Published papers

Background: Esophagectomy is one of the most invasive surgical treatments for digestive tract cancer, and the blood levels of inflammatory cytokines such as interleukin-1, interleukin-6, and interleukin-8 are increased for several hours after surgery or in patients experiencing postoperative complications. CXCR2, an interleukin-8 receptor, is reportedly expressed in several carcinomas, and interleukin-8 signaling promotes cancer cell proliferation. The impact of postoperative complications following esophagectomy on long-term survival is controversial. In this study, we demonstrate the significance of CXCR2 expression and validate the effects of CXCR2 expression and postoperative complications on long-term prognosis of esophageal squamous cell carcinoma using resected specimens. Methods: Eighty-two specimens were sectioned from archived, paraffin-embedded tumor tissues obtained from patients with esophageal squamous cell carcinoma who underwent esophagectomy and extended lymphadenectomy for complete resection of cancer in our institute between 1997 and 2002. Immunohistochemistry was performed using a polyclonal antibody to CXCR2, and the correlation of stainability with clinicopathological factors and long-term survival was examined. Results: CXCR2 was expressed in 33 of 82 (40.2%) specimens. In the CXCR2-positive group, the recurrence-free survival and overall survival rates of patients who developed postoperative complications were both significantly lower than those for patients who did not develop any complications. In contrast, in the CXCR2-negative group, there was no significant difference in long-term prognosis between patients with and without complications. CXCR2 positivity combined with postoperative complications was an independent risk factor for subsequent tumor recurrence, showing the highest hazard ratio. Conclusions: Our results suggest that the patients with CXCR2-positive esophageal cancer who develop postoperative complications have a poor prognosis and should be carefully followed. Trial registration: This study was approved by Keio University School of Medicine Ethics Committee with a trial registration number of 2011-241.

Background: Several studies have reported that postoperative enteral nutrition (EN) reduced complications and decreased weight loss and hospital stay periods; however, the majority of patients analyzed in these studies underwent open thoracic surgery. No studies have been conducted regarding EN in patients after thoracoscopic esophagectomy as a less invasive surgery. The aim of this study was to investigate the efficacy of EN after thoracoscopic esophagectomy. Methods: Fifty patients who underwent thoracoscopic esophagectomy for esophageal cancer were divided into two groups: parenteral nutrition (PN; n = 25) and EN (n = 25). The rate of weight loss at postoperative day (POD) 14, levels of prealbumin at POD 10, postoperative complications until POD 14, and other perioperative data were collected for each group. Results: This study analyzed data for 47 patients. The rate of weight loss at POD 14 was significantly lower in the EN group (3.0 ± 3.2 %) than in the PN group (4.0 ± 3.6 %; p = 0.020). Prealbumin levels were 21.0 ± 7.5 mg/dL in the PN group and 18.4 ± 5.8 mg/dL in the EN group at POD 10, with no significant differences between the groups. However, the incidence of postoperative pneumonia was higher in the PN group (30.4 %) than in the EN group (12.5 %). Conclusions: EN could suppress weight loss and reduce the incidence of pneumonia after thoracoscopic esophagectomy.

Background: Remnant gastric cancer (RGC) is one of the less prevalent gastric cancers. The purpose of this study was to explore the clinicopathological characteristics and results of the operation of RGC following distal gastrectomy. In particular, we examined factors related to prognosis. Methods: Between January 1970 and December 2012, 122 patients with RGC following distal gastrectomy underwent further surgery and were analyzed retrospectively. Results: Initial gastric diseases included benign (49 patients, 40.2 %) and malignant diseases (73 patients, 59.8 %). Reconstructions by initial surgery included Billroth I (80 patients, 65.6 %) and Billroth II (42 patients, 34.4 %). Tumors were located at anastomotic (44 patients, 36.1 %) and nonanastomotic sites (78 patients, 63.9 %). There were 59 patients (48.4 %) classified with pathological (p) stage I, 19 as p stage II (15.6 %), 22 as p stage III (18.0 %), and 22 (18.0 %) as p stage IV. A total of 100 patients (82.0 %) underwent curative resection, and 22 underwent noncurative resection. The number of cases of postoperative morbidity, 90-day mortality, and adjuvant chemotherapy were 23 (18.9 %), 3 (2.5 %), and 20 (16.4 %), respectively. Univariate and multivariate analyses were performed to identify the prognostic factors of RGC. Multivariate analysis revealed historical periods, pathological venous invasion, curative resection, and postoperative morbidity to be independent prognostic factors. Conclusions: The prognosis of patients with RGC can be improved by aggressively performing curative resection without causing complications.

Purpose/Aim: We performed a randomized, prospective animal study to investigate whether inhibiting the renin-angiotensin system with a (pro)renin receptor blocker (PRRB) prevents acute lung injury (ALI) in a rodent model. Materials: We used Thirty-six male Sprague-Dawley rats. We administered lipopolysaccharide (LPS; 2 mg/kg) intratracheally with or without PRRB pretreatment (1 mg/kg/d). Methods: We performed bronchoalveolar lavage (BAL) and lung removal at 4 h after LPS administration and measured levels of inflammatory cytokines, high mobility group box 1 (HMGB-1) protein, and total protein in bronchoalveolar lavage fluid (BALF). Myeloperoxidase (MPO) activity was detected in lung tissue homogenates using a sensitive ELISA. We performed hematoxylin and eosin staining and immunohistochemical staining for nonproteolytically activated prorenin in the left lung. Results: The PRRB decreased leukocyte counts and total protein, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-2, IL-6, and IL-10 levels in the BALF and MPO activity in lung tissue. The PRRB reduced interstitial edema, hemorrhage, and the neutrophil count in the lung tissues. Consistent with the reduction in lung tissue damage, immunohistochemical staining showed that the PRRB decreased the amount of nonproteolytically activated prorenin. Conclusions: The PRRB blocked LPS-induced inflammatory response in the lung and protected against ALI. Therefore, it is a potential therapeutic agent for preventing ALI.

Background: The correlation between postoperative systemic inflammation and cancer survival needs to be elucidated. This study evaluated postoperative inflammation using the peak concentration of postoperative serum C-reactive protein (CRP) levels and duration of CRP elevation, then investigated its correlation with prognosis. Methods: The study retrospectively reviewed 216 consecutive patients who underwent curative transthoracic esophagectomy at the authors’ institution between 2004 and 2012. The postoperative serum CRP levels in 215 patients were analyzed during 14 days after esophagectomy. The patients’ characteristics, surgical procedures, postoperative complications, and survival were investigated. To evaluate postoperative inflammatory status objectively using CRP, patients with a delayed CRP level peak and persistent CRP elevation were classified as having an intense postoperative inflammatory response (IIR). Results: The distributions of postoperative pathologic stages 0, 1, 2, 3, and 4 were respectively 5, 70, 58, 66, and 16. Regarding postoperative complications, pneumonia was diagnosed in 42 patients (20 %), anastomotic leakage in 32 patients (15 %), and superficial surgical-site infection in 21 patients (10 %). A delayed CRP level peak was observed in 88 patients (41 %) and persistent CRP elevation in 49 patients (23 %). Overall, 31 patients (14 %) were classified as having IIR. In the survival analysis, the patients with IIR showed a significantly shorter overall survival. In the multivariate analysis, using histology, neoadjuvant treatment, field of lymph node dissection, pathologic stage, and IIR as covariates, IIR was seen as a significantly independent predictive factor for overall survival (hazard ratio 2.019; P = 0.019). Conclusions: In this study, IIR was significantly correlated with postoperative survival. Therefore, the oncologic benefit of reducing postoperative inflammation in esophageal cancer needs to be investigated.

Background: Recent improvements in the survival of patients after esophagectomy have led to an increasing occurrence of gastric cancer in the reconstructed gastric tube (GTC). The aim of this study was to assess generational changes in the clinicopathological characteristics and treatment of GTCs in a single center.Methods: Thirteen GTC lesions in ten patients were diagnosed and treated at Keio University Hospital between 2006 and 2014. In our previous study, we reported eight cases of GTC [1]. We compared clinicopathological characteristics and treatment of GTC, as well as overall survival achieved in this study with those in our previous study [1].Results: In this study, median patient age at the time of GTC detection was 74 years (range 62–81 years) and the median interval between esophagectomy and GTC detection was 95 months (range 21–159 months). Nine (69 %) of 13 lesions satisfied the criteria for endoscopic resection. On comparing this study with our previous study, there were no significant differences in patient age at the time of GTC detection, the interval between esophagectomy and GTC detection, or pathological stage [1]. Compared with our previous study, the use of less invasive treatments, such as endoscopic submucosal dissection and partial gastric tube resection with sentinel lymph node dissection, generationally increased and a significant difference was observed in the type of GTC treatment [1]. However, there was no significant difference in overall survival between the studies.Conclusion: Long-term periodic endoscopy permits less invasive treatments and combinations of various treatments for effective GTC therapy.

Background: Basaloid squamous cell carcinoma (BSCC) is a relatively rare, malignant disease of the esophagus. The prognosis of patients with BSCC is thought to be poorer than that of typical squamous cell carcinoma (SCC), but the treatment strategy for BSCC is generally the same as that for typical SCC. This study examined the diagnosis, the clinical and pathological characteristics, and the results of therapy in patients with BSCC.Methods: The medical records for 13 patients with pathologically confirmed esophageal BSCC were extracted. The pretreatment endoscopic diagnosis and the pathological diagnosis after resection were reviewed for each patient, and the histological features and patient outcome were examined. We especially focus on histological difference and endoscopic findings of the 13 patients with BSCC.Results: Macroscopically, BSCC was mainly visualized as an elevated lesion with normal epithelium on the surface layer which indicated the tumor growth into submucosa. Further pathological examination allowed the 13 BSCC patients to be grouped into 2 groups according to differences in the microscopic appearances of the BSCC cancer cells: a typical BSCC pattern and a pattern similar to that of poorly differentiated SCC. Six of the patients who received an esophagectomy as the primary treatment died, and only 1 patient survived. Two patients who received chemoradiotherapy before an esophagectomy did not develop recurrences. Almost all the patients who died as a result of the recurrence of esophageal cancer had a lymph node recurrence. Prognoses of BSCCs with a pattern similar to that of poorly differentiated SCC without preoperative chemotherapy were poorer than BSCCs with a typical BSCC pattern, while BSCC with a pattern similar to poorly differentiated SCC with preoperative chemotherapy showed good prognoses than BSCC without preoperative chemotherapy.Conclusions: BSCC esophageal cancer mainly appears as an elevated lesion with submucosal growth, which can be diagnosed preoperatively by understanding of macroscopic characteristics of esophageal BSCC. The outcome of the BSCC patients in the present study was relatively poor, while pretreatment diagnosis of BSCC influences the strategy of treatment and pathological diagnosis including histological difference of BSCC may lead to appropriate treatment and better prognosis of esophageal BSCC.

Background: Esophagectomy for esophageal cancer is one of the most invasive operative procedures. Surgical stress induces the release of proinflammatory cytokines, and overproduction induces a systemic inflammatory response syndrome, which may lead to acute lung injury and multiple organ dysfunction syndrome. In addition, surgical stress may cause immunosuppression, which may affect not only perioperative mortality but also long-term survival.Methods: Between 2006 and 2013, levels of perioperative serum cytokines were evaluated in 90 patients who underwent esophagectomy for esophageal carcinoma. The serum interleukin (IL)-6, IL-8, and IL-10 levels were measured by enzyme-linked immunosorbent assays. We reviewed and assessed medical records, including cytokine profiles, and determined the factors affecting postoperative serum cytokine levels.Results: These cytokine levels peaked on postoperative day 1 and decreased gradually. Of the clinicopathologic factors, a thoracoscopic approach was a significant factor in attenuating IL-6 and IL-8 levels on postoperative day 1 in multivariate analysis, and a longer operative time was a significant factor in increasing these levels. During postoperative days 3–7, the thoracoscopic approach and early enteral nutrition were significant factors in attenuating serum cytokine changes in multivariate analysis, and postoperative infectious complications were significant factors in increasing these levels.Conclusions: The thoracoscopic approach and early enteral nutrition could attenuate the cytokine change after esophagectomy, and a longer operative time and postoperative infectious complication could increase it. We should undertake strategies to minimize the surgical stress to reduce potential short-term and long-term consequences for patients.

Background: Serum bilirubin levels frequently increase after esophagectomy for esophageal cancer. Several studies have reported hyperbilirubinemia in patients with postoperative complications. We aimed to perform a detailed large-scale analysis to clarify this association.Methods: We compared postoperative serum bilirubin levels of 200 patients with esophageal cancer who underwent esophagectomy, with and without postoperative complications, from January 2008 to July 2013 at Keio University Hospital, Tokyo, Japan. We also analyzed other risk factors for postoperative hyperbilirubinemia by univariate and multivariate analyses in an attempt to determine the mechanism of postoperative hyperbilirubinemia.Results: Hyperbilirubinemia (total bilirubin >2.0 mg/dL) occurred in 71 patients (35.5 %). The mean total bilirubin peak level was 1.5 mg/dL in patients without complications, 2.0 mg/dL in those with at least one complication, 2.1 mg/dL in those with pneumonia, and 2.3 mg/dL in those with anastomotic leakage. Bilirubin levels were significantly higher in each complication group than in the non-complication group (p < 0.05 for all). Risk factors of postoperative hyperbilirubinemia by univariate analysis were the preoperative bilirubin level, video-assisted thoracoscopic surgery, three-field lymph node dissection, thoracic duct resection, prolonged surgical duration, severe complications (Clavien–Dindo grade ≥3), and severe anastomotic leakage (Clavien–Dindo grade ≥3). In contrast, the pT factor and postoperative enteral nutrition were negatively associated with postoperative hyperbilirubinemia. Risk factors by multivariate analysis were the preoperative bilirubin level, prolonged surgical duration, severe complications, and postoperative enteral nutrition.Conclusions: Although various factors impact postoperative hyperbilirubinemia, postoperative complications were most significantly associated with postoperative hyperbilirubinemia. Patients with postoperative hyperbilirubinemia after esophagectomy must be managed more carefully because unnoticed complications may be associated with hyperbilirubinemia.

Aim: The aim of this phase I study was to adjust the dose of cisplatin as adjuvant combination chemotherapy with S-1 in an outpatient setting for gastric cancer.Patients and Methods: The first course was initiated with S-1 monotherapy on days 1-28. From the second to the sixth course, S-1 was administered on days 1-28 and cisplatin was added on days 1, 15, and 29. The dose level of cisplatin was escalated as follows: 20 mg/m2 (level 1); 25 mg/m2 (level 2); 30 mg/m2 (level 3). Dose-limiting toxicity was a delay factor of the start of the next course due to incomplete recovery.Results: The maximum tolerated and recommended doses were confirmed as level 3 and level 2, respectively.Conclusion: Although further clinical trials are recommended to evaluate efficacy, this combination of S-1 plus cisplatin regimen is expected to become a standard adjuvant treatment for gastric cancer in the outpatient setting.

AIM: To evaluate the effectiveness of trimodal imaging endoscopy (TME) to detect another lesion after endoscopic submucosal dissection (ESD) for superficial gastric neoplasia (SGN).METHODS: Surveillance esophagogastroduodenoscopy (EGD) using a TME was conducted in 182 patients that had undergone ESD for SGN. Autofluorescence imaging (AFI) was conducted after white-light imaging (WLI). When SGN was suspicious, magnifying endoscopy with narrow-band imaging (ME-NBI) was conducted. Final diagnoses were made by histopathologic findings of biopsy specimens. The detection rates of lesions in WLI, AFI, and NBI, and the characteristics of lesions detected by WLI and ones missed by WLI but detected by AFI were examined. The sensitivity, specificity, and accuracy of endoscopic diagnosis using WLI, AFI and ME-NBI were evaluated.RESULTS: In 242 surveillance EGDs, 27 lesions were determined pathologically to be neoplasias. Sixteen early gastric cancers and 6 gastric adenomas could be detected by WLI. Sixteen lesions were reddish and 6 were whitish. Five gastric neoplasias were missed by WLI but were detected by AFI, and all were whitish and protruded gastric adenomas. There was a significant difference in color and pathology between the two groups (P = 0.006). Sensitivity, specificity and accuracy in MENBI were higher than those in both WLI and AFI. Specificity and accuracy in AFI were lower than those in WLI.CONCLUSION: Surveillance using trimodal imaging endoscopy might be useful for detecting another lesion after endoscopic submucosal dissection for superficial gastric neoplasia.

We describe a patient with solitary lymph node (LN) metastasis after three endoscopic mucosal resections (EMRs) in which a gastrointestinal stromal tumor was difficult to differentiate from the carcinoid and lymphoma tumors. A 77-year-old man underwent three EMRs at 62, 72, and 75 years of age, and all resections were determined to be curative. However, 2 years after the last EMR, screening abdominal ultrasonography detected a 20-mm solitary tumor at the lesser curvature of the upper stomach. Laparoscopic tumor resection confirmed the pathological diagnosis. Intraoperative pathological diagnosis showed that the adenocarcinoma was compatible with recurrence of gastric cancer; thus, total gastrectomy with D1 lymphadenectomy was performed. Metastasis was not recognized by pathological examination but was detected by preoperative radiological examinations of the LN. We report a rare recurrence case after several EMRs of intramucosal gastric cancers.

Despite the benefits of imatinib for treating gastrointestinal stromal tumors (GIST), the prognosis for high risk GIST and imatinib-resistant (IR) GIST remains poor. The mechanisms of imatinib resistance have not yet been fully clarified. The aim of the study was to establish imatinib-resistant cell lines and investigate nilotinib, a second generation tyrosine kinase inhibitor (TKI), in preclinical models of GIST and imatinib-resistant GIST. For a model of imatinib-resistant GIST, we generated resistant cells from GK1C and GK3C cell lines by exposing them to imatinib for 6 months. The parent cell lines GK1C and GK3C showed imatinib sensitivity with IC50of 4.59±0.97 μM and 11.15±1.48 μM, respectively. The imatinib-resistant cell lines GK1C-IR and GK3C-IR showed imatinib resistance with IC50values of 11.74±0.17 μM (P<0.001) and 41.37±1.07 μM (P<0.001), respectively. The phosphorylation status of key cell signaling pathways, receptor tyrosine kinase KIT (CD117), platelet-derived growth factor receptor alpha (PDGFRA) and downstream signaling kinases: serine-threonine kinase Akt (AKT) and extracellular signal-regulated kinase 1/2 (ERK1/2) or the non-receptor tyrosine kinase: proto-oncogene tyrosine-protein kinase Src (SRC), was analyzed in established cell lines and ERK1/2 phosphorylation was found to be increased compared to the parental cells. Nilotinib demonstrated significant antitumor efficacy against GIST xenograft lines and imatinib-resistant GIST cell lines. Thus, nilotinib may have clinical potential for patients with GIST or imatinib-resistant GIST.

Purpose The purpose of this study was to establish a prognostic indicator based on preoperative plasma fibrinogen and serum albumin levels (FA score) in esophageal cancer patients and to compare the correlation with survival to that of the Glasgow prognostic score. Methods Patient characteristics, clinicopathological factors, and preoperative biochemical markers (fibrinogen, albumin, and C-reactive protein) were investigated in esophageal cancer patients who underwent transthoracic esophagectomy. Pretreatment fibrinogen and albumin levels were reviewed in patients who received neoadjuvant treatment. Patients with elevated fibrinogen and decreased albumin levels were allocated a score of 2, those with only one of these abnormalities were allocated a score of 1, and those with neither of these abnormalities were allocated a score of 0. The fibrinogen cut-off value was defined as 350 mg/dL according to our previous report, and the albumin cut-off value was defined as the lower quartile. Results Among 199 consecutive patients, the interquartile range of preoperative albumin was 3.8-4.3 g/dL and the cut-off value was 3.8 g/dL. Thus, 108 (54 %), 68 (34 %), and 23 (12 %) patients had an FA score of 0, 1, and 2. The patients with a high preoperative FA score showed considerably shorter disease-free survival (DFS) and overall survival (OS). Multivariate analysis showed that pretreatment stage and preoperative FA score were independently associated with postoperative DFS and OS. Conclusions Preoperative FA score was significantly associated with postoperative survival in esophageal cancer patients, and the prognostic value is currently being validated in a prospective multicenter cohort study.

Intra-abdominal desmoid tumors are rare and most often occur in patients with a history of familial adenomatous polyposis, surgery, or pregnancy. We report a case of an intra-abdominal desmoid tumor mimicking the recurrence of gastric cancer. A 57-year-old male had undergone distal gastrectomy for advanced gastric cancer. Serum levels of carcinoembryonic antigen were found to be elevated 27 months after surgery. Computed tomography revealed a 15-mm mass in the mesentery of the transverse colon. In addition, radiotracer fluorodeoxyglucose uptake of the tumor was detected by positron emission tomography. The patient was diagnosed with gastric cancer recurrence, and chemotherapy consisting of cisplatin and S-1 was commenced. After five courses of chemotherapy, although no significant clinical response was seen, no new lesions were seen either. Thus, a curative resection of the recurrent tumor seemed possible, which was successfully performed. Histological examination of the resected specimen revealed spindle-shaped tumor cells with collagen fiber progression; no cancer cells were detected. The tumor was diagnosed as an intra-abdominal desmoid tumor. We report a rare case of an intra-abdominal desmoid tumor that mimicked a recurrent tumor arising from gastric cancer. In patients with history of surgery for intra-abdominal malignancies, it may be difficult to distinguish the recurrence of malignancy from desmoid tumors but the possibility of desmoid tumors must be considered in the differential diagnosis.

Background: CC-chemokine receptor 7 (CCR7), a known lymph node homing receptor for immune cells, has been reported as a key molecule in lymph node metastasis. We hypothesized a clinicopathological correlation and functional causality between CCR7 expression and lymph node metastasis in patients with esophageal squamous cell carcinoma (ESCC).Methods: We performed immunohistochemical analysis of 105 consecutive and 61 exclusive pathological T1 ESCC patients, followed by adhesion assay and in vivo experiment using a newly developed lymph node metastasis mouse model. The adhesive ability in response to CC-chemokine ligand 21/secondary lymphoid-tissue chemokine (CCL21/SLC) was assessed in the presence or absence of lymphatic endothelial cells and anti-CCR7 antibody. We established a heterotopic transplantation mouse model and analyzed lymph node metastasis by quantitative real-time RT-PCR.Results: Positive CCR7 expression in immunohistochemistory was detected in 28 (27%) of 105 consecutive patients and 17 (28%) of 61 T1 patients, which significantly correlated with lymph node metastasis (p = 0.037 and p = 0.040, respectively) and poor five-year survival (p = 0.013 and p = 0.012, respectively). Adhesion assay revealed an enhanced adhesive ability of CCR7-expressing cells in response to CCL21/SLC, in particular, in the presence of lymphatic endothelial cells (p = 0.005). In the mouse model, lymph nodes from mice transplanted with CCR7-expressing cells showed significantly higher DNA levels at 5 weeks (p = 0.019), indicating a high metastatic potential of CCR7-expressing cells.Conclusion: These results demonstrated the significant clinicopathological relationship and functional causality between CCR7 expression and lymph node metastasis in ESCC patients.

We report the successful management of a case of anastomotic leakage with a lung fistula as a complication of esophagectomy by use of a double elementary diet tube.

Purpose: We investigated the association between the Revised Cardiac Risk Index (RCRI) and postoperative outcomes in patients undergoing non-cardiac surgery. Methods: The predictive value of the RCRI for the risk of perioperative complications, length of hospital stay and hospital cost were evaluated from a prospective cohort of 119 patients aged ≥65 years undergoing elective major digestive, breast or vascular surgery. Results: Comparing three groups RCRI 0, 1 and ≥2, the morbidity rates were 0, 30 and 68 %; the median length of hospitalization was 5, 14 and 28 days; and the median cost was 665,000, 1,480,000 and 2,160,000 yen, respectively. The mortality rate was 0 % in all groups. The RCRI 0 group included only non-high-risk (breast and peripheral vascular) surgeries. In addition, comparing the two groups by excluding non-high-risk surgeries (RCRI 1 and ≥2), the median morbidity rates were 31 and 67 %, the median length of hospitalization was 15 and 28 days, and the median cost was 1,550,000 and 2,130,000 yen, respectively. The RCRI score was the only independent predictor of the perioperative complications. Conclusions: In the case of non-cardiac surgery, the RCRI can identify patients at higher risk of perioperative complications, a prolonged hospital stay and higher hospital cost.

Recent advances in endoscopic procedures, such as narrow band imaging systems and magnifying endoscopy, have enabled the precise observation of the hypopharynx and cervical esophagus. We developed endoscopic laryngo-pharyngeal surgery (ELPS) as minimally invasive surgery for superficial carcinoma of the larynx and pharynx. First, we insert the laryngoscope with endoscopic guide and place it at on the upper part of the vocal cord. We lift the larynx by the laryngoscope and fix the laryngoscope. The curved laryngoscope gives us a good visual field and working space between the hypopharynx and the cervical esophagus. After lifting the larynx using the laryngoscope, the endoscopist inserts the endoscope and the operator inserts the forceps and electric device transorally. After iodine staining, we mark the normal mucosa just 1-2 mm away from the cancer margin and inject Epinephrine-added physiological saline solution to the subepithelial layer. After the circumferential cutting, we resect the lesion with the forceps and electric device. ELPS for superficial carcinoma of the hypopharynx and cervical esophagus is a feasible and effective treatment.

Background: We examined whether tumor growth is enhanced by cecal ligation and puncture (CLP) and suppressed by a neutrophil elastase inhibitor, sivelestat. Materials and Methods: C57BL/6 mice were divided in CLP/sivelestat, CLP alone, and control (simple laparotomy) groups. Murine CT26 colon carcinoma cells were injected subcutaneously into the back of each mouse and tumor growth and serum cytokine levels were assessed. Results: Mice subjected to CLP alone exhibited enhanced tumor growth compared to controls with subcutaneously injected CT26 cells (0.64±0.24 g vs. 0.021±0.027 g, p<0.001), while treatment with CLP/sivelestat produced smaller tumors than CLP alone (0.28±0.23 g vs. 0.64±0.24 g, p=0.006). Cytokine assays showed suppressed production of interleukin (IL)-6 and IL-10 in the CLP/sivelestat group, and increased IL-6 and IL-10 in the CLP-alone group. Conclusion: Intraabdominal inflammation induced by CLP enhances the growth of subcutaneously implanted tumors, while perioperative administration of sivelestat suppresses tumor growth by affecting systemic inflammation.