Takahiro Toyokawa

Impact of the Preoperative Controlling Nutritional Status (CONUT) Score on the Survival after Curative Surgery for Colorectal Cancer.

Background Recently, the preoperative immune-nutritional status has been reported to correlate with the survival rate in patients with colorectal cancer (CRC). However, there have been no reports on the relationship between the controlling nutritional status (CONUT) score and the clinical outcome after curative surgery for CRC. We herein evaluated the prognostic significance of the CONUT score in patients with CRC, and then compared the accuracy of the CONUT score and the prognostic nutritional index (PNI) as a predictor of survival. Methods We retrospectively reviewed a database of 204 patients who underwent curative surgery for Stage II/III CRC. Patients were divided into two groups according to the CONUT score and the PNI. Results The five-year cancer-specific survival (CSS) rate was significantly higher at 92.7% in the low CONUT group, compared to a rate of 81.0% in the high CONUT group (p=0.0016). The five-year CSS was 71.2% in the low PNI group and 92.3% in the high PNI group, which showed a significant difference (p=0.0155). A multivariate analysis showed that lymph node metastasis and the CONUT score were independent risk factors for CSS. Conclusion This study suggested that the CONUT score is a strong independent predictor of the survival among CRC patients.

Phosphorylated Smad2 in Advanced Stage Gastric Carcinoma

BackgroundTransforming growth factor β (TGFβ) receptor signaling is closely associated with the invasion ability of gastric cancer cells. Although Smad signal is a critical integrator of TGFβ receptor signaling transduction systems, not much is known about the role of Smad2 expression in gastric carcinoma. The aim of the current study is to clarify the role of phosphorylated Smad2 (p-Smad2) in gastric adenocarcinomas at advanced stages.MethodsImmunohistochemical staining with anti-p-Smad2 was performed on paraffin-embedded specimens from 135 patients with advanced gastric adenocarcinomas. We also evaluated the relationship between the expression levels of p-Smad2 and clinicopathologic characteristics of patients with gastric adenocarcinomas.ResultsThe p-Smad2 expression level was high in 63 (47%) of 135 gastric carcinomas. The p-Smad2 expression level was significantly higher in diffuse type carcinoma (p = 0.007), tumours with peritoneal metastasis (p = 0.017), and tumours with lymph node metastasis (p = 0.047). The prognosis for p-Smad2-high patients was significantly (p = 0.035, log-rank) poorer than that of p-Smad2-low patients, while a multivariate analysis revealed that p-Smad2 expression was not an independence prognostic factor.ConclusionThe expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma.

Prognostic significance of the lymphocyte-to-monocyte ratio in patients with metastatic colorectal cancer

AIM To evaluate the prognostic significance of the lymphocyte to monocyte ratio (LMR) in patients with unresectable metastatic colorectal cancer who received palliative chemotherapy. METHODS A total of 104 patients with unresectable metastatic colorectal cancer who underwent palliative chemotherapy were enrolled. The LMR was calculated from blood samples by dividing the absolute lymphocyte count by the absolute monocyte count. Pre-treatment LMR values were measured within one week before the initiation of chemotherapy, while post-treatment LMR values were measured eight weeks after the initiation of chemotherapy. RESULTS The median pre-treatment LMR was 4.16 (range: 0.58-14.06). We set 3.38 as the cut-off level based on the receiver operating characteristic curve. Based on the cut-off level of 3.38, 66 patients were classified into the high pre-treatment LMR group and 38 patients were classified into the low pre-treatment LMR group. The low pre-treatment LMR group had a significantly worse overall survival rate (P = 0.0011). Moreover, patients who demonstrated low pre-treatment LMR and normalization after treatment exhibited a better overall survival rate than the patients with low pre-treatment and post-treatment LMR values. CONCLUSION The lymphocyte to monocyte ratio is a useful prognostic marker in patients with unresectable metastatic colorectal cancer who receive palliative chemotherapy.

The outcome of surgical treatment for elderly patients with gastric carcinoma

The aim of this study was to clarify the operative mortality and long‐term survival of gastrectomy for elderly patients with gastric cancer.

Gastric metastasis from renal cell carcinoma with gastrointestinal bleeding: a case report and review of the literature.

A 61-year-old man presented to our hospital with hypercalcemia and elevated C reactive protein (CRP). Evaluation revealed renal cell carcinoma (RCC) with metastasis to lung, bone, and brain. He underwent partial resection of the right kidney and a left nephrectomy. Histopathologic findings of resected tumors were consistent with clear cell RCC. Whole-brain irradiation was performed for management of brain metastasis. Postoperatively, he was treated with molecularly targeted therapy using a mammalian target of rapamycin inhibitor. Approximately 14 months later, he suffered an episode of upper gastrointestinal bleeding with secondary anemia and melena. Upper gastrointestinal endoscopy revealed a distinctly protruding lesion in the gastric body. Biopsy of the gastric lesion showed metastatic clear cell RCC. He underwent partial gastrectomy. His postoperative course was uneventful. However, 4 months after surgery, he died from brain metastasis. Metastatic RCC to the stomach, although rare, should be suspected in any patient with a history of RCC who presents with gastrointestinal symptoms.

Intranodal Lymphangiogenesis Precedes Development of Lymph Node Metastasis and Accelerates Progression of Gastric Cancer

IntroductionPeritumoral lymphangiogenesis is significantly correlated with lymph node metastasis and poor prognosis in various cancers. However, there are few reports concerning the role of intranodal lymphangiogenesis in lymphatic metastasis. The aim of this study was to examine the association of lymphangiogenesis in regional lymph nodes with the progression of gastric cancer.Materials and MethodsLymphatic vessel density (LVD) was immunohistochemically estimated in 1,596 lymph nodes from 52 patients who underwent gastrectomy.ResultsIntranodal LVD was significantly correlated with the size of metastasis and the progression of cancer. Patients in the high LVD group had significantly poorer prognosis relative to patients in the low LVD group. Furthermore, expression of VEGF-C mRNA was significantly up-regulated in lymph nodes of pathological node positive patients compared to node negative patients.DiscussionThus, intranodal lymphangiogenesis was correlated with nodal metastasis and poor prognosis of patients with gastric cancer. Lymphangiogenesis in regional lymph nodes plays an early role in spreading of tumor cells through the lymphatic system to distant organs in gastric cancer.

Clinical impact of the extent of lymph node micrometastasis in undifferentiated-type early gastric cancer.

Objective: Lymph node (LN) metastasis is one of the most important prognostic factors for undifferentiated-type early gastric cancer (EGC). The aim of this study was to examine expansion of micrometastasis in regional LNs to clarify the importance of lymphadenectomy for undifferentiated-type EGC. Methods: Clinicopathological features of 307 patients with undifferentiated-type EGC who underwent gastrectomy with lymphadenectomy between 1997 and 2010 at the Department of Surgical Oncology, Osaka City University, were retrospectively reviewed. Micrometastasis in LNs was detected by immunohistochemistry using anticytokeratin antibody. Results: The incidence of LN metastasis was 1.8% in patients with mucosal (pT1a) tumors and 17.3% in those with submucosal (pT1b) tumors. Multivariate analysis revealed that lymphatic invasion and tumor depth were independently related to LN metastasis. Micrometastasis was found in 41 (13.3%) patients. Twenty-two patients with pN0 had micrometastasis in the perigastric region. Micrometastasis had spread to the area along the left gastric or common hepatic artery in 12 patients. Patients with an upgraded stage by micrometastasis had significantly worse disease-free survival. Conclusions: LN micrometastasis was observed beyond the perigastric LNs and correlated with poor outcomes in patients with undifferentiated-type EGC. These data underscore the importance of adequate lymphadenectomy for patients with undifferentiated-type EGC.

Current status in remnant gastric cancer after distal gastrectomy.

Remnant gastric cancer (RGC) and gastric stump cancer after distal gastrectomy (DG) are recognized as the same clinical entity. In this review, the current knowledges as well as the non-settled issues of RGC are presented. Duodenogastric reflux and denervation of the gastric mucosa are considered as the two main factors responsible for the development of RGC after benign disease. On the other hand, some precancerous circumstances which already have existed at the time of initial surgery, such as atrophic gastritis and intestinal metaplasia, are the main factors associated with RGC after gastric cancer. Although eradication of Helicobacter pylori (H. pylori) in remnant stomach is promising, it is still uncertain whether it can reduce the risk of carcinogenesis. Periodic endoscopic surveillance after DG was reported useful in detecting RGC at an early stage, which offers a chance to undergo minimally invasive endoscopic treatment or laparoscopic surgery and leads to an improved prognosis in RGC patients. Future challenges may be expected to elucidate the benefit of eradication of H. pylori in the remnant stomach if it could reduce the risk for RGC, to build an optimal endoscopic surveillance strategy after DG by stratifying the risk for development of RGC, and to develop a specific staging system for RGC for the standardization of the treatment by prospecting the prognosis.

Tumor-Associated Macrophages Extend Along Lymphatic Flow in the Pre-metastatic Lymph Nodes of Human Gastric Cancer

BackgroundTumor-associated macrophages (TAMs) correlate with lymphangiogenesis in primary lesions and with lymph node (LN) metastasis of several cancers. However, the association of TAMs in regional LNs with lymphatic spread of cancer remains unclear. The purpose of this study was to evaluate the distribution of TAMs in draining LNs and the impact of TAMs on the establishment of LN metastasis of gastric cancer.MethodsThe number and distribution of TAMs in regional LNs that were obtained from 49 patients who underwent radical surgery for gastric cancer at Osaka City University Hospital in 2011 were assessed. TAMs were defined as immunohistochemically CD163 positive cells. The association of the TAM density with lymph node metastasis and the lymphatic drainage route of the stomach were investigated.ResultsA high density of TAMs was significantly associated with pathologically positive lymph nodes and pathological TNM stage. The density of TAMs was increased in LNs with micro metastasis compared with those without metastasis. There was a significant, positive correlation between TAM number and lymphatic vessel density in LNs. In nonmetastatic LNs, TAMs were likely to accumulate in the neighborhood of the primary lesion. In addition, the density of TAMs in distant LNs was significantly increased in patients in whom LN metastasis was observed in perigastric LNs.ConclusionsAccumulated TAMs may induce lymphangiogenesis and prepare an environment that facilitates cancer proliferation in LNs. Our findings might provide a conceptual framework for understanding the lymphatic spreading of cancer and for designing future therapeutic strategies for gastric cancer.

Thoracoscopic Esophagectomy in the Prone Position Versus in the Lateral Position for Patients With Esophageal Cancer: A Comparison of Short-term Surgical Results

Aim: Thoracoscopic esophagectomy (TE) in the prone position for patients with esophageal cancer has received a great deal of attention. We retrospectively compared clinical outcomes and surgical stress of TE in the prone position (TE-P) and in the lateral position (TE-L) at our institution. Methods: A total of 58 consecutive patients (28 in the TE-L group and 30 in the TE-P group) were studied. Between the 2 groups, clinical outcomes and various parameters were compared. Results: There were no hospital deaths in both TEL and TEP groups. Blood loss during the thoracoscopic part of the surgery were significantly (P<0.01) lower in the TE-P group (118±72 mL) compared with the TE-L (245±203 mL) group. The incidence of respiratory complications tended to be lower (P=0.07) in the TE-P group (3.3%) than in the TE-L (17.8%) group. The duration of systemic inflammatory response syndrome condition was significantly (P=0.02) shorter in the TE-P group (1.5±2.5 d) than in TE-L (3.6±3.5 d) group. The levels of serum C-reactive protein on postoperative days 1 and 2 were significantly (P<0.01) lower in the TE-P group than in the TE-L group. Conclusions: TE-P for patients with esophageal cancer was safe and feasible. TE-P might be a potentially less invasive procedure than TE-L.