Go Ohira

Targeting superoxide dismutase to renal proximal tubule cells inhibits nephrotoxicity of cisplatin and increases the survival of cancer-bearing mice

Because cis-diamminedichloroplatinum(II) (cisplatin) which generates reactive oxygen species induces renal dysfunction, administration of a large dose for killing cancer cells is highly limited. We recently synthesized a cationic superoxide dismutase (SOD) (hexamethylenediamine-conjugated SOD, AH-SOD) which rapidly accumulates in renal proximal tubule cells and inhibits oxidative injury of the kidney. Treatment of Ehrlich ascites tumor cells (EATC)-bearing mice with cisplatin sufficient for killing tumor cells increased their motality. The motality of cisplatin-treated EATC-bearing mice was markedly decreased by AH-SOD. These results suggest that targeting SOD to renal proximal tubule cells might permit the administration of high doses of cisplatin and related anticancer agents without causing renal injury.

HER3 Overexpression as an Independent Indicator of Poor Prognosis for Patients with Curatively Resected Pancreatic Cancer

Objective: The association between human epidermal growth factor receptor 3 (HER3) overexpression and survival in patients with curatively resected pancreatic cancer was investigated. Methods: Tissue samples from 126 pancreatic cancers without hematogenous or peritoneal metastases recovered from macroscopically curative resection were fixed with formalin, embedded in paraffin and subjected to immunohistochemical staining. Semiquantitative scores of zero (no staining or staining in less than 10% of cancer cells), 1+, 2+, or 3+ were assigned to each sample based on the intensity of staining. Scores of 2+ or 3+ were defined as HER3-positive staining, i.e., HER3 overexpression. Results: HER3 overexpression was observed in 52 of the 126 tissue samples (41.3%). There were no associations between HER3 overexpression and clinicopathological factors, including tumor location, tumor size, tumor differentiation, T/N categories according to the International Union against Cancer, and serum carbohydrate antibody 19-9 level (CA19-9). Univariate analysis demonstrated the median survival time of patients with HER3 overexpression was 37.2 months, while that of patients with HER3-negative samples was 58.6 months (p = 0.008). HER3 overexpression, lymph node metastasis, and elevated serum CA19-9 level were independent predictors of poor prognosis based on multivariate survival analysis. Conclusion: A new prognostic predictor, HER3 overexpression, was identified for resected pancreatic cancer.

Significance of phospho-vascular endothelial growth factor receptor-2 expression in pancreatic cancer

Vascular endothelial growth factor receptors (VEGFRs) are mainly expressed by endothelial cells, but they are also expressed by some cancer cells, including pancreatic cancer. The objective of this study was to evaluate the significance of VEGFRs expression in pancreatic cancer cells. A total of 107 primary pancreatic tumors were stained with antibodies against VEGFR‐1, VEGFR‐2, phospho‐VEGFR‐2 (pVEGFR‐2), VEGFR‐3, VEGF‐A, VEGF‐C, and VEGF‐D. VEGFR‐2 and pVEGFR‐2 expression were positive in 74 (69%) and 54 (50%) of 107 pancreatic cancers. There was a significant correlation (P < 0.001) between VEGFR‐2 expression and pVEGFR‐2 expression. pVEGFR‐2 was significantly associated with invasion to the anterior capsule of pancreas (P = 0.032) and arterial invasion (P = 0.012). In contrast, VEGFR‐1 and VEGFR‐3 expression was only observed in 13 (12%) and 15 (14%) of 107 pancreatic cancers, and was not associated with any clinicopathological features. The prognosis of pVEGFR‐2 positive patients with stage IIA tumors was significantly (P = 0.0441) poorer than that of pVEGFR‐2‐negative patients. VEGF‐A, VEGF‐C, and VEGF‐D expression was positive in 42 (39%), 82 (77%), and 39 (36%) of 107 pancreatic cancers, respectively. The prognosis for VEGF‐A‐positive patients was significantly (P = 0.0425) poor, but not for VEGF‐C‐positive and VEGF‐D‐positive patients. A multivariate analysis indicated pVEGFR‐2 expression to be an independent prognostic factor, but not VEGF‐A. These findings suggested that VEGFR‐2 signaling might therefore be associated with the prognosis of patients with pancreatic cancer. The expression of pVEGFR‐2 might be a novel predictive prognostic marker for patients with pancreatic cancers, especially at clinical stage IIA. (Cancer Sci 2010)

A case of bilateral pheochromocytoma during pregnancy

BackgroundPheochromocytoma is a disease where catecholamines are secreted. If pheochromocytoma occurs during pregnancy, it can be difficult to diagnose because it is similar to pregnancy-induced hypertension. Furthermore, bilateral pheochromocytoma during pregnancy is even rarer than unilateral pheochromocytoma.Case presentationA 32-year-old primigravida, who was 12 weeks’ pregnant, was aware of right abdominal discomfort. Masses in both adrenal glands were observed by abdominal ultrasonography. She was diagnosed with pheochromocytoma. Bilateral adrenalectomy was undertaken at 15 weeks’ gestation and she continued pregnancy. At 39 weeks’ gestation, a healthy male neonate was delivered. She was discharged on the 4th postpartum day.ConclusionsWe present a case of bilateral pheochromocytoma during pregnancy that was diagnosed in the first trimester. Differentiating pheochromocytoma from pregnancy-induced hypertension is important. Early diagnosis and appropriate blood pressure management with medical treatment followed by surgical removal of the tumor results in good maternal and fetal outcomes.

The Clinical Indications for Limited Surgery of Intraductal Papillary Mucinous Neoplasms of the Pancreas.

BackgroundThere are many reports about limited surgery for intraductal papillary mucinous neoplasms (IPMNs) of the pancreas. However, there is no consensus on limited surgery for IPMNs. The primary objective of this study was to define the clinical indications for limited surgery for IPMNs.MethodsThe data of 98 patients who underwent curative resections for IPMN were retrospectively analyzed. IPMNs were classified into four different pathological grades: low-grade dysplasia (LGD), intermediate-grade dysplasia (IGD), high-grade dysplasia (HGD), and invasive carcinoma (Inv-IPMN). Inv-IPMNs were divided into T1a, T1b, and T1c or over T1c (≥T1c). Based on preoperative radiological findings, IPMNs were stratified into the three groups using the 2012 International Consensus Guidelines: worrisome features, high-risk stigmata (HRS), and others.ResultsThere were no positive lymph node cases and no recurrent cases of LGDs, IGDs, and HGDs. On the other hand, positive lymph node cases in T1a, T1b, and ≥T1c were seen in 37.5, 20, and 22.2% of cases, respectively. The recurrence rates of T1a, T1b, and ≥T1c were 50, 40, and 55.6%, respectively. Of the HRS cases, 30 (73.2%) were malignant and 25 (61%) were Inv-IPMN. HRS showed sensitivity of 92.6%, specificity of 77.5%, and accuracy of 81.6% to identify Inv-IPMN by preoperative imaging.ConclusionsLimited surgery such as parenchyma-sparing pancreatectomy should be avoided for all cases of Inv-IPMNs, because every Inv-IPMN including T1a has the potential for lymph node metastasis and recurrence. HRS had high preoperative diagnostic ability for predicting Inv-IPMN. For cases that meet HRS criteria, pancreatectomy with lymphadenectomy is needed, and limited surgery should be withheld.

Doublecortin and CaM kinase-like-1 as an independent prognostic factor in patients with resected pancreatic carcinoma

AIM To elucidate the effect of expression of doublecortin and CaM kinase-like-1 (DCLK1) in patients with pancreatic ductal adenocarcinoma (PDAC). METHODS Tumor specimens were obtained from 136 patients with pancreatic cancer who had undergone resection without preoperative therapy between January 2000 and December 2013 at the Department of Surgical Oncology, Osaka City University. The resected specimens were analyzed for associations with clinicopathological data, including DCLK1 expression, epithelial mesenchymal transition (EMT) marker expression, and cancer stem cell (CSC) marker expression. Univariate and multivariate survival analyses were performed and we assessed the association between DCLK1 expression and clinicopathological factors, including the EMT marker and CSC marker. RESULTS In total, 48.5% (66/136) of the pancreatic cancer samples were positive for DCLK1. Patients with DCLK1-positive tumors had significantly shorter survival times than those with DCLK1-negative tumors (median, 18.7 mo vs 49.5 mo, respectively; P < 0.0001). Positive DCLK1 expression correlated with histological grade (P = 0.0290), preoperative CA19-9 level (P = 0.0060), epithelial cell adhesion molecule (EpCAM) expression (P = 0.0235), and the triple-positive expression of CD44/CD24/EpCAM (P = 0.0139). On univariate survival analysis, five factors were significantly associated with worse overall survival: histological grade of G2 to G4 (P = 0.0091), high preoperative serum SPan-1 level (P = 0.0034), R1/2 (P < 0.0001), positive expression of DCLK1 (P < 0.0001) or CD44 (P = 0.0245). On multivariate survival analysis, R1/2 [odds ratio (OR) = 2.019, 95% confidence interval (CI): 1.380-2.933; P = 0.0004] and positive DCLK1 expression (OR = 1.848, 95%CI: 1.2854-2.661; P = 0.0009) were independent prognostic factors. CONCLUSION DCLK1 expression was found to be an independent prognostic factor and it may play a crucial prognostic role by promoting acquisition of stemness.

The impact of the preoperative peripheral lymphocyte count and lymphocyte percentage in patients with colorectal cancer.

PurposeWe evaluated the prognostic significance of the peripheral lymphocyte count and lymphocyte percentage, which reflect the preoperative immune status, in patients with colorectal cancer (CRC) and then compared their accuracy as predictors of the survival.MethodsWe retrospectively reviewed a database of 362 patients. We classified the patients into high lymphocyte count and low lymphocyte count groups. We also classified the patients into high lymphocyte percentage and low lymphocyte percentage groups.ResultsThe 5-year relapse-free survival (RFS) rate in the high lymphocyte count group tended to be higher than that in the low lymphocyte count group. The 5-year overall survival (OS) rate in the high lymphocyte count group was significantly higher than that in the low lymphocyte count group. In contrast, the 5-year RFS and OS rates in the high lymphocyte percentage group were both significantly higher than those in the low lymphocyte percentage group. A multivariate analysis showed that the lymphocyte percentage was independently associated with the OS.ConclusionsThese findings suggest that the lymphocyte percentage is a good predictor of the OS and may be a stronger predictor of survival than the lymphocyte count in CRC patients.

Giant duodenal ulcers after neurosurgery for brainstem tumors that required reoperation for gastric disconnection: a report of two cases

BackgroundDespite the efficacy of pharmacotherapy for gastrointestinal ulcers, severe cases of bleeding or perforation due to gastrointestinal ulcers still occur. Giant duodenal ulcer perforation is an uncommon but difficult-to-manage pathology with a high mortality rate. We report two cases of giant duodenal ulcer perforation after neurosurgery for brainstem tumors that needed reoperation for gastric disconnection because of postoperative leakage and bleeding.Case presentationBoth cases had undergone neurosurgery for brainstem tumors, and the patients were in a shock state for several days with peritonitis due to giant duodenal perforation. In Case 1, antrectomy with Billroth II reconstruction was performed. However, reoperation for gastric disconnection was needed because of major leakage of gastrojejunostomy and jejunojejunostomy. In Case 2, an omental patch, cholecystectomy, and insertion of a bile drainage tube from the cystic duct were performed for the giant duodenal ulcer, but leakage and bleeding from the ulcer edge required reoperation for gastric disconnection.ConclusionsBrainstem tumors in these cases might have been related to duodenal ulcer perforation with late diagnosis that progressed to severe sepsis. For giant duodenal ulcer perforation with poor general condition, simple closure including omental patch or antrectomy with reconstruction is hazardous. Antrectomy with gastric disconnection, meaning gastrostomy, duodenostomy, feeding jejunostomy and cholecystectomy, is recommended.

Efficacy of transhepatic anterior approach to the inferior vena cava for malignant pheochromocytoma invading right posterior lobe of the liver: a case report

Introduction: The anterior approach to the inferior vena cava (IVC) by the liver hanging maneuver is effective in resecting large retrohepatic tumors without mobilizing the right lobe. Case present...

A case of complete splenic infarction after laparoscopic spleen-preserving distal pancreatectomy

BackgroundLaparoscopic spleen-preserving distal pancreatectomy (LSPDP), a newly developed operative procedure, is indicated for benign and low-grade malignant disease of the pancreas. However, few studies have reported on postoperative splenic infarction after LSPDP.Case presentationWe report a case of complete splenic infarction and obliteration of the splenic artery and vein after LSPDP. The patient was a 69-year-old woman with a 35-mm cystic tumor of the pancreatic body who underwent LSPDP. Although the operation was completed with preservation of the splenic artery and vein, postoperative splenic infarction was revealed with left back pain and fluid collection around the stump of the pancreas on postoperative day 9. Fortunately, clinical symptoms disappeared within days and additional splenectomy was not needed. Splenic infarction was attributed to scattered micro-embolizations within the spleen after drawing strongly on the tape encircling the splenic vessels.ConclusionPreserving splenic vessels in LSPDP is a demanding procedure. To prevent splenic infarction in LSPDP, we should carefully isolate the pancreatic parenchyma from the splenic vessels, and must avoid drawing tightly on the vessel loop encircling splenic vessels.