Kegg Pathway: Pancreatic cancer

Histol Histopathol. 2010 Jan; 25(1): 63-72
Heiskala K, Arola J, Heiskala M, Andersson LC

Reg IV (RELP), a Regenerating protein family member, is constitutively expressed in neuroendocrine cells of the intestinal mucosa. The helix-loop-helix transcription factor Hath1 is the human homologue of murine Math1, which regulates the embryonic differentiation of neural and intestinal secretory lineage cells. Hath1 is constitutively expressed in a subset of mature secretory gastrointestinal cells. We investigated by immunohistochemistry the expression of Reg IV and Hath1 in 63 neuroendocrine tumors. Intestinal neuroendocrine neoplasms showed co-expression of Reg IV and Hath1, as did parathyroidal and Merkel cell tumors. Lung small-cell carcinoma and gastric mucocellular carcinoma expressed only Reg IV. Pancreatic islet-derived tumors, pheochromocytomas, and paragangliomas expressed only Hath1. Lymph node and liver metastases retained the tissue-specific expression patterns. These distinct expression profiles may be useful for differential diagnostics of metastatic lesions of neuroendocrine tumors. The dissimilar expression patterns suggest that the proteins belong to different signaling pathways and are activated at different stages of neuroendocrine differentiation. Local Reg IV expression may be influenced by the growth factors bFGF and HGF and/or their receptors CD138 and c-met, which were found to co-localize with Reg IV in intestinal neuroendocrine tumors.

Pancreas. 2009 Nov 16;
Mauro LV, Grossoni VC, Urtreger AJ, Yang C, Colombo LL, Morandi A, Pallotta MG, Kazanietz MG, Bal de Kier Joffé ED, Puricelli LL

OBJECTIVE:: Our objective was to study the role of protein kinase C delta (PKCdelta) in the progression of human Pancreatic carcinoma. METHODS:: Protein kinase C delta expression in human ductal carcinoma (n = 22) was studied by immunohistochemistry. We analyzed the effect of PKCdelta overexpression on in vivo and in vitro properties of human ductal carcinoma cell line PANC1. RESULTS:: Human ductal carcinomas showed PKCdelta overexpression compared with normal counterparts. In addition, in vitro PKCdelta-PANC1 cells showed increased anchorage-independent growth and higher resistance to serum starvation and to treatment with cytotoxic drugs. Using pharmacological inhibitors, we determined that phosphatidylinositol-3-kinase and extracellular receptor kinase pathways were involved in the proliferation of PKCdelta-PANC1. Interestingly, PKCdelta-PANC1 cells showed a less in vitro invasive ability and an impairment in their ability to migrate and to secrete the proteolytic enzyme matrix metalloproteinase-2. In vivo experiments indicated that PKCdelta-PANC1 cells were more tumorigenic, as they developed tumors with a significantly lower latency and a higher growth rate with respect to the tumors generated with control cells. Besides, only PKCdelta-PANC1 cells developed lung metastasis. CONCLUSION:: Our results showed that the overexpression of PKCdelta in PANC1 cells induced a more malignant phenotype in vivo, probably through the modulation of cell proliferation and survival, involving phosphatidylinositol-3-kinase and extracellular receptor kinase signaling pathways.

Pancreas. 2009 Nov 16;
Fritz S, Fernández-Del Castillo C, Iafrate AJ, Mino-Kenudson M, Neyhard N, Lafemina J, Stirman A, Warshaw AL, Thayer SP

OBJECTIVES:: Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas are a unique entity with malignant potential. Histologically, Pancreatic ductal adenocarcinoma (PDAC) arising in IPMN (intraductal papillary mucinous carcinoma [IPMC]) appears similar to sporadic PDAC; biologically, however, IPMC seems to have a less aggressive clinical course. Little is known about the genetic signature of IPMC. In this study, we describe a novel xenograft model and cell culture created to biologically and genetically characterize these tumors. METHODS:: Xenograft mice and cell lines were created from IPMC. Global genomic changes were evaluated by cytogenetic analysis and array comparative genomic hybridization. Specific mutations and sonic hedgehog (Shh) pathway activity were examined and xenografts evaluated for sensitivity to anti-Shh therapy. RESULTS:: Cytogenetic analysis showed a tetraploid karyotype with multiple aberrations. KRAS and p53 mutations and overexpression of the Shh pathway were identified. Array comparative genomic hybridization revealed multiple chromosomal aberrations comparable with previously published data in IPMNs. Murine xenograft tumors were sensitive to anti-Shh treatment. CONCLUSIONS:: Characterization of IPMC cell lines and xenografts reveals similarities to previously published data on IPMN. In comparison to PDAC, moreover, these data reveal shared aberrations and distinct genomic changes. Thus, these xenograft model and cell lines may be useful for future preclinical investigations.

Pancreas. 2009 Nov 16;
Lau MK, Davila JA, Shaib YH

OBJECTIVES:: cancer of the body/tail of the pancreas is frequently separated from Pancreatic head tumors. No studies have examined whether the demographics, disease characteristics, and patient survival with Pancreatic body/tail cancers are different from Pancreatic head tumors. METHODS:: We used the Surveillance, Epidemiology, and End Results (SEER) registry to identify 43,946 cases of Pancreatic cancer. The yearly incidence and survival rates were calculated. Cox proportional hazards model examined temporal trends in survival. RESULTS:: The incidence rate for Pancreatic head cancer has remained at 5.6% per 100,000, whereas the rate for Pancreatic body/tail cancers has increased by 46% between 1973 and 2002. The 3-year survival rate has increased slightly for both groups. The Cox proportional hazards model analysis confirms this improvement. The 3-year survival rate for local-stage Pancreatic body/tail cancer is 20.0% compared with 9% for local-stage Pancreatic head cancer. CONCLUSIONS:: This study indicates that the incidence of Pancreatic head cancer has remained stable, whereas the incidence of Pancreatic body/tail cancers is rising. Despite higher survival rates among patients with Pancreatic head cancer compared with those with Pancreatic body/tail cancers in several variables, patients with local-stage Pancreatic body/tail cancers had higher survival rates compared with local-stage Pancreatic head cancer.

Oncology. 2009 Nov 17; 77(5): 300-303
Nakai Y, Isayama H, Sasaki T, Sasahira N, Ito Y, Kogure H, Togawa O, Matsubara S, Arizumi T, Yagioka H, Yashima Y, Kawakubo K, Mizuno S, Yamamoto K, Hirano K, Tsujino T, Ijichi H, Toda N, Tada M, Kawabe T, Omata M

Objectives: We performed a pilot study of a modified combination chemotherapy regimen with S-1 plus gemcitabine for patients with advanced Pancreatic cancer. Methods: Gemcitabine was administered at a dose of 1,000 mg/m(2) in a 30-min intravenous injection on days 1 and 15. S-1 was administered orally at a dose of 40 mg/m(2) twice daily for 14 consecutive days followed by a 14-day rest. Each cycle was repeated every 28 days. Results: Sixteen patients were enrolled. No complete response was observed and partial response was observed in 5 patients (31.3%), stable disease in 10 patients (62.5%) and progressive disease in 1 patient (6.3%). The median time to progression was 10.0 months (95% CI 4.4-N.A.) and the median survival time was 20.4 months (95% CI 8.6-24.1 months). The major toxicities were grade 3 neutropenia (25.0%) and grade 3 anemia (6.3%). There were no grade 4 toxicities. Conclusions: Combination therapy with gemcitabine and S-1 using the modified 4-week schedule was well tolerated and efficacious for advanced Pancreatic cancer.

Dig Surg. 2009 Nov 13; 26(5): 378-383
Nieminen A, Kokkola A, Ylä-Liedenpohja J, Louhimo J, Mustonen H, Puolakkainen P

Background: Early gastric cancer (EGC) is associated with better prognosis than advanced cancer of the stomach. Unfortunately, EGC accounts for a minority of operated gastric cancers in Europe. The aim of this study was to evaluate the clinical characteristics of EGC and the outcome after surgery. Methods: The study group comprised 94 EGC patients having undergone surgery at Helsinki University Central Hospital between April 1983 and July 2007. Results: The overall 5-year survival rate of EGC patients was 92.4%. Tumor location in the upper part of the stomach and mixed histological type impaired the prognosis (p = 0.043 and 0.008, respectively). The probability of lymph node metastasis was significantly higher when the tumor infiltrated gastric submucosa rather than mucosa (p = 0.012). Existence of lymph node or distant metastases decreased the survival rates (both p < 0.001). Total gastrectomy, Pancreatic resection, and extended D2 lymph node dissection increased the complication rate, but did not have effect on survival. Conclusion: The overall prognosis of EGC is favorable. The survival rates of EGC decreased when the tumor was located in the upper part of the stomach or was of mixed histological type, or the patient had lymph node or distant metastasis.

N Engl J Med. 2009 Nov 19; 361(21): 2094-2096
Hidalgo M, Maitra A

Gastroenterol Hepatol. 2009 Nov 16;
Vida Pérez L, González Galilea A, Fraga Rivas E

In patients with Pancreatic cancer, the most frequent symptoms are abdominal pain, weight loss and jaundice. Upper gastrointestinal bleeding produced by gastric varices is a rare entity in these patients and requires the presence of splenic vein thrombosis (SVT) to be excluded. We describe the case of a young man who presented to the emergency department with hematemesis. Diagnostic tests revealed primary Pancreatic lymphoma (PPL), which provoked splenic vein thrombosis, collateral circulation and the formation of isolated bleeding gastric varices. To date, we have found no reports in the literature of PPL with this form of presentation. Finally, we review the literature, with emphasis on the importance of excluding splenic vein thrombosis in patients with isolated gastric varices, and discuss certain features of the diagnosis and treatment of PPL.

Gastrointest Endosc. 2009 Nov 16;
Dewitt J, Yu M, Al-Haddad MA, Sherman S, McHenry L, Leblanc JK

BACKGROUND: The expected survival after the EUS-FNA diagnosis of malignant ascites or liver metastases from Pancreatic cancer is not known. OBJECTIVE: To report overall and 1-year survival in these patients. DESIGN: Retrospective cohort series. SETTING: Tertiary referral hospital. PATIENTS: Consecutive subjects with newly diagnosed Pancreatic cancer from June 1998 and March 2008 in whom EUS-FNA of the liver or ascitic fluid confirmed hepatic metastases or malignant ascites. INTERVENTIONS: Calculation of survival after diagnosis by using the Social Security Death Index. MAIN OUTCOME MEASUREMENTS: Survival after EUS-FNA diagnosis of stage IV Pancreatic cancer. RESULTS: EUS-FNA identified liver metastases and malignant ascites from primary Pancreatic cancer in 75 and 13 patients, respectively, and all 88 died during follow-up. For all 88 patients, the 1-year survival rate and median survival were 3.4% (95% CI, 1.1%-10.4%) and 82 days (range 2-754 days), respectively. The 1-year survival rates for those with liver metastases (4.0% [95% CI, 1.3%-12.1%]) and for those with malignant ascites (0% [95% CI, 0-24.7%]) were similar (P = 1.0). The median survival for patients with liver metastases of 83 days (range 2-754 days) was similar to that for those with malignant ascites (64 days; range 2-153 days) (P = .13). No clinical variable considered predicted survival of more than, less than, or 3 months. LIMITATIONS: Retrospective series with variable treatment for malignancy. CONCLUSIONS: In patients with Pancreatic cancer, identification of malignant ascites or liver metastases by EUS-FNA is associated with a very poor prognosis.

Gastrointest Endosc. 2009 Nov 16;
Kumon RE, Pollack MJ, Faulx AL, Olowe K, Farooq FT, Chen VK, Zhou Y, Wong RC, Isenberg GA, Sivak MV, Chak A, Deng CX

BACKGROUND: Quantitative spectral analysis of the radiofrequency (RF) signals that underlie grayscale EUS images can be used to provide additional, objective information about tissue state. OBJECTIVE: Our purpose was to validate RF spectral analysis as a method to distinguish between (1) benign and malignant lymph nodes and (2) normal pancreas, chronic pancreatitis, and Pancreatic cancer. DESIGN AND SETTING: A prospective validation study of eligible patients was conducted to compare with pilot study RF data. PATIENTS: Forty-three patients underwent EUS of the esophagus, stomach, pancreas, and surrounding intra-abdominal and mediastinal lymph nodes (19 from a previous pilot study and 24 additional patients). MAIN OUTCOME MEASUREMENTS: Midband fit, slope, intercept, and correlation coefficient from a linear regression of the calibrated RF power spectra were determined. RESULTS: Discriminant analysis of mean pilot-study parameters was then performed to classify validation-study parameters. For benign versus malignant lymph nodes, midband fit and intercept (both with t test P < .058) provided classification with 67% accuracy and area under the receiver operating curve (AUC) of 0.86. For diseased versus normal pancreas, midband fit and correlation coefficient (both with analysis of variance P < .001) provided 93% accuracy and an AUC of 0.98. For Pancreatic cancer versus chronic pancreatitis, the same parameters provided 77% accuracy and an AUC of 0.89. Results improved further when classification was performed with all data. LIMITATIONS: Moderate sample size and spatial averaging inherent to the technique. CONCLUSIONS: This study confirms that mean spectral parameters provide a noninvasive method to quantitatively discriminate benign and malignant lymph nodes as well as normal and diseased pancreas.

cancer Sci. 2009 Oct 12;
Huang J, Yao WY, Zhu Q, Tu SP, Yuan F, Wang HF, Zhang YP, Yuan YZ

XAF1 (X chromosome-linked inhibitor of apoptosis [XIAP]-associated factor 1) is a novel XIAP modulator that negatively regulates the anti-apoptotic effects of XIAP and sensitizes cells to other cell death triggers. It has been reported to be downregulated in a variety of human cancer cell lines. However, the role of XAF1 in Pancreatic carcinogenesis remains unclear. In the present study, we investigated the prognostic values of XAF1 expression and its regulation in cancer cell growth and apoptosis both in vitro and in vivo. From the immunohistochemistry staining of tissue microarray, 40 of 89 (44.9%) Pancreatic specimens showed low levels of XAF1 expression. Statistical analysis suggested the downregulation of XAF1 was significantly correlated with tumor staging (P = 0.047) and those patients with low XAF1 levels had shorter survival times (P = 0.0162). Multivariate analysis indicated that XAF1 expression was an independent prognostic indicator of the survival of patients with Pancreatic cancer (P = 0.007). Furthermore, we found that restoration of XAF1 expression mediated by Ad5/F35 virus suppressed cell proliferation and induced cell cycle arrest and apoptosis, accompanied by the activation of caspases 3, 8, and 9 and poly(ADP-ribose) polymerase as well as increased level of cytochrome c and Bid cleavage. Notably, XAF1 restoration robustly decreased survivin expression rather than XIAP. In addition, in vivo s.c. xenografts from Ad5/F35-XAF1 treatment, which showed less cellular proliferation and enhanced apoptosis, were significantly smaller than those from control groups. Our findings document that XAF1 is a valuable prognostic marker in Pancreatic cancer and could be a potential candidate for cancer gene therapy. (cancer Sci 2009).

Expert Opin Ther Targets. 2009 Dec; 13(12): 1429-1438
Broadhead ML, Dass CR, Choong PF

Background: Pigment epithelium-derived factor (PEDF) is an emerging anti-cancer agent that targets both tumor tissue and its supporting vasculature. These direct and indirect effects of PEDF have been examined in vitro and in vivo for a range of malignancies. Objective: This review seeks to present PEDF as a potential anti-cancer agent with applications across multiple malignancies. We refer closely to experimental methodology whilst still highlighting the clinical significance of PEDF in cancer, drawing on biological findings in vitro and in vivo. Methods: A Pubmed database search was performed limiting the scope of this discussion paper mainly to PEDF's biological role in cancer, specifically lung, breast, prostatic, ovarian and Pancreatic carcinomas, melanoma, glioma and osteosarcoma. Conclusions: The biological roles of PEDF are diverse and multidimensional. As an anti-cancer agent, PEDF has great potential as a focused anti-neoplastic therapy against a variety of tumor types.

Int J cancer. 2009 Nov 17;
Li YY, Wang YY, Taniguchi T, Kawakami T, Baba T, Ishibashi H, Mukaida N

We previously demonstrated that Pim-3, a proto-oncogene with serine/threonine kinase activity, was aberrantly expressed in malignant lesions but not normal tissues of endoderm-derived organs, including the pancreas, liver, colon, and stomach. Moreover, aberrantly expressed Pim-3 can prevent tumor cell apoptosis by inactivating a pro-apoptotic molecule, Bad, and enhancing the expression of an anti-apoptotic molecule, Bcl-X(L). These observations prompted us to speculate that a chemical targeting Pim-3 kinase may be a good candidate for a novel type of anti-cancer drug. Hence, we screened various low-molecule compounds by examining their capacity to inhibit Pim-3 kinase activity in vitro. We observed that some synthetic intermediates of stemonamide can inhibitin vitro activities of Pim-3 kinase and its related kinases, such as Pim-1 and Pim-2. Moreover, these compounds inhibit in vitro cell proliferation of various human Pancreatic, hepatocellular, and colon cancer cell lines. Furthermore, the compounds can induce apoptosis of human Pancreatic cancer cell linesin vitro by reducing the amount of phospho-Ser(112)-Bad, but not total amounts of Bad and Pim-3. Finally, when the compound was administered to nude mice injected with a human Pancreatic cancer cell line, it retarded tumor growth by increasing apoptotic cell numbers and decreasing proliferating cell numbers without causing serious adverse effects on blood counts. These observations indicate that the chemicals and its related compounds may be effective for the treatment of tumors of endoderm-derived organs, particularly the pancreas. (c) 2009 UICC.

Zhonghua Wei Chang Wai Ke Za Zhi. 2009 Nov; 12(6): 581-583
Hu X, Tian DY, Cao L

OBJECTIVE: To evaluate the clinicopathologic features and the efficacy of surgical treatment in gastric stump cancer. METHODS: Forty-two patients undergone operation for gastric stump cancer, including 9 cases with Billroth I( reconstruction and 33 cases with Billroth II( reconstruction, in our department were enrolled in the study. Clinicopathological features, 5-year survival rate and prognostic factors were analyzed retrospectively. RESULTS: Gastric stump cancer occurred more frequently in anastomotic site and poorly-differentiated cancer was the common histological type. For patients with Billroth I( reconstruction, the rates of lymph node metastasis in No.1, No.3, No.10, No.11 stations were more than 30.0%, and that in No.12 station was 22.2%. For patients with Billroth II( reconstruction, the rates of lymph node metastasis in No.1, No.2, No.3, No.4, No.10, No.11, No.12 stations were more than 30.0%, and that in No.14 station was 25.0%. The rate of lymph node metastasis in jejunal mesentery was 27.3%. The percentage of Pancreatic invasion and hepatoduodenal ligament invasion were 66.7% and 33.3% respectively for patients with Billroth I( reconstruction. The percentage of transverse colon invasion and Pancreatic invasion were 25.0% and 75.0% respectively for patients with Billroth II( reconstruction. The overall 5-year survival rate of patients with gastric stump cancer was 0.38. The 5-year survival rates in I( , II( , III( and IIII( were 0.86, 0.50, 0.13 and 0 respectively. There were significant differences among stages(P <0.05). CONCLUSIONS: Gastric stump cancer has a particular pattern in lymph node metastasis and direct organ invasion. Surgical resection is an effective therapeutic strategy for this disease.

cancer Chemother Pharmacol. 2009 Nov 18;
Ishii Y, Suzuki S, Takahashi Y, Takayama T, Asai S

PURPOSE: S-1 is an oral anticancer drug containing tegafur (FT), a pro-drug of fluorouracil, combined with two modulators, 5-chloro-2,4-dihydroxypyridine and potassium oxonate (Oxo), at a molar ratio of 1:0.4:1. CYP2A6 genetic polymorphism and dihydropyrimidine dehydrogenase (DPD) inhibition are important for the antitumor effect of S-1. Exploiting the usefulness of the 2-(13)C-uracil breath test (UrBT) as an indicator of DPD activity, we examined whether the results of CYP2A6 genetic polymorphism analysis and UrBT could be used to predict the antitumor effect of S-1. METHODS: Thirty-four patients with advanced or recurrent cancer (15, 16 and 3 with gastric, colorectal and Pancreatic cancer, respectively) were orally administered 40 mg/m(2) S-1 twice daily in the morning and evening. Eighteen patients with a complete response (CR)/partial response (PR) (2 with CR, 16 with PR) and 16 with progressive disease (PD) were compared with respect to CYP2A6 genetic polymorphisms (1- vs. 2-allele mutation), UrBT results, and plasma FT and 5-fluorouracil levels at 3 h after S-1 ingestion in the morning. RESULTS: On multivariate analysis between the CR/PR and PD groups, only the UrBT results was an independent factor of CR/PR to S-1 (95% CI 1.02-1.10). CONCLUSION: These results suggest that the anticancer effect of S-1 can be predicted by performing UrBT 3 h after the initial oral S-1 administration.

Br J cancer. 2009 Nov 17;
Chen G, Tian X, Liu Z, Zhou S, Schmidt B, Henne-Bruns D, Bachem M, Kornmann M

Background:Secreted protein acidic and rich in cysteine (SPARC) is a multi-faceted protein-modulating cell-cell and cell-matrix interactions. In cancer, SPARC can be not only associated with a highly aggressive phenotype, but also acts as a tumour suppressor. The aim of this study was to characterise the function of SPARC and its modulation by fibroblast growth factor receptor (FGFR) 1 isoforms in Pancreatic ductal adenocarcinoma (PDAC).Methods and results:Exogenous SPARC inhibited growth, movement, and migration. ShRNA inhibition of endogenous SPARC in ASPC-1 and PANC-1 cells resulted in increased anchorage-dependent and -independent growth, transwell migration, and xenograft growth as well as increased mitogenic efficacy of fibroblast growth factor (FGF) 1 and FGF2. Endogenous SPARC expression in PANC-1 cells was increased in FGFR1-IIIb over-expressing cells, but decreased in FGFR1-IIIc over-expressing cells. The up-regulation of endogenous SPARC was abrogated by the p38-mitogen-activated protein kinase inhibitor SB203580. SPARC was detectable in conditioned medium of Pancreatic stellate cells (PSCs), but not PDAC cells. Conditioned medium of PDAC cells reduced endogenous SPARC expression of PSCs.Conclusion:Endogenous SPARC inhibits the malignant phenotype of PDAC cells and may, therefore, act as a tumour suppressor in PDAC. Endogenous SPARC expression can be modulated by FGFR1-III isoform expression. In addition, PDAC cells may inhibit endogenous SPARC expression in surrounding PSCs by paracrine actions.British Journal of cancer advance online publication, 17 November 2009; doi:10.1038/sj.bjc.6605440 www.bjcancer.com.

Br J cancer. 2009 Nov 17;
Bilim V, Ougolkov A, Yuuki K, Naito S, Kawazoe H, Muto A, Oya M, Billadeau D, Motoyama T, Tomita Y

Background:Renal cell carcinoma (RCC) is highly resistant to chemotherapy because of a high apoptotic threshold. Recent evidences suggest that GSK-3beta positively regulates human Pancreatic cancer and leukaemia cell survival in part through regulation of nuclear factor (NF-kappaB)-mediated expression of anti-apoptotic molecules. Our objectives were to determine the expression pattern of GSK-3beta and to assess the anti-cancer effect of GSK-3beta inhibition in RCC.Methods:Immunohistochemistry and nuclear/cytosolic fractionation were performed to determine the expression pattern of GSK-3beta in human RCCs. We used small molecule inhibitor, RNA interference, western blotting, quantitative RT-PCR, BrDU incorporation and MTS assays to study the effect of GSK-3beta inactivation on renal cancer cell proliferation and survival.Results:We detected aberrant nuclear accumulation of GSK-3beta in RCC cell lines and in 68 out of 74 (91.89%) human RCCs. We found that pharmacological inhibition of GSK-3 led to a decrease in proliferation and survival of renal cancer cells. We observed that inhibition of GSK-3 results in decreased expression of NF-kappaB target genes Bcl-2 and XIAP and a subsequent increase in renal cancer cell apoptosis. Moreover, we show that GSK-3 inhibitor and Docetaxel synergistically suppress proliferation and survival of renal cancer cells.Conclusions:Our results show nuclear accumulation of GSK-3beta as a new marker of human RCC, identify that GSK-3 positively regulates RCC cell survival and proliferation and suggest inhibition of GSK-3 as a new promising approach in the treatment of human renal cancer.British Journal of cancer advance online publication, 17 November 2009; doi:10.1038/sj.bjc.6605437 www.bjcancer.com.

Gan To Kagaku Ryoho. 2009 Nov; 36(11): 1877-1880
Aizaki K, Kohno S, Sasaki K, Fujihira D, Koike T, Norimatsu T, Funatsu K, Ohya Y, Shino M, Yoshida T, Tanaka T, Matsushita T, Hokari T, Kawakami S, Takano S, Kazama A

The patient was a 55-year-old man who was treated with S-1 and paclitaxel(PTX)combination chemotherapy for inoperable advanced gastric cancer in whom an abdominal CT examination had revealed peritoneal dissemination, Pancreatic invasion, and ascites. A total of 15 courses of S-1 120mg/day for 2 weeks followed by a 2-week rest period and PTX 90mg/ body on day 1, 8, and 15 were administered. The CT examination after the completion of chemotherapy showed resolution of the ascites, and no evidence of peritoneal dissemination was observed on the images. The tumor marker values had also decreased, but because of severe manifestations of pyloric stenosis, distal gastrectomy and D1 lymph node dissection were performed. Intraoperative exploration revealed total scarring of the peritoneal dissemination and no evidence of Pancreatic invasion. We reported this case because of the long-term combination chemotherapy with no major adverse effects and the fact that resection was possible.

Expert Rev Mol Med. 2009; 11: e34
Chandana S, Mahadevan D

Biological complexity, inaccessible anatomical location, nonspecific symptoms, lack of a screening biomarker, advanced disease at presentation and drug resistance epitomise Pancreatic ductal adenocarcinoma (PDA) as a poor-prognosis, lethal disease. Twenty-five years of research (basic, translational and clinical) have barely made strides to improve survival, mainly because of a fundamental lack of knowledge of the biological processes initiating and propagating PDA. However, isolation of pancreas cancer stem cells or progenitors, whole-genome sequencing for driver mutations, advances in functional imaging, mechanistic dissection of the desmoplastic reaction and novel targeted therapies are likely to shed light on how best to treat PDA. Here we summarise current knowledge and areas where the field is advancing, and give our opinion on the research direction the field should be focusing on to better deliver promising therapies for our patients.

J Cutan Pathol. 2009 Nov 16;
Swick BL, Gordon JR

Cutaneous metastases from transitional cell carcinoma of the bladder are rare and most often associated with a deeply invasive primary tumor. This case report describes a 69-year-old male with previously resected superficially invasive primary transitional cell carcinoma of the bladder who presented with distant cutaneous and central nervous system metastases associated with recurrent bladder cancer. In addition, this case highlights the differential diagnosis of metastatic carcinomas that display a CK7/CK20 positive immunophenotype including transitional cell carcinoma, Pancreatic carcinoma, cholangiocarcinoma and rare gastric carcinomas.