Go Miyata

Prospective Comparison of Surgery Alone and Chemoradiotherapy With Selective Surgery in Resectable Squamous Cell Carcinoma of the Esophagus

PURPOSE Esophagectomy remains the mainstay treatment for esophageal cancer, although retrospective studies have suggested that chemoradiotherapy (CRT) is as effective as surgery. To determine whether CRT can substitute for surgery as the primary treatment modality, we performed a prospective direct comparison of outcomes after treatment in patients with resectable esophageal cancer who had received CRT and those who had undergone surgery. METHODS AND MATERIALS Eligible patients had resectable T1-3N0-1M0 thoracic esophageal cancer. After the surgeon explained the treatments in detail, the patients selected either CRT (CRT group) or surgery (OP group). The CRT course consisted of two cycles of cisplatin and fluorouracil with split-course concurrent radiotherapy of 60Gy in 30 fractions. Patients with progressive disease during CRT and/or with persistent or recurrent disease after CRT underwent salvage resection. RESULTS Of 99 eligible patients with squamous cell carcinoma registered between January 2001 and December 2005, 51 selected CRT and 48 selected surgery. Of the patients in the CRT group, 13 (25.5%) underwent esophagectomy as salvage therapy. The 3- and 5-year survival rates were 78.3% and 75.7%, respectively, in the CRT group compared with 56.9% and 50.9%, respectively, in the OP group (p = 0.0169). Patients in the OP group had significantly more metastatic recurrence than those in the CRT group. CONCLUSIONS Treatment outcomes among patients with resectable thoracic esophageal squamous cell carcinoma were comparable or superior after CRT (with salvage therapy if needed) to outcomes after surgery alone.

High incidence of reflux esophagitis observed by routine endoscopic examination after gastric pull-up esophagectomy

A gastric tube has been widely used for reconstruction of the esophagus after esophagectomy for esophageal cancer. Reflux esophagitis after esophagectomy is frequently observed. Therefore we retrospectively investigated the risk factors for reflux esophagitis after gastric pull-up esophagectomy in 74 outpatients with thoracic esophageal cancer. Reflux esophagitis was diagnosed endoscopically. Esophagitis was classified according to the Los Angeles classification. Reflux symptoms, medications, and the surgical procedure were reviewed. The relation between reflux symptoms and reflux esophagitis and the influence of the anastomotic site were evaluated. Reflux esophagitis was observed in 53 patients. Severe esophagitis (grade C or D) was found in 75.6% of these patients. Although all patients with esophagitis took antacid agents, histamine receptor-2 blocker was effective in only 35% of them. The correlation between reflux symptoms and reflux esophagitis was not significant. Reflux esophagitis was present in 56.4% of patients with neck anastomosis and in 88.6% of patients with intrathoracic anastomosis (p = 0.0039). We concluded that routine endoscopic examination is necessary after gastric pull-up esophagectomy because reflux esophagitis is not diagnosed based on reflux symptoms. When a gastric tube is used for reconstruction after esophagectomy, neck anastomosis is recommended to lower the risk of reflux esophagitis.

Significance of CD133 expression in esophageal squamous cell carcinoma

BackgroundCD133 was recently reported to be a cancer stem cell marker and a prognostic marker for several tumors. However, few studies have investigated CD133 expression in esophageal squamous cell carcinoma (ESCC). Therefore, we examined whether CD133 could serve as a prognostic marker of ESCC and investigated the correlation between CD133 expression and the clinicopathological findings of ESCC patients and several markers.MethodsWe studied 86 ESCC patients who underwent curative surgery without neoadjuvant treatment at Tohoku University Hospital (Sendai, Japan) between January 2000 and December 2005. We analyzed tissue specimens by immunohistochemical staining for CD133, p53, p16, p27, murine double minute 2 (MDM2), Ki-67, and epidermal growth factor receptor (EGFR).ResultsPathological tumor depth and tumor stage were significantly more advanced among CD133-negative patients than among CD133-positive patients. A log-rank test showed that CD133 immunoreactivity was significantly correlated with the overall survival of the patients (P = 0.049). However, multivariate analysis showed that it was not significantly correlated (P = 0.078). Moreover, CD133 was significantly positively correlated with p27 immunoreactivity (P = 0.0013) and tended to be positively correlated with p16 immunoreactivity (P = 0.057). In addition, p16 immunoreactivity was correlated with smoking history (P = 0.018), pathological lymph node status (P = 0.033), and lymphatic invasion (P = 0.018).ConclusionsThis study indicated that CD133 immunoreactivity is a good predictor of prognosis in ESCC patients. In addition, CD133 may play a role in the regulation of tumor cell cycle through p27 and p16 in ESCC. At present, it thus remains controversial whether CD133 expression is a valid prognostic marker for ESCC. To elucidate this relationship, further investigations are required.

Long-Term Results of Radiochemotherapy for Solitary Lymph Node Metastasis After Curative Resection of Esophageal Cancer

PURPOSE To evaluate the long-term efficacy and toxicity of definitive radiochemotherapy for solitary lymph node metastasis after curative surgery of esophageal cancer. METHODS AND MATERIALS We performed a retrospective review of 35 patients who underwent definitive radiochemotherapy at Tohoku University Hospital between 2000 and 2009 for solitary lymph node metastasis after curative esophagectomy with lymph node dissection for esophageal cancer. Radiotherapy doses ranged from 60 to 66 Gy (median, 60 Gy). Concurrent chemotherapy was platinum based in all patients. The endpoints of the present study were overall survival, cause-specific survival, progression-free survival, irradiated-field control, overall tumor response, and prognostic factors. RESULTS The median observation period for survivors was 70.0 months. The 5-year overall survival was 39.2% (median survival, 39.0 months). The 5-year cause-specific survival, progression-free survival, and irradiated-field control were 43.3%, 31.0% and 59.9%, respectively. Metastatic lesion, size of the metastatic lymph node, and performance status before radiochemotherapy were significantly correlated with prognosis. Complete response and partial response were observed in 22.9% and 57.1% of the patients, respectively. There was no Grade 3 or higher adverse effect based on the Common Terminology Criteria for Adverse Events (CTCAE v3.0) in the late phase. CONCLUSIONS Based on our study findings, approximately 40% of patients with solitary lymph node metastasis after curative resection for esophageal cancer have a chance of long-term survival with definitive radiochemotherapy.

Esophagectomy using a thoracoscopic approach with an open laparotomic or hand-assisted laparoscopic abdominal stage for esophageal cancer: analysis of survival and prognostic factors in 315 patients.

&NA;Survival and prognostic factors were analyzed in 315 patients with esophageal cancer undergoing thoracoscopic-assisted esophagectomy (TAE). The 5-year survival rate of 57.8% was satisfactory, indicating the oncological feasibility of TAE. Perioperative outcomes affected overall survival in the whole cohort but not in the subgroup treated with 2 endoscopic stages. Objective:To estimate the oncological feasibility of thoracoscopic-assisted esophagectomy (TAE) for esophageal cancer and to clarify the prognostic impact of perioperative factors after TAE. Background:Favorable perioperative outcomes of TAE versus open surgery have been demonstrated. However, survival data after TAE in a large cohort are limited, and no information on the prognostic influence of perioperative factors after TAE is available. Methods:Prospectively collected data for 315 patients undergoing TAE for esophageal cancer were analyzed. Survival was compared with the Kaplan-Meier analysis and Cox regression analysis between 2 surgical approaches: thoracoscopic and hand-assisted laparoscopic esophagectomy (THLE) and thoracoscopic and open laparotomic esophagectomy (TOE). Factors affecting overall survival were identified with Cox multivariate regression analysis in the whole cohort and the THLE subgroup. Results:THLE and TOE were performed in 153 and 162 patients, respectively. The overall 5-year survival of the whole cohort was 57.8%, with no difference between the THLE and the TOE group. Multivariate analysis of the 315 patients identified the following prognostic factors: blood loss, blood transfusion, intensive care unit stay, cardiovascular complications, pathological T and N stages, lymphatic invasion, intramural metastasis, and number of metastatic nodes. In the THLE subgroup, cerebral comorbidity, histological subtype, pathological T stage, and number of metastatic nodes were independent prognostic factors. Conclusions:TAE was oncologically feasible. Perioperative factors affected survival in the whole cohort, but did not in the THLE subgroup. However, the reduced perioperative factor effect in this subgroup would be small because the survival rates of the 2 surgical approaches were equal.

Steroid and xenobiotic receptor in human esophageal squamous cell carcinoma: A potent prognostic factor

Steroid and xenobiotic receptor (SXR) is a nuclear receptor activated by diverse exogenous and endogenous compounds and has been demonstrated to play a pivotal role in detoxification through its regulation of various metabolizing enzymes and transporters. Recent studies also demonstrated the potential roles of SXR in the regulation of apoptosis and inflammation in various carcinoma cells, but the status of SXR in human esophageal squamous cell carcinoma (ESCC) has not been examined. Therefore, in this study, we performed immunohistochemical and quantitative RT‐PCR evaluations in human ESCC in order to clarify its biological and clinical significance. We first immunolocalized SXR in 73 human ESCC cases. SXR immunoreactivity was detected in the nuclei, or in both nuclei and cytoplasm of carcinoma cells (98%, 20% of cases, respectively). The status of nuclear SXR immunoreactivity was inversely correlated with histological grade, lymph node status, ki67/MIB1 labeling index, and positively correlated with retinoid X receptor α status. In addition, high nuclear SXR expression was significantly correlated with favorable clinical outcome of the patients. Multivariate analysis further demonstrated SXR status in carcinoma cells as an independent favorable prognostic factor of the patients. Results of quantitative RT‐PCR study demonstrated that SXR mRNA expression was detected in three of five cases, and was marked higher in the cancerous tissue than non‐neoplastic tissue of these patients. This is the first study to demonstrate the status of SXR in human ESCC and the results suggest that SXR is a potent favorable prognostic factor of human ESCC. (Cancer Sci 2009)

Estrogen receptor α and β in esophageal squamous cell carcinoma

A gender difference has been reported in the morbidity of esophageal squamous cell carcinoma (ESCC). Estrogens have been proposed to play a role in this difference but the details have not yet been clarified. Therefore, in the present study, we examined the status of estrogen receptor (ER)α and ERβ in 90 Japanese ESCC patients. ERα and ERβ immunoreactivity was detected in the nuclei of ESCC cells (41.1 and 97.8%, respectively). There was a significant positive association between the ERβ H score and histological differentiation (P = 0.0403), TNM‐pM (LYM) (P = 0.00164) and Ki67/MIB1 LI of carcinoma cells (P = 0.0497, r = 0.207). In addition, the ERβ status of carcinoma cells was significantly correlated with unfavorable clinical outcome of the patients. Multivariate analysis further revealed the ERβ status in carcinoma cells as an independent unfavorable prognostic factor of these patients. We further examined the effects of estrogen treatment on ESCC cell line (ECGI‐10) transfected with ERα or ERβ in vitro. The number of ECGI‐10 transfected with ERβ was increased by estradiol or ERβ specific agonist but estradiol did not exert any effect upon the cell number of ECGI‐10 transfected with ERα. In summary, the results of the present study clearly demonstrate that the status of ERβ in ESCC was closely associated with the unfavorable prognosis, possibly through altering cell proliferation of carcinoma cells. (Cancer Sci 2012; 103: 1348–1355)

Comparison of short-term outcomes between prone and lateral decubitus positions for thoracoscopic esophagectomy

AbstractBackgroundProne thoracoscopic esophagectomy was introduced at our institution from 2012. This study describes our experiences of the main differences between thoracoscopic esophagectomy in the prone and traditional left lateral decubitus positions together with an analysis of the short-term surgical outcomes.MethodIn total, 87 patients undergoing thoracoscopic esophagectomy between January 2012 and October 2013 at Tohoku University Hospital were enrolled; of these, 54 and 33 patients were operated in the prone (Group P) and lateral decubitus (Group L) positions, respectively.ResultsThe background of the patients was similar, and there was no in-hospital mortality. There were no significant differences between the groups in terms of whole surgical duration, thoracic duration, and number of dissected lymph nodes. Total blood loss and thoracic estimated blood loss were significantly lower in Group P than Group L. Furthermore, postoperative pulmonary complications, intensive care unit stay, and hospital stay were significantly lower in Group P.ConclusionThoracoscopic esophagectomy in the prone position is feasible and safe. The prone position technique may be superior to conventional lateral decubitus position esophagectomy.

The Dissection Profile and Mechanism of Tissue-Selective Dissection of the Piezo Actuator-Driven Pulsed Water Jet as a Surgical Instrument: Laboratory Investigation Using Swine Liver

Background/Purpose: The water jet technique dissects tissue while sparing cord-like structures such as blood vessels. The mechanism of such tissue-selective dissection has been unknown. The novel piezo actuator-driven pulsed water jet (ADPJ) system can achieve dissection with remarkably reduced water consumption compared to the conventional water jet; however, the systems characteristics and dissection capabilities on any organ have not been clarified. The purposes of this study were to characterize the physical properties of the novel ADPJ system, evaluate the dissection ability in swine organs, and reveal the mechanism of tissue-selective dissection. Methods: The pulsed water jet system comprised a pump chamber driven by a piezo actuator, a stainless steel tube, and a nozzle. The peak pressure of the pulsed water jet was measured through a sensing hole using a pressure sensor. The pulsed water jet technique was applied on swine liver in order to dissect tissue on a moving table using one-way linear ejection at a constant speed. The dissection depth was measured with light microscopy and evaluated histologically. The physical properties of swine liver were evaluated by breaking strength tests using tabletop universal testing instruments. The liver parenchyma was also cut with three currently available surgical devices to compare the histological findings. Results: The peak pressure of the pulsed water jet positively correlated with the input voltage (R2 = 0.9982, p < 0.0001), and this was reflected in the dissection depth. The dissection depth negatively correlated with the breaking strength of the liver parenchyma (R2 = 0.6694, p < 0.0001). The average breaking strengths of the liver parenchyma, hepatic veins, and Glissons sheaths were 1.41 ± 0.45, 8.66 ± 1.70, and 29.6 ± 11.0 MPa, respectively. The breaking strength of the liver parenchyma was significantly lower than that of the hepatic veins and Glissons sheaths. Histological staining confirmed that the liver parenchyma was selectively dissected, preserving the hepatic veins and Glissons sheaths in contrast to what is commonly observed with electrocautery or ultrasonic instruments. Conclusions: The dissection depth of liver tissue is well controlled by input voltage and is influenced by the moving velocity and the physical properties of the organ. We showed that the device can be used to assure liver resection with tissue selectivity due to tissue-specific physical properties. Although this study uses an excised organ, further in vivo studies are necessary. The present work demonstrates that this device may function as an alternative tool for surgery due to its good controllability of the dissection depth and ability of tissue selectivity.

A Strategy for Supraclavicular Lymph Node Dissection Using Recurrent Laryngeal Nerve Lymph Node Status in Thoracic Esophageal Squamous Cell Carcinoma

BACKGROUND The desirability of supraclavicular lymph node (LN) dissection, which is the cervical part of three-field LN dissection, has been discussed for a long time. In this study, we examine the pattern of supraclavicular LN metastasis in esophageal cancer, with a particular focus on the correlation between recurrent laryngeal nerve (RLN) LN and supraclavicular LN metastasis. METHODS In all, 220 cases of R0 resected T1 to T3 squamous cell carcinomas were retrospectively examined. All of these patients underwent bilateral RLN LNs dissection; none received cancer treatment before surgery. RESULTS Of 21 upper esophageal cancer cases, 33.3% of the patients had metastasis in the supraclavicular LN. Every patient in whom supraclavicular LN metastasis developed had metastasis in the RLN LN. Of 141 cases of middle esophageal cancer, 19.1% had metastasis in the supraclavicular LN. Among the patients whose RLN LN metastasized, 38.3% had metastasis in the supraclavicular LN. A similar correlation between RLN LN and supraclavicular LN metastasis was observed in lower esophageal cancer cases, especially in T3 cases. When considering cancers of the esophagus and patients who had metastasis in the supraclavicular LN, our data demonstrated that RLN LN metastasis did not always lead to metastasis on the same side of the supraclavicular LN. CONCLUSIONS The status of the RLN LN can be an indicator of supraclavicular LN dissection in upper esophageal cancer patients and advanced cases of middle and lower esophageal cancer patients. Bilateral supraclavicular LN dissection should be recommended even when only unilateral RLN LN metastasis occurs.