Kenji Koneri

Angiogenesis and Tumor Proliferation/Metastasis of Human Colorectal Cancer Cell Line SW620 Transfected with Endocrine Glands-Derived-Vascular Endothelial Growth Factor, As a New Angiogenic Factor

Endocrine glands-derived-vascular endothelial growth factor (EG-VEGF) was recently cloned as a new angiogenic factor that selectively acts on the endothelium of endocrine gland cells. We evaluated the involvement of EG-VEGF in colorectal cancer. The expression of EG-VEGF was confirmed in all of the colorectal cancer cell lines. (On the other hand, the expression of EG-VEGF mRNA was not detected in colorectal normal mucosae.) Stable EG-VEGF infectors of colorectal cancer cell line SW620 were produced, EG-VEGF transfectants were implanted into cecum and s.c., and cell proliferation was evaluated. Angiogenesis was evaluated by dorsal air sac method. Liver metastasis was evaluated after the implantation of EG-VEGF transfectants into the mouse spleen. Tumor proliferation (cecum, s.c.) was significantly higher in the EG-VEGF transfectants than in the control cells. The small vessels were significantly increased in EG-VEGF transfectants as compared with those in control cells. Also, liver metastatic ratio was higher in the EG-VEGF transfectants than in the control cells. In this study, EG-VEGF, a new angiogenic factor, may lead to angiogenesis, promoting cell proliferation and liver metastasis in colorectal cancers. When the EG-VEGF gene-overexpressing colorectal cancer cell line that had been treated with phosphorothioate antisense EG-VEGF oligonucleotides was injected s.c. into mice, angiogenesis and tumor growth were inhibited. Although the novel angiogenesis factor EG-VEGF was not expressed in the normal colorectal mucosa, it was expressed in colorectal cancer cells, which indicates that it is a cancer-specific and possibly tissue-specific angiogenesis factor in the large intestine, and which suggests that it can be targeted by a novel antiangiogenesis therapy.

Ascending colon cancer with hepatic metastasis and cholecystolithiasis in a patient with situs inversus totalis without any expression of UVRAG mRNA: report of a case.

Situs inversus totalis refers to an inverted position of part or all of the viscera, which represents a mirror-image of the normal location, and it is a relatively rare condition that occurs in one in 4 000–8 000 people in Japan. We herein report a patient demonstrating a combination of situs inversus totalis, colon cancer with hepatic metastasis, and cholecystolithiasis, who was treated surgically. We found no expression of UVRAG mRNA in our case, thus suggesting that the UVRAG gene is partly responsible for this condition.

Ruptured mucinous cystic neoplasm with an associated invasive carcinoma of pancreatic head in a pregnant woman: Report of a case and review of literature

Mucinous cystic neoplasm (MCN) of the pancreas is characterized by mucin‐producing columnar epithelium and an ovarian‐type stroma. It occurs almost exclusively in women and is almost always located in the pancreatic body or tail. Here, we report a case of large MCN located in the pancreatic head but not in the body nor tail in a 32‐year‐old pregnant woman, which was thought to have grown rapidly during pregnancy. It was ruptured at 34 weeks of gestation and the patient was admitted to the emergency department of the University of Fukui Hospital with an acute abdomen. Emergency cesarean section followed by pancreaticoduodenectomy was performed. The tumor consisted of many small cysts lined by a single‐layer of mucinous epithelium with papillary growth and partial solid parts showing invasive growth and sarcomatoid changes, indicating mucinous cystic neoplasm with an associated invasive carcinoma (previously referred as mucinous cystadenocarcinoma). Thickened septa revealed ovarian‐type stroma strongly positive for α‐inhibin and partly positive for progesterone receptor immunohistochemically. We also review and discuss previous reports of MCNs including those with an associated invasive carcinoma in pregnant patients.

Modified Gluteus Maximus V-Y Advancement Flap for Reconstruction of Perineal Defects After Resection of Intrapelvic Recurrent Rectal Cancer: Report of a Case

Technical advances in myocutaneous flap preparation have resulted in primary reconstruction now being generally indicated for malignant tumors extensively infiltrating the pelvic cavity and perineum. Pelvic tumor resection can dramatically improve the health-related quality of life (QOL) of patients with locally recurrent rectal cancer complicated by infection and pain. However, the removal of a wide area of perineum by these two procedures often leaves a large dead space. A gluteal thigh muscle, rectus abdominis muscle, or pedicle myocutaneous flap is usually made to reconstruct such extensive perineal defects. The subject of this case report was a 76-year-old woman with recurrent rectal cancer in the pelvis after abdominoperineal resection. The large pelvic tumor, which was causing severe pain, was resected and the extensive perineal defects were reconstructed using a modified maximus V-Y advancement flap. The operating time was approximately 30 min, and the pain after surgery was much less severe. Moreover, she could walk the day after surgery and returned to normal daily life without requiring prolonged bed rest. No infection developed in the intrapelvic dead space postoperatively. This technique proved very useful for improving the patients QOL.

Five-Year Survival of Alpha-Fetoprotein-Producing Gastric Cancer with Synchronous Liver Metastasis: A Case Report

Alpha-fetoprotein-Producing gastric cancer is associated with poor prognosis because of frequent liver and lymph node metastasis. We present a case with synchronous liver metastasis who survived for 5 years. A 69-year-old man with upper abdominal pain was referred to our hospital. Gastrointestinal endoscopy revealed a Borrmann II-like tumor in the lower part of the stomach. Computed tomography revealed a tumor in the left lobe of the liver. Serum alpha-fetoprotein levels were markedly increased. We performed distal gastrectomy after administering oral tegafur/gimeracil/oteracil potassium and administered hepatic intra-arterial cisplatin injection. Liver metastasis showed partial response on computed tomography. Despite left hepatic lobectomy, further metastases to the liver and mediastinal lymph nodes became difficult to control. After sorafenib tosylate administration, stabilization of the disease was observed for 4 months. We conclude that hepatic intra-arterial chemotherapy and oral administration of sorafenib tosylate may potentially improve the prognosis in such cases.

Chemo-hyperthermic peritoneal perfusion (CHPP) for appendiceal pseudomyxoma peritonei

BackgroundPseudomyxoma peritonei is derived mostly from the rupture of an appendiceal cystic tumor and produces a large quantity of mucinous substance. Though its malignancy level is low, radical resection is difficult and its prognosis is poor. In some institutes in European countries and the United States, multidisciplinary treatment with chemo-hyperthermia at a relatively low temperature is performed following subtotal peritonectomy. We carried out high-temperature chemo-hyperthermic peritoneal perfusion following incomplete resections of mucinous tumors in six patients.MethodsAfter resection of the main tumor and macroscopic gross tumor resection of dissemination, heated perfusate containing anticancer agents was poured into the peritoneal cavity and stirred and pumped into a circulation between the abdomen and a reservoir. The temperature of the surface of the peritoneum was maintained at around 43°C.ResultsThe intraperitoneal space was sufficiently heated without severe complications. The pathological diagnosis in four of the patients was peritoneal mucinous carcinomatosis, and in the other two patients, it was intermediate type between peritoneal mucinous carcinomatosis and disseminated peritoneal adenomucinosis. Two patients died, 15 and 26 months after the treatment. The other four patients have survived for 4, 24, 26, and 80 months now, and two of them, who have survived for 26 and 80 months, received a second treatment 18 and 32 months, respectively, after the initial treatment. These results seemed not to be inferior to those in the reports from institutes in Europe and the United States which performed subtotal peritonectomy and then used mild hyperthermia in chemo-hyperthermia.ConclusionFor treating pseudomyxoma peritonei, hightemperature chemo-hyperthermic peritoneal perfusion following incomplete tumor resection is effective even without peritonectomy.

Biliopancreatic fistula and abscess formation in the bursa omentalis associated with intraductal papillary mucinous cancer of the pancreas.

We describe an unusual case of biliopancreatic fistula, free perforation, and subsequent abscess formation within the lesser peritoneal sac associated with intraductal papillary mucinous carcinoma (IPMC). A 71-year-old man presented with general fatigue and loss of appetite that had persisted for 1 month. Abdominal computed tomography (CT) revealed findings consistent with an intraductal papillary mucinous neoplasm (IPMN) of the pancreas, accompanied by abscess formation in the bursa omentalis. Gastrointestinal fiberscopy revealed a swollen papilla of Vater expanded by sticky mucus, and a communication between the pancreatic duct and bile duct was demonstrated by the injection of indigo carmine solution into the pancreatic duct. Percutaneous transhepatic abscess drainage (PTAD) was performed on the day of admission. After this procedure, the patient was managed for 1 month and supported nutritionally with glycemic control for diabetes mellitus. After admission, the patient had an episode of obstructive jaundice that was treated by retrograde biliary drainage. Pancreaticoduodenectomy with lymph node dissection was then performed. Pathological examination revealed IPMN with patchy, scattered carcinoma of the pancreatic head and uncinate process with the formation of a biliopancreatic fistula. Bile duct epithelium in the area of the biliopancreatic fistula demonstrated atypical papillary epithelium suggestive of tumor invasion.

Expression of prokineticin-receptor2(PK-R2) is a new prognostic factor in human colorectal cancer

The increased invasiveness of colorectal cancer cells is important for progression and metastasis to the surrounding organs. According to recent molecular biological studies, signaling through transmembrane Prokineticin-Receptor2(PK-R2) is likely involved in the ability of tumor cell to invade. However, no studies have evaluated the relationship between PK-R2 expression, ability of cancer to invade/metastasize, and patient prognosis in cases of resected colorectal cancer. Accordingly, we have examined these factors in the present study. Immunohistochemical staining was performed to detect PK-R2 in the primary lesion and adjacent normal large intestine mucosa of 324 colorectal cancer patients who underwent resection surgery at our department. Additionally, we conducted clinicopathologic examinations and analyzed patient prognoses with the Kaplan-Meier method. Further, multivariate analysis was conducted using a cox-proportional hazard model. PK-R2 expression was observed on the cellular membrane of the primary lesion in 147 of 324 cases (45.3%) of human colorectal cancer. PK-R2 expression was associated with a higher incidence of vascular invasion, lymph node metastasis, hepatic metastasis, and hematogenous metastasis. Further, prevalence of PK-R2 expression increased as tumor stage increased. In stage III curative resection cases, where recurrence is the most serious problem, cases that expressed PK-R2 had a significantly lower 5-year survival rate (82.1% versus 66.8%) and higher recurrence compared to those cases with no PK-R2 expression. In the multivariate analysis for prognosis, PK-R2 expression was found to be an independent factor(ratio2.621). PK-R2 expression could be one of the new prognostic factors in human colorectal cancer.

Partial response after transcatheter arterial infusion chemotherapy in a patient with systemic chemotherapy-resistant unresectable colon cancer and hepatic metastasis: (case report)

We report here a case of partial response to hepatic arterial infusion chemotherapy in a patient who developed serious hepatic failure due to unresectable colorectal cancer and hepatic metastasis and showed resistance to systemic chemotherapy with molecular targeted drugs, mFOLFOX6, and FOLFIRI. The patient was a 60-year-old woman who underwent sigmoidectomy for sigmoid colon cancer, lateral posterior hepatic segmentectomy for metastatic liver cancer, and postoperative radiation therapy for metastatic lung cancer. As first-line systemic chemotherapy, mFOLFOX6 (oxaliplatin, 5-fluorouracil, and leucovorin), bevacizumab + FOLFIRI (irinotecan, 5-fluorouracil, leucovorin), and anti-epidermal growth factor receptor antibody + irinotecan were administered, in that order. However, recurrent hepatic metastasis was exacerbated, which induced serious hepatic failure manifested by general malaise, jaundice, abnormal hepatic function, difficulty in walking due to bilateral lower extremity edema, and decreased appetite. The patient was admitted in a serious condition. After hospitalization, the patient received hepatic arterial infusion chemotherapy with 5-fluorouracil and l-leucovorin. After two complete courses, the symptoms improved. The patient’s performance status also improved, and she was discharged from the hospital. Four months after discharge, the patient had continued outpatient chemotherapy and maintained excellent performance status. Although HAIC is not presently considered an alternative to systemic chemotherapy, it is sometimes effective in patients who show resistance to molecular targeted drug therapy, FOLFOX, and FOLFIRI, and in whom hepatic metastasis is a key factor in determining prognosis and serious hepatic failure. Further studies should be performed in the future to verify these findings.

Thin-slice CT findings of biliary stricture due to blunt abdominal trauma: reports of three cases

Thin-slice CT findings were reviewed in three patients with biliary stricture due to blunt abdominal trauma. In all cases, the stricture was located at the suprapancreatic portion of the common bile duct. Central enhancement with a low attenuation rim at the bile duct between the stricture and the papilla of Vater was apparent in all cases. Ancillary findings such as focal renal laceration (1 case) and left rib fracture (1 case) were also seen. These CT findings may help in the diagnosis of biliary injury for patients with blunt abdominal trauma.