Comparison of neoadjuvant chemotherapy versus upfront surgery with or without chemotherapy for patients with clinical stage III esophageal squamous cell carcinoma.

Neoadjuvant chemotherapy (NAC) and chemoradiotherapy have been shown to extend postoperative survival, and preoperative therapy followed by esophagectomy has become the standard treatment worldwide for patients with esophageal squamous cell carcinoma (ESCC). The Japan Clinical Oncology Group 9907 study showed that NAC significantly extended survival in advanced ESCC, but the survival benefit for patients with clinical stage III disease remains to be elucidated. We compared the survival rates of NAC and upfront surgery in patients with clinical stage III ESCC. Consecutive patients histologically diagnosed as clinical stage III (excluding cT4) ESCC were eligible for this retrospective study. Between September 2002 and April 2007, upfront transthoracic esophagectomy was performed initially and, for patients with positive lymph node (LN) metastasis in a resected specimen, adjuvant chemotherapy using cisplatin and 5-fluororouracil every 3 weeks for two cycles was administered (Upfront surgery group). Since May 2007, a NAC regimen used as adjuvant chemotherapy followed by transthoracic esophagectomy has been administered as the standard treatment in our institution (NAC group). Patient characteristics, clinicopathological factors, treatment outcomes, post-treatment recurrence, and overall survival (OS) were compared between the NAC and upfront surgery groups. Fifty-one and 55 patients were included in the NAC and upfront surgery groups, respectively. The R0 resection rate was significantly lower in the NAC group than in the upfront surgery group (upfront surgery, 98%; NAC, 76%; P = 0.003). In the upfront surgery group, of 49 patients who underwent R0 resection and pathologically positive for LN metastasis, 22 (45%) received adjuvant chemotherapy. In the NAC group, 49 (96%) of 51 patients completed two cycles of NAC. In survival analysis, no significant difference in OS was observed between the NAC and upfront surgery groups (NAC: 5-year OS, 43.8%; upfront surgery: 5-year overall surgery, 57.5%; P = 0.167). Patients who underwent R0 resection showed significantly longer OS than did those who underwent R1, R2, or no resection (P = 0.001). In multivariate analysis using age, perioperative chemotherapy, depth of invasion, LN metastasis, surgical radicality, postoperative pneumonia, and anastomotic leakage as covariates, LN metastasis [cN2: hazard ratio (HR), 1.389; P = 0.309; cN3: HR, 16.019; P = 0.012] and surgical radicality (R1: HR, 3.949; P = 0.009; R2 or no resection: HR, 2.912; P = 0.022) were shown to be significant independent prognostic factors. In clinical stage III ESCC patients, no significant difference in OS was observed between NAC and upfront surgery. Although potential patient selection bias might be a factor in this retrospective analysis, the noncurative resection rate was higher after NAC than after upfront surgery. The survival benefit of more intensive NAC needs to be further evaluated.

[Surgical treatment of adenocarcinoma in Barrett's esophagus and prognosis].

There is no consensus regarding the surgical approach to adenocarcinoma in Barrett's esophagus. From 1980 to 1988, 8 patients with adenocarcinoma in Barrett's esophagus were treated at the National Cancer Center Hospital. Seven patients underwent subtotal esophagectomy with extended lymph node dissection, and one transhiatal esophagogastrectomy with regional lymph node dissection. In 4 patients tumor invasion was limited within the submucosa and in 4 within the muscularis propria. Four of 8 patients had stage I disease. The 5-year survival rate for the 8 patients was 64.3%. Some reports have indicated that endoscopic survey for Barrett's esophagus is important for early diagnosis. We conclude that survival after esophagectomy for adenocarcinoma in Barrett's esophagus is dependent on the method of operation, and that patients with early lesions may expect significantly better survival after extended lymph node dissection.

Assessment of cervical lymph node metastasis in the staging of thoracic esophageal carcinoma.

BACKGROUND: Cervical lymph node metastases (CLM) from esophageal carcinoma are regarded as a part of the M component of the TNM classification. Patients with CLM, however, can experience extended survival after cervical lymph node dissection, unlike patients with other M components. METHODS: Among 844 patients with thoracic esophageal carcinoma, 197 underwent esophagectomy with three-field dissection of the cervical, mediastinal, and abdominal lymph nodes (3FD). The survival of patients with CLM was compared with that of patients with hematogenous metastasis (HM), and the prognostic value of CLM was assessed. RESULTS: The survival curve for patients with CLM was significantly better than that for patients with HM (P = 0. 002). Among the 197 patients who underwent 3FD, 46 (23.4%) had histologic CLM. Of the 165 patients without hematogenous metastases, 22 (13.3%) had histologic CLM. The survival curve for the patients with histologic CLM was not significantly differ from that for patients with mediastinal or abdominal lymph node metastasis (P = 0. 127, P = 0.155) by univariate analyses. CONCLUSIONS: The significantly better survival of patients with CLM compared with that of patients with HM strongly suggests that CLM carries a prognosis different from the other M components in the staging of thoracic esophageal carcinoma. Because the survival curve for patients after 3FD was similar to that of patients with metastasis in the mediastinum or abdomen, we feel CLM should be included in the N component.

Breast cancer in Cowden's disease: a case report with review of the literature.

We report a case of invasive breast cancer in a 62-year-old female patient with Cowden's disease. A left modified radical mastectomy was performed and histopathology of the tumor showed invasive ductal carcinoma, histological grade 3, without lymph node metastasis. The patient had a past history of endometrial cancer at 55 but did not have a family history of malignant disease. Goiter was palpable but aspiration cytology revealed no malignancy. There were several papillomas on the oral mucosa and multiple papillomatous lesions on the right femur. Barium X-ray and endoscopic examination revealed multiple, small, hyperplastic polypoid lesions on the esophagus, stomach and rectum. Histopathology of the biopsy specimens from the esophagus and stomach showed acanthotic squamous epithelium and foveolar hyperplastic polyps. The patient was followed up closely to monitor the thyroid lesions and polyposis of the digestive tract. A total of 12 breast cancer patients who also had Cowden's disease have been reported in Japan and these cases are reviewed in this report.

Novel exons located more than 200 kb downstream of the previously described 3' exon of the K-sam gene for generating activated forms of KGF receptor.

The K-sam gene was first identified as an amplified gene in the poorly differentiated types, especially in the scirrhous type, of gastric cancers. We have recently found and reported that the carboxyl-terminal exons of K-sam are frequently deleted in the scirrhous type of gastric cancer. The deletion generates preferential expression of at least six novel K-sam-II mRNAs: K-sam-IIH1, -IIH2 and -IIH3/O4, and K-sam-IIO1, -IIO2, and -IIO3, which encode novel proteins lacking the transformation-inhibitory sequence or activated K-sam proteins. In this study, we investigated expression of the previously described K-sam-IIC1 and -IIC3 mRNAs and the novel six K-sam-II mRNAs in 14 gastric cancer cell lines, 7 breast cancer cell lines, and 20 human normal tissues. All the six novel K-sam-II mRNAs were expressed preferentially in the cell lines derived from the scirrhous type of gastric cancers but not in the 7 breast cancer cell lines and the 20 human normal tissues. We further determined the positional relationship of four exons of H1, O1, O2, and O3 out of the six exons of H1, H2, H3/O4, O1, O2, and O3, and found that these four novel K-sam exons were located more than 200 kb downstream of the previously described carboxyl-terminal exon of the K-sam gene. Expression of K-sam-IIH1, -IIO1, and -IIO2 mRNAs encoding activated K-sam products in the scirrhous type of gastric cancer cell lines HSC39, OCUM2M, HSC59, and HSC60 was not due to the deletion of the C1 exon of K-sam.