Ken Eto

Dual‐specificity tyrosine‐regulated kinase 2 is a suppressor and potential prognostic marker for liver metastasis of colorectal cancer

Colorectal cancer is a common cancer and a leading cause of cancer‐related death worldwide. The liver is a dominant metastatic site for patients with colorectal cancer. Molecular mechanisms that allow colorectal cancer cells to form liver metastases are largely unknown. Activation of epithelial–mesenchymal transition is the key step for metastasis of cancer cells. We recently reported that dual‐specificity tyrosine‐regulated kinase 2 (DYRK2) controls epithelial–mesenchymal transition in breast cancer and ovarian serous adenocarcinoma. The aim of this study is to clarify whether DYRK2 regulates liver metastases of colorectal cancer. We show that the ability of cell invasion and migration was abrogated in DYRK2‐overexpressing cells. In an in vivo xenograft model, liver metastatic lesions were markedly diminished by ectopic expression of DYRK2. Furthermore, we found that patients whose liver metastases expressed low DYRK2 levels had significantly worse overall and disease‐free survival. Given the findings that DYRK2 regulates cancer cell metastasis, we concluded that the expression status of DYRK2 could be a predictive marker for liver metastases of colorectal cancer.

Thymidine phosphorylase mRNA expression may be a predictor of response to post‑operative adjuvant chemotherapy with S‑1 in patients with stage III colorectal cancer

The aim of the present study was to investigate markers in surgically resected specimens of colorectal cancer that can be used to predict the response to chemotherapy. The mRNA expression levels of enzymes involved in 5-fluorouracil (5-FU) metabolism and folate metabolism were measured in formalin-fixed, paraffin-embedded tumor sections obtained from the primary tumors of 54 patients with resected stage II or III colorectal cancer who received S-1 for one year. The 5-FU metabolizing enzymes studied were thymidylate synthase, dihydropyrimidine dehydrogenase and thymidine phosphorylase (TP). The folate metabolizing enzymes studied were folypolyglutamate synthetase, γ-glutamyl hydrolase and dihydrofolate reductase. The associations between the mRNA expression levels of these enzymes and clinical variables were investigated. Tumors were classified as exhibiting high or low expression as compared with the median mRNA expression level of each metabolizing enzyme defined as the cutoff value. The associations between the high and low expression levels of each enzyme and disease-free survival (DFS) were analyzed with the use of Kaplan-Meier curves and the log-rank test. DFS was not significantly associated with the relative mRNA expression level of any metabolizing enzyme in the study group as a whole, but there was a trend toward longer DFS in patients with high TP expression (P=0.066). In patients with stage III colorectal cancer, high TP expression was associated with significantly improved outcomes compared with low TP expression (P=0.039). These results indicate that the mRNA expression of TP, a metabolizing enzyme of 5-FU, is a significant predictor of response to post-operative chemotherapy with S-1 in patients with stage III colorectal cancer.

A comparison of laparoscopic energy devices on charges in thermal power after application to porcine mesentery.

Introduction: Advances in energy devices have played a major role in the rapid expansion of laparoscopic surgery. However, complications due to these energy devices are occasionally reported, and if the characteristics of these devices are not well understood, serious complications may occur. This study evaluated various typical energy devices and measured temperature rises in the adjacent tissue and in the devices themselves. Equipment and Methods: We used the following 7 types of energy devices: AutoSonix (AU), SonoSurg (SS), Harmonic Scalpel (HS), LigaSure Atlas (LA), LigaSure Dolphin Tip (LD), monopolar diathermy (Mono), and bipolar scissors (Bi). Laparoscopy was performed under general anesthesia in pigs, and the mesentery was dissected using each energy device. Tissue temperature at a distance of 1 mm from the energy device blade before and after dissection was measured. Temperature of the device blade both before and after dissection, time required for dissection, and interval until the temperature fell to 100°C, 75°C, and 50°C were documented. Results: Temperature of the surrounding tissue using each device rose the most with the Mono (50.5±8.0°C) and the least with the HS in full mode (6.2±0.7°C). Device temperature itself rose the highest with the AU in full mode (318.2±49.6°C), and the least with the Bi (61.9±4.8°C). All ultrasonic coagulation and cutting devices (AU, SS, and HS) had device temperatures increase up to ≥100°C, and even at 8 seconds after completing dissection, temperatures remained at ≥100°C. Conclusions: Because the adjacent tissue temperature peaked with the Mono, cautious use near the intestine and blood vessels is necessary. In addition, the active blades of all ultrasonic coagulation and cutting devices, regardless of model, developed high temperatures exceeding 100°C. Therefore, an adequate cooling period after using these devices is therefore necessary between applications.

Hepatic Inflammatory Pseudotumor With Elevated Serum CA19-9 Level Mimicking Liver Metastasis From Rectal Cancer: Report of a Case

Inflammatory pseudotumor (IPT) of the liver is rare, and differential diagnosis from malignant tumors is difficult. We herein report a case of IPT of the liver with marked elevation of carbohydrate antigen 19-9 (CA19-9). A 72-year-old woman, who underwent low anterior resection for rectal cancer, had low-grade fever and epigastric pain. The patient has well-controlled idiopathic thrombocytopenic purpura (ITP) with steroid maintenance treatment. Abnormal laboratory findings included serum carcinoembryonic antigen of 15.9 ng/mL and CA19-9 up to 14,632 U/mL. Computed tomography revealed a low-density lesion, and magnetic resonance imaging demonstrated a high intensity lesion on T1, T2-weighted, and diffusion-weighted images (55 × 22 mm in the Couinauds segment 4 of the liver). However, 1 month after the appearance of the symptom, serum level of CA19-9 suddenly decreased to 37 U/mL. The tumor decreased spontaneously to 20 × 10 mm. Seven months later, the tumor had reduced to 18 × 11 mm. With a diagnosis of IPT, the patient remains well without regrowth of the tumor at 1 year follow-up after CA19-9 decrease to normal limits.

Standardization of surgical procedures to reduce risk of anastomotic leakage, reoperation, and surgical site infection in colorectal cancer surgery: a retrospective cohort study of 1189 patients

PurposeAnastomotic leakage (AL) and surgical site infection (SSI) are prevalent complications of colorectal surgery. To lower this risk, we standardized our surgical procedures in 2012, with a preferential use of laparoscopic approach (LS) for both colon and rectal surgery, combined with triangulating anastomosis (TA) for colon surgery and defunctioning ileostomy (DI) for low anterior resection. Our aim was to evaluate the outcomes of our standardized procedures.MethodsThe incidence rate of AL (primary outcome) and of reoperation and SSI (secondary outcome) was compared before (early period, n = 648) and after (late period, n = 541) standardization, through a retrospective analysis.ResultsThe incidence rate of AL (6.6 versus 1.8%; P = 0.001), reoperation (3.5 versus 0.7%; P = 0.0012), and SSI (7.7 versus 4.6%; P = 0.029) was lower in late than in the early period. For colon cancer, TA and LS reduced the risk of AL (2.1 versus 0.3%, P = 0.020, for TA, and 3.2 versus 0.4%, P = 0.0027, for LS) and reoperation (2.9 versus 0.3%, P = 0.003, for TA, and 2.5 versus 0.2%, P = 0.0040, for LS). For rectal cancer, the incidence of all adverse outcomes (AL, reoperation, and SSI) was lower in cases treated by LS. However, the incidence of AL was lower in the late than in early period (P = 0.002) and with LS (P = 0.002). On multivariate analysis, late period and LS were independent factors of a lower risk of adverse outcomes.ConclusionsOur surgical standardization seems to be effective in lowering the risks of AL, reoperation, and SSI after colorectal cancer surgery.

Use of Balloon Enteroscopy in Preoperative Diagnosis of Neurofibromatosis-Associated Gastrointestinal Stromal Tumours of the Small Bowel: A Case Report

Neurofibromatosis type I (NF1) is one of the most common inheritable disorders and is associated with an increased risk of gastrointestinal stromal tumours (GISTs). However, the predominant location of these lesions in the small bowel makes them difficult to diagnose. We report the successful use of balloon enteroscopy in conjunction with conventional methods for clinical diagnosis of jejunal GISTs in a 70-year-old man with NF1 who presented with melaena. The importance of screening NF1 patients for GISTs and the complementary role of balloon enteroscopy with capsule endoscopy in such diagnoses is discussed.

Nafamostat Mesilate Enhances the Radiosensitivity and Reduces the Radiation-Induced Invasive Ability of Colorectal Cancer Cells

Neoadjuvant chemoradiotherapy followed by radical surgery is the standard treatment for patients with locally advanced low rectal cancer. However, several studies have reported that ionizing radiation (IR) activates nuclear factor kappa B (NF-κB) that causes radioresistance and induces matrix metalloproteinase (MMP)-2/-9, which promote tumor migration and invasion. Nafamostat mesilate (FUT175), a synthetic serine protease inhibitor, enhances the chemosensitivity to cytotoxic agents in digestive system cancer cells by inhibiting NF-κB activation. Therefore, we evaluated the combined effect of IR and FUT175 on cell proliferation, migration and invasion of colorectal cancer (CRC) cells. IR-induced upregulation of intranuclear NF-κB, FUT175 counteracted this effect. Moreover, the combination treatment suppressed cell viability and induced apoptosis. Similar effects were also observed in xenograft tumors. In addition, FUT175 prevented the migration and invasion of cancer cells caused by IR by downregulating the enzymatic activity of MMP-2/-9. In conclusion, FUT175 enhances the anti-tumor effect of radiotherapy through downregulation of NF-κB and reduces IR-induced tumor invasiveness by directly inhibiting MMP-2/-9 in CRC cells. Therefore, the use of FUT175 during radiotherapy might improve the efficacy of radiotherapy in patients with CRC.

Laparoscopic surgical challenge for T4a colon cancer

For patients with T4a colon cancer, the risk of peritoneal dissemination after surgery remains unclear. Seven hundred and eleven patients with T3 or T4a colon cancer, 80 years of age or younger, underwent curative resection (open surgery in 512 and laparoscopic surgery in 199) at the four Jikei University hospitals between 2006 and 2012. Their risk factors for peritoneal dissemination after surgery were evaluated retrospectively. Number of lymph node metastases, postoperative liver metastases and postoperative peritoneal dissemination events in the T4a group were significantly greater than the number in the T3 group. Peritoneal dissemination after surgery developed in four patients (0.7%) in the T3 group and in six patients (5%) in the T4a group. Risk factors for peritoneal dissemination consisted of macroscopic type (P = 0.016), serosal invasion (P = 0.017) and number of lymph node metastases (P = 0.009) according to the Cox proportional hazards regression model. However, tumor diameter and surgical approach (laparoscopic vs open) were not significant factors for peritoneal dissemination. There were no significant differences between the postoperative relapse‐free survival rates for each surgical approach within the T3 or T4a group. Because of comparable postoperative peritoneal dissemination in T3 and T4a colon cancer by the surgical approach (laparoscopic or open), laparoscopic surgery for patients with T4a colon cancer seems justified.

Mesothelial cyst with endometriosis mimicking a Nuck cyst

We report a case of mesothelial cyst protruding from the right femoral ring with suspected endometriosis in a 35-year-old woman, who complained of a lump with a diameter of 6 cm in the right inguinal region. Although she had the hormone therapy during the next 8 months for the diagnosis of extragenital endometriosis, her symptoms did not improve. The clinical suspicion of a Nuck cyst with endometriosis, supported by ultrasonography and magnetic resonance imaging, was confirmed by histopathological examination of the surgical specimen. Authors herein report this unusual case and review the literature.

Arterial Infusion Chemotherapy in Patient with Repeated Recurrent Tumor of Cecal Cancer: Report of a Case

Purpose: We report a patient with a repeated recurrent tumor after Right-hemicolectomy for advanced cecal cancer who was treated by intra-arterial infusions of 5-fluorouracil (5-FU). Methods: A computed tomography scan revealed a pelvic mass involving the psoas major muscle and quadratos lumborum muscle, in contact with the widely projecting toward L2-S2. The fluorodeoxyglucose-positron emission tomography (FDG-PET) revealed an accumulation spot in the same place. This case was deemed in operable, and one-shot bolus of 5-FU was administered through the tumor feeding arteries: the left 3rd, 4th lumbar, and ilio - lumbar arteries at a dosage of 250 mg/body from each artery. Results: A partial regression of the tumor was observed by computed tomography. The serum level of carbohydrate antigen 19–9 returned normal in 8 months. During chemotherapy, the side effect and complications were tolerable, and she experienced only grade-1 nausea caused by 5-fluorouracil. Conclusion: A long–time, intra-arterial 5-fluorouracil infusion could control effectively and safely.