[Collision Lung Cancer Consisting of Squamous Cell Carcinoma and Adenocarcinoma which Showed Identical Epidermal Growth Factor Receptor Mutation;Report of a Case].

We report a 79-year-old woman with collision cancer in the right middle lobe of the lung. She had a persistent abnormal shadow after treatment for pneumonia pointed out in right middle lung field on chest radiogram, and referred to our hospital. On examination, the chest computed tomography showed a pure-solid mass of 7.6 cm in diameter in right middle lobe of the lung which was thought to invade the superior pulmonary vein. She underwent a successful right pneumonecomty, and the postoperative course was uneventful. The tumor proved to be a collision cancer consisting of poor differentiated squamous cell carcinoma and invasive adenocarcinoma, lepidic predominanat by pathological examination. Epidermal growth factor receptor mutations (L858R) were found in both squamous cell carcinoma and adenocarcinoma of the tumor, possibly suggesting the same origin of both histological types.

Functional role of CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia.

Cancer development is often preceded by the appearance of preneoplastic lesions. In gastric carcinogenesis, chronic inflammation and histopathologic progression of the stomach epithelium lead to the development of metaplasia and eventually adenocarcinoma. The cell surface protein CD44, especially its variant isoforms (CD44v), has been implicated in metaplasia-carcinoma sequence progression in the stomach. We recently found that CD44v interacts with and stabilizes xCT, a subunit of the cystine transporter system xc(-), in cancer cells and thereby increases cystine uptake and confers resistance to various types of cellular stress in vivo. The functional relevance of CD44v and xCT in the development of preneoplastic lesions, however, has remained unknown. We have now examined the role of the CD44v-xCT system in the development of spasmolytic polypeptide-expressing metaplasia (SPEM) in mouse models of gastric carcinogenesis. CD44v was found to be expressed de novo in SPEM, and CD44v(+) metaplastic cells manifested upregulation of xCT expression compared with CD44v(-) cells. Genetic ablation of CD44 or treatment with sulfasalazine, an inhibitor of xCT-dependent cystine transport, suppressed the development of SPEM and subsequent gastric tumor growth. Therapy targeted to CD44v-xCT could thus prove effective for prevention or attenuation of the CD44v-dependent development of preneoplastic lesions and cancer.

[A patient with advanced gastric cancer who responded to neoadjuvant S-1 plus cisplatin chemotherapy].

The patient was a 49-year-old man who was diagnosed as having gastric cancer and was suspected of having lymph node metastasis on computed tomography( CT) scans. He received neoadjuvant chemotherapy with S-1 and cisplatin (CDDP). He underwent total gastrectomy after 2 courses of neoadjuvant chemotherapy. The pathological effect was Grade 1b. The patient was treated with oral S-1 as postoperative adjuvant chemotherapy on an outpatient basis, and there are no signs of recurrence as of 3 years and 10 months after surgery.

Clinical significance of dihydropyrimidine dehydrogenase and thymidylate synthase expression in patients with pancreatic cancer.

BACKGROUND: Little is known about the clinical significance of TS and DPD in pancreatic cancer. We aimed to evaluate TS and DPD expression levels in not only pancreatic cancer but also surrounding normal pancreatic tissues to assess the clinical implications of the expression of TS and DPD in this study. PATIENTS AND METHODS: Pancreatic cancer and normal pancreatic tissues were obtained from 18 patients with pancreatic cancer who underwent pancreatic resection to measure TS and DPD activities. The TS and DPD activities were determined by enzyme-linked immunosorbent assay using non-fixed fresh-frozen specimens. RESULTS: Pancreatic cancer tissues had significantly higher DPD and TS enzyme activities than surrounding normal tissue. Anaplastic ductal carcinoma had higher DPD and TS activities than the other histological types. Patients with high DPD in this study demonstrated poorer prognosis than those with low DPD. On the other hand, there was no statistically significant difference in survival between the high and the low TS groups. CONCLUSIONS: The efficacy of 5-FU may be lower in pancreatic cancer tissue than in normal tissue because DPD activity is upregulated in pancreatic cancer tissue compared to normal pancreatic tissue. It is necessary to develop an effective 5-FU delivery system and/or 5-FU combined with an inhibitor for DPD that can be used when 5-FU must be administered to patients with pancreatic cancer. High DPD activity may be a prognostic factor in patients with pancreatic cancer.

Primary leiomyosarcoma of the inferior vena cava: case report.

The patient was a 63-year-old woman with a chief complaint of blood-stained sputum. A tumor of the inferior vena cava was found on chest computed tomography (CT) and identified as a primary tumor based on multidetector CT and contrast-enhanced MR angiography. An intrapelvic tumor was also discovered. On autopsy, the two tumors were diagnosed as leiomyosarcoma and ovarian fibroma, respectively.

Characteristics of ectopic pancreas in dynamic gadolinium-enhanced MRI.

The characteristics of jejunal ectopic pancreas in dynamic gadolinium-enhanced magnetic resonance imaging are described in a 40-year-old man with bowel obstruction. The pre-contrast signal intensity and post-contrast enhancement pattern of ectopic pancreas are the same as those of the pancreas.

[Acute liver injury with hepatic encephalopathy associated with gemcitabine administration for adjuvant chemotherapy in an HBV carrier with pancreatic cancer].

A 75-year-old woman was admitted to our department because of epigastric pain. Imagings revealed cancer of the head of the pancreas. She was an HBV carrier, although no liver dysfunction was observed. Her serum HBV-DNA level was lower than 2.6. We performed pancreaticoduodenectomy for pancreatic cancer. No postoperative complication was observed. The histopathological diagnosis was tubular adenocarcinoma of the pancreas. As a postoperative adjuvant chemotherapy, gemcitabine hydrochloride (GEM) was injected at a dose of 800mg/m2 once a week. Disorientation and jaundice were observed after six doses of GEM. Blood chemistry revealed that total bilirubin and ammonia were abnormally elevated, and that blood coagulant factors were diminished. Serum HBV-DNA level was lower than 2.6. It showed no reactivation of HBV. Abdominal CT showed no recurrence but fatty liver. Fresh frozen plasma was supplied and branched chain amino acids were injected after GEM was administration discontinued. Lactulose was also given orally. With these conservative treatments, she recovered completely. Careful monitoring of liver function during GEM administration is required in a HBV carrier.

Spleen and gastrosplenic ligament preserving distal pancreatectomy under a minimum incision approach assisted by laparoscopy.

BACKGROUND: As a modification of hand-assisted laparoscopic pancreatectomy, we devised a method of spleen and gastrosplenic ligament preserving distal pancreatectomy, in which pancreatic resection is performed under direct vision extracorporeally. METHODS: The distal pancreas and spleen are pulled out of the peritoneal cavity through the minilaparotomy at the epigastrium following hand-assisted laparoscopic dissection of the distal pancreas. Spleen-preserving pancreatectomy is performed safely under direct vision. The gastrosplenic ligament is also preserved to prevent splenic volvulus after the operation. The transected main pancreatic duct is doubly ligated, and the transected pancreatic stump is sewn manually. The preserved spleen and splenic vessels are placed back in the peritoneal cavity after resection. RESULTS: In the current study (n = 3), overall morbidity rate, including splenic volvulus and pancreatic fistula, was 0%. CONCLUSION: Preservation of the gastrosplenic ligament and extracorporeal preparation of the transected pancreatic stump under direct vision are useful measures in spleen-preserving distal pancreatectomy under a minimum incision approach assisted by laparoscopy.

[A 6-year-survival case of esophageal adenosquamous cancer with liver metastases cured by multidisciplinary therapy].

A 65-year-old man was diagnosed as esophageal cancer with multiple liver metastases (S2 10 mm, S7 10 mm, S8 15 mm). The preoperative diagnosis was stage IV (T 3 N 3 M 1 Pl 0), and he was operated palliatively by esophagocardiofundectomy and intrathoracic anastomosis for oral food intake. The postoperative histological diagnosis was adenosquamous carcinoma. One month after the operation he was administered orally UFT-E (300 mg/day) and PSK (3g/day). He was also treated by hepatic arterial infusion therapy with CDDP (10 mg/week). After 180 mg of CDDP, liver metastases were evaluated for PR. This therapy was discontinued after 410 mg of CDDP by vomiting and hypotension. 16 months after, DOC (20 mg/week) was given by arterial infusion and CR of liver metastases was achieved 18 months after. Then he was given 840 mg of DOC and oral administration of UFT-E and PSK was performed for about 5 years. He was free from the recurrence of cancer as an outpatient and had a good QOL. We think that esophageal cancer with liver metastasis should be aggressively treated surgically so as to allow oral food intake, and liver metastasis should be treated with chemotherapy because postoperative hepatic arterial infusion therapy is effective and provides a good QOL.

[Utility of convex echo probe in laparoscopic radio frequency ablation therapy for hepatocellular carcinoma].

We have examined the utility of the convex echo probe, which has the fine gutter of a puncture needle in laparoscopic radio frequency ablation therapy. When we use a flexible linear echo probe in RFA treatment, we have to puncture tumor with the hand piece in free hand. But it is difficult to treat in the case of HCC which is located in S1 and the lower area of S5 and S6 because we have a narrow space where colon, duodenum and netz are close for safe and exact puncturing of the tumor. We used a convex echo probe in RFA to the above mentioned area of the liver. We punctured with the hand piece exactly and easily without preliminary puncturing of the tumor. So we can perform RFA treatment successfully and safely by a choice of an appropriate echo probe.

Choledochal cyst during pregnancy: case report and literature review of treatment.

Choledochal cysts are uncommon conditions, usually diagnosed during childhood, but rarely during pregnancy. Choledochal cysts during pregnancy carry several risks, including development of biliary tract cancer and peritonitis due to rupture of dilated cysts induced by pregnancy itself. We present here a case of choledochal cyst during pregnancy, and discuss appropriate treatments for choledochal cysts first presenting during pregnancy. A 25-year-old primigravida at 15 weeks' gestation was admitted to our hospital with abdominal pain. Magnetic resonance cholangiopancreatography diagnosed a type 1 choledochal cyst without a mass lesion. A healthy baby arrived without complication at 38 weeks' gestation. The patient underwent cholecystectomy and choledochal cyst excision. The postoperative course was uneventful with discharge on day 8. Pathological examination diagnosed no malignant feature. Surgery may be performed after delivery for choledochal cysts first presenting during pregnancy, and monitoring with magnetic resonance imaging, blood tests, and ultrasonography is necessary during observation.

NO donor and MEK inhibitor synergistically inhibit proliferation and invasion of cancer cells.

Nitric oxide (NO) shows tumoricidal activity. We had previously reported that NO downregulates the phosphatidylinositol-3-kinase/Akt pathway, but upregulates the MEK/ERK pathway downstream of growth factor signaling. We hypothesized that NO donor and MEK inhibitor in combination synergistically inhibit the viability of cancer cells compared to either NO donor or MEK inhibitor alone. We determined the effects of S-nitrosoglutathione (GSNO, NO-donor) and U0126 (MEK inhibitor) on insulin-like growth factor-I (IGF-I) and epidermal growth factor (EGF) signaling, proliferation and invasion in cancer cell lines. GSNO inhibits phosphorylation of IGF-I receptor (IGF-IR), EGF receptor (EGFR) and Akt, but upregulates ERK1/2 phosphorylation in MIAPaCa-2 and HCT-116 cells after stimulation by IGF-I and EGF. On the other hand, U0126 inhibits phosphorylation of ERK1/2, but upregulates phosphorylation of IGF-IR and EGFR in MIAPaCa-2 and HCT-116 cells. The combination of GSNO and U0126 downregulates phosphorylation of IGF-IR, EGFR, Akt and ERK1/2 after stimulation by IGF-I and EGF. GSNO as well as U0126, inhibits the proliferation of MIAPaCa-2, HCT-116, Panc-1, MCF-7, HT-29 and AGS cells in a dose-dependent manner. GSNO and U0126 in combination synergistically inhibit proliferation and invasion of cancer cells. These results indicate that the combined treatment of NO donor and MEK inhibitor may be promising in cancer therapy.

Solid-pseudopapillary pancreatic tumor, mimicking submucosal tumor of the stomach: A case report.

Solid-pseudopapillary tumors of the pancreas (SPTs) are comparatively rare and have low malignancy, with a predilection for young women. Diagnosis is difficult when a SPT develops in a boundary region with other organs. Here, we report a 42-year old woman with a SPT of the pancreas mimicking a submucosal tumor of the stomach on imaging. She was admitted to our hospital complaining of abdominal pain. We suspected a submucosal tumor of the stomach from the findings of endoscopy, endoscopic ultrasonography and abdominal computed tomography. However, angiography showed that some of the tumor vessels arose from the pancreas. Intraoperative findings revealed the tumor originated from the pancreas. Therefore, distal pancreatectomy was performed. The pathological diagnosis was SPT of the pancreas.

Nitric oxide inhibits the proliferation and invasion of pancreatic cancer cells through degradation of insulin receptor substrate-1 protein.

Nitric oxide (NO), which plays a role in the posttranslational modification of proteins, exhibits tumoricidal activity. However, the mechanism remains largely unclear. We investigated whether the regulation of insulin receptor substrate (IRS)-1 protein expression and insulin/insulin-like growth factor (IGF) signaling by NO is involved in the proliferation and invasion of pancreatic cancer cells. NO donor inhibited insulin/IGF-I-stimulated phosphorylation of insulin receptor/IGF-I receptor, IRS-1, Akt/PKB, and glycogen synthase kinase-3beta along with decreased expression of IRS-1 protein in MIAPaCa-2 cells, whereas NO donor enhanced the phosphorylation of extracellular signal-regulated kinase-1/2. In contrast, a selective inducible nitric oxide synthase inhibitor, 1400W, upregulated the expression of IRS-1 protein and the phosphorylation of IRS-1, Akt/PKB, and glycogen synthase kinase-3beta, along with enhanced proliferation and invasion of Panc-1 cells expressing inducible nitric oxide synthase protein. NO donor induced IRS-1 protein reduction through increased ubiquitination and degradation. For the detection of the site responsible for NO-induced ubiquitination, IRS-1 deletion mutant genes were transfected and overexpressed in MIAPaCa-2 cells. The results indicate that the COOH terminus of the IRS-1 protein is required for NO donor-induced ubiquitination and protein degradation. Cells stably transfected with COOH-terminal deletion mutants of IRS-1 exhibited reduced IGF signaling and cell proliferation compared with vector alone-transfected cells, with no influence of NO on IGF signaling and invasion, although stable transfectants with full-length IRS-1 protein exhibited remarkable NO-induced reduction in IGF signaling, cell proliferation, and invasion. These findings indicate that NO inhibits the proliferation and invasion of pancreatic cancer cells, at least in part, through upregulation of IRS-1 protein degradation and resultant downregulation of the insulin/IGF-I-Akt pathway.

Is an estimation of physiologic ability and surgical stress able to predict operative morbidity after pancreaticoduodenectomy?

BACKGROUND: Mortality rates after pancreaticoduodenectomy (PD) are below 4% in high volume centers, although morbidity rates still remain high. Therefore, it is important to clarify a predictor associated with operative morbidity after PD. The estimation of physiologic ability and surgical stress (E-PASS) score has been developed for comparative audit in general surgical patients. OBJECTIVE: To evaluate whether E-PASS scoring system could predict the occurrence of complications after PD. METHODS: We performed retrospective analysis of 69 patients (42.0% pancreatic cancer, 31.9% bile duct cancer, and others) who underwent PD using the E-PASS as a predictor of morbidity. Correlations between the incidence rates of postoperative complications and the preoperative risk score (PRS), surgical stress score (SSS) and comprehensive risk score (CRS) of the E-PASS scoring system were evaluated. RESULTS: Of the 69 patients 30 (43.5%) experienced a total of 54 postoperative complications. All E-PASS scores, especially PRS and CRS were significantly higher in the patients with postoperative complications than in the patients without complication. The complication rate gradually increased as the PRS, SSS and CRS score increased. Under receiver operating characteristic analysis, if a cut-off point of CRS was 0.75, sensitivity and specificity for the prediction of operative morbidity after PD was 80.0 and 79.5%, respectively. Neoadjuvant chemotherapy and intraoperative radiation therapy (IORT) did not influenced on operative morbidity after PD. CONCLUSION: E-PASS scoring system is useful to evaluate for morbidity after PD. Neoadjuvant chemotherapy and IORT could be adapted without significant extra risk for surgical complication.

Detection of liver metastases secondary to pancreatic cancer: utility of combined helical computed tomography during arterial portography with biphasic computed tomography-assisted hepatic arteriography.

BACKGROUND: This study was designed to define the diagnostic advantage of computed tomography during arterial portography (CTAP) combined with computed tomography-assisted hepatic arteriography (CTHA) for the preoperative detection of liver metastases secondary to pancreatic cancer compared with that of multidetector computed tomography (MDCT). METHODS: From January 2002 to December 2007, we retrospectively studied 197 consecutive patients with pancreatic cancer. MDCT was performed on 192 patients prior to preoperative visceral angiography; 153 patients underwent CTAP + CTHA at the time of preoperative angiography. RESULTS: Liver metastases were identified in 39 patients by means of MDCT. Of the 153 patients who had no evidence of liver metastases on MDCT, 129 patients underwent CTAP + CTHA, and 53 of these 129 patients (41.1%) were diagnosed as having liver metastases that could not be detected by MDCT. These tumors missed by MDCT ranged from 3 to 15 mm in size. On CTAP + CTHA, a solitary nodule in the liver was detected in 11 patients, 2 nodules were detected in 6 patients, 3 lesions were detected in 2 patients, and ≧4 lesions were detected in 34 patients. The sensitivity and specificity of CTAP + CTHA versus MDCT were 94.2 versus 48.4% and 82.7 versus 97.9%, respectively. CONCLUSIONS: The combination of CTAP and CTHA is useful to confirm liver metastases and can potentially offer more accurate staging of pancreatic cancer compared with MDCT.

Combined chemotherapy of irinotecan and low-dose cisplatin (I/low-P) against metastatic biliary tract cancer.

There is no established or effective standard therapy for metastatic biliary tract cancer, resulting in poor prognosis. Recently, we performed combination chemotherapy of irinotecan and low-dose cisplatin (I/low-P) for three consecutive patients with metastatic biliary tract cancer. The regimen of I/low-P therapy consisted of irinotecan (60 mg/m(2)) and low-dose cisplatin (6 mg/m(2)), administered by intravenous infusion weekly or biweekly. Of the three patients, two showed a partial response, with durations of more than 20 months, and 2 months, respectively, while the third patient had stable disease for 3 months. One patient, who had jaundice, had grade 3 thrombocytopenia, but the other patients did not have any severe toxicities. Survival times were more than 20 months, 10 months, and 13 months, respectively. These outcomes suggest that I/low-P therapy is safe and may be worth trying as a first-line chemotherapy for patients with metastatic biliary tract cancer.