Paclitaxel-based chemotherapy for advanced pancreatic cancer after gemcitabine-based therapy failure: a case series of 5 patients.

BACKGROUND/OBJECTIVES: Gemcitabine (GEM) is a gold-standard chemotherapy agent for advanced pancreatic cancer. Because of the malignant character of the disease, nearly all patients show disease progression despite treatment with GEM-based chemotherapy; therefore, second-line chemotherapy may be beneficial for these patients. We report a retrospective analysis of 5 patients with advanced pancreatic cancer, treated with a paclitaxel-containing regimen as second-, third- or fourth-line chemotherapy after various therapies, such as a GEM-based regimen, S-1 regimen, and chemoradiation. We retrospectively analyzed the efficacy and adverse events, and evaluated the paclitaxel-containing regimens. A review of the literature is also discussed. RESULTS: The median overall survival from the start of salvage therapy was 10.7 months. The disease control rate of the paclitaxel-containing regimen according to RECIST criteria was 60%, including complete response in 0 patients, partial response in 3, and stable disease in 2. Two patients had malignant ascites at the start of this salvage therapy, and in both of them the ascites and clinical complaints improved. Grade 3 and 4 hematological adverse events were observed in 2 patients and 1 patient, respectively. CONCLUSION: Salvage paclitaxel-based therapy could be beneficial to advanced pancreatic cancer patients who maintain good performance status after several chemotherapy failures.

Bacterial DNA promotes proliferation of rat pancreatic stellate cells thorough toll-like receptor 9: potential mechanisms for bacterially induced fibrosis.

OBJECTIVES: We hoped to clarify the possible role of CpG DNA as a trigger factor for overt pancreatic inflammation of pancreatic stellate cells (PSCs). METHODS: Pancreatic stellate cells were isolated from the male Lewis rat. The expression of Toll-like receptor 9 (TLR9) messenger RNA and protein were evaluated by reverse transcription-polymerase chain reaction and immunofluorescent cytochemistry. Internalization of CpG DNA was analyzed by confocal laser scanning microscopy. Pancreatic stellate cells were incubated with CpG DNA, and then cell proliferation and migration were assessed. RESULTS: Constitutive expression of TLR9 occurs at the messenger RNA and protein levels. After several minutes of CpG DNA administration, CpG DNA was observed on the cell membrane surface and in the cytoplasm and found to be translocating into the perinucleus of PSCs. Pancreatic stellate cells migrated and proliferated in dose- and time-dependent manners in response to simulation by CpG DNA. Proliferation of PSCs was observed 3 hours after administration (earlier than platelet-derived growth factor-induced proliferation), suggesting that PSCs respond readily to provide innate immunity. Endosomal acidification inhibitors attenuated CpG DNA-induced signaling, leading to suppression of DNA synthesis by PSCs. CONCLUSIONS: Our findings demonstrate that bacterial DNA promotes migration and proliferation of PSCs and suggest that bacterial DNA can initiate and sustain pancreatic inflammation and fibrosis by means of TLR9.

A case of lipomatous pseudohypertrophy of the pancreas diagnosed by typical imaging.

CONTEXT: Lipomatous pseudohypertrophy of the pancreas is an extremely rare disease, and is characterized by the replacement of pancreatic acinar cells with adipose tissue, although the pancreatic duct and islets are preserved. CASE REPORT: We report the case of a 64-year-old female who was undergoing treatment for Hashimoto's disease at a nearby clinic. For the previous two years, she had experienced an unpleasant feeling in the upper abdominal area after eating oily foods. For the previous six months, she had also suffered from lower-back pain, and presented at our hospital. Abdominal computed tomography and magnetic resonance imaging revealed marked fat replacement over the entire pancreas. Endoscopic retrograde cholangiopancreatography revealed no anatomical abnormality or narrowing of the main pancreatic duct; the main pancreatic duct was normal up to the pancreatic tail and the branches of the pancreatic duct did not show any abnormalities. While the serum levels of the pancreatic enzymes were considerably low, according to the data of the pancreatic exocrine function test (N-benzoyl-tyrosyl-p-aminobenzoic acid test), endocrine function was maintained. On the basis of the abovementioned findings, we diagnosed lipomatous pseudohypertrophy of the pancreas. CONCLUSIONS: Lipomatous pseudohypertrophy of the pancreas is a very rare disease characterized by the disappearance of pancreatic exocrine tissue due to adipose tissue replacement, although the pancreatic duct and islets remain intact. Even though it has been suggested that the diagnosis of lipomatous pseudohypertrophy of the pancreas should be based on histological findings, this case indicated the possibility that lipomatous pseudohypertrophy of the pancreas may be diagnosed solely by typical imaging findings and serological data.

Fractalkine and TGF-beta1 levels reflect the severity of chronic pancreatitis in humans.

AIM: To clarify whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of chronic pancreatitis (CP). This study aimed at clarifying whether serum chemokine and cytokine levels can become useful biological and functional markers to assess the severity of CP. METHODS: Serum monocyte chemoattractant protein-1 (MCP-1), transforming growth factor beta-1 (TGF-beta1), and soluble type fractalkine (s-fractalkine) concentrations were examined in patients with CP (n = 109) and healthy controls (n = 116). Severity of disease was classified in patients with CP by a staging system. Relationships between stage-specific various clinical factors and serum MCP-1, TGF-beta1, and s-fractalkine levels were investigated. Furthermore, 57 patients with non-alcoholic CP were similarly evaluated in order to exclude influence of alcohol intake. RESULTS: Patients with CP showed significant higher levels of serum TGF-beta1 and s-fractalkine, but not MCP-1, compared to the controls. Serum TGF-beta1 in the severe stage and s-fractalkine in the mild and the severe stage of CP significantly increased compared to those of controls. However, it was observed that both TGF-beta1 and s-fractalkine levels were affected by alcohol intake. In patients with non-alcoholic CP, serum TGF-beta1 showed significant increase in the moderate stage of CP, and serum s-fractalkine revealed significant increase in the early stage of CP. CONCLUSION: It is suggested that the measurement of serum F-fractalkine is useful to diagnose early-stage CP. Moreover, the combined determination of both, s-fractalkine and TGF-beta1, in human sera may be helpful in evaluating the severity status of CP.

[A case of pancreatic ductal adenocarcinoma with rapid progress in a young man].

A 17-year-old man was admitted to hospital because of epigastric pain. Various imaging studies showed a solid tumor (4cm in diameter) in the tail of the pancreas, multiple hypovascular tumors in liver. Serum levels of DUPAN2, SPAN1 and NSE were elevated slightly. Biopsy of hepatic tumor demonstrated that tumor cells had eosinophilic cytoplasm generally and unevenly distributed polymorphic nucleus. These data suggested that this tumor is poorly differentiated pancreatic carcinoma originated from the epithelium. Therefore, we administered 5-fluorouracil and cisplatin, combined with gemcitabine. The clinical status improved temporarily by the treatment, however, worsened rapidly. He died 81days after the treatment. Final diagnosis of autopsy was pancreatic ductal adenocarcinoma. Pancreatic ductal adenocarcinoma in the young patients is rare, and we reported this case in addition to consideration on literature.

[Clinical features and management of pancreatic cancer with bone metastases].

Prognosis of pancreatic cancer is one of the worst among various cancers, however, incidence of bone metastasis has been increased even in pancreatic cancer in recent years. Therefore, we examined clinical features of pancreatic cancer presenting bone metastases who were treated in our cancer center, and propose how to manage these patients. We experienced 13 patients (7.3%) with pancreatic cancer with bone metastases during 2000-2003. Among these patients, pancreatic cancer was located at pancreatic body to tail in 10 cases, while it was located at pancreatic head in 3 cases. Liver metastasis was noted in 7 of 13 cases with bone metastases. Radiographical imagings of bone lesions revealed osteolytic bone destruction, and serum levels of bone resorption marker, 1CTP, were elevated in these patients. Stimulation of osteoclastic bone resorption is a critical step for bone metastasis, thus, serum levels of cytokines (PTHrP, IL-6, VEGF), which exert a promotive effect on bone resorption, were measured. Serum levels of IL-6 and VEGF were elevated in most of these patients, while elevation of serum PTHrP levels was found in 3 of 13 patients with bone metastases. Survival periods of pancreatic cancer patients with bone metastases was not long, however, treatment for bone metastases is important in terms of quality of life (QOL). An earlier diagnosis is essential to prevent deterioration in the QOL of pancreatic cancer patients presenting bone metastases. Periodical measurement of serum 1CTP in addition to bone scintigraphy is helpful for the earlier diagnosis for bone metastases.