for esophageal endocrine cell carcinoma. CONCLUSION: This study showed that positivity for all expressions of Syn, CgA, and CD56, and a high NSE value were significantly worse prognostic factors for ENEC patients than other expression patterns and may be important prognostic biomarkers of ENEC.

CD36 Expression Is Associated with Cancer Aggressiveness and Energy Source in Esophageal Squamous Cell Carcinoma.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) is an important cause of cancer-related death worldwide. CD36, a long-chain fatty acid (FA) receptor, can initiate metastasis in human oral squamous cell carcinoma (SCC), and its expression is associated with poor prognosis in several cancers. The clinical significance of CD36 expression and its function in ESCC remain unknown. METHODS: We examined the clinical significance of CD36 expression in 160 ESCC samples using immunohistochemical staining. Functional analysis was performed to determine the association between CD36 and ESCC characteristics (proliferative ability, invasive ability, and energy source dependency). RESULTS: Thirty (18.8%) ESCC cases showed high CD36 expression, indicating a significant association with progression. CD36 suppression inhibited proliferation and invasiveness in ESCC cells. ESCC cells with CD36 suppression used specific essential amino acids (EAAs) as energy sources. Cell viability depended on FAs under CD36 expression. The viability of ESCC cells with CD36 suppression depended on EAAs but not FAs. CONCLUSIONS: CD36 may be a good biomarker and therapeutic target in ESCC. Our data provide new insights into the basic mechanism of CD36-dependent energy utilization for ESCC survival. CD36 might be a key regulator of the dependency of FAs as energy source in ESCC cells.

Clinical features of idiopathic esophageal perforation compared with typical post-emetic type: a newly proposed subtype in Boerhaave's syndrome.

BACKGROUND: n our previous nationwide survey report on esophageal perforation, we proposed the existence of cases with idiopathic esophageal perforation at a certain rate. AIMS: To elucidate the clinical characteristics of idiopathic esophageal perforation, we performed a comparative analysis between cases with idiopathic type and post-emetic type esophageal perforation. METHODS: This study enrolled 139 patients with esophageal perforation (post-emetic type: idiopathic type = 115:24) as the subjects of nationwide survey on esophageal perforation. We conducted detailed studies on chief complaints, inflammatory responses, initial diagnosis, location and situation of the perforation site, time to therapeutic intervention, and prognosis between the two groups. RESULTS: Compared with post-emetic type, cases of idiopathic type tended to exhibit rear-side perforation (p = 0.052) and significantly less presented chest pain (p = 0.002). Consequently, cases of idiopathic type significantly missed to diagnose as esophageal perforation compared with post-emetic type (p = 0.042). With regard to inflammatory response, cases of post-emetic type experienced hyperthermia compared with idiopathic type (p = 0.033). On the other hand, cases of idiopathic type exhibited significantly higher level of C-reactive protein than post-emetic type (p = 0.004). In addition, it took longer time until starting treatment in the cases of idiopathic type (p < 0.0001) and the cases of idiopathic type showed significantly worse prognosis than the cases of post-emetic type (p = 0.009). CONCLUSION: This study first focused on the characteristics of idiopathic esophageal perforation that have been included in so-called Boerhaave's syndrome. The pathophysiology of the idiopathic type should be separately understood from post-emetic type, because the diagnostic and prognostic features largely differ.

A nationwide survey on esophageal gastrointestinal stromal tumors at accredited institutions by the Japan Esophageal Society.

BACKGROUND: As esophageal gastrointestinal stromal tumors (GISTs) are very rare, their clinicopathological features remain obscure. We conducted a nationwide survey to clarify the characteristics of these tumors and to establish a consensus on their diagnosis and treatment. METHODS: The clinicopathological information of patients with esophageal GISTs who underwent treatment between January 2010 and June 2016 at the accredited institutions by the Japan Esophageal Society was collected via a questionnaire method and analyzed statistically. RESULTS: Fifty-one patients (29 men and 22 women; median age, 68 years) were recruited from 31 institutions. Diagnosis was triggered most frequently during screening and other disease scrutiny. Symptoms were seen only in 17 patients: highest in 11 patients with dysphagia. Thirty-five patients underwent surgery alone; 15 patients, surgery with imatinib therapy; and one patient, endoscopic resection. The tumors preferentially occurred in the lower and middle parts of the thoracic esophagus, with a median size of 36.5 mm. Neoadjuvant and adjuvant imatinib therapies were performed in seven and eight patients, respectively. Administration of imatinib 400 mg/day was the standard regimen. Postoperative follow-up observations were conducted mostly via computed tomography (CT) scans every 3 or 6 months until 5 years after surgery. The tumors recurred in ten patients within 5 years postoperatively (high risk, 38.5%; intermediate risk, 20%; low risk, 0%; very low risk, 0%; three cases of relapse with an unknown risk assessment). A patient with a high-risk GIST died from the tumor 54 months after surgery. CONCLUSIONS: This nationwide survey revealed the current status of esophageal GISTs in Japan and provided important information for making a consensus on the treatment and follow-up method.

Pathophysiology of Vomiting and Esophageal Perforation in Boerhaave's Syndrome.

BACKGROUND AND AIMS: Boerhaave's syndrome, involving esophagus rupture, is considered a pathological response to vomiting that may occur just before perforation. However, the mechanism of vomiting and occurrence of this disease have not been clearly demonstrated. METHODS: We identified patients with esophageal perforation between 1995 and 2017 and reviewed endoscopic findings at retching during upper gastrointestinal endoscopy. Finally, we proposed a theory for the underlying pathological mechanism. RESULTS: We retrospectively investigated 10 patients with esophageal perforation between 1995 and 2017. All patients presented after vomiting associated with large volumes of food and alcohol intake. Nine were treated by primary closure of the perforation and drainage of the thoracic cavity, and one was conservatively treated. In all cases, the perforations were longitudinal tears (1-4 cm) and located in the left of the esophagus, just above the gastric cardia. CONCLUSIONS: We hypothesize that vomiting occurred by retrograde propagation of gastrointestinal motor contraction from the jejunum to the gastric antrum, followed by prolapse of the gastric fornix mucosal into the esophagus. Subsequent esophageal perforation probably resulted from excessive prolapse due to strong contraction and destruction of the muscularis mucosa of the left side of abdominal esophagus, with longitudinal stretching of the whole left esophageal wall due to traction. We also propose that Boerhaave's syndrome is defined as "post-emetic esophageal perforation" to ensure broader recognition and more expedient diagnosis and treatment. Remaining conditions without any definite causes may be labeled "idiopathic" or "spontaneous" rupture of the esophagus.

A national survey on esophageal perforation: study of cases at accredited institutions by the Japanese Esophagus Society.

OBJECTIVE: To get a clear view of the current state of treatment for esophageal perforation in Japan. Esophagus perforations are the most serious gastrointestinal tract perforations and are associated with high morbidity and mortality. The optimal treatment choice remains unknown. METHODS: We conducted a retrospective clinical review of 182 esophageal perforation cases at 108 hospitals accredited by the Japanese Esophageal Society between January 2010 and December 2015. RESULTS: We found that 20.9% of patients were incorrectly diagnosed initially. We observed mediastinum emphysema in 83.5% of patients, and serious abscess formations of the mediastinum and intrathoracic cavity in 38.6% and 29.6%, respectively. The lower esophagus was the most commonly perforated site (77.7%). Management of esophageal perforations included nonoperative treatment in 20 patients (11%) and operative treatment in 162 patients (89%). The overall mortality rate was 6.9%. The survivors had significantly shorter times from symptom appearance to visit (p = 0.0016), and from time to visit to diagnosis confirmation (p = 0.0011). Moreover, patients older than 65 years, white blood cells less than 3000/mm3, C-reactive protein > 10 mg/L, or abscesses in the thoracic cavity showed significantly higher mortality than others. CONCLUSION: Shortening the time from onset to the start of treatment contributes to reduce mortality in patients with esophageal perforation. Moreover, strict medical treatment is necessary to lower the mortality rate of elderly patients with strong inflammation and abscesses in the thoracic cavity.

Demonstration of PAM4-OCDM system with electrical amplitude-level pre-tuning and post-equalization for data centers applications.

A PAM4-OCDM system with optical multi-/demultiplexing and electrical pre-/post-processing is proposed for short-reach applications. We experimentally demonstrate, for the first time, a power-efficient 4 OC x 10 GSymbol/s PAM4-OCDM system. The four PSK-OCs are simultaneously generated using a single light source and a passive multiport optical encoder and received by a single optical decoder and cascaded DSP. The effectiveness of the electrical-domain amplitude level pre-tuning and post-equalizer are demonstrated, considering different values of shot and beat noises.

Elucidation of the Anatomical Mechanism of Nodal Skip Metastasis in Superficial Thoracic Esophageal Squamous Cell Carcinoma.

BACKGROUND: Lymph node metastasis (LNM) is a standard mechanism of cancer progression in esophageal squamous cell carcinoma (ESCC). We aimed to clarify the anatomical mechanism of skip nodal metastasis to mediastinal zones by analyzing the relationship between LNM to sentinel zones and lymphatic vessel counts in the muscle layer adjacent to the outer esophagus. METHODS: We examined the surgical records of 287 patients with ESCC who underwent potentially curative surgery (three-field lymphadenectomy) and whole esophagi, including pharynges and stomachs from 10 cadavers, to determine the number of lymphatic vessels in the intra-outer longitudinal muscle layer adjacent to the outer esophagus of the cervical (Ce), upper thoracic, middle thoracic (Mt), lower thoracic (Lt), and abdominal esophagi (Ae). RESULTS: The frequency of LNM to the middle mediastinal and supraclavicular zones, including the Mt and Ce, respectively, was lower than to the upper and lower mediastinal and abdominal zone in patients with superficial and advanced thoracic ESCC. In cadavers, the lymphatic vessel counts of the intra-outer longitudinal muscle layer in the Mt and Ce were significantly lower than those of the Lt and Ae, suggesting that lymphatic flow toward the outside of the Mt and Ce was not more abundant than to other sites. CONCLUSION: Our anatomical data suggested that the absence of intra-muscle lymphatic vessels in the middle mediastinal and supraclavicular zones causes skip LNM in patients with thoracic ESCC. Thus, standard esophagectomy with lymph node dissection, including distant zones, may be appropriate for treating patients with superficial thoracic ESCC.

Collective compensation of an inter-chip intensity discrepancy for a 4ch QPSK FE-SOCDM system with Si-based ODFT and electrical DFT.

An intensity-sloped optical code with an optical chip-pulse stream generated by Si-based ODFT suffers from crosstalk and signal-to-noise (SNR) degradation. To mitigate these problems related to code-orthogonality reduction, we propose a simple intensity-discrepancy-compensation scheme that involves adjusting the chip-level intensity in the digital-domain. We numerically show a 0.1 dB SNR improvement for 40 Gb/s quadrature phase-shift keying (QPSK) Fourier-encoded synchronized optical code division multiplexing (FE-SOCDM) signal when multiplexing 1 dB/chip intensity-sloped optical codes. A proof-of-principle experiment achieves a 0.3 dB received power improvement using intensity-discrepancy compensation for two optical code multiplexing signals with 1.5 dB/chip.

Correlation between high FBXW7 expression in pretreatment biopsy specimens and good response to chemoradiation therapy in patients with locally advanced esophageal cancer: A retrospective study.

BACKGROUND AND OBJECTIVES: Esophageal squamous cell carcinoma (ESCC) exhibits good reactivity to chemoradiation therapy (CRT). The dysregulation of F-Box and WD Repeat Domain Containing 7 (FBXW7) is associated with therapeutic resistance in cancer cells. However, the correlation between FBXW7 expression and CRT sensitivity in patients with clinical ESCC has been investigated only in few studies. Therefore, this study aimed to elucidate the significance of FBXW7 expression in pretreatment biopsy specimens from patients with ESCC receiving CRT. METHODS: We investigated the relationship between FBXW7 expression and CRT sensitivity in 30 pretreatment biopsy specimens with histological grades of post-CRT surgically resected tumors. Furthermore, we evaluated the effects of high FBXW7 expression on the sensitivity to cytotoxic agents, including docetaxel and nedaplatin, and radiation in ESCC cells in vitro. RESULTS: High FBXW7 expression before CRT correlated with a good pathological CRT response in patients with advanced ESCC (P < .05). Further, our in vitro data showed that both chemo and radiation sensitivity increased in TE-8 and KYSE140 cells overexpressing FBXW7 compared with mock cells because of the degradation of the anti-apoptotic protein MCL1. CONCLUSIONS: The evaluation of FBXW7 expression before CRT treatment is a potential predictor of good responders among patients with ESCC receiving CRT.