Masafumi Inomata

Pathology and prognosis of gastric carcinoma

The most important parameters predicting outcome of patients with gastric carcinoma are the depth of wall invasion and the status of lymph node metastasis, but the prognostic significance of histologic type is unclear. The aim of this study was to clarify the prognostic value of two major histologic types of gastric carcinoma, that is well and poorly differentiated types.

Short-term surgical outcomes from a randomized controlled trial to evaluate laparoscopic and open D3 dissection for stage II/III colon cancer: Japan Clinical Oncology Group Study JCOG 0404.

Objective:A randomized controlled trial to confirm the non-inferiority of laparoscopic surgery to open surgery in terms of overall survival was conducted, and short-term surgical outcomes are demonstrated. Background:The efficacy and safety outcome of laparoscopic surgery for clinical stages II/III colon cancer undergoing Japanese D3 dissection are still unclear. Methods:Eligibility criteria included colon cancer; tumor located in the cecum, ascending, sigmoid, or rectosigmoid colon; T3 or T4 without involvement of other organs; N0–2; and M0. Patients were randomized preoperatively and underwent tumor resection with D3 dissection. Safety analyses were conducted by per-protocol set. Results:A total of 1057 patients were randomized between October 2004 and March 2009. By per-protocol set, 524 patients who underwent open surgery and 533 patients who underwent laparoscopic surgery were analyzed. D3 dissection was performed in 521 (99.4%) patients in the open surgery arm and 529 (99.2%) patients in the laparoscopic surgery arm. Conversion to open surgery was needed for 29 (5.4%) patients. Patients assigned to laparoscopic surgery had less blood loss (P < 0.001), although laparoscopic surgery lasted 52 minutes longer (P < 0.001). Laparoscopic surgery was associated with a shorter time to pass first flatus, decreased use of analgesics after 5 postoperative days, and a shorter hospital stay. Morbidity [14.3% (76/533) vs 22.3% (117/524), P < 0.001] was lower in the laparoscopic surgery arm. Conclusions:Short-term surgical safety and clinical benefits of laparoscopic D3 dissection were demonstrated. The primary endpoint will be reported after the primary analysis, planned for 2014.

Laparoscopy-assisted Billroth-I gastrectomy (LADG) for cancer: our 10 years' experience.

To evaluate laparoscopy-assisted Billroth-I gastrectomy (LADG), we examined the outcome of its use over the last 10 years. From December 1991 to December 2001, 116 patients with early gastric cancer underwent LADG in the surgical department of Oita Medical University and Koga hospital by the same surgical staffs. An operation record and clinical sheets were reviewed to obtain the operative findings, clinical course, and pathologic findings of resected specimens to evaluate the usefulness of LADG in the management of early gastric cancer. In all LADG procedures, regional lymph nodes dissection (D1+&agr;) was successfully performed using laparoscopy. The mean operative duration and blood loss were 234 minutes and 139 mL, respectively. There were only four major complications, including pneumonia, leakage of anastomosis, pancreatic injury, and anastomotic stenosis, but all these cases were successfully treated conservatively. The mean length of postoperative stay was 16.3 ± 2.5 days. All patients except one, who died not of cancer but of cerebral bleeding, were alive without recurrence or port-site metastasis during mean follow-up period of 45 months. We successfully performed 116 LADG procedures over 10 years. This procedure is recommended for the treatment of patients with early gastric cancer because of the associated good prognosis and several benefits, including less invasiveness and early recovery.

Prognostic effect of lymph node micrometastasis in patients with histologically node-negative gastric cancer

BackgroundThere is no consensus as to the impact of lymph node micrometastasis on survival of patients with gastric cancer. The aim of this study was to clarify the prognostic significance of lymph node micrometastasis in patients with histologically node-negative gastric cancerMethodsLymph nodes (n=2039) from 64 patients with histologically node-negative gastric cancer (T2, T3) were evaluated for micrometastasis. Three serial 5-μm sections of the resected lymph nodes were prepared for immunohistochemical staining with the anti-cytokeratin antibody CAM 5.2.ResultsMicrometastasis was found in 73 of 2039 nodes (4%) and 20 of 64 patients (32%). The 5-year survival rate was significantly lower for patients with lymph node micrometastasis than for those without lymph node micrometastasis (66% vs. 95%,P<.01). The 5-year survival rate was significantly lower when there were four or more positive micrometastatic nodes (94% vs. 29%,P <.01) and when there were extragastric micrometastatic nodes (89% vs. 53%,P<.01).ConclusionsLymph node micrometastasis was associated with poor outcome in patients with histologically node-negative gastric cancer. The number and the level of lymph node micrometastases are useful prognostic markers for deciding treatment strategies for additional therapy and follow-up.

Immunohistochemical Study of c-erbB-2 Protein in Colorectal Cancer and the Correlation with Patient Survival

We related events in immunohistochemical studies on formalin-fixed, paraffin-embedded preparations of 146 colorectal cancer patients. One hundred (68.5%) revealed cytoplasmic staining and only 3 of the 100 showed membranous staining. Western blot analysis revealed proteins with molecular masses of 185 and 155 kD following immunohistochemical membranous and cytoplasmic staining, but only a 155-kD protein following cytoplasmic staining. Amplification of the c-erbB-2 gene was detected in 2 of 44 cases (4.5%). Cytoplasmic c-erbB-2 overexpression correlated with tumor size (p < 0.01), subserosal invasion (p < 0.05), liver metastasis (p < 0.01) and Dukes’ classification. Overall survival rates and survival rates for Dukes’B patients were significantly lower in the group with cytoplasmic c-erbB-2 overexpression than in the group without cytoplasmic c-erbB-2 overexpression. Multivariate regression analysis showed cytoplasmic c-erbB-2 overexpression to be an independent prognostic factor for colorectal cancer. These results suggest that overexpression of cytoplasmic c-erbB-2 protein plays an important role in the progression of colorectal cancer and is considered to be an independent prognostic indicator of this lesion.

Hyaluronic acid stimulates tumor-cell proliferation at wound sites

BACKGROUND For EMR, the submucosal injection of sodium hyaluronate has become popular, because this substance creates a more prominent and longer-lasting mucosal protrusion than normal saline solution. However, the effects of sodium hyaluronate on tumor growth at wound sites remain unclear. METHODS For these experiments, a murine model with artificial wounds was used. Forty mice were randomly divided into two groups according to the substance to be injected into a wound: a sodium hyaluronate group and a control group. Tumors were created by inoculation of transplantable adenocarcinoma cell line colon 26. Two weeks later, the size, weight, proliferating cell nuclear antigen-labeling index, and CD44 expression of the subcutaneous tumors were compared between the two groups of mice. RESULTS There were significantly greater increases in the growth and the weight of subcutaneous tumors in the sodium hyaluronate group compared with the control group. The PCNA-labeling index of cancer cells also was higher in the sodium hyaluronate group. Immunohistochemistry and Western blot analysis demonstrated that the CD44 protein expression of cancer cells was higher in the sodium hyaluronate group vs. the control group. CONCLUSIONS In this study, sodium hyaluronate enhanced both tumor growth and CD44 expression of cancer cells at wound sites, suggesting that the use of sodium hyaluronate for EMR might stimulate the growth of residual tumor cells.

Distribution of lymph node metastasis and level of inferior mesenteric artery ligation in colorectal cancer.

To investigate the distribution of lymph node metastasis along the inferior mesenteric artery (IMA) and clarify whether high ligation of the IMA is important or not, we examined the surgical results of 172 patients with cancer of the sigmoid colon and rectum. Histologically, lymph node metastasis was absent in 108 (63%) patients and present in 64 (37%) patients. The distribution was adjacent to the wall of the rectum (35.5%) and sigmoid colon (10.5%), along the IMA (7.7%) and sigmoid colic artery (6.3%), and at the root of the IMA (0.7%, 1 of 135 patients). The presence of lymph node metastasis was predicted by the operative findings of lymph node metastasis (p < 0.01) and serosal invasion (p < 0.05) and by the histologic type of tumor (p < 0.05). These results indicate that lymph node metastasis at the root of the IMA is rare, and complete removal of the pericolic and intermediate nodes (D2 dissection) without high ligation of the IMA is feasible for cancer of the sigmoid colon and rectum.

Prognostic significance of intrahepatic lymphatic invasion in patients with hepatic resection due to metastases from colorectal carcinoma

Intrahepatic spread from liver metastases of colorectal carcinoma has been well described; however, its prognostic value after hepatectomy is controversial. To clearly determine factors predicting survival after hepatectomy in such patients, the authors evaluated 14 clinicopathologic factors of liver metastasis from colorectal carcinoma with special reference to intrahepatic lymphatic invasion.

Minimally invasive approaches for gastric cancer—Japanese experiences

Since development of laparoscopy‐assisted distal gastrectomy with lymph node dissection in 1991 in Japan, laparoscopic gastrectomy (LAG) is improving and evolving. Recently, advanced LAG techniques including D2 lymph node dissection or anastomosis after total gastrectomy have been developed. Retrospective and prospective multicenter studies have been conducted for early and non‐early gastric cancers to establish high‐quality evidence. This review summarizes the current trends of minimally invasive approaches for gastric cancer based on current Japanese experiences. J. Surg. Oncol. 2013;107:282–288.

Open versus laparoscopic resection of primary tumor for incurable stage IV colorectal cancer: a large multicenter consecutive patients cohort study.

Objective:To investigate the hypothesis that laparoscopic primary tumor resection is safe and effective when compared with the open approach for colorectal cancer patients with incurable metastases. Background:There are only a few reports with small numbers of patients on laparoscopic tumor resection for stage IV colorectal cancer. Methods:Data from consecutive patients who underwent palliative primary tumor resection for stage IV colorectal cancer between January 2006 and December 2007 were collected retrospectively from 41 institutions. Short- and long-term outcomes were compared between patients who underwent laparoscopic or open resection. Results:A total of 904 patients (laparoscopic group: 226, open group: 678) with a median age of 64 years (range: 22–95) were included in the analysis. Conversion was required in 28 patients (12.4%) and the most common reasons for conversion (23/28: 82%) were bulky or invasive tumors. There was no 30-day postoperative mortality in either group. The complication rate (NCI-CTCAE grade 2–4) after laparoscopic surgery (17%) was significantly lower than that after open surgery (24%) (P = 0.02), and the difference was greater (4% vs 12%; P < 0.001) when we limited the analysis to severe (≥grade 3) complications. The median length of postoperative hospital stay in the laparoscopic group was significantly shorter than that in the open group (14 vs 17 days; P = 0.002). In univariate analysis, overall survival for the laparoscopic group was significantly better than that for open surgery (median survival time: 25.9 vs 22.3 months, P = 0.04), although no difference was apparent in multivariate analysis. Conclusions:Compared with open surgery, laparoscopic primary tumor resection has advantages in the short term and no disadvantages in the long term. It is a reasonable treatment option for certain stage IV colorectal cancer patients with incurable disease.