Hiroshi Sato

Prognostic evaluation for squamous cell carcinomas of the lower thoracic esophagus treated with three-field lymph node dissection

OBJECTIVE The efficacy of esophagectomy with three-field lymph node dissection in surgical treatment for patients with squamous cell carcinomas of the lower thoracic esophagus remains controversial. This report documents the outcomes of this surgical procedure for a large series. METHODS From February 1986 to November 1998, 437 patients with squamous cell carcinomas of the thoracic esophagus underwent transthoracic esophagectomy with three-field lymph node dissection. One hundred and sixteen of these had cancer of the lower thoracic esophagus. To avoid the influence of adjuvant therapy on survival, 20 who also received radiation and/or chemotherapy were excluded, leaving 96 patients who were retrospectively analyzed. RESULTS The operative morbidity, and 30-day and in-hospital mortality rates were 62, 0, and 3%, respectively. The overall 1-, 3-, and 5-year survival rates were 89, 65, and 59%, with a median survival of 76 months. In those with lymph node metastases (66% of cases), the values were 87, 56, and 48%, as compared with 94, 84, and 79%, respectively (P=0.005) for patients without lymph node metastasis. Factors significantly influencing the overall survival rates were patient age (> or = 65 vs. <65), clinical N status (cN1 vs. cN0), clinical M status (cM1 vs. cM0), longitudinal tumor length of resected specimen (> or =5 vs. <5 cm), pathologic T status (pT3 vs. pT1, 2), pathologic N status (pN1 vs. pN0), lymphatic invasion (positive vs. negative), vascular invasion (positive vs. negative) and intramural metastasis (present vs. absent). Independent prognostic factors for survival determined by multivariate analysis were pathologic T status (P=0.02), pathologic N status (P=0.03), and presence of intramural metastasis (P=0.04). Additional pathologic M1 status, cervical or celiac lymph node metastasis, was without significant influence. CONCLUSIONS Patients with pathologic T3 tumors with both pathologic N1 status and the presence of intramural metastasis in the lower thoracic esophagus had a poor prognosis. Cervical or celiac lymph node metastasis in patients with carcinomas of the lower thoracic esophagus should be distinguished from pathologic M1 status in the UICC-TNM staging system.

Increased neutrophil-to-lymphocyte ratio is a novel marker for nutrition, inflammation and chemotherapy outcome in patients with locally advanced and metastatic esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is one of the most common types of cancer, and its progression is strongly influenced by the presence of inflammation. Recently, there has been growing interest in the host inflammatory response, and increasing evidence has indicated that the neutrophil-to-lymphocyte ratio (NLR), a useful marker of systemic inflammation, may be an effective prognostic indicator in various types of malignant diseases. In the present study, 260 patients with ESCC were enrolled, including 110 who received chemoradiation therapy (CRT) involving irradiation and chemotherapy of 5-fluorouracil and cisplatin, and 150 received chemotherapy using 5-fluorouracil and cisplatin (FP). The patients of each group were both divided into two groups according to their NLR: High NLR (NLR>3.0) and low NLR (NLR≤3.0). Serum levels of prealbumin and retinol binding protein, which are nutritional parameters, were both significantly inversely correlated with NLR in patients treated with CRT, and patients treated with FP. Levels of CRP, a marker of inflammation, were significantly correlated with NLR, and stimulation indices, markers of immune reactions, were inversely correlated with NLR in both of CRT patients and FP patients. In patients treated with CRT, a partial response was significantly higher in patients with a low NLR and with progressive disease compared to those with a high NLR. In patients treated with FP, a partial response was also significantly higher in patients with a low NLR and with progressive disease compared to those with a high NLR. The overall survival of patients with CRT and FP were both significantly worse in patients with a high NLR than in those with a low NLR. NLR may serve as a useful marker of the tumor response, immune suppression, malnutrition and prognosis upon CRT or FP in patients with locally advanced or metastatic ESCC.

Comparison of curative surgery and definitive chemoradiotherapy as initial treatment for patients with cervical esophageal cancer

Esophagectomy and definitive chemoradiotherapy are recognized standard initial treatment modalities for cervical esophageal cancer. The goal of this study was to compare the treatment outcomes of curative surgery with those of chemoradiotherapy in patients who had potentially resectable tumor and who were candidates for surgery. We evaluated the data from 49 consecutive patients who were diagnosed with potentially resectable cervical esophageal cancer and who were deemed candidates for surgery. Thirteen patients were included in the surgery group, and 36 patients were included in chemoradiotherapy group. Baseline characteristics were balanced between the two groups. In the chemoradiotherapy group, the complete response rate was 58.3%. There was no significant difference in 5-year overall survival when comparing the surgery group and the chemoradiotherapy group (surgery, 60.6%; chemoradiotherapy, 51.4%; P = 0.89). In the chemoradiotherapy group, of the 15 patients who failed to respond to initial treatment, 11 patients subsequently underwent salvage surgery. In conclusion, curative surgery and chemoradiotherapy as initial treatment for cervical esophageal cancer have comparable survival outcomes. Chemoradiotherapy should be selected as the initial larynx-preserving treatment for patients with cervical esophageal cancer although chemoradiotherapy non-responders require additional treatment, including salvage surgery.

Risk Factors for Residual Tumors in Surgery Following Neoadjuvant Chemotherapy for Thoracic Esophageal Cancer

Abstract Background: Neoadjuvant chemotherapy (NAC) followed by esophagectomy is considered the standard treatment for resectable advanced esophageal squamous cell carcinoma in Japan. The purpose of this study was to identify the risk factors for residual tumors in surgery following NAC. Patients and Method: We reviewed the medical records of patients in our institution selected by using the following criteria: (1) pathologically confirmed squamous cell carcinoma or adenosquamous carcinoma before treatment; (2) cT1-3; and (3) receipt of thoracotomy with the intention of curative resection after NAC composed of 5-fluorouracil plus cisplatin between 2007 and 2010. The patients were divided into the complete resection group (R0 group) and the macroscopic or microscopic residual tumor group (R(+) group). Results: Eighty-eight patients were eligible (R0, 70 patients; R1, 9 patients; R2, 7 patients; and not resected, 2 patients). There were more cT3 cancers and clinical node-positive diseases in the R(+) group ...

Esophageal bypass in two patients with a complete response after definitive chemoradiotherapy for thoracic esophageal cancer

Abstract Esophageal bypass is a palliative operation for patients with unresectable esophageal cancer and impaired oral intake. This method is recently used to treat complications such as stenosis associated with esophageal cancer or esophagorespiratory fistula after chemoradiotherapy (CRT). However, its outcome has not been evaluated. We describe the effectiveness of esophageal bypass after CRT in two patients with a complete response (CR) but marked deterioration of quality of life due to esophageal stenosis after definitive CRT. The first patient had metastases in the right recurrent nerve lymph nodes and refused to undergo radical resection. The second patient had unresectable esophageal cancer due to invasion into the right subclavian artery. Both patients responded to esophageal bypass with good oral intake and without relapse. These two cases demonstrate that esophageal bypass can be a good, low-invasive surgical option for patients with CR but with esophageal stenosis after definitive CRT.

Development of novel treatment with a bioabsorbable esophageal patch for benign esophageal stricture

Using a large animal model, we examined whether circumferential stricture after esophageal endoscopic submucosal dissection (ESD) can be treated by grafting a bioabsorbable esophageal patch. Circumferential ESD was performed on the thoracic esophagus in pigs (n = 6) to create a stricture, for which one of the following interventions was performed: (1) the stricture site was longitudinally incised, and an artificial esophageal wall (AEW) was grafted after placing a bioabsorbable stent (AEW patch group, n = 3); (2) endoscopic balloon dilation (EBD) was performed every other week after stricture development (EBD group, n = 3). In both groups, esophageal fluoroscopy was performed 8 weeks after the interventions, and the esophagus was excised for histological examination of the patched site. In the AEW patch group, esophageal fluoroscopy revealed favorable passage through the patched site. Histologically, the mucosal epithelium and lamina propria had regenerated as in the normal area. In the EBD group, the circumferential stricture site showed marked thickening, and there were hypertrophic scars associated with epithelial defects on the luminal surface. Histologically, defects of the mucosal epithelium and full-thickness proliferation of connective tissue were observed. AEW patch grafting was suggested to be a potentially novel treatment strategy for post-ESD esophageal circumferential stricture.

Defining the Optimal Cut-off Values and Research Methodology for Evaluating Systemic Inflammatory Markers in Clinical Outcome Prediction: Reply

We read with interest the letter to the editor from Lye et al. concerning our article, ‘‘Correlation between the pretherapeutic neutrophil to lymphocyte ratio and the pathologic response to neoadjuvant chemotherapy in patients with advanced esophageal cancer’’ [1]. In their letter, they note that, despite a number of studies in esophageal cancer using a neutrophil to lymphocyte ratio (NLR) ranging between 2.2 and 5.0, no optimal cut-off values have so far been established [1–4]. The NLR has been reported to be a useful biomarker for predicting the prognosis among various cancers, yet no cutoff values have been established for those cancers either [5–8]. In three of the four studies reporting use of the NLR for esophageal cancer, the cut-off points were defined by each author [2–4]. Perhaps they did not use receiver operating characteristics (ROC) curve analysis, because they did not mention how they established their cut-off points. In every case, the clinical outcome endpoints were disease-free survival and overall survival, and adenocarcinoma was the main histological subtype, with a range between 73 and 81 % [2–4]. Our report of patients with advanced esophageal cancer differed in that it focused on the pathological response to neoadjuvant chemotherapy (NAC) [1]. Approximately 84 % of the patients had squamous cell carcinoma. The optimal NLR cut-off value was 2.2, which was determined by receiver operating characteristics (ROC) curve analysis. There were many differences between our results and the previous reports. It is important to avoid the influence of confounding factors. The patients with advanced esophageal cancer who received preoperative chemotherapy followed by surgery were enrolled in our study. All patients were newly diagnosed, had adequate organ function, and had received no prior treatment. Patients with pneumonia were excluded. No patients concurrently received immune-modulators including steroids. The NLR was calculated before the NAC to avoid any influence of the treatment. In contrast, some of the patients in previous reports received neoadjuvant therapy, which may have affected not only the immune reactions but also survival rates [2– 4]. There were many other differences, such as the patients’ background, treatment strategy, and NLR optimal cut-off values in the published reports [1–4]. Therefore, the evaluation of systemic inflammatory markers in the prediction of the clinical outcome was difficult for us. To accurately interpret these results requires consideration of the patient variables, the differences in treatment, and the timing of NLR calculation, among other parameters. Our study was a retrospective, single-center study. Larger well-designed, prospective studies are required to resolve these problems.

A Case of Esophagolymphnodal Fistula due to Tuberculous Cervical Lymphadenitis

症例は79歳の女性で, 平成16年1月頃より嚥下時違和感が出現した. 前医で上部消化管内視鏡検査を施行 (GIF) し, 頸部食道癌疑いで当院に紹介された. GIFでは, 上切歯列16～19cmの右壁に約3cm大の瘻孔形成を伴う深い潰瘍性病変を認めた. 生検では強い炎症所見を伴う肉芽組織を認めた. CTでは101Rにリンパ節腫大を認め, 食道との間に瘻孔を形成していた. 喀痰培養検査ではMRSA・緑膿菌が陽性, 抗酸菌染色検査は陰性. 悪性所見が否定できないため, 6月上旬に手術を施行した. 食道壁に切開を加えた直視下の生検では, 肉芽腫性の炎症所見で, 抗酸菌染色検査が陽性であった. 結核性リンパ節炎による食道への瘻孔形成と判断し, 手術を終了した. 本症例はリンパ節転移を伴う頸部食道癌の画像所見と類似した結核性頸部リンパ節炎であり, 癌の確診がつかない場合, 結核性病変の可能性も十分考慮すべきである.