[A Resected Case of Intraperitoneal Foreign Body Granuloma Mimicking Peritoneal Dissemination].

Foreign body granuloma(FBG)is a granuloma that occurs due to chronic inflammation caused by various residual foreign objects. In the field of gastrointestinal surgery, intraperitoneal foreign body granulomas(IPFBGs)are often caused by sutures materials or residual gauzes, but those caused by food residue are extremely rare. We present an IPFBG case of food residue caused by anastomotic leakage, which was difficult to be distinguished from peritoneal dissemination. The patient is a 74- year-old male. Anastomotic leakage occurred following low anterior resection for rectal cancer, peritoneal drainage and ileostomy were performed. 1.5 years after rectal resection, liver metastasis was diagnosed by CT and peritoneal dissemination was diagnosed by PET-CT. Both lesions were resected at the same time. The pathological findings were liver metastasis and FBG. It was presumed to be an FBG formed by food residue left behind after anastomotic leakage. It has reported that FBG caused by residual gauzes were shown a ring-shaped uptake by PET-CT, but that was not observed in our case. In addition, since a nodule suspected of liver metastasis was observed simultaneously, we considered no differential diagnosis other than peritoneal dissemination. IPFBG resembling peritoneal dissemination, occurred after anastomotic leakage. A food residue can cause IPFBG, it is necessary to consider IPFBG in decision making treatment strategy for peritoneal nodule.

[A Strategy of Treatment for Perforated Gastric Cancer].

In past reports, the incidence of gastric perforation accounts for 0.08 to 3.6% of all gastric cancers, and the proportion of perforated gastric cancer(PGC)in gastric perforations is 26 to 32%. In the treatment of PGC, critical care for peritonitis, diagnosis of gastric cancer and curability for gastric cancer are required simultaneously, so it is not easy to decide the treatment strategies. Therefore, for the purpose to consider treatment strategies for PGC, we conducted a clinicopathological study on PGC in our hospital for the past 12 years. There were 22 cases of PGC, and we analyzed clinicopathologically 19 cases excluding perforation during endoscopic resection and perforation during chemotherapy. The R0 surgery group tended to have a good prognosis even in PGC cases, and there was surgery-related death in the one-stage gastrectomy group. So it was considered desirable to perform radical surgery after the general condition was stable by the treatment of peritonitis was given priority in the PGC.

Spontaneous Rupture of Renal Metastasis from Hepatocellular Carcinoma.

We report a rare life-threatening case of spontaneous rupture of renal metastasis from hepatocellular carcinoma (HCC) that was managed by emergent transcatheter arterial embolization (TAE). A 76-year-old woman diagnosed with HCC presented with acute back pain in her right side and was transferred to our hospital. Initial enhanced computed tomography revealed retroperitoneal hemorrhage from the right kidney, which was retrospectively diagnosed as a spontaneous rupture of the metastatic renal tumor from the primary HCC. Detailed examination identified an active retroperitoneal hemorrhage from the lesion and the patient's condition became hemodynamically unstable; hence emergent TAE was performed. The hospitalization period after the TAE was uneventful and sorafenib was subsequently administered. Unfortunately, two months after the TAE, the tumor locally progressed within the retroperitoneal space. Tumors were controlled by repeated TAE as the patient did not want to undergo a nephrectomy. Consequently, she survived for more than one year after emergent TAE, exhibiting low levels of tumor marker. After rupture of the metastatic renal HCC, tumors were expected to progress into the retroperitoneal space, and nephrectomy was the next possible radical treatment to offer the best chance of long-term disease control.

Prognostic impact of tumor IL-6 expression after preoperative chemoradiotherapy in patients with advanced esophageal squamous cell carcinoma.

Elevated serum interleukin-6 (IL-6) levels have been associated with tumor progression and poor prognosis in patients with esophageal carcinoma. The purpose of the present study was to clarify such a relationship in patients with esophageal squamous cell carcinoma with a focus on the possible influence of chemoradiotherapy (CRT) on tumor IL-6 expression. Data regarding 41 patients with clinical T3-T4 tumors who underwent induction chemoradiotherapy followed by surgery (CRT group) and 60 patients with clinical T1-T4 tumors who underwent surgery alone (Surgery group) between 2001 and 2010, were retrospectively analyzed. Tumor IL-6 expression in resected specimens was evaluated by immunohistochemistry. Tumor IL-6 expression was detected in patients with advanced tumors in the Surgery group (21.1% in p(stage) III-IV vs. 0.2% in p(stage) I-II; 27.8% in pT3-4 vs. 0% in pT1-2), and also correlated with primary tumor progression and surgical curability in the Surgery group. In addition, patients with IL-6-positive tumors had significantly shorter overall survival than those with IL-6-negative tumors in the CRT group, and tumor IL-6 expression had an independent prognostic value in multivariate analysis, whereas no significant difference in overall survival was observed between patients with IL-6-positive and those with IL-6-negative tumors in the Surgery group. These results indicate that pre-treatment tumor IL-6 expression correlates with primary tumor progression, and CRT-induced tumor IL-6 expression predicts poor prognosis.

Overexpression of IL-6 by gene transfer stimulates IL-8-mediated invasiveness of KYSE170 esophageal carcinoma cells.

Interleukin-6 (IL-6) has been associated with disease progression and poor prognosis in esophageal carcinoma. The aim of this study was to investigate the possible influence of IL-6 on the biological activities of esophageal carcinoma cells in terms of invasiveness. The human esophageal carcinoma cell line, KYSE170, was transfected with a plasmid vector expressing IL-6, and a stable transfectant overexpressing IL-6 was established. Invasiveness was evaluated by an invasion assay and compared between IL-6 and control transfectants. The invasiveness of the IL-6 transfectant was significantly higher than that of the control transfectant, and was significantly reduced by IL-6-specific siRNA. In reverse transcriptase-polymerase chain reaction (RT-PCR) analysis, IL-8 expression was significantly higher in the IL-6 transfectant than in the control transfectant, whereas the expression of Hepatocyte growth factor (HGF) and Vascular endothelial growth factor (VEGF) was not different. IL-8 expression in the IL-6 transfectant was significantly inhibited by IL-8-specific siRNA, whereas IL-6 expression was not. In addition, the invasiveness of the IL-6 transfectant was significantly reduced by IL-8-specific siRNA. These results indicate that the overexpression of IL-6 increases the invasiveness of KYSE170 esophageal carcinoma cells and IL-6-induced IL-8 plays a predominant role in increasing invasiveness.

COX-2 overexpression Induced by gene transfer reduces sensitivity of TE13 esophageal carcinoma cells to 5-fluorouracil and cisplatin.

Previous clinicopathological studies demonstrated that overexpression of cyclooxygenase-2 (COX-2) is associated with a poor treatment response of esophageal carcinoma. The aim of this study was to elucidate the role of COX-2 overexpression in the chemosensitivity of esophageal carcinoma cells. TE13 human esophageal squamous cell carcinoma cells were transfected with a COX-2 constitutive expression vector, and stable transfectants overexpressing COX-2 were established. COX-2 overexpression in COX-2 transfectants was confirmed with western blotting and prostaglandin-E(2) (PGE(2)) assay. Chemosensitivity testing revealed that sensitivity of COX-2 transfectants to 5-fluorouracil and cisplatin was significantly lower than in control vector-only transfectants, and that sensitivity of COX-2 transfectants was restored by the transfection of COX-2-specific siRNA. In addition, expression of antiapoptotic B-cell lymphoma-extra large (BCL-xL) and myeloid cell leukaemia-1 (MCL-1) was increased in COX-2 transfectants. These results indicate that COX-2 overexpression may reduce the chemosensitivity of esophageal carcinoma cells through up-regulation of the expression of antiapoptotic BCL-2 family proteins.

Time course of serum C-reactive protein levels during induction chemoradiotherapy and its correlation with treatment response and survival in patients with advanced esophageal squamous cell carcinoma.

Preoperative serum C-reactive protein (CRP) levels have been shown to be of prognostic significance in patients with advanced esophageal carcinoma. However, the clinical significance of serum CRP levels in patients with unresectable or marginally resectable tumors in the absence of induction therapy has not been fully elucidated in relation to treatment response and prognosis. Thirty-four patients with clinical T3-T4 esophageal squamous cell carcinoma who underwent induction chemoradiotherapy (CRT) followed by esophagectomy were enrolled in this retrospective study. Serum CRP levels were measured during the course of CRT, i.e., prior to, during (1, 2, 3 and 4 weeks following initiation) and after CRT (prior to surgery). The association between CRP levels, CRT response and survival was analyzed. Elevated serum CRP levels exhibited a favorable decrease 2-3 weeks following CRT initiation in pathological responders and CRP ≤0.3 mg/dl at 2 and 3 weeks following CRT initiation, as well as prior to surgery, was significantly correlated with responders. In patients with pretreatment CRP >0.3 mg/dl (67.6% of patients in this study), CRP ≤0.3 mg/dl at 2 and 3 weeks following CRT initiation predicted responders with accuracies of 87.0 and 73.9%, respectively. In the univariate survival analysis, CRP levels 3 weeks following CRT initiation, as well as CRP levels prior to surgery and pathological stage, were significant prognostic factors, although CRP levels prior to surgery was the only independent prognostic factor in the multivariate analysis. Serum CRP levels during the course of CRT may be of prognostic and predictive significance for the CRT response in patients with unresectable or marginally resectable esophageal squamous cell carcinoma who undergo induction CRT.

PSK induces apoptosis through the inhibition of activated STAT3 in human esophageal carcinoma cells.

PSK, a protein-bound polysaccharide, is widely used in Japan as an immunopotentiating biological response modifier for cancer patients. PSK exerts antitumor activities through stimulation of the host's immune response; however, few studies have addressed the direct actions of PSK on tumor cells. Recently, it has been found that STAT3 is aberrantly activated in various types of malignancies, and plays a crucial role in tumor cell proliferation and survival. In the present study, STAT3 was constitutively activated in KYSE170 and TE13 esophageal carcinoma cells, and PSK inhibited proliferation and induced apoptosis in these cells in a dose-dependent manner. Based on these findings, the relationship between STAT3 and apoptosis in these cells was investigated. Results showed that PSK inhibited the expression of activated STAT3 and stimulated the expression of pro-apoptotic Bax in a dose-dependent manner, without affecting the expression of anti-apoptotic Bcl-xL and Mcl-1. These results indicate that PSK may induce apoptosis in esophageal carcinoma cells by inhibiting the expression of activated STAT3.

[A case of residual metastatic lymph node lesion following definitive chemoradiotherapy for T4 esophageal cancer, successfully treated by outpatient clinic-based sequential chemotherapy with docetaxel followed by S-1].

Patients with T4 esophageal cancer generally have poor prognosis. Of these patients, prognosis of non-responder to chemoradiothrapy (CRT) is extremely poor. We report a case of residual lymph node metastasis following definitive CRT, which showed a good response to outpatient clinic-based chemotherapy consisting of docetaxel (DOC) followed by S-1 in a patient with T4 esophageal cancer. The patient was a 65-year-old man with the diagnosis of squamous cell carcinoma of the middle thoracic esophagus with the 5 cm size lymph node metastasis with tracheal invasion along right recurrent laryngeal nerve [T4 (106recR-rt subclavian A) N2M0, Stage IVa]. He underwent induction chemotherapy with two courses of FP followed by one course of DCF. As a result, primary tumor was judged as complete response on endoscopy, and the lymph node lesion was judged as partial response, but unresectable on CT. Then, he underwent definitive CRT (FP+60 Gy). Following CRT, although the lymph node lesion was judged as non-CR on CT, a significant decrease of FDG uptake (PET-CR) was observed on PET-CT. Five months later, a recurrence of the lymph node lesion was observed on PET-CT. Then, he underwent outpatient clinic-based chemotherapy with DOC( 60 mg/m², triweekly) followed by S-1( 80 mg/ body/day, 6 weeks/course, administration for 4 weeks with 2 weeks cessation). DOC was administered for 8 months, and was converted to S-1 because of the regrowth of the lesion on PET-CT. After 3 months following initiation of S-1, a remarkable decrease of the lesion was observed on PET-CT. During outpatient clinic observation, the residual lymph node lesion after definitive CRT was well controlled over 1 year, and no new metastatic lesions were observed at other sites. Sequential chemotherapy with DOC followed by S-1 may be effective in controlling progression of resistant tumor against prior CRT.

Overexpression of Interleukin-6 suppresses cisplatin-induced cytotoxicity in esophageal squamous cell carcinoma cells.

Interleukin-6 (IL-6) expression at local tumor sites or in systemic circulation is associated with disease progression and poor prognosis of esophageal cancer. The aim of this study was to investigate the possible influence of IL-6 on biological activities of esophageal cancer cells in terms of chemosensitivity. Human esophageal cancer cell lines TE13 and KYSE170 were transfected with a plasmid vector expressing IL-6 and stable transfectants overexpressing IL-6 were thus established. The sensitivity of IL-6 transfectants to cisplatin was evaluated using a WST-8 assay and cell-cycle analysis. In addition, the inhibitory effects of IL-6-specific siRNAs were investigated. IL-6 transfectants showed significantly reduced sensitivity to cisplatin compared to control transfectants. In addition, the reduced cisplatin sensitivity of IL-6 transfectants was restored by pretreatment with IL-6-specific siRNA. These results suggest that intracellular IL-6 expression in tumor cells may acts as a resistance factor against cisplatin-based treatments for esophageal cancer.

[Early prediction of treatment response by serum CRP levels in patients with advanced esophageal cancer who underwent definitive chemoradiotherapy].

Serum CRP has been shown to be associated with the progression of esophageal cancer. The purpose of this study was to examine the relationship between treatment response and serum CRP levels in time course during definitive chemoradiotherapy (CRT) in terms of early prediction of CRT response by serum CRP. The subjects of this study were 36 patients with cT3/cT4 esophageal squamous cell carcinoma who underwent definitive CRT in our hospital. Serum CRP levels during definitive CRT (pretreatment, 1W, 2W and 3W after CRT initiation) were compared between CR and non-CR group. In addition, partition model was constructed to discriminate CR with non-CR and the prediction accuracy was evaluated. The patients were consisted of 28 males and 8 females. At pretreatment diagnosis, tumors were categorized as T3 (n=21) and T4 (n=15). Thirty four patients received FP-based chemotherapy and 2 patients received docetaxel-based chemotherapy. Treatment responses were categorized as CR (n=8), PR (n=14), NC (n=2) and PD (n=12). Serum CRP levels at the time of 2W after CRT initiation (CRT2W) in CR group were low compared to those in non-CR group (p=0.071). The partition model was constructed based on CRP levels at CRT2W. The prediction accuracies to discriminate CR from non-CR by CRP≤0.1 were 50%, 82%, and 75% in sensitivity, specificity and accuracy, respectively. Serum CRP is a useful biomarker for an early prediction of CRT response.