Paratracheal air cyst and bronchogenic cyst in patients with esophageal cancer who received thoracoscopic esophagectomy: A case series of three patients.

INTRODUCTION AND IMPORTANCE: Mediastinal cystic lesions, such as paratracheal air cyst (PTAC) and bronchogenic cyst (BC), are rare anomaly usually found incidentally in thoracic imaging. Special attention is needed in the case of thoracic surgery. CASE PRESENTATION: All three patients were male, 71, 73, and 76 years old. Preoperative CT showed each had a lobular cystic lesion at the right posterolateral side of trachea in the thoracic outlet 11, 14, and 19 mm in size, respectively, with air density and tracheal communication, leading to a diagnosis of PTACs. An oval cystic lesion, 7 mm in size, was found in one patient at the right lateral side of the upper esophagus with low density and without tracheal communication, leading to a diagnosis of paraesophageal BC. Intraoperative findings of the three PTACs demonstrated a soft bulge from the membranous portion of trachea that was left intact. The BC had an oval elastic structure, mimicking a metastatic lymph node, and was removed with the mediastinal lymph nodes. Histological examination showed ciliated columnar epithelium, confirming a diagnosis of BC. CLINICAL DISCUSSION: PTACs are associated with increased intraluminal pressure due to chronic lung disease. BCs are congenital anomalies that originate from abnormal budding of the embryonic foregut. CONCLUSION: PTACs and BCs need to be considered in preoperative image diagnosis in patients with esophageal cancer. PTACs should be left intact to avoid tracheal injury, while removal of isolated BCs is recommended as a diagnostic and therapeutic measure.

Metachronous rupture of a residual pancreaticoduodenal aneurysm after release of the median arcuate ligament: a case report.

BACKGROUND: Multiple pancreaticoduodenal artery aneurysms in association with median arcuate ligament syndrome (MALS) are relatively rare. A treatment option, such as a median arcuate ligament (MAL) release or embolization of the aneurysms, should be considered in such cases, but the treatment criteria remain unclear. CASE REPORT: A 75-year-old man was transferred to our hospital because of a ruptured pancreaticoduodenal aneurysm. Emergency angiography showed stenosis of the root of the celiac axis (CA), a ruptured aneurysm of the posterior inferior pancreaticoduodenal artery (PIPDA), and an unruptured aneurysm of the anterior inferior pancreaticoduodenal artery (AIPDA). Coil embolization of the PIPDA was performed. Five days after embolization, the gallbladder became necrotic due to decreased blood flow in the CA region, and an emergency operation was performed. We performed a cholecystectomy and released the MAL to normalize the blood flow of the CA region. However, the patient died on postoperative day 8 because of rupture of the untreated aneurysm of the AIPDA. CONCLUSIONS: This is the first report of metachronous ruptures of multiple pancreaticoduodenal aneurysms due to MALS, even after a MAL release. Although rare, a residual aneurysm in the pancreatic head region may need to be embolized quickly.

[A Case of Long-Term Survival Following Two-Stage Surgery for Perforated Advanced Gastric Cancer Caused by Chemotherapy].

A 74-year-old man with bloody vomit was diagnosed as having clinical Stage Ⅳ advanced gastric cancer with lymph node metastasis around the abdominal aorta. Initially, for curative surgery, he was administered neoadjuvant chemotherapy. On day 32, in the second course of chemotherapy containing S-1 after 12 courses of chemotherapy containing S-1 and cisplatin, he developed pan-peritonitis owing to the perforation of gastric cancer caused by chemotherapy, and thus, we performed emergency omental implantation and peritoneal drainage. He was discharged from the hospital after 14 days with no trouble. His gastric cancer was judged to be resectable without retaining metastatic lymph nodes based on intraoperative findings and abdominal computed tomography. Therefore, 3 months after the emergency surgery, he underwent total gastrectomy with D1+(+No. 11d)lymphadenectomy. The postoperative course was uneventful. He rejected adjuvant chemotherapy despite our recommendation. Regrettably, intraabdominal dissemination was observed 15 months after total gastrectomy, and he then received chemotherapy again. He has remained alive for 57 months after the first visit to our hospital.

[A case of locally advanced pancreatic cancer successfully resected after gemcitabine+S-1 therapy].

A 6 1-year-old man who was admitted to our hospital because of obstructive jaundice. He was diagnosed with locally advanced cancer of the pancreatic head on computed tomography. Gemcitabine (1,000 mg/m² on days 8 and 15, every 21 days) + S-1 (6 0 mg/m² on day 1-15, every 21 days) chemotherapy was administered because the tumor had invaded the common hepatic artery and portal vein. The tumor was reduced following 9 months of chemotherapy. Thus, subtotal stomach- preserving pancreaticoduodenectomy (SSPPD)was performed. The histopathological findings indicated no invasion of the cancer into the surrounding tissues. No recurrence has occurred 7 months after surgery. Neoadjuvant chemotherapy is important for effective treatment of locally advanced pancreatic cancer.

Prognostic significance of NANOG and KLF4 for breast cancer.

BACKGROUND: Some of the induced pluripotent stem cell (iPS cell)-inducing factors have been reported to be expressed in breast cancer. The aim of the present study was to examine the relationship between the expression of iPS cell-inducing factors and the prognosis of breast cancer patients. METHODS: In 100 breast cancer patients, the expression of c-MYC, KLF4, NANOG, OCT4, and SOX2 was determined by immunohistochemistry using a tissue microarray analysis. RESULTS: Patients with strong expression of NANOG had significantly lower disease-free survival (DFS) and overall survival rates than those with weak expression of NANOG (P = 0.004 and 0.033, respectively). In contrast, patients with strong expression of KLF4 had better DFS (P = 0.014). CONCLUSIONS: Strong expression of NANOG is an indicator of a poor prognosis for breast cancer patients, whereas KLF4 is a favorable prognostic indicator. Our results suggest that NANOG stimulates the growth and metastasis of breast cancer cells, whereas KLF4 inhibits these processes.

A case of progressing focal nodular hyperplasia and its molecular expression pattern.

We report the case of an adult male with progressing focal nodular hyperplasia (FNH). Although imaging studies suggested that the tumor was a classical FNH, the tumor biopsy showed glutamine synthetase expression and heat shock protein 70 in part of the tumor. As we could not definitely distinguish this case of FNH from early hepatocellular carcinoma (HCC), we performed laparoscopic partial hepatectomy. The surgical resected specimen showed that the tumor had a central scar with vascular and cholangiolar proliferation, which is compatible with FNH. Immunohistochemical analysis showed that the molecular expression pattern was compatible with FNH in the center of the tumor, whereas it partly resembled early HCC in the periphery of the tumor. FNH progression is occasionally found, and the molecular pattern of the progressing area in FNH might resemble that of early HCC due to morphologic and phenotypic changes induced by the regenerative mechanism and the alteration of blood flow. We should carefully observe progressing FNH.

Expression of GLUT-1 and GLUT-3 in xanthogranulomatous cholecystitis induced a positive result on ¹8F-FDG PET: report of a case.

Although several reports have revealed that fluorine-18 fluorodeoxyglucose positron emission tomography ((18)F-FDG PET) is useful for differentiating between benign and malignant lesions in the gallbladder, the positive results of (18)F-FDG PET are not specific for malignancy because (18)F-FDG is also accumulated in inflammatory lesions. It is known that the most important pathway for (18)F-FDG to enter the cell body is mediated by the facilitative glucose transporter-1 (GLUT-1) through GLUT-3. We herein present a case of xanthogranulomatous cholecystitis (XGC) with a positive result on (18)F-FDG PET. In this case, GLUT-1 and GLUT-3 were both positively expressed in inflammatory cells at the gallbladder wall of XGC and this is the first report to reveal GLUT expression in XGC. This report reveals that surgeons should carefully consider the appropriate treatment of gallbladder tumor, even with a positive result on (18)F-FDG PET.

Glucose transporter 3 and 1 may facilitate high uptake of 18F-FDG in gastric schwannoma.

Recently, some gastric schwannomas have been reported to have high uptake of FDG. However, Glut-1 was reported to be negative in gastric schwannomas tested. A 64-year-old female patient received a laparoscopic partial gastrectomy for a FDG PET-positive submucosal tumor (SUVmax 6.61). The resected tumor was diagnosed as a benign gastric schwannoma. Glut family immunohistochemical examination revealed diffuse positive expression of Glut-3 and partial positive expression of Glut-1. On the other hand, Glut-2 and Glut-4 expression in the tumor were negative. This case suggested that Glut-3 and Glut-1 expression were facilitators of high FDG uptake in the benign gastric schwannoma.

Clinicopathological significance of deoxycytidine kinase expression in esophageal squamous cell carcinoma.

Deoxycytidine kinase (dCK) mediates the rate-limiting catabolic step in the activation of gemcitabine. Gemcitabine is a key drug for pancreatic and biliary tract cancer. However, gemcitabine is not widely used for esophageal squamous cell carcinoma (ESCC). In this study, we analyzed the expression of dCK in ESCC and evaluated the possibility of gemcitabine treatment for ESCC. In total, 76 ESCC patients who underwent esophagectomy between 1990 and 2008 were analyzed. dCK expression was analyzed immunohistochemically using tissue microarray and compared to the clinocopathological characteristics of the patients. Results identified 41 patients positive for dCK and 35 patients negative for dCK. A significant association was observed between dCK expression and gender (P=0.01), whereas the remaining factors were not associated with dCK expression. Prognosis of the patients with a high dCK expression was significantly worse than that of the patients with a low dCK expression (P=0.022). Furthermore, dCK expression was an independent prognostic factor regarding cause-specific prognosis (risk ratio, 2.2; P=0.031). In conclustion, the results of the present study suggested that dCK expression is a prognostic factor of the ESCC patients.

Expression of aquaporin-1 is a poor prognostic factor for stage II and III colon cancer.

Colorectal cancer is a major cause of cancer-related mortality worldwide, with a high incidence of recurrence following curative resection, particularly among patients with stage II and III disease. There is therefore a need for novel prognostic biomarkers for advanced colon cancer and it was recently reported that aquaporin-1 (AQP1) may be associated with aggressive characteristics of colon cancer cells in experimental data. The association of clinicopathological findings with AQP1 expression was evaluated by tissue microarray (TMA) analysis, to determine whether AQP1 is a prognostic biomarker for colon cancer. A total of 120 consecutive stage II and III colon cancer patients (51 with stage II and 69 with stage III) who underwent curative resection between 1997 and 2008 were analyzed. The TMA was prepared from archival formalin-fixed, paraffin-embedded tissue blocks. Immunostaining was graded semi-quantitatively by considering the staining intensity and the percentage of positive tumor cells. Results showed the AQP1-positive rate to be 35.8%. The expression of AQP1 was associated with lymph node metastasis, lymphovascular and vascular invasion. The 5-year survival rate of the AQP1-positive and -negative groups was 73.7 and 87.9%, respectively. The survival rate of the positive group was significantly lower compared to that of the negative group (P=0.030). Furthermore, the expression of AQP1 was an independent poor prognostic factor according to the multivariate analysis. Therefore, AQP1 may be a promising candidate as a prognostic biomarker for colon cancer.

Establishment and characterization of a novel xenograft model of human gastrointestinal stromal tumor in mice.

BACKGROUND: The clinical outcome of gastrointestinal stromal tumor (GIST) has been improved by the introduction of molecular-targeting drugs. However, resistance to these drugs appears during the course of treatment. The aim of this study was to establish and characterize a human xenograft model of GIST. MATERIALS AND METHODS: GIST tissue from a patient with esophageal GIST was implanted under the skin of a NOD-SCID mouse. The tumor became successfully engrafted and we investigated the effects of imatinib and sunitinib on this model. KIT mutation was investigated by complementary DNA analysis, and c-KIT (CD117) expression was evaluated by immunohistological staining. RESULTS: cDNA analysis of the tumor revealed a KIT mutation in exon 11. c-KIT expression was observed in each passaged tumor. Both imatinib and sunitinib significantly reduced the size of the xenograft tumor. CONCLUSION: We established a novel xenograft model of human GIST in mice. This xenograft model may be useful for studying GIST.

Expression analysis of iPS cell - inductive genes in esophageal squamous cell carcinoma by tissue microarray.

AIM: To understand the role of iPS inductive genes in esophageal cancer, we examined the expression of Sex determining region Y-box 2 (SOX2), Octamer-binding transcription factor 3/4 (OCT3/4), Krueppel-like factor 4 (KLF4), c-Myelocytomatosis viral oncogene (c-MYC) and Tir Na Nog (NANOG) using an esophageal squamous cell carcinoma tissue micrroarray. MATERIALS AND METHODS: The immunohistochemical expression levels of the five genes were compared to the clinicopathological data of the 81 patients with esophageal cancer. RESULTS: There was no relationship between the expression of the five genes and TNM factors of the patients. High expression of NANOG was an independent favorable prognostic factor (p=0.041). Among the patients who received postoperative cisplatin-based chemotherapy, patients with NANOG-positive tumor had significantly better prognosis than those whose tumors were NANOG negative (p=0.024). On the other hand, those with c-MYC-positive expression tended to have a worse prognosis and were resistant to cisplatin-based chemotherapy. CONCLUSION: NANOG expression was found to be an independent prognostic factor for patient with esophageal cancer. Patients with NANOG-positive expression tumor may be good candidates for cisplatin-based treatment.

Establishment and characterization of a new human gallbladder carcinoma cell line.

BACKGROUND: Prognosis for patients with gallbladder carcinoma (GBC) is poor and the standard treatment for GBC has not yet been established. MATERIALS AND METHODS: We established the human GBC cell line TYGBK-1, from a patient with papillary, tubular adenocarcinoma. RESULTS: The doubling time was 48 hours. This cell line has a missense mutation of p53 and no mutation of the K-RAS gene. This cell line was transplantable to nude mice. We characterized the sensitivity of TYGBK-1 to gemcitabine. We also examined the association of two gemcitabine-related genes (deoxycytidine kinase, dCK, and Hu antigen R, HuR). Among four GBC cell lines (TYGBK-1, NOZ, G-415, TGBC2TKB), TYGBK-1 and NOZ exhibited sensitivity to gemcitabine. Furthermore, these cells expressed both dCK and HuR mRNA, rather than gemcitabine-resistant cells. CONCLUSION: The newly established GBC cell line TYGBK-1, may represent an effective tool for development of chemotherapeutic treatment for GBC.

Successful enucleation of a fluorine-18-fluorodeoxyglucose positron emission tomography positive esophageal leiomyoma in the prone position using sponge spacer and intra-esophageal balloon compression.

Recently, prone position esophagectomy for esophageal cancer is thought to be an easier and safer procedure. Here, we introduced prone position for enucleation of the fluorine-18-fluorodeoxyglucose positron emission tomography (FDG-PET) positive esophageal leiomyoma. The patient was a 47-year-old man with a 4 cm mid-thoracic esophageal submucosal tumor. The tumor was enucleated safely without injury of the esophageal mucosa under the gravity effect of the prone position with use of a sponge spacer and Sengstaken-Blakemore balloon. Postoperative examination revealed that the tumor was a leiomyoma that was positive for smooth muscle actin and negative for CD117. Postoperative course was uneventful and the patient was discharged on day 7 after the operation. The prone position with use of a sponge spacer and Sengstaken-Blakemore balloon was a safer and easier procedure for the enucleation of the esophageal submucosal tumor.

Prognostic significance of aquaporins in human biliary tract carcinoma.

Aquaporins (AQPs) are important in controlling bile formation, however, the exact role of AQPs in human biliary tract carcinogenesis has not been clearly defined. In this study, we analyzed AQP-1, -4, -5 and -8 expression immunohistochemically using tissue microarrays (TMAs) in 81 samples. (45 gallbladder carcinomas and 36 bile duct carcinomas). The survival of patients with high AQP-5 expression was longer compared to that of patients with low AQP-5 expression (P=0.017). Cox's proportional hazard model revealed that AQP-5 expression was an independent prognostic factor (RR, 0.38; P=0.025). Chi-square analysis revealed that high AQP-5 expression correlated to small tumor size in biliary tract carcinoma patients (P=0.006). With regard to the expression of other AQPs, depth of tumor invasion, histological type and serum carbohydrate antigen 19-9 (CA19-9) were associated with high AQP-1 expression (P=0.039, 0.011 and 0.032). However, AQP-4 and AQP-8 expression had no association with clinicopathological factors. Among the 10 patients who underwent gemcitabine (GEM) plus S-1 postoperative chemotherapy, the group of patients (n=5) with high AQP-5 expression were associated with higher rates of both overall and disease-free survival (log-rank P=0.033, 0.002). In conclusion, the results of this study suggest that AQP-5 expression may be associated with prognosis and drug sensitivity in biliary tract carcinoma.

Usefulness of blood supply visualization by indocyanine green fluorescence for reconstruction during esophagectomy.

BACKGROUND: Adequate blood supply for the reconstructed organ is important for safe esophagogastric anastomosis during esophagectomy. Recently, indocyanine green (ICG) has been used for visualization of the blood supply when anastomosis is performed in vascular surgery. To visualize the blood supply for reconstruction, we employed ICG fluorescence during esophagectomy. METHODS: From August 2008, 40 patients received cervical or thoracic esophagectomy. They consisted of 33 patients having esophagectomy for thoracic esophageal cancer, 3 being treated for cervical esophageal cancer, and 4 with double cancer of the thoracic and cervical regions. Before and after pulling up the reconstructed organ, 2.5 mg of ICG was injected as a bolus. Then ICG fluorescence was detected by a camera and recorded. RESULTS: ICG fluorescence was easily detected in all patients at 1 min after injection. The vascular network was well visualized in the gastric wall, colonic grafts, and free jejunal grafts. In five patients, we also performed anastomosis between the short gastric vein and the external cervical vein or superficial cervical vein. The intraoperative and postoperative course of all patients was uneventful apart from three anastomotic leakages. CONCLUSIONS: ICG fluorescence can be employed to evaluate the blood supply to reconstructed organs and can be useful in selecting the patients who do not need additional vessel anastomosis. However, anastomotic leakage was not reduced, so the microcirculation detected by ICG fluorescence did not necessarily provide appropriate blood supply for a viable anastomosis.

Clinical significance of biliary vascular anatomy of the right liver for hilar cholangiocarcinoma applied to left hemihepatectomy.

OBJECTIVES: To evaluate the influence of confluence pattern of the right posterior sectional bile duct (RPSBD) on clinocopathological outcome in patients with hilar cholangiocarcinoma who underwent left hemihepatectomy (LH). SUMMARY BACKGROUND DATA: Biliary vascular anatomy may affect the cutting line of proximal bile ducts, especially in case of LH, because of the shorter distance from the sectional ramification to the ductal confluence. However, there were few studies as to the relationship between anatomic variation and clinocopathological outcome. METHODS: A total of 209 patients with hilar cholangiocarcinoma underwent surgical resection. We retrospectively investigated confluence patterns of the RPSBD in relation to the right portal vein (RPV) by preoperative imaging studies in 63 patients who underwent LH, and classified them into 3 groups (supraportal type: the RPSBD runs cranially around the RPV; infraportal type: the RPSBD runs caudally to the RPV; combined type: one segmental duct runs infraraportally and the other supraportally to the RPV). Furthermore, the effects of these variations on clinocopathological outcome were evaluated. RESULTS: The supraportal type was observed in 53 cases (84.1%), the infraportal type in 8 cases (12.7%), and the combined type in 2 cases (3.2%). Although most of the clinocopathological features were similar between the groups, positive margin of proximal bile duct was significantly lower in the infraportal group, as compared with the supraportal group. Furthermore, it was noted that there was no incidence of bilioenteric anastomotic leakage in the infraportal group. CONCLUSIONS: Negative proximal margin and secure reconstruction were more easily achieved in the infraportal group than in the supraportal group. Preoperative evaluation of confluence pattern of RPSBD may be clinically useful for the management of hilar cholangiocarcinoma when applied to left-sided hepatectomy.

Continuous irrigation with suction started at early days after pancreatic surgery prevents severe complications.

The management of pancreatic leakage is important after pancreatic resection because such leakagge can be associated with additional complications. In this paper, we present a new therapy "irrigation with suction" after pancreatic surgery. The addition of suction permits the start of irrigation early after surgery and prevents severe post-operative complications. Between January 1995 and June 2003, 29 consecutive patients underwent surgical treatment of the pancreas for a variety of indications. Among them, 18 patients were treated with continuous irrigation with suction prophylactically. In these 29 patients, we did not encounter any additional complications such as intraabdominal hemorrhage or abscess formation. A representative case report demonstrates the application of this treatment. The irrigation with suction therapy was started on the first post-operative day after the pylorus-preserving pancreatoduodenectomy with left lobectomy of the liver. CT with irrigation of contrast reagent showed that the reagent did not spread to the uninvolved abdominal area, and the patient did not develop hemorrhage or abscess. It seems that continuous irrigation with suction therapy was effective in preventing additional serious complications after pancreatic resection.

[A successfully resected case of colorectal cancer with multiple liver metastases treated with FOLFIRI after failure of mFOLFOX6].

A sixty-year-old man was admitted with anorexia and abdominal mass. Colonoscopy revealed type 2 tumor at sigmoid colon. Computed tomography (CT) demonstrated multiple liver metastases. The patient was diagnosed as sigmoid colon cancer with multiple liver metastases. The patient was treated with mFOLFOX6 as neoadjuvant chemotherapy because the liver metastases were unresectable. However, after 2 cycles of mFOLFOX6, the level of CEA and CA19-9 much increased. The regimen was replaced by FOLFIRI. The level of CEA and CA19-9 decreased after 2 cycles of FOLFIRI. CEA and CA19-9 further decreased and colonoscopy and CT revealed a partial response after 5 cycles of FOLFIRI. The patient was subjected to curative resection. Sigmoidectomy and liver resection were performed. Histological response was Grade 1b at liver metastasis. The patient was discharged and had an uneventful recovery. Six months after surgery, CEA and CA19-9 decreased to normal level, and the patient is free of recurrence. Neoadjuvant chemotherapy for metastatic colorectal cancer may render some unresectable patients resectable, affording these patients the possibility of prolonged survival. However, the optimal approach is unknown.

Treatment with an oral fluoropyrimidine, S-1, plus cisplatin in patients who failed postoperative gemcitabine treatment for pancreatic cancer: a pilot study.

BACKGROUND: This study set out to evaluate, in patients with gemcitabine-resistant pancreatic cancer, the response rate and toxicity of S-1 plus cisplatin (CDDP). METHODS: Seventeen patients with histologically diagnosed invasive ductal pancreatic cancer were enrolled in this study. All patients had growing recurrent pancreas cancer despite the administration of gemcitabine. Thirteen patients underwent pancreatectomy, and 2 underwent choledochojejunostomy and gastrojejunostomy without pancreatectomy. S-1 (80 mg/m(2) per day) was orally administered for 21 consecutive days, followed by a 14-day rest period. CDDP (40 mg/m(2)) in 500 ml saline was administered by intravenous drip on day 8. This schedule was repeated every 5 weeks until the occurrence of disease progression, unacceptable toxicities, or the patient's refusal to continue. RESULTS: Five (29.4%) patients achieved a partial response and 2 (11.8%) had stable disease. In 5 of 15 patients (33.3%) who had elevated serum carbohydrate antigen (CA)19-9 levels at the start of treatment the CA19-9 was reduced by more than 50%. The median survival time was 10 months (range, 20 months), with 63.7% and 31.9% of patients alive at 6 and 12 months, respectively. Major adverse reactions in the 15 patients included gastrointestinal toxicities of grade 1 or 2. Only one patient (5.9%) developed grade 3 leucopenia. CONCLUSION: S-1 with CDDP has a promising effect against gemcitabine-resistant pancreatic cancer, with easily manageable toxicities. Further investigation of this regimen is warranted in patients with pancreatic cancer, especially in comparison with gemcitabine.