Masaki Sakamoto

Enhanced angiogenesis due to inflammatory cytokines from pancreatic cancer cell lines and relation to metastatic potential.

Objectives: To investigate the mechanisms of metastasis formation in human pancreatic carcinoma, we examined the angiogenic capabilities of human pancreatic cancer cell lines with different metastatic potentials and the roles of inflammatory cytokines. Methods: Interleukin (IL)-8 secretion by human pancreatic cancer cells stimulated with IL-1&agr; or IL-1 receptor antagonist (IL-1ra) was measured by enzyme-linked immunosorbent assay (ELISA). We then examined how cancer cells with different metastatic potentials influenced the proliferation and tube formation of human umbilical vein endothelial cells (HUVECs) using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide dye reduction method (MTT assay) and an angiogenesis assay, respectively. We also examined the role of inflammatory cytokines in relation to tumor metastatic potential and angiogenesis. Results: IL-8 secretion levels by pancreatic cancer cells were regulated by IL-1&agr; and correlated with metastatic potential. Both HUVEC proliferation and tube formation were strongly enhanced by coculture with metastatic pancreatic cancer cells and were enhanced to a similar extent by culture in the presence of IL-1&agr; and IL-8. In contrast, blockade of IL-1&agr; or IL-8 inhibited HUVEC proliferation and angiogenesis. Conclusions: The inflammatory cytokines IL-1&agr; and IL-8 may have an important role in metastasis via vascular endothelial cell proliferation and angiogenesis.

Laparoscopic Management of Small Bowel Incarceration Caused by a Broad Ligament Defect: Report of a Case

We report the case of a 94-year-old woman who presented with signs of a small bowel obstruction many years after an appendectomy. Abdominal computed tomography (CT) scan showed discontinuity of the small bowel at a point next to the uterus. We made a provisional diagnosis of an internal hernia through a defect in the broad ligament and performed laparoscopic exploration, which revealed a viable ileal loop incarcerated through the broad ligament. Thus, CT scan may be useful for diagnosing this type of defect preoperatively, whereby open surgery can be avoided.

Anticipatory nausea among ambulatory cancer patients undergoing chemotherapy: prevalence, associated factors, and impact on quality of life.

The purposes of this study were to investigate the prevalence of anticipatory nausea (AN), its associated factors, and its impact on quality of life (QOL) among ambulatory cancer patients receiving chemotherapy. Patients were randomly selected to participate in this study, and were asked to complete the Morrow Assessment of Nausea and Emesis scale, the Hospital Anxiety and Depression Scale, the Short‐form Supportive Care Needs Survey questionnaire, and the European Organization for Research and Treatment of Cancer QLQ‐C30 questionnaire. Complete data were available for 214 patients. A total of 10.3% of the patients experienced very mild to severe AN. The presence of AN was significantly associated with most domains of the investigated patients’ outcome, including psychological distress and perceived needs, with the exception of the health system and information domain of patients’ needs, and the physical functioning domain of QOL. Anticipatory nausea was also associated with QOL even after adjustments for age, sex, performance status, and psychological distress. The prevalence of AN in ambulatory cancer patients who receive chemotherapy may not be as high as previously reported. However, given its potentially significant impact on relevant outcome, including QOL, AN should not be neglected in current clinical oncology practice. (Cancer Sci 2010; 101: 2596–2660)

Good Death in Elderly Adults with Cancer in Japan Based on Perspectives of the General Population

To investigate concepts relevant to a good death in elderly adults with cancer.

Granulocyte-colony stimulating factor producing rectal cancer

BackgroundGranulocyte-colony stimulating factor (G-CSF)-producing cancer has been reported to occur in various organs, especially the lung. However, G-CSF-producing colorectal cancer (CRC) has never been reported in the English literature.Case presentationA 57-year-old man was admitted for the surgical removal of a rectal cancer. Some hepatic tumors in the liver were revealed concurrently, and their appearance suggested multiple liver metastases. Low anterior resection was performed. with the help of histopathological examination and immunohistochemical studies, we diagnosed this case to be an undifferentiated carcinoma of the rectum. After the operation, the white blood cell (WBC) count increased gradually to 81,000 cells/μL. Modified-FOLFOX6 therapy was initiated to treat the liver metastases, but there was no effect, and peritoneal dissemination had also occurred. The serum level of G-CSF was elevated to 840 pg/mL (normal range, <18.1 pg/mL). Furthermore, immunohistochemistry with a specific monoclonal antibody against G-CSF was positive; therefore, we diagnosed this tumor as a G-CSF-producing cancer. The patient died from rapid growth of the liver metastases and peritoneal dissemination 2 months after surgery.ConclusionThis is the first case of G-CSF-producing rectal cancer, and its prognosis was very poor.

Use of barbed suture for peritoneal closure in transabdominal preperitoneal hernia repair.

AIM To investigate the use of the V-Loc wound closure device for transabdominal preperitoneal hernia repair. METHODS We performed conventional transabdominal preperitoneal hernia repair in 19 patients, including one single incisional case using V-Loc. Except for the use of V-Loc for peritoneal closure, the procedures were the same as those used in conventional techniques. RESULTS Although the operators included 2 residents who have no experience in laparoscopic herniorrhaphy and intracorporeal suture, the operations were completed. We believe that V-Loc is especially suitable for inexperienced surgeons and the use of V-Loc reduces the operative time by a small amount but reduces operator stress significantly. CONCLUSION We conclude that V-Loc is the ideal peritoneal closure device for transabdominal preperitoneal hernia repair.

Glial Cell Line-Derived Neurotrophic Factor Enhances Nuclear Factor-κB Activity and Invasive Potential in Human Pancreatic Cancer Cells

Objectives: The invasive potential is increased by glial cell line–derived neurotrophic factor (GDNF) in human pancreatic cancer cell lines. We researched whether the signaling pathway activated by GDNF correlates with the nuclear factor-κB (NF-κB) in human pancreatic cancer cell lines and whether the inhibition of NF-κB activity is associated with suppression of invasive potential. Methods: Proliferation of human pancreatic cancer cell lines (BxPC-3 and MIA PaCa-2) was measured by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays (MTT assay). NF-κB activity was examined by dual luciferase assay and electrophoretic mobility shift assay. In addition, to investigate the invasive potential, an in vitro invasion assay was performed. Results: Proliferation of both cell lines was decreased by a protea-some inhibitor, MG132, in a dose-dependent manner, but proliferation of control and IκBαM vector–transfected BxPC-3 cells was similar. The invasion cell number and the NF-κB activity were increased by GDNF stimulation. However, in the presence of MG132 or IκBαM, which blocks the nuclear localization of NF-κB, both were significantly suppressed. Furthermore, reduced activity of both remained unchanged by GDNF stimulation. Conclusion: These results indicate that GDNF promotes NF-κB activation and that the latter is involved in the invasive potential of human pancreatic cancer cells.

Prevalence, course and factors associated with delirium in elderly patients with advanced cancer: a longitudinal observational study

OBJECTIVE The aim of this study was to investigate the prevalence of delirium on admission, the course of delirium during a 2-week period after admission and factors associated with delirium on admission, among elderly patients with advanced cancer. METHODS Patients aged ≥ 65 years with incurable lung or gastroenterological cancer and the Eastern Cooperative Oncology Group Performance Status 2 or greater were continuously sampled after admission to a university hospital. Participants were evaluated for DSM-IV-TR delirium by trained psychiatrists and the delirium subtype was assessed using the Delirium Motor Subtype Scale within 4 days after admission and again 2 weeks later. In addition, we assessed associated factors with delirium on admission. RESULTS Among 73 eligible patients, complete data were available from 61 on admission and 49 after 2 weeks. Twenty-six patients (43%) met delirium criteria on admission (hypoactive: 58%, unspecified: 35%, hyperactive: 4%, mixed: 4%). Of these, 19 (73%) remained delirious 2 weeks later. Of 35 patients without delirium on admission, 21 (60%) remained delirium-free 2 weeks later and 7(20%) became delirious. Overall, 33/61 (54%) developed delirium at some point during the study. Patients receiving steroids at admission were more likely to have delirium (odds ratio = 5.0; 95% confidence interval = 1.5-16). CONCLUSIONS Given the high prevalence of the delirium, all patients with advanced cancer should be screened for delirium both on admission and regularly thereafter. In addition, medical staff should be aware that steroid use on admission is an additional indicator of elevated risk for delirium.

Palliative Percutaneous Jejunal Stent for Patients with Short Bowel Syndrome

Gastrointestinal obstruction is a common preterminal event in patients with gastric and pancreatic cancer who often undergo palliative bypass surgery. Although endoscopic palliation with self-expandable metallic stents has emerged as a safe and effective alternative to surgery, experience with this technique remains limited. In particular, a proximal jejunal obstruction requires more technical expertise than a duodenal obstruction. Palliative treatment modalities include both surgical and nonsurgical approaches. In this report, we describe the successful placement of self-expandable metallic stents at the proximal jejunum using a combination of percutaneous endoscopic, intraoperative, and transstomal stenting. Usually endoscopy is not indicated in cases of proximal jejunal obstruction, but some cases may require palliative endoscopy instead of bypass operation.

An endocrine cell carcinoma with gastric-and-intestinal mixed phenotype adenocarcinoma component in the stomach.

A 77‐year‐old man complained of bodyweight loss, and a Borrmann 3 type lesion was observed endoscopically in the anterior wall of angular region of the stomach. The endocrine cell carcinoma (ECC) having the cytoplasmic staining of chromogranin A (CgA) was detected pathologically in the biopsy samples. The patient underwent distal gastrectomy plus systemic lymph node (LN) dissection (D2 LN dissection), and pathological examination revealed ECC invading the subserosa, and no LN metastasis (pT2N0M0). None of the gastric and intestinal endocrine cell marker expression was apparent in the ECC cells. The lesion also contained a moderately differentiated type tubular adenocarcinoma component, which was judged to be gastric‐and‐intestinal mixed (GI type) phenotype, using gastric and intestinal exocrine cell markers. After the surgery, he left the hospital and started oral doxifluridine (600 mg/day). The patient now (March 2008, about 19 months since the surgery) continues this chemotherapy with no recurrence. In conclusion, we experienced ECC with a GI type adenocarcinoma component. The ECC cases with the GI type adenocarcinoma component may have a relatively good prognosis, being similar to the results of advanced gastric cancers from the viewpoint of gastric and intestinal phenotypic expression.