[A Case of Intraductal Pancreatic Mallignant Tumor with Difficulty in Differentiating between IPMN and ITPN].

The patient was a male in his early 60s. Diabetes had aggravated 6 months earlier, and the patient was referred to our hospital for close examination. On contrast CT, enhanced mass shadows filling the lumen of the main pancreatic duct, which was dilated throughout the pancreas, were observed, and the mass was diagnosed as an adenocarcinoma on EUS-FNA. Based on these findings, main-duct IPMN was suspected and total pancreatectomy was performed. On macroscopic observation of the resected specimen, outgrowth of a solid tumor was observed in the main pancreatic duct, whereas only low-level mucus retention was noted in the pancreatic duct. Histopathological examination revealed a papillary/tubular tumor growth, suggesting interstitial infiltration throughout the pancreas. On immunostaining, the tumor was partially positive for MUC5AC, based on which the patient was diagnosed with an intraductal pancreatic mallignant tumor, with difficulty in differentiating between IPMC and ITPC. Clinicopathologically, many aspects regarding ITPN remain unclear. Further accumulation of such cases and investigation of the tumor pathology are necessary.

Preoperative evaluation of accessory hepatic ducts by drip infusion cholangiography with CT.

BACKGROUND: This retrospective study aimed to investigate the incidence of each type of accessory hepatic duct by drip infusion cholangiography with CT (DIC-CT). METHODS: Five hundred sixty nine patients who underwent preoperative DIC-CT and laparoscopic cholecystectomy were reviewed. Accessory hepatic ducts were classified as follows: type I (accessory hepatic ducts that merged with the common hepatic duct between the confluence of the right and left hepatic ducts and the cystic duct confluence), type II (those that merged with the common hepatic duct at the same site as the cystic duct), type III (those that merged with the common bile duct distal to the cystic duct confluence), type IV (the cystic duct merged with the accessory hepatic duct), and type V (accessory hepatic ducts that merged with the common hepatic or bile duct on the left side). RESULTS: Accessory hepatic ducts were observed in 50 patients. Type I, II, III, IV, and V accessory hepatic ducts were detected in 32, 3, 1, 11, and 3 patients, respectively. Based on their drainage areas, the accessory hepatic ducts were also classified as follows: a posterior branch in 22 patients, an anterior branch in 9 patients, a combination of posterior and anterior branches in 16 patients, a left-sided branch in 2 patients, and a caudate branch in 1 patient. None of the patients with accessory hepatic ducts suffered bile duct injuries. CONCLUSION: There are a number of variants of the accessory hepatic duct. DIC-CT is useful to detect the accessory hepatic duct.

[Metastatic Pancreatic Carcinoma from Renal Cell Carcinoma Indistinguishable from Primary Pancreatic Endocrine Tumor - A Case Report].

A hypervascularized tumor was detected in a 65-year-old man who had underwent a nephrectomy for a right renal cell carcinoma at the age of 55 years. We diagnosed the tumor as a non-functioning pancreatic neuroendocrine tumor or a metastatic tumor from the renal cell carcinoma. We performed distal pancreatectomy with splenectomy and lymph node dissection. The tumor was histopathologically diagnosed as metastatic renal cell carcinoma.

[Metastatic breast cancer with microangiopathic hemolytic anemia successfully treated by using eribulin].

A 48-year-old woman was diagnosed with metastatic breast carcinoma and multiple bone metastases as well as a brain metastasis in 2004. Multiple bone metastases and brain metastases were also diagnosed in 2005, 2006, and 2010, but she remained stable with the use of chemotherapy and hormonal therapy for about 8 years. In 2013, severe anemia occurred, and the patient was diagnosed with microangiopathic hemolytic anemia (MHA). She was treated with eribulin(1.4 mg/m²), and recovered successfully after treatment. Approximately 8 months have elapsed after initiating the therapy, and there has been no recurrence. MHA associated with breast cancer is very rare, and is regarded as a disease with a poor prognosis. However, eribulin could be a valid treatment for prolonging the survival of patients with MHA associated with breast cancer.

[Squamous cell carcinoma of the anal canal showing complete response after concurrent chemoradiotherapy and S-1 plus mitomycin C - a case report].

The patient was a 65-year-old man who underwent colonoscopy for melena. Following a biopsy, the patient was diagnosed with anal canal squamous cell carcinoma. A computed tomography (CT) scan revealed metastasis to the regional lymph nodes. The proposed treatment regimen comprised radiotherapy combined with S-1 and mitomycin C (MMC). Dur- ing radiotherapy (59.6 Gy in 32 fractions), 10mg/m² MMC was administered, as an intravenous bolus injection, on days 1 and 29. S-1 was administered orally, at a dose of 80 mg/m², on days 1-14 and 29-42. No serious adverse events were observed during chemoradiotherapy; the observed adverse events were leukemia (Grade 2), diarrhea (Grade 1), anorexia (Grade 1), and radiation dermatitis (Grade 1). After 8 weeks of treatment, no tumors, only scar tissue could be detected by using colonoscopy, and a CT scan revealed a remarkable reduction in regional lymph node metastases. The patient achieved a complete response.

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.

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.

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.

Elevated serum CRP levels after induction chemoradiotherapy reflect poor treatment response in association with IL-6 in serum and local tumor site in patients with advanced esophageal cancer.

BACKGROUND AND OBJECTIVES: Elevated serum CRP levels are associated with tumor progression and poor prognosis of esophageal cancer. The aim of this study was to clarify the clinical significance of CRP in relation to response to chemoradiotherapy in patients with esophageal cancer. METHODS: The relationship between serum CRP levels and response to chemoradiotherapy and prognosis was analyzed in 34 patients with advanced esophageal squamous cell carcinoma who underwent induction chemoradiotherapy followed by surgery. The relationship between response to chemoradiotherapy and interleukin-6 (IL-6) expression in sera and tumor tissues was also analyzed. RESULTS: Although elevated serum CRP levels were associated with poor response to chemoradiotherapy, significant difference in CRP levels between pathological responders (n = 18) and non-responders (n = 16) was observed after chemoradiotherapy, but not before. Patients with elevated CRP levels had shorter cause-specific survival, but significant difference was observed only after chemoradiotherapy. In addition, serum levels of IL-6 were also associated with poor treatment response following chemoradiotherapy and were correlated with residual tumor volume. IL-6 expression was detected in residual tumor tissues by immunohistochemistry. CONCLUSIONS: Elevated serum CRP levels after chemoradiotherapy may predict poor response to chemoradiotherapy more accurately than before chemoradiotherapy, and IL-6 may be a possible target associated with chemoradiotherapy resistance.

[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.

[Usefulness of esophageal stenting by using a covered self-expandable metallic stent for esophagorespiratory fistula associated with esophageal carcinoma].

We report three cases of esophagorespiratory fistula associated with esophageal carcinoma successfully treated with esophageal stenting by using a covered self-expandable metallic stent (SEMS). All three cases had advanced esophageal carcinoma at middle thoracic esophagus with esophagorespiratory fistula at the level of esophageal carcinoma. Case 1 is a 58-year-old man who had lung abscess due to esophagopulmonary fistula caused after induction chemoradiotherapy. He underwent a surgical resection of the affected lung and intraoperative esophageal stenting with dietary intake starting on day 26 after stenting. Case 2 is a 60-year-old man with esophagopulmonary fistula caused after primary chemotherapy. He started to take an oral intake on day 3 after esophageal stenting. Case 3 is a 68-year-old man with esophagobronchial fistula detected at the first medical examination. He started to take an oral diet on day 7 after esophageal stenting. All three cases had a rapid improvement of respiratory symptoms, pneumonia and malnutrition by esophageal stenting leading to marked improvement of impaired general condition. Esophageal stenting is a useful method for palliation of esophageal carcinoma with respiratory fistula.

[Surgically resected local recurrence after endoscopic submucosal dissection of esophageal cancer--a case report].

We report a case of surgically resected esophageal cancer which was locally recurred after endoscopic submucosal dissection. A 66-year-old man was admitted to our hospital because of further examination and a treatment of superficial esophageal cancer. A type 0-IIb+IIa cancer occupying the whole circumference of the lumen of the middle to lower esophagus was revealed. The depth of the invasion was judged to be T1a-EP or LPM by endoscopic ultrasonography, and no metastasis to other organs or lymph nodes was detected. Endoscopic submucosal dissection (ESD) was performed. However, macroscopic residual cancer didn't seem to exist. Pathological diagnosis was squamous cell carcinoma, moderately differentiated, the depth of tumor invasion was T1a-LPM. The presence of the residual cancer of the horizontal cut margin could not be judged because en bloc resection could not be achieved. After that, endoscopic balloon dilatation of the esophageal stenosis was performed repeatedly for about one year. Then, he was diagnosed as the local recurrence of the squamous cell carcinoma of the esophagus. Thoraco-abdominal esophagectomy reconstructed by stomach tube via a retrosternal route was undergone. The final stage of the lesion was judged T3N1M0 (Stage III, UICC) by the histological examination from the resected specimen. After the operation, he is receiving adjuvant chemotherapy and alive without recurrence. When endoscopic resection of the esophageal cancer is performed to the lesion, which relatively indicated to endoscopic resection or outside the guideline criteria for endoscopic resection, it is important that we choose the appropriate treatment protocol obtaining an informed consent from the patient sufficiently.

[Radiofrequency ablation for postoperative recurrent of metastatic lesions of esophageal cancer].

Radiofrequency ablation (RFA) was performed for the postoperative recurrent of metastatic lesions of esophageal cancer in 6 patients. All patients were males, and the median age was 59. Surgical curativities were A (3 cases), B (2) and C (1). The recurrent sites were intramediastinal omentum of gastric tube (2 cases), rt lung (2), rt adrenal grand (1) and liver (1). Four cases had a single recurrent lesion and the two had multiple lesions consisted of a single lesion as RFA target, and the lesions in a different site that were simultaneously treated by other therapeutic modalities. The median time of recurrence was 12 months after esophagectomy. RFA was performed once in the 3 cases, and twice in the other 3 cases. Therapeutic effect evaluated by CT was CR (2 cases), PR (3) and SD (1). No serious complications associated with RFA procedure were observed. Three patients died due to cancer recurrence within 7 months after RFA. However, RFA-treated lesions were well controlled to the end. RFA are safe and minimally invasive, thus, can be repeatedly performed technique that can induce a good local control of the target lesion equivalent to surgical resection. RFA is applicable as an effective local therapy for the recurrent or metastatic lesions of esophageal cancer.

[PSK-mediated growth suppression and enhancement of 5-FU/docetaxel-induced cytotoxicity in human esophageal cancer cell lines].

PSK, a protein-bound polysaccharide, is widely used for treating cancer patients as an immunostimulant. However, its direct action on cancer cells is not fully understood. In the present study, we investigated direct effects of PSK alone or in combination with 5-FU, CDDP and docetaxel on tumor growth by using esophageal cancer cell lines, KYSE170 and TE13. Cells were incubated with different concentrations of PSK for 72 hour, and cell viability was determined by WST-8 assay, and cell cycle was analyzed by flow cytometry. As a result, PSK of 100 microg/mL induced growth suppression dose-dependently in the both cell lines, and flow cytometric analysis showed a PSK dose-dependent increase of sub-G1 cells indicating apoptotic cells. In addition, when cells were incubated with different concentrations of 5-FU and docetaxel in the presence of PSK at the dose of 5 microg/mL showing no growth suppression, cytotoxicity induced by 5-FU and docetaxel was significantly enhanced. These results indicate that PSK not only shows tumor growth suppression by apoptosis induction, but also enhances 5-FU and docetaxel-induced cytotoxicity.

[The IL-6 and COX-2 expression related to sensitivity of chemoradiotherapy and prognosis in esophageal carcinoma].

Chemoradiation therapy (CRT) for esophageal cancer induces inflammatory responses within tumor tissues. Inflammatory cells infiltrated into the tumor tissues may modulate the CRT responses via inflammation-related molecules such as IL-6 or COX-2. In the present study, we investigated a relationship between IL-6/COX-2 expression and CRT responses for esophageal cancer. A surgical resection following CRT was performed, and the specimens from the patients with cT3/T4 esophageal squamous cell examined for IL-6/COX-2 expression in both residual cancer and stromal cells by immunohistochemical staining. CRT responses were divided into responder group (Grade 1b and Grade 2) and non-responder group (Grade 1a). COX-2 in cancer cells and IL-6 in stromal cells were associated with non-responder and responder, respectively. In addition, IL-6 in stromal cells was significantly correlated with overall survival. Our data suggest that inflammatory responses concomitant with CRT responses could play a role in chemoradiation responses and prognosis.