Feasibility of esophageal reconstruction using a pedicled jejunum with intrathoracic esophagojejunostomy in the upper mediastinum for esophageal cancer.

OBJECTIVE: An alternative conduit is needed when the gastric tube cannot be used as an esophageal substitute for reconstruction after esophagectomy. We adopted pedicle jejunal reconstruction with intrathoracic anastomosis in the upper mediastinum under such circumstances. The aim of this study was to evaluate the feasibility of this technique. METHODS: Two hundred and ten patients with esophageal cancer underwent esophagectomy and reconstruction from 1998 to 2013. Among them, 6 patients underwent colon interposition (colon group) and 13 underwent jejunum reconstruction (jejunum group) including 8 thoracoscopic anastomosis. The operative results of both groups were compared with those of 191 gastric tube reconstructions (stomach group). RESULTS: The operative times in the colon and jejunum groups were significantly longer than that in the stomach group (P = 0.001 and P = 0.018, respectively). The colon group showed more operative blood loss and more frequent anastomotic leakage and ischemic stenosis of the conduit than did the stomach group (1605 vs. 530 g, P = 0.007; 50 vs. 12.6 %, P = 0.035; 16.7 vs. 0 %, P = 0.03, respectively). There was no anastomotic leakage, conduit necrosis and mortality in the jejunum group. Ischemic stenosis of the conduit occurred more frequently in jejunum group than in the stomach group (23.1 vs. 0 %, P < 0.001). However, the stenosis could be managed safely with endoscopic treatment. Patient survival in the colon and jejunum groups was consistent with that in the stomach group. CONCLUSIONS: Pedicle jejunal reconstruction with intrathoracic anastomosis can be performed safely under thoracotomy or thoracoscopic surgery when stomach cannot be used as an esophageal substitute after esophagectomy.

Oncologic outcomes of thoracoscopic esophagectomy with extended lymph node dissection: 10-year experience from a single center.

BACKGROUND: The oncologic feasibility of video-assisted thoracoscopic (VATS) radical esophagectomy for esophageal cancer has yet to be proven. We evaluated the oncologic outcome of VATS-esophagectomy by reviewing our 10-year experience, with particular emphasis on the effect of lymph node dissection. METHODS: From January 2003 to December 2012, 146 patients with esophageal cancer underwent completion of VATS-esophagectomy in the left lateral position. RESULTS: The mean follow-up period was 37.1 months. Forty-six patients (31.5 %) had recurrence of cancer. Primary recurrence was hematogenous, lymphatic, peritoneal dissemination, pleural dissemination, locoregional, or port site in 20 (13.7 %), 23 (15.8 %), 2 (1.4 %), 5 (3.4 %), 4 (2.7 %), and 1 (0.67 %) patients, respectively. Pleural dissemination occurred more frequently after noncurative operation than curative operation (p = 0.010). The frequency of lymphatic metastasis within the mediastinal regional lymph nodes in the dissection field was only 5.5 %. The overall 5-year survival rate of stage I, II, and III disease after curative VATS-esophagectomy was 79.1, 77.9, and 56.7 %, respectively. T4 tumor, lymph node metastasis, R1 or 2, and concomitant lymph node metastasis in the cervical, mediastinal, and abdominal fields were indicators of unfavorable outcome. The lymph nodes in the abdominal region and those around the bilateral recurrent laryngeal nerves (RLNs) were frequent metastasis sites. Patients who had metastasis only around RLNs had favorable survival comparable to node-negative cases after curative VATS-esophagectomy. CONCLUSIONS: Video-assisted thorascopic-esophagectomy has an excellent locoregional control effect with favorable oncologic outcome. The lymph node dissection procedure by VATS-esophagectomy has survival benefit for the patients having lymph node metastasis around bilateral RLNs.

VEGF is a target molecule for peritoneal metastasis and malignant ascites in gastric cancer: prognostic significance of VEGF in ascites and efficacy of anti-VEGF monoclonal antibody.

BACKGROUND: In gastric cancer, poor prognosis is associated with peritoneal dissemination, which often accompanies malignant ascites. We searched for a target molecule in peritoneal metastasis and investigated its clinical utility as a biomarker. METHODS: Biopsy specimens from both primary lesions and peritoneal metastasis, and if possible, malignant ascites, were obtained from 40 patients with gastric cancer. Vascular endothelial growth factor (VEGF) expression was analyzed by immunohistochemical staining and enzyme-linked immunosorbent assay. RESULTS: VEGF expression was seen in 70% of peritoneal samples. Of the 40 patients, 35 had malignant ascites. These 35 patients were divided into two groups: 15 with ascites found beyond the pelvic cavity (large group) and 20 whose ascites were within the pelvic cavity (small group). The two groups did not significantly differ by serum VEGF levels, but ascites VEGF levels in the large group were significantly higher than in the small group (P < 0.0001). Serum VEGF and ascites VEGF levels were highly correlated in the large group (r = 0.686). A high ascites VEGF level was found to be a risk factor for survival (P = 0.045). We include a report of a patient with chemoresistant refractory gastric cancer and symptomatic ascites who obtained 8 months of palliation from systemic bevacizumab. CONCLUSION: Anti-VEGF therapies are promising, and the ascites VEGF level is an important marker in managing patients with gastric cancer and peritoneal metastasis.

[A case of gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor].

We report a case of gastric adenosquamous carcinoma producing granulocyte-colony stimulating factor (G-CSF). A 60- year-old man was admitted to our hospital complaining of upper abdominal pain. Endoscopic examination revealed a large type 5 advanced gastric cancer with bleeding from the low body of stomach to the antrum, accompanied with para-aortic and mesenteric lymph node metastasis. He had marked leukocytosis, and serum levels of G-CSF were elevated. Histological diagnosis of the biopsy specimen was adenosquamous carcinoma producing G-CSF. We attempted combination chemotherapy with docetaxel, cisplatin and S-1(DCS). After 1 course of treatment, the primary lesion was reduced in size. However, the size of the metastatic lymph node was larger. Chemotherapy was not effective enough, and the patient died 3 months after ending chemotherapy.

Tumor-derived trypsin enhances proliferation of intrahepatic cholangiocarcinoma cells by activating protease-activated receptor-2.

In primary malignant liver tumors, trypsinogen-immunoreactivity was present in 70% of intrahepatic cholangiocarcinoma (ICC) specimens, but absent in hepatocellular carcinoma (HCC) specimens. We suggest the secretion of trypsinogen to be a key difference in biological behavior between ICC and HCC cells. The purpose of this study was to investigate the secretion of tumor-derived trypsin and the expression of its specific receptor, protease-activated receptor-2 (PAR-2), in ICC using cell lines and surgical specimens. The expression of trypsinogen-1 mRNA was observed in three of four ICC cell lines, but none of three HCC cell lines. Western blot analysis detected trypsinogen-1 in serum-free conditioned medium from one of the ICC cell lines positive for the mRNA. Gelatin zymography revealed a gelatinolytic activity for trypsin, the activated form of trypsinogen, in the same conditioned medium. PAR-2 mRNA and protein were observed in ICC cell lines. The proliferative activity of ICC cells was increased by concentrations of trypsin as low as 10 nM, and peaked at 100 nM. The effect of trypsin was suppressed by a serine protease inhibitor, gabexate mesilate. PAR-2 expression was detected in 64% of ICC surgical specimens immunohistochemically. In addition, stroma fibroblasts expressed PAR-2 in 52% of ICC specimens. These results suggest that trypsinogen-1 contributes to the growth of ICC cells and also tumor-associated fibroblasts.