[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.

The modified Glasgow Prognostic Score (mGPS) is a good predictor of indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers.

BACKGROUND: Patients with unresectable pancreatic and biliary cancers sometimes need decompression due to obstruction of the gastrointestinal tract and/or biliary tract. The aim of this study was to determine the prognostic factors associated with an indication for palliative bypass surgery in patients with unresectable pancreatic and biliary cancers. METHODS: Between April 2005 and September 2011, 37 patients with unresectable pancreatic and biliary cancers underwent palliative bypass surgery. Prognostic factors were searched for among clinical characteristics, operation-related factors, and tumor-related factors using a prospective database. RESULTS: The median survival time (MST) of these patients was 4.6 months, with a 6-month survival rate of 40.5 %. A multivariate Cox proportional hazards regression analysis revealed that mGPS >2 was the only independent prognostic factor for bypass surgery. Patients with an mGPS of 2 had an MST of 1.7 months, and they had a significantly worse prognosis than mGPS 0-1 patients with an MST of 6.3 months. CONCLUSIONS: The mGPS is useful for predicting survival after surgical decompression due to gastrointestinal obstruction in patients with unresectable pancreatic and biliary cancers. Patients with a poor mGPS may not be indicated for palliative bypass surgery.

An autopsy study to clarify characteristics of local recurrence after extended pancreatectomy with intraoperative radiation therapy in patients with pancreatic cancer.

PURPOSE: Local relapses frequently occur even after curative resection of pancreatic cancer. To control local recurrence, we adopted extended radical resection combined with intraoperative radiation therapy. METHODS: A retrospective review was conducted on 41 patients who underwent extended radical pancreatectomy combined with intraoperative radiation therapy for pancreatic cancer. Fourteen patients underwent autopsies. We took en bloc specimens of the abdominal aorta with surrounding connective tissue to evaluate histological characteristics of local status at autopsies. RESULTS: Autopsies disclosed microscopic local recurrence in five (36%) of the 14 patients, although no evidence of local relapse was observed in either follow-up images or macroscopic findings at autopsy. Of the three patients with R1 resection, two had no local recurrence microscopically at autopsy. Histological features of local recurrence in autopsy samples showed small numbers of cancer cells surrounded by thick connective tissue without mass formation. CONCLUSIONS: The autopsy study revealed that a characteristic of local recurrence after this treatment was tiny cancer cells scattered in dense connective tissue; these cells were undetected by follow-up imaging.

Carcinogenesis of intraductal papillary mucinous neoplasm of the pancreas: loss of microRNA-101 promotes overexpression of histone methyltransferase EZH2.

BACKGROUND: The mechanisms of IPMN carcinogenesis are as yet unclear. This study aimed to determine whether expression of EZH2 promotes neoplastic progression of IPMN and PDCA, and to elucidate regulation of EZH2 expression by miR-101. METHODS: EZH2 mRNA and protein expression were investigated in 8 human pancreatic cancer cell lines by PCR and western blotting. Pre-miR-101 and anti-miR-101 were transfected into pancreatic cancer cells to elucidate EZH2 regulation by miR-101. To evaluate whether EZH2 modulates malignant progression of IPMN, EZH2 expression in IPMN was examined by immunohistochemistry. Next, we collected malignant and benign cells from FFPE samples of IPMNs using laser capture microdissection and extracted the RNA. miR-101 expression in IPMN was assessed using real-time PCR. RESULTS: All pancreatic cancer cell lines expressed EZH2 mRNA and protein. The induction of miR-101 by transfection of pre-miR-101 in MIA PaCa-2 was closely related to a reduction in EZH2 protein production compared with control, whereas there was little difference in the expression of EZH2 mRNA. Anti-miR-101 transfected pancreatic cancer cells showed an increase in EZH2 protein, while the level of EZH2 mRNA was not elevated. Immunohistochemistry revealed that the expression of EZH2 was significantly higher in malignant than benign IPMN. Expression of miR-101 was significantly lower in malignant IPMN than benign IPMN. CONCLUSIONS: MiR-101 targets EZH2 at the posttranscriptional level, and loss of miR-101 could be a trigger for the adenomacarcinoma sequence of IPMN by upregulation of EZH2. This study suggests miR-101-EZH2 blockade as a potential therapeutic target in IPMN carcinogenesis.

Adenocarcinoma of the minor duodenal papilla: report of a case.

We report a case of adenocarcinoma of the minor duodenal papilla, a rare type of duodenal neoplasm. A 76-year-old man with a history of surgery for rectal cancer and gastric cancer was referred to us after a follow-up upper gastrointestinal endoscopy revealed an abnormal elevation in the minor duodenal papilla. The pathological diagnosis of a biopsy specimen was adenocarcinoma. Preoperative examination of other organs revealed a tumor in the ascending colon, which was also identified as adenocarcinoma. We performed synchronous pancreatoduodenectomy and ileocecal resection with lymph node dissection. Histopathological examination of the resected specimen revealed that the papilla tumor arose from the duodenal mucosa and infiltrated the submucosa of the duodenal wall, but not the pancreatic parenchyma. Based on these findings, we diagnosed primary adenocarcinoma of the minor duodenal papilla. To our knowledge, this is only the sixth such case reported in the English-language literature, and we review all six cases after this case report.

Perioperative intra-arterial and systemic chemotherapy for pancreatic cancer.

BACKGROUND: Even after curative resection of pancreatic cancer, there is a high probability of systemic recurrence. This indicates that subclinical metastases are already present at the time of operation. The purpose of this study was to assess the feasibility and outcomes of patients who received a novel multimodality therapy combining pancreatic resection and intraoperative radiation therapy (IORT) with pre- and postoperative chemotherapy for pancreatic cancer. METHODS: For eligible patients with pancreatic cancer, 5-FU was administered at a dose of 125 mg/m(2)/day on days 1-5 every week as a continuous pancreatic and hepatic arterial infusion, and gemcitabine was infused intravenously at a dose of 800 mg/m(2) per day once per week for 2 weeks for preoperative chemotherapy. Pancreatic resection combined with IORT was performed 1 week after preoperative chemotherapy. Postoperative chemotherapy was performed in the same way as preoperative chemotherapy. We performed an intention-to-treat analysis for all enrolled patients. RESULTS: This study enrolled 44 patients. The most common toxicities were hematological and gastrointestinal events. Grade 3/4 hematological toxicities were observed during preoperative chemotherapy, although there were no grade 3/4 nonhematological events. Postoperative chemotherapy-related toxicities were more critical and frequent than preoperative ones. There were no pre- or postoperative chemotherapy-associated deaths. Median overall survival was 36.5 months with 30.5% overall 5-year survival. CONCLUSIONS: This multimodality therapy is feasible and promises to contribute to survival. It should be evaluated in a phase III setting.

Small solid pseudopapillary tumor of the pancreas in a 32-year-old man: report of a case.

A solid pseudopapillary tumor (SPT) of the pancreas is a rare neoplasm that mainly occurs in young women. We herein report the case of a small SPT arising from the head of the pancreas in an asymptomatic 32-year-old man, plus a literature review of this tumor. A 32-year-old man was admitted to our department at Kumamoto University Hospital for the evaluation of a pancreatic mass. The tumor had central necrosis, which was poorly perfused on contrast-enhanced computed tomography (CT) and which had a high intensity on T2-weighted magnetic resonance imaging (MRI). Histology revealed the lesion to be a solid pseudopapillary tumor of the pancreas, with the characteristic pseudopapilla formation and central degeneration. However, no capsule formation was observed. The tumor was positive for CD56, CD10, alpha1-antitrypsin, alpha1-antichymotrypsin, beta-catenin, and progesterone receptor. However, the tumor was negative for pancreatic hormones, chromogranin-A, carcinoembryonic antigen, and carbohydrate antigen 19-9. We diagnosed the patient to have an SPT based on these histological findings. Small-sized solid pseudopapillary tumors of the pancreas are being increasingly recognized because of the recent advances in CT and MRI. We should also consider SPT even if it occurs in a male when the tumor contains necrosis-suspected areas which are poorly perfused on contrast-enhanced CT with a high intensity on T2-weighted MRI.

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.

Pancreatoduodenectomy using a no-touch isolation technique.

BACKGROUND: Pancreatoduodenectomy is the only effective treatment for cancers of the periampullary region. Because surgeons usually grasp tumors during pancreatoduodenectomy, this procedure may increase the risk of squeezing and shedding the cancer cells into the portal vein, retroperitoneum, and/or peritoneal cavity. In an effort to overcome these problems, we have developed a surgical technique for no-touch pancreatoduodenectomy. METHODS: From March 2005 through May 2008, 42 patients have been operated on following this technique. Resected margins were microscopically analyzed. RESULTS: We describe a technique for pancreatoduodenectomy using a no-touch isolation technique. We resect cancers with wrapping them within Gerota's fascia and transect the retroperitoneal margin along the right surface of the superior mesenteric artery and abdominal aorta without grasping tumors. CONCLUSIONS: No-touch pancreatoduodenectomy has many potential advantages that merit further investigation in future randomized controlled trials.

Cancer cells spread through lymph vessels in the submucosal layer of the common bile duct in gallbladder carcinoma.

INTRODUCTION: In the present study, we performed immunohistochemical staining with a lymphatic epithelium-specific marker, D2-40, to analyze the status of lymphatic spreading in the hepatoduodenal ligament in T2 gallbladder carcinoma (GC). METHODS: One hundred and eighty-six paraffin-embedded specimens from 15 T2 GC patients were reviewed. RESULTS: Lymph vessels lined with D2-40 were visualized in the submucosal layer of the common bile duct in all cases. In 3 of 15 patients, clusters of cancer cells were identified in the submucosal lymph vessels of the extrahepatic bile duct, and this lymphatic invasion of cancer cells failed to be detected with only conventional hematoxylin-eosin staining. The frequency of the invasion to the submucosal lymph vessels in T2 GC correlated with presence of microscopic invasion to hepatoduodenal ligament and perineural invasion. CONCLUSION: There were lymph vessels in the submucosal layer of the common bile duct, and cancer cells can spread through these channels in addition to the large lymph vessels in subserosal layer around the extrahepatic bile duct in GC. The present results would support the concept of en bloc resection of the extrahepatic bile duct in curative resection for T2 GC.

Long-term outcomes of extended radical resection combined with intraoperative radiation therapy for pancreatic cancer.

BACKGROUND/PURPOSE: Systemic and/or local recurrence often occurs even after curative resection for pancreatic cancer (PC). To prevent local relapse we adopted an extended radical resection combined with intraoperative radiation therapy in patients with PC, and all the patients were followed for more than 5 years. METHODS: We assessed the long-term outcomes of 41 patients who underwent this combined therapy. The cumulative survival curve in this series was depicted using the Kaplan-Meier method. Statistical analyses were performed using the log-rank test. RESULTS: The actual 5-year survival rate was 14.6%, with a median survival time of 17.6 months. Six patients have been 5-year survivors. Local recurrence occurred in only 2 patients (5.0%). Cancer-related death occurred in 32 patients, 18 of whom had liver metastases. The patients with liver metastases had a significantly shorter survival time than those with other cancer-related causes of death. Patients with n3 lymph node involvement, extrapancreatic nerve plexus invasion, and stage IV disease had significantly poorer prognoses than patients without these characteristics. CONCLUSIONS: Our combined therapy for patients with PC contributed to local control; however, it provided no survival benefit, because of liver metastases.

Oxysterol binding protein-related protein-5 is related to invasion and poor prognosis in pancreatic cancer.

In previous studies, the gene expression profiles of two hamster pancreatic cancer cells with different potentials for invasion and metastasis were analyzed. In the present study, we identified that one of the genes expressed strongly in the highly metastatic cell line is hamster oxysterol binding protein-related protein (ORP)-5. The aim of the present study was to clarify the relationship between ORP5 and invasion and poor prognosis of human pancreatic cancer. Invasion assays were carried out in both hamster and human pancreatic cancer cells by suppressing the ORP5 gene with short interfering RNA or inducing its expression by introducing an expression vector. To evaluate the relationship between ORP5 and the characteristics of human pancreatic cancer, 56 pancreatic cancer tissue specimens were analyzed and the ORP5 expression in each pancreatic cancer tissue specimen was analyzed by immunohistochemistry. In both the hamster and human pancreatic cancer cells, suppression of ORP5 significantly reduced the invasion rate of the cells and induction of ORP5 significantly enhanced the invasion rate of the cells. In the clinical sample, the median survival times of the patients with ORP5-positive (n = 33) and ORP5-negative (n = 23) cancer were 8.3 and 17.2 months, respectively (P = 0.02). Also, the 1-year survival rates of patients with ORP5-positive and ORP5-negative cancer were 36.4 and 73.9%, respectively (P = 0.005). The ORP5 expression level was related to both invasion and poor prognosis in human pancreatic cancer. These findings suggest that the expression of ORP5 may induce cancer cell invasion, resulting in the poor prognosis of pancreatic cancer.

Percutaneous transfistulous pancreatic duct drainage and interventional pancreatojejunostomy as a treatment option for intractable pancreatic fistula.

We present 2 techniques for treatment of intractable pancreatic fistula: percutaneous transfistulous pancreatic duct drainage and interventional pancreatojejunostomy. Percutaneous transfistulous pancreatic duct drainage can be effective for intractable fistulas that communicate with the main pancreatic duct. Because drainage itself is not enough for a complete cure of this complication when it occurs in cases after pancreatoduodenectomy (PD), interventional pancreatojejunostomy is applicable.

Complete remission of pancreatic cancer after multiple resections of locally pancreatic recurrent sites and liver metastasis: report of a case.

Pancreatic cancer has the most dismal prognosis of all gastrointestinal cancers. We herein report a case of complete remission from pancreatic cancer by multire-sections of locally pancreatic recurrent sites and liver metastasis over a 14-year period. A 60-year-old man was admitted to our hospital because of a neoplasm of the tail of the pancreas in April 1992. A distal pancreatectomy was curatively performed on this patient. At 1 year after surgery a solitary liver metastasis appeared, and we thus performed a partial hepatectomy. Thereafter, local recurrences appeared twice and we performed a pancreatectomy each time. Finally, we performed a total pancreatectomy. The histopathological findings of specimens of the pancreas showed papillary adenocarcinoma, although the original pancreatic tumor also demonstrated areas of tubular adenocarcinoma. Metastatic liver tumor showed tubular adenocarcinoma. The patient has survived for 14 years since the first operation. This is a rare case of a long survival of a patient with pancreatic cancer due to its histopathology and biologic characteristics.

Pancreatic schwannoma: report of a case.

Among pancreatic neoplasms, pancreatic schwannoma is quite rare. We report a case of solitary pancreatic schwannoma, plus a literature review of this tumor. A 71-year-old woman was diagnosed by abdominal ultrasonography as having a pancreatic tumor and was hospitalized in our department at Kumamoto University Hospital on January 26, 2006. Abdominal computed tomography, magnetic resonance imaging, and endoscopic ultrasonography all showed this tumor, which was located in the body of the pancreas, to have cystic and solid components, and with a septum in the cystic part of the lesion. The tumor, preoperatively identified as a mucinous cystic neoplasm, was clearly separated from the normal pancreatic parenchyma. We performed a spleen-preserving distal pancreatectomy with a lymph node dissection on February 7, 2006. A histopathological examination of the resected specimen by means of hematoxylin and eosin revealed the tumor to consist of two parts: one with a compact spindle cell pattern (Antoni type A), and the other showing degeneration of fat (Antoni type B). We also found positive results for immunohistochemical staining for S-100 and vimentin. These findings confirmed the tumor's classification as a pancreatic schwannoma.

Efficacy of radiotherapy for PV and IVC tumor thrombosis in unresectable HCC.

BACKGROUND/AIMS: The purpose of this study is to evaluate the effect of radiation therapy (RT) for tumor thrombosis (TT) in the major portal vein (PV) or inferior vena cava (IVC) from unresectable hepatocellular carcinoma. METHODOLOGY: Fifteen HCC patients with main PVTT (n = 10) and IVCTT (n 5) were treated with three-dimensional conformal RT between 2001 and 2004. The mean dose was 38.5 Gy (range 28 to 54Gy). The concurrent therapies to intrahepatic tumor included transcatheter arterial chemoembolization (TACE) in 7, TACE + hepatic arterial infusion in 2 and systemic chemotherapy in 1 patient. The therapeutic effect was assessed by tumor regression for TT. RESULTS: An objective response was observed in 3 of 15 patients (20%). There were no patients with progressive disease. The median survival time was 10 months. In 12 cases with stable disease, time to progression (TTP) estimated above 6 months were 42% (5/12 cases). In univariate analysis, therapeutic effect and TTP were affected to survival time. All patients did not have severe deterioration of liver function. CONCLUSIONS: In the current study, we concluded that RT was superior treatment in terms of local control capability and was useful to continue further treatment because RT did not make liver function worse.

Local pancreatic resection with preoperative endoscopic transpapillary stenting.

BACKGROUND: Pancreatic fistula, although not common, can cause serious complications after pancreatectomy. During local pancreatectomy, injury to the main pancreatic duct (in addition to the accessory and side branch ducts) increases the risk of pancreatic fistula formation. Nonetheless, local pancreatic resection maintains the advantage of preserving pancreatic parenchyma. METHODS: In this study, we reviewed the cases of 5 patients who underwent preoperative endoscopic transpapillary pancreatic stenting to help prevent refractory fistula development after local pancreatic resection. RESULTS: Stenting was successful in all 5 patients, and none developed a refractory grade C postoperative pancreatic fistula. CONCLUSIONS: These results suggest that in selected patients, preoperative endoscopic pancreatic stenting may be an effective prophylactic measure to lower the risk of refractory grade C fistula formation after local pancreatic resection.

Predictive factors for platelet increase after partial splenic embolization in liver cirrhosis patients.

BACKGROUND AND AIM: Partial splenic embolization (PSE) is often performed for improving thrombocytopenia in cirrhotic patients. We investigated the largely unclear predictive factors for platelet increase at both 1 month and 1 year after PSE. METHODS: Aimed at increasing the platelet count, PSE was performed in 42 cirrhotic patients with thrombocytopenia (platelets < 80 x 10(4)/mL) caused by hypersplenism. The clinical data were analyzed to clarify the predictive factors for platelet increase at 1 month (n = 42) and 1 year (n = 38) after PSE. RESULTS: The mean splenic infarction ratio was 76.7% +/- 11.2%. The platelet count increased to 259% +/- 112% and 228% +/- 75% of the pretreatment values at 1 month and at 1 year after PSE, respectively. Stepwise multiple linear regression analysis showed that the infarcted splenic volume had a positive independent association with the increase in platelet count at both 1 month (P = 0.00004) and 1 year (P = 0.005) after PSE (increase in platelet count (x10(4)/mL): at 1 month = 0.752 + 0.018 x infarcted splenic volume (mL), R(2) = 0.344; at 1 year = 2.19 + 0.01 x infarcted splenic volume (mL), R(2) = 0.203). Receiver operating characteristic analysis yielded a cut-off value of 388 mL of infarcted splenic volume for achieving an increase of 5.0-8.0 x 10(4)/mL in platelet count at 1 year. CONCLUSIONS: PSE can reduce the platelet pool and induce an increase in platelet count. This increase is greatly dependent on the infarcted splenic volume.

Comparison of intrahepatic and pancreatic perfusion on fusion images using a combined SPECT/CT system and assessment of efficacy of combined continuous arterial infusion and systemic chemotherapy in advanced pancreatic carcinoma.

PURPOSE: The purpose of this study was to compare intrahepatic and pancreatic perfusion on fusion images using a combined single-photon emission computed tomography (SPECT)/CT system and to evaluate the efficacy of combined continuous transcatheter arterial infusion (CTAI) and systemic chemotherapy in the treatment of advanced pancreatic carcinoma. MATERIALS AND METHODS: CTAI was performed in 33 patients (22 men, 11 women; age range, 35-77 years; mean age, 60 years) with stage IV pancreatic cancer with liver metastasis. The reservoir was transcutaneously implanted with the help of angiography. The systemic administration of gemcitabine was combined with the infusion of 5-fluorouracil via the reservoir. In all patients we obtained fusion images using a combined SPECT/CT system. Pancreatic perfusion on fusion images was classified as perfusion presence or as perfusion absent in the pancreatic cancer. Using WHO criteria we recorded the tumor response after 3 months on multislice helical CT scans. Treatment effects were evaluated based on the pancreatic cancer, liver metastasis, and factors such as intrahepatic and pancreatic perfusion on fusion images. For statistical analysis we used the chi-square test; survival was evaluated by the Kaplan Meier method (log-rank test). RESULTS: On fusion images, pancreatic and intrahepatic perfusion was recorded as hot spot and as homogeneous distribution, respectively, in 18 patients (55%) and as cold spot and heterogeneous distribution, respectively, in 15 (45%). Patients with hot spot in the pancreatic tumor and homogeneous distribution in the liver manifested better treatment results (p < 0.05 and p < 0.01, respectively). Patients with hot spot both in the pancreatic cancer and in the liver survived longer than those with cold spot in the pancreatic cancer and heterogeneous distribution in the liver (median +/- SD, 16.0 +/- 3.7 vs. 8.0 +/- 1.4 months; p < 0.05). CONCLUSIONS: We conclude that in patients with advanced pancreatic cancer, CTAI with systemic chemotherapy appeared to be effective and may prolong their survival. The development of a reservoir port system allowing for the homogeneous distribution of anticancer drugs is necessary to improve the prognosis of patients with advanced pancreatic cancer.