Validation of the cutoff values for the number of metastatic lymph nodes for esophageal cancer staging: a multi-institutional analysis of 655 patients in Japan.

BACKGROUND: The number of metastatic lymph nodes (LNs) is an important prognostic factor for esophageal cancer, and N staging is important for prognostic stratification. The optimal cutoff values for clinical (cN) and pathologic N (pN) staging should be reconsidered following advances in neoadjuvant therapy. METHODS: The study included 655 patients who underwent esophagectomy between January 2014 and December 2016 in four high-volume centers in Japan. Optimal cutoff values for the number of metastatic LNs in cN and pN staging were examined using X-tile, and their prognostic performance was validated using the Kaplan-Meier method. RESULTS: The cutoff values were 1, 2, and 3 for cN staging and 1, 3, and 7 for pN staging. Prognosis was significantly better in patients with cN0 than in those with modified (m)-cN1 (p = 0.0211). However, prognosis was not significantly different among the patients with m-cN1, m-cN2, and m-cN3 disease. Prognosis was significantly different among the patients with pN0, pN1, pN2, and pN3 disease (pN0 vs pN1, p < 0.0001; pN1 vs pN2, p < 0.0001; pN2 vs pN3, p < 0.0001). In patients who received preoperative neoadjuvant therapy, prognosis, which was not significantly different among the patients with cN0, m-cN1, m-cN2, and m-cN3 disease (cN0 vs m-cN1, p = 0.5675; m-cN1 vs m-cN2, p = 0.4425; m-cN2 vs m-cN3, p = 0.7111), was significantly different among the patients with pN0, pN1, pN2, and pN3 disease (pN0 vs pN1, p = 0.0025; pN1 vs pN2, p = 0.0046; pN2 vs pN3, p = 0.0104). CONCLUSIONS: cN has no prognostic impact in patients who underwent preoperative treatment followed by esophagectomy, despite the optimization of cN classification. The conventional TNM8th pN classification is useful for predicting prognosis even for patients who have undergone preoperative treatment. The conventional cutoffs for metastatic LNs in the International Union against Cancer tumor node metastasis staging system are valid and can be effectively used in clinical practice.

Surgical outcomes of reconstruction using the gastric tube and free jejunum for cervical esophageal cancer: analysis using the National Clinical Database of Japan.

BACKGROUND: Cervical esophageal cancer accounts for a small proportion of all esophageal cancers. Therefore, studies examining this cancer include a small patient cohort. Most patients with cervical esophageal cancer undergo reconstruction using a gastric tube or free jejunum after esophagectomy. We examined the current status of postoperative morbidity and mortality of cervical esophageal cancer based on big data. METHODS: Based on the Japan National Clinical Database, 807 surgically treated patients with cervical esophageal cancer were enrolled between January 1, 2016, and December 31, 2019. Surgical outcomes were retrospectively reviewed for each reconstructed organ using gastric tubes and free jejunum. RESULTS: The incidence of postoperative complications related to reconstructed organs was higher in the gastric tube reconstruction (17.9%) than in the free jejunum (6.7%) for anastomotic leakage (p < 0.01), but not significantly different for reconstructed organ necrosis (0.4% and 0.3%, respectively). The incidence rates of overall morbidity, pneumonia, 30-day reoperation, tracheal necrosis, and 30-day mortality using these reconstruction methods were 64.7% and 59.7%, 16.7% and 11.1%, 9.3% and 11.4%, 2.2% and 1.6%, and 1.2% and 0.0%, respectively. Only pneumonia was more common in the gastric tube reconstruction group (p = 0.03), but was not significantly different for any other complication. CONCLUSIONS: The incidence of overall morbidities and reoperation, especially anastomotic leakage after gastric tube reconstruction, suggested a necessity for further improvement. However, the incidence of fatal complications, such as tracheal necrosis or reconstructed organ necrosis, was low for both reconstruction methods, and the mortality rate was acceptable as a means of radical treatment.

Prognostic impact of carcinoembryonic antigen in 1822 surgically treated esophageal squamous cell carcinoma: multi-institutional study of the Japan Esophageal Society.

BACKGROUND: Previous studies have evaluated the clinicopathological significance of carcinoembryonic antigen (CEA) of esophageal cancer in relatively small numbers of patients. Therefore, this study aimed to clarify the prognostic significance of CEA in 1822 patients with esophageal squamous cell carcinoma (SCC). METHODS: Based on the Japanese Esophageal Society nationwide multi-institutional retrospective study, a total of 1,748 surgically treated ESCC from 15 hospitals were enrolled to evaluate prognostic impact of preoperative CEA values. Among them, 605 patients were categorized to up-front surgery group, and 1,217 patients were categorized to neoadjuvant therapy group. The CEA threshold for positivity was 3.7 ng/ml. The clinicopathological and prognostic impact of CEA was evaluated by univariate and multivariate analysis in each treatment modality groups. RESULTS: In total, the CEA positive rate was 25.8% (470/1822). CEA-positive status was significantly associated with distant metastasis (P = 0.004) but not associated with other factors. CEA-positive status was associated with poor overall survival (P < 0.001) in univariate analysis as well as multivariate analysis (P = 0.003). CONCLUSIONS: CEA was an independent prognostic determinant of overall survival in esophageal SCC. Based on the subgroup analysis, regardless of the treatment modality, patients with high pretreatment CEA showed poor overall survival.

A survey of the clinical outcomes of cervical esophageal carcinoma surgery focusing on the presence or absence of laryngectomy using the National Clinical Database in Japan.

BACKGROUND: One upside of cervical esophageal carcinoma is that radical surgery can be performed by laryngectomy, even for tumors with tracheal invasion. However, this approach drastically reduces the quality of life, such as by losing the vocal function. Cervical esophageal carcinoma is rare, and no comprehensive reports have described the current state of surgery. Using a Japanese nationwide web-based database, we analyzed the surgical outcomes of cervical esophageal carcinoma to evaluate the impact of larynx-preserving surgery. METHODS: Based on the Japan National Clinical Database, 215 surgically treated cases of cervical esophageal carcinoma between January 1, 2018, and December 31, 2019, were enrolled. Clinical outcomes were compared between the larynx-preserved group and the laryngectomy group. RESULTS: Ninety-four (43.7%) patients underwent larynx-preserving surgery. A total of 177 (82.3%) patients underwent free jejunum reconstruction. More T4b patients and more patients who underwent preoperative radiotherapy were in the laryngectomy group. There were no significant differences in the frequency and the severity of morbidities between the two groups. However, in the laryngectomy group, in-hospital death within 30 days after surgery was observed in 1 patient, and the postoperative hospital stay was significantly longer (P = 0.030). In the larynx-preserved group, recurrent nerve paralysis was observed in 24.5%. Re-operation (35.3%, P = 0.016), re-intubation (17.6%, P = 0.019) and tracheal necrosis (17.6%, P = 0.028) were significantly more frequent in patients who underwent pharyngolaryngectomy with total esophagectomy and gastric tube reconstruction than in others. CONCLUSION: Larynx-preserving surgery was therefore considered to be feasible because it was equivalent to laryngectomy regarding the short-term surgical outcomes.

Identification of PDHX as a metabolic target for esophageal squamous cell carcinoma.

The metabolism in tumors is reprogrammed to meet its energetic and substrate demands. However, this metabolic reprogramming creates metabolic vulnerabilities, providing new opportunities for cancer therapy. Metabolic vulnerability as a therapeutic target in esophageal squamous cell carcinoma (ESCC) has not been adequately clarified. Here, we identified pyruvate dehydrogenase (PDH) component X (PDHX) as a metabolically essential gene for the cell growth of ESCC. PDHX expression was required for the maintenance of PDH activity and the production of ATP, and its knockdown inhibited the proliferation of cancer stem cells (CSCs) and in vivo tumor growth. PDHX was concurrently upregulated with the CD44 gene, a marker of CSCs, by co-amplification at 11p13 in ESCC tumors and these genes coordinately functioned in cancer stemness. Furthermore, CPI-613, a PDH inhibitor, inhibited the proliferation of CSCs in vitro and the growth of ESCC xenograft tumors in vivo. Thus, our study provides new insights related to the development of novel therapeutic strategies for ESCC by targeting the PDH complex-associated metabolic vulnerability.

Oral infectious bacteria in dental plaque and saliva as risk factors in patients with esophageal cancer.

BACKGROUND: High levels of periodontopathic bacteria as well as Streptococcus anginosus were detected in cancer tissue from patients with esophageal cancer. An association between oral infectious bacteria and esophageal cancer has been reported. METHODS: Characteristics of the oral microbiota and periodontal conditions were studied as clinicopathologic factors in patients with esophageal cancer. The study included 61 patients with esophageal cancer and 62 matched individuals without any cancers. Samples of subgingival dental plaque and unstimulated saliva were collected to evaluate the prevalence and abundance of the following oral bacteria using a real-time polymerase chain reaction assay: Aggregatibacter actinomycetemcomitans, Fusobacterium nucleatum, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia, Treponema denticola, and S. anginosus. RESULTS: In the cancer group, the prevalence of all bacteria, with the exception of F. nucleatum, in dental plaque; the prevalence of A. actinomycetemcomitans in saliva; the abundance of all bacteria, with the exception of F. nucleatum and P. intermedia, in dental plaque; and the abundance of A. actinomycetemcomitans and S. anginosus in saliva were significantly higher. Furthermore, a logistic regression analysis suggested that the prevalence of T. forsythia and S. anginosus in dental plaque and of A. actinomycetemcomitans in saliva, as well as a drinking habit, were associated with a high risk of esophageal cancer, with a high odds ratio. CONCLUSIONS: The current findings have potential implications for the early diagnosis of esophageal cancer.

New Assay System Elecsys Anti-p53 to Detect Serum Anti-p53 Antibodies in Esophageal Cancer Patients and Colorectal Cancer Patients: Multi-institutional Study.

BACKGROUND: Several recent studies suggest that serum anti-p53 antibodies (s-p53-Abs) may be combined with other markers to detect esophageal and colorectal cancer. In this study, we assessed the sensitivity and specificity of s-p53-Abs detection of a new electrochemiluminescence immunoassay (ECLIA; Elecsys anti-p53). METHODS: Elecsys anti-p53 assay was used to analyze the level of s-p53-Abs in blood sera from patients with esophageal or colorectal cancer taken before treatment. Control blood sera from healthy volunteers, patients with benign diseases, and patients with autoimmune diseases served as a reference. In addition, squamous cell carcinoma antigen (SCC-Ag) and cytokeratin 19 fragments (CYFRA21-1) were assessed in patients with esophageal cancer, and carcinoembryonic antigen (CEA) and carbohydrate antigen (CA) 19-9 were assessed in patients with colorectal cancer. RESULTS: Samples from 281 patients with esophageal cancer, 232 patients with colorectal cancer, and 532 controls were included in the study. The median value of s-p53-Abs in control samples was < 0.02 µg/mL (range < 0.02-29.2 µg/mL). Assuming 98% specificity, the cut-off value was determined as 0.05 µg/mL. s-p53-Abs were detected in 20% (57/281) of patients with esophageal cancer and 18% (42/232) of patients with colorectal cancer. In combination with SCC-Ag and CEA, respectively, s-p53-Abs detected 51% (144/281) of patients with esophageal and 53% (124/232) of patients with colorectal cancer. CONCLUSIONS: The new s-p53-Abs assay Elecsys anti-p53 was useful in detecting esophageal and colorectal cancers with high specificity. Adding s-p53-Abs to conventional markers significantly improved the overall detection rates.

Molecular motion in the nanospace of MOFs upon gas adsorption investigated by in situ Raman spectroscopy.

Molecular motions taking place in the nanospace of metal-organic frameworks (MOFs) are an interesting research subject, although not yet fully investigated. In this work, we utilized in situ Raman spectroscopy in the ultralow-frequency region to investigate the libration motion (including the rotational motion of phenylene rings) of MOFs, in particular [Cu2(bdc)2(dabco)] (Cu-JAST-1), where bdc = 1,4-benzenedicarboxylate and dabco = 1,4-diazabicyclo[2.2.2]octane. The libration mode of Cu-JAST-1 was found to be significantly suppressed by the adsorption of various guest molecules, such as CO2, Ar, and N2. In addition, an appreciable correlation between the libration mode and adsorption equilibrium time was identified, which provides useful novel tools in the design of MOFs acting as molecular adsorption and separation materials.

Histological changes in the human esophagus following triamcinolone injection to prevent esophageal stricture after endoscopic submucosal dissection.

BACKGROUND: Locoregional steroid injection prevents post-endoscopic submucosal dissection (ESD) esophageal stricture, but histological changes that occur following steroid injection in the human esophagus are unclear. This study investigated the histopathological characteristics caused by locoregional triamcinolone acetonide (TA) injection using human esophagectomy specimens. METHODS: From January 2014 to December 2019, among 297 patients (373 lesions) who underwent esophageal ESD, 13 patients who underwent additional esophagectomy after ESD were examined. Seven patients (TA group) with wide excisions were injected with TA after ESD and another six patients (Non-TA group) with smaller tumors were not injected with TA. The clinical background of these patients and histopathological features of ESD ulcer scar obtained from esophagectomy specimens were retrospectively investigated. RESULTS: The circumferential rate of ESD excision was more than three-quarters in all cases in the TA group, whereas it was less than three-quarters in the Non-TA group. No other statistical difference in the clinical background was found between the two groups. The subepithelial fibrous tissue of the ESD ulcer scar in the TA group was significantly thinner than that in the Non-TA group (P < 0.05). There was no significant difference in the thickness of the regenerated epithelium and muscularis propria layer of the ESD ulcer scar. CONCLUSIONS: Histological finding of thinning of the subepithelial fibrous tissue of ESD ulcer scar in the human esophagus after TA injection was obtained. This suggests that TA suppresses the proliferation of the fibrous tissue of the subepithelial layer to help prevent esophageal stricture after widespread ESD in the human esophagus.

Feasibility and Safety of Early Oral Intake and Discharge After Total or Proximal Gastrectomy: An Analysis of Consecutive Cases Without Exclusion Criteria.

BACKGROUND: Postoperative feeding is administered relatively early in gastric surgery, especially distal gastrectomy, but its feasibility and safety for proximal gastric surgery remains unclear. METHODS: We retrospectively analyzed 91 consecutive patients who underwent total or proximal gastrectomy between 2014 and 2019. Baseline and perioperative results were prospectively recorded in our dataset. In our clinical pathway, sips of water and a soft diet were allowed on postoperative days 1 and 3. Discharge was set at days 6-8, and clinical pathway completion was defined as discharge by postoperative day 8. RESULTS: Median patient age was 69 years, and 25 patients (27%) were aged ≥ 75 years. Fifty-nine patients (65%) had comorbidities. Esophageal involvement occurred in 12 patients (13%), and there were 28 cases (31%) of pathological stage IA. The open approach was applied in 22 patients (24%), laparoscopy was applied in 53 patients (58%), and the robotic approach was applied in 16 patients (18%). Total gastrectomy was performed in 56 patients (62%) and proximal gastrectomy was performed in 35 patients (38%). Overall and severe (Clavien-Dindo grade III or higher) complications occurred in 24 (26%) and 9 (10%) patients, respectively. There were four cases (4%) of esophagojejunal leakage (three with esophagogastric junction cancer, one with long-term corticosteroid use). Clinical pathway completion was achieved in 66 patients (73%), with readmission of five cases (5%). CONCLUSIONS: Early feeding and discharge for total or proximal gastrectomy is feasible and safe as long as it is carefully applied to high-risk patients, but we must be aware of the relatively higher readmission rate of this patient group.

The Impact of Hybrid Minimally Invasive Esophagectomy with Neck-Abdominal First Approach on the Short- and Long-Term Outcomes for Esophageal Squamous Cell Carcinoma.

BACKGROUND: Currently, there is no consensus for an optimal minimally invasive esophagectomy (MIE) approach. This study aimed to compare hybrid MIE (hMIE) with neck-abdominal first approach to standard open esophagectomy (OE). METHODS: Data from a cohort of 301 patients were retrospectively analyzed. All participants received either hMIE or OE for the treatment of esophageal squamous cell carcinoma at Tokyo Medical and Dental University between January 2003 and December 2013. Analyses included propensity score matching and the Kaplan-Meier statistical method to determine overall survival (OS) and disease-free survival (DFS) of the cohort. RESULTS: After one-to-one propensity score matching, there were 68 patient pairs. The hMIE group had significantly lower incidence of severe postoperative complications (20.1% vs. 7.4%; p = 0.026) and severe respiratory complications (7.4% vs. 0%; p = 0.058) than the OE group. The 5-year oncological outcomes of the two groups were almost equivalent (OS: OE, 55.0%; hMIE, 69.0%; p = 0.063 and DFS: OE, 54.0%; hMIE, 62.0%; p = 0.28). CONCLUSIONS: This study compared hMIE with neck-abdominal first approach to standard OE. The results showed significantly less severe postoperative complications for hMIE with neck-abdominal first approach in comparison with OE, without a compromise in long-term oncological outcomes.

Correction to: Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives.

The article Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives, written by Masanori Tokunaga, Yuya Sato, Masatoshi Nakagawa, Tomoki Aburatani, Takatoshi Matsuyama, Yasuaki Nakajima and Yusuke Kinugasa was originally published Online First without Open Access.

Perioperative chemotherapy for locally advanced gastric cancer in Japan: current and future perspectives.

The standard treatment for locally advanced gastric cancer differs across the world. In western countries, perioperative chemotherapy or postoperative adjuvant chemoradiotherapy are the preferred treatment options, whereas in Asia, D2 gastrectomy followed by postoperative adjuvant chemotherapy is standard. In Japan, adjuvant chemotherapy with S-1 is the standard treatment for pStage II gastric cancer, whereas adjuvant chemotherapy with a doublet regimen is preferred for pStage III gastric cancer. The efficacy of preoperative neoadjuvant chemotherapy using S-1 plus cisplatin, has been investigated in selected patients with expected poor survival outcomes. To expand the indications for neoadjuvant chemotherapy, a clinical trial investigating the efficacy of preoperative S-1 plus oxaliplatin in patients with cStage III (cT3-4N1-3) gastric cancer (JCOG1509) is ongoing in Japan. The addition of immune checkpoint inhibitors to cytotoxic chemotherapy also seems promising and is being investigated in international randomized clinical trials. Although we have to await the final results of these studies, preoperative neoadjuvant chemotherapy is a promising treatment strategy and likely to become standard treatment for locally advanced gastric cancer in Japan.

CHAC1 overexpression in human gastric parietal cells with Helicobacter pylori infection in the secretory canaliculi.

BACKGROUND: Cation transport regulator 1 (CHAC1), a newly discovered enzyme that degrades glutathione, is induced in Helicobacter pylori (H. pylori)-infected gastric epithelial cells in culture. The CHAC1-induced decrease in glutathione leads to an accumulation of reactive oxygen species and somatic mutations in TP53. We evaluated the possible correlation between H. pylori infection and CHAC1 expression in human gastric mucosa. MATERIALS AND METHODS: Both fresh-frozen and formalin-fixed paraffin-embedded tissue samples of gastric mucosa with or without H. pylori infection were obtained from 41 esophageal cancer patients that underwent esophago-gastrectomy. Fresh samples were used for real-time polymerase chain reaction for H. pylori DNA and CHAC1 mRNA, and formalin-fixed samples were used for immunohistochemistry with anti-CHAC1 and anti-H. pylori monoclonal antibodies. Double-enzyme or fluorescence immunohistochemistry and immuno-electron microscopy were used for further analysis. RESULTS: Significant CHAC1 overexpression was detected in H. pylori-infected parietal cells that expressed the human proton pump/H,K-ATPase α subunit, whereas a constitutively low level of CHAC1 mRNA expression was observed in the other samples regardless of the H. pylori infection status, reflecting the weak CHAC1 expression detected by immunohistochemistry in the fundic-gland areas. Immuno-electron microscopy revealed intact H. pylori cells in the secretory canaliculi of infected parietal cells. Some parietal cells exhibited positive nuclear signals for Ki67 in the neck zone of the gastric fundic-gland mucosa with H. pylori infection. CONCLUSION: Cation transport regulator 1 overexpression in H. pylori-infected parietal cells may cause the H. pylori-induced somatic mutations that contribute to the development of gastric cancer.

Need and demand for nutritional counselling and their association with quality of life, nutritional status and eating-related distress among patients with cancer receiving outpatient chemotherapy: a cross-sectional study.

PURPOSE: Patients with cancer often experience general nutritional problems as the disease progresses. We aimed to examine if there is a need and demand for nutritional counselling among cancer outpatients, and explore relevant psychological factors pertaining to eating and nutrition. METHODS: A survey was conducted among adult patients receiving outpatient chemotherapy at the Tokyo Medical and Dental University Hospital. The participants completed self-report questionnaires, which included questions on their nutritional state (Patient-Generated Subjective Global Assessment Short Form), experience of eating-related distress and quality of life (QOL) (European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire-C30). RESULTS: Of the 151 (median age, 66.5 years) participants, 42 had a demand for nutritional counselling. Patients' experience of eating-related distress and demand for nutritional counselling were significantly associated, particularly in regard to 'conflicts over food between patients and the people surrounding them' (p = 0.005), 'concerns about food' (p = 0.007) and 'self-motivated effect related to nutrition' (p = 0.018). A significant association was also observed between the demand for nutritional counselling and global health status (p = 0.028), emotional functioning (p = 0.022), cognitive functioning (p = 0.028) and social functioning (p = 0.040) in terms of QOL. Patients with a low QOL tended to demand nutritional counselling. CONCLUSIONS: The demand for nutritional counselling was associated with QOL and eating-related distress. Therefore, medical staff caring for patients with cancer, such as attending physicians, dietitians, nurses, clinical psycho-oncologists, social workers and psychiatric oncologists, should collaborate and share information to provide nutritional counselling.

Comparative Study of Predictive Mortality Scores in Esophagectomy with Three-Field Lymph Node Dissection in Patients with Esophageal Cancer.

BACKGROUND/AIM: Esophagectomy is still the best therapeutic option for curing resectable esophageal cancer (EC). Radical surgical resection with three-field lymphadenectomy (3FLD) is a potentially curative treatment option. We compared the predictive accuracy of 5 different scores in patients with EC who underwent 3FLD. METHODS: Five years' worth of medical records in a single institution were analyzed (January 2010 to January 2015) from 311 patients who underwent esophagectomy for EC. We selected 191 in whom 3FLD was performed. Mortality was calculated based on 5 predictive scores. Outcomes measures were intraoperative mortality, 30-day mortality, and 1- and 2-year mortality after surgery. RESULTS: Intraoperative mortality and 30-day mortality after surgery was 0%; 1 and 2-year mortality were 19.8 and 31.4%, respectively. The area under the curve showed poor discriminatory power for all 5 scores (<0.7). In one-way analysis of variance, for 1 year mortality, Portsmouth-Physiological and Operative Severity Score for mortality (P-Possum) was significant (p = 0.0424); in a multivariable analysis for 2-year mortality, P-Possum (p < 0.0001) remained significant. CONCLUSION: There is no accurate prognosis score for esophagectomy in patients who undergo high-risk procedures like 3FLD. New scores are needed to predict the mortality after 3FLD with good discriminatory power. Independent factors affect survival and may function as the baseline for obtaining a new accurate mortality score.

[Esophageal Reconstruction with Ileocolon].

Herein, we described the surgical technique of esophageal reconstruction using ileocolon with preserved ileocolic vessels. Although colon reconstruction is a difficult reconstruction method that includes all the essence of digestive surgery, it is a procedure that esophageal surgeons should fully understand and learn.

A feasibility study of mediastinoscopic radical esophagectomy for thoracic esophageal cancer from the viewpoint of the dissected mediastinal lymph nodes validated with thoracoscopic procedure: a prospective clinical trial.

PURPOSE: A prospective trial evaluated the feasibility and safety of "mediastinoscopic esophagectomy with lymph node dissection" (MELD). METHODS: Eligible patients had thoracic esophageal squamous cell carcinoma, excluding T4, a bulky primary lesion or distant metastasis. Ten patients were enrolled and treated between September 2015 and March 2018. Additionally, to verify the integrity of the mediastinal lymph node dissection, thoracoscopic observation and lymph node dissection were followed. The primary end point was the integrity of mediastinal lymph node dissection. The secondary end points were the short-term outcomes, including mortality and morbidity. RESULTS: The median number of dissected lymph nodes in the upper mediastinal to cervical region and middle to lower mediastinal region by mediastinoscopy/thoracoscopy was 27/0.5 and 11.5/0, respectively. The median total operation time was 615 min, the median bleeding amount was 476 ml, and the median postoperative hospital stay was 15.5 days. Regarding complications of more than grade III according to the Clavien-Dindo classification, four had sputum excretion difficulty, one had pneumothorax and one had bilateral recurrent nerve palsy, but none required conversion to thoracotomy, and no operative deaths occurred. CONCLUSION: Although the rate of recurrent nerve palsy still should be reduced, our mediastinoscopic lymphadenectomy technique is closely similar to radical esophagectomy.

A Pilot Trial of S-1 and Paclitaxel in Unresectable or Postoperative Recurrent Esophageal Squamous Cell Carcinoma Pretreated by Fluorouracil, Cisplatin, and Docetaxel Chemotherapy.

BACKGROUND/AIMS: This study documents the clinical efficacy and toxicity of S-1 and paclitaxel (S1/PTX) in patients with unresectable or postoperative recurrent esophageal squamous cell carcinoma (ESCC) who had been previously treated with fluorouracil (5FU), cisplatin, and docetaxel. METHODS: Twenty-eight ESCC patients treated using S1/PTX at our institute since 2010 were enrolled in this study. S1 was administered orally at a dose of 80 mg/m2/day from days 1 to 14, and PTX was administered intravenously on days 1 and 8 at a dose of 80-100 mg/m2. RESULTS: A total of 106 cycles (median 2.5 cycles, range 1-12 cycles) were administered. The response rate was 14.8%, including 3 complete responses. The median progression-free survival time was 137 days, and the median overall survival time was 306 days. Severe neutropenia occurred in 13 patients, and 3 showed febrile neutropenia. All non-hematological toxicities were mild, and peripheral nerve paralysis was observed in 2 patients. CONCLUSION: S1/PTX was found to have tolerable clinical efficacy in terms of the response rate, survival and toxicity in patients with unresectable or postoperative recurrent ESCC who had previously been treated with 5FU, cisplatin, and docetaxel.

Anatomical study of the left superior mediastinal lymphatics for tracheal branches of left recurrent laryngeal nerve-preserving mediastinoscope-assisted surgery in esophageal cancer.

PURPOSE: Curative treatment of esophageal cancer requires meticulous superior mediastinal lymphadenectomy, in addition to esophagectomy, because superior mediastinal lymph node metastases are common in esophageal cancer. When preserving the tracheal branches of the left recurrent laryngeal nerve (RLN), good anatomical understanding is required for confirmation of the positional relationships between the courses of lymphatic vessels, lymph node distribution, and the left RLN and its tracheal branches. We performed a detailed anatomical examination of these relationships. METHODS: Macroscopic anatomical observation and histological examination was performed on cadavers. In addition to hematoxylin and eosin staining, immunostaining using antipodoplanin antibody D2-40 (podoplanin) was performed to identify the lymphatic vessels. RESULTS: The tracheal branches of the left RLN were clearly observed, but no lymphatic vessels crossing the ventral or dorsal side of the branches were identified either macro-anatomically or histologically. CONCLUSION: No complex lymphatic network structure straddling the plane composed of tracheal branches of the left RLN was found in the left superior mediastinum. This suggests that dissection of the lymph nodes around the left RLN via the pneumomediastinum method using the left cervical approach may allow preservation of the tracheal branches of the left RLN by maintaining dissection accuracy.