Prognostic Significance of Microscopic Positive Margins for Gastric Cancer Patients with Potentially Curative Resection

Background  

Most previous studies concerning the impact of positive margins on patient outcomes were based on patients with D1 lymphadenectomy. The prognostic significance of positive margins for patients with D2/D3 lymphadenectomy has not been investigated.     

Prognostic Impact of Circumferential Resection Margin in Rectal Cancer Treated with Preoperative Chemoradiotherapy

Background

The circumferential resection margin (CRM) is a strong prognostic factor in rectal cancer. The purpose of this study was to investigate the relationship between CRM distance and recurrence in patients with locally advanced rectal cancer who received preoperative chemoradiotherapy (CRT).

Methods

We analyzed data for 561 patients who underwent preoperative CRT and curative surgery for locally advanced rectal cancer between August 2001 and December 2008. CRM was divided into four groups: group 1, CRM > 2 mm; group 2, 1.1–2.0 mm; group 3, 0.1–1.0 mm; and group 4, 0 mm. We assessed the associations of CRM with local recurrence and disease-free survival.

Results

Groups 1, 2, 3, and 4 comprised 487, 36, 20, and 18 patients, respectively. The local recurrence rate was highest and the disease-free survival rate was lowest in group 4, followed by groups 3, 2, and 1. Survival was similar between groups 2 and 1. Local recurrence rates were lower in groups 3, 2, and 1 than in group 4 [hazard ratio (HR) 0.28, 95 % confidence interval (CI) 0.09–0.91, P = 0.035; HR 0.11, 95 % CI 0.03–0.46, P = 0.002; HR 0.18, 95 % CI 0.08–0.42, P < 0.0001, respectively]. Disease-free survival rates were higher in groups 3, 2, and 1 than in group 4 (HR 0.32, 95 % CI 0.13–0.75, P = 0.009; HR 0.24, 95 % CI 0.10–0.54, P = 0.001; HR 0.26, 95 % CI 0.14–0.48, P < 0.0001, respectively).

Conclusions

After preoperative CRT, CRM distance provides useful information for risk stratification in the recurrence of rectal cancer.     

Microscopic Tumor Cell Dissemination in Gastric Cancer

Purpose There is still much controversy surrounding the prognostic significance of microscopic tumor cell dissemination in gastric cancer and its correlation with histopathologic parameters. We herein investigate such dissemination, predominantly restricted to the subserosa, in patients with gastric cancer.Methods Intraoperative bone marrow aspiration was done in 26 patients undergoing resection of gastric carcinoma. Peritoneal lavage could not be done in 8 of these 26 patients. The R0-resection rate was 84% (n = 22). A cytokeratin-directed antibody and an antibody directed against carcinoembryonic antigen served for the immunocytochemical detection of tumor cells, and the alkaline phosphatase antialkaline phosphatase method was used for visualization.Results The bone marrow aspirate and peritoneal lavage fluid were immunocytochemically positive in 31% and 56% of the patients, respectively. There was a trend (P = 0.10) towards higher overall survival rates in patients with negative bone marrow samples than in those with tumor cells detected in bone marrow samples. Analyzing the results of peritoneal lavage did not reveal any significant differences. In the group of T1/2 cancers, survival was significantly worse if the bone marrow was positive for tumor cells, with 3-year survival rates of 25% vs 77%, respectively (P < 0.05).Conclusion The rates of tumor cell dissemination into the bone marrow or into the peritoneal cavity were within the scope of previous reports. Dissemination into the bone marrow resulted in significantly impaired survival in patients with T1 and T2 gastric carcinoma, and it did not correlate with known prognostic parameters.     

Tumor Diameter as a Prognostic Factor in Patients with Gastric Cancer

Background  The aim of this study was to evaluate the prognostic value of tumor diameter in gastric cancer. Methods  The study group comprised a series of 1215 patients who underwent curative gastrectomy. The appropriate tumor diameter cutoff value was determined. Prognostic factors were evaluated by univariate and multivariate analyses. Results  The tumor diameter cutoff value was 100 mm. Multivariate analysis showed that tumor site, macroscopic appearance, tumor diameter, depth of invasion, and presence of lymph node metastasis independently affected prognosis in all patients. Multivariate analysis of patients with larger tumors identified depth of invasion as an independent prognostic factor. A comparison between patients with smaller and larger tumors showed marked differences in the survival of those with stage II, IIIA, and IIIB tumors. A comparison of clinicopathological factors between stage II and III patients revealed that tumors occupying the entire stomach, ill-defined, undifferentiated, and serosa-penetrating tumors, and peritoneal metastases were far more frequent in patients with larger tumors. Conclusions  Tumor diameter in gastric cancer is a reliable prognostic factor that might be a candidate for use in the staging system. To improve outcomes for patients with tumors ≥100 mm in diameter, it is necessary to establish therapeutic strategies for peritoneal metastasis, particularly in stage II and III tumors.     

Prognostic Significance of Perineural Invasion in Patients with Gastric Cancer Who Underwent Curative Resection

Background

The prognostic significance of perineural invasion (PNI) in gastric cancer has been previously investigated in a few studies, but had not reached a consensus. The aim of this study was to determine the prognostic value of PNI in patients with gastric cancer who underwent curative resection.

Materials and Methods

We retrospectively analyzed 238 patients who had undergone curative gastrectomy. Paraffin sections of surgical specimens from all patients were stained with hematoxylin and eosin. PNI was defined when carcinoma cells infiltrated into the perineurium or neural fascicles. PNI and the other prognostic factors were evaluated by univariate and multivariate analysis.

Results

PNI was detected as positive in 180 of the 238 patients (75.6%). pT stage, tumor size, lymph node metastasis, clinical stage, tumor differentiation, Borrmann classification, histological type, lymphatic vessel invasion, and blood vessel invasion were closely associated with the presence of PNI. The PNI-positive tumors had significantly larger size and more lymph node metastasis than the PNI-negative tumors (P = .001 and P < .001, respectively). The median survival of the PNI-positive patients was significantly worse than that of the PNI-negative patients (28.1 vs. 64.9 months, P = .001). Multivariate analysis indicated that the positivity of PNI was an independent prognostic factor (P = .02, hazard ratio [HR]: 2.75; 95% confidence interval [95% CI]:1.12–3.13) as were classical clinicopathological features.

Conclusion

Our results showed that the frequency of PNI was high in patients with gastric cancer who underwent curative gastrectomy and the proportion of PNI positivity increased with progression and clinical stage of disease. PNI may be useful in detecting patients who had poor prognosis after curative resection in gastric cancer.     

The Node Ratio as Prognostic Factor after Curative Resection for Gastric Cancer

Introduction

The depth of the tumor invasion and nodal involvement are the two main prognostic factors in gastric cancer. Staging systems differ among countries and new tools are needed to interpret and compare results and to reduce stage migration. The node ratio (NR) has been proposed as a new prognostic factor.

Materials and Methods

We retrospectively reviewed 282 patients who underwent curative resection for gastric cancer at Parma University Hospital between 2000 and 2007. TNM stage, NR, overall survival, survival according to nodal status, and survival according to the total number of nodes retrieved were calculated.

Results

At univariate analysis, the TNM stage, number of metastatic nodes, NR, and depth of tumor invasion, but not the number of nodes retrieved, were significant prognosis factors. Patients with more than 15 nodes retrieved in the specimen survived significantly longer (p?<?0.04). This was confirmed for all N or NR classes within N groups. There was a correlation between the number of nodes retrieved and N but not with the NR category. NR was an independent prognostic factor at Cox regression.

Conclusion

NR is a reliable and sensitive tool to differentiate patients with similar characteristics, probably more so than the TNM system. NR is not strictly related to the number of nodes retrieved and this may potentially decrease the stage migration phenomenon. More trials are needed to validate this factor.     

Palliative Resection in Noncurative Gastric Cancer Patients

Background  

Palliative resection for noncurable gastric cancer remains controversial, especially in the elderly. This retrospective study was designed to elucidate the clinicopathological factors and operative outcome in patients undergoing palliative gastric resection.     

Clinical Impact of Positive Surgical Margin Status on Gastric Cancer Patients Undergoing Gastrectomy

Background  

The clinical impact of positive surgical margin on the overall survival and recurrence pattern for gastric cancer (GC) patients undergoing intension curative resection has not yet been well investigated.     

Prognostic Factors for Survival in Patients with Hepatic Recurrence After Curative Resection of Gastric Cancer

Background  This study was done to evaluate the prognostic factors that may affect the survival of patients with recurrent hepatic metastasis after curative resection of gastric cancer. Methods  We reviewed the medical records of 73 patients with recurrent hepatic metastasis after surgical treatment of gastric cancer from January 1995 to December 2005. Prognostic factors were classified into three groups: primary tumor factors, recurrent hepatic factors, and treatment factors. The prognostic values of these factors were assessed using univariate and multivariate analyses by the log-rank test in the Kaplan-Meier method and Cox’s proportional hazard model. Results  The overall median survival rate of the 73 study patients was 20.0 months [95% confidence interval (CI) 15.4–24.6 months]. The median survival rate after diagnosis of recurrent hepatic metastasis was 5 months (95% CI 3.5–6.5 months). Univariate analysis showed that the favorable prognostic factors were stage I and II among the primary tumor factors, no extrahepatic metastasis and unilobar distribution among the recurrent hepatic factors, and radiofrequency ablation (RFA) ± chemotherapy among the treatment factors when operative treatment had been excluded. The independent favorable prognostic factors revealed by the multivariate analysis were no extrahepatic metastasis and RFA ± chemotherapy. The median survival rate of patients who had two favorable prognostic factors was 27 months (95% CI 0–66.38 months). Conclusions  Improvement in the survival rate can be expected with RFA ± chemotherapy for patients with recurrent gastric cancer in the liver without extrahepatic metastasis.     

The Prognostic Value of Varying Definitions of Positive Resection Margin in Patients with Colorectal Cancer Liver Metastases

Background

Varying definitions of resection margin clearance are currently employed among patients with colorectal cancer liver metastases (CRLM). Specifically, a microscopically positive margin (R1) has alternatively been equated with an involved margin (margin width?=?0 mm) or a margin width <?1 mm. Consequently, patients with a margin width of 0–1 mm (sub-mm) are inconsistently classified in either the R0 or R1 categories, thus obscuring the prognostic implications of sub-mm margins.

Methods

Six hundred thirty-three patients who underwent resection of CRLM were identified. Both R1 definitions were alternatively employed and multivariable analysis was used to determine the predictive power of each definition, as well as the prognostic implications of a sub-mm margin.

Results

Five hundred thirty-nine (85.2%) patients had a margin width ≥?1 mm, 42 had a sub-mm margin width, and 52 had an involved margin (0 mm). A margin width ≥?1 mm was associated with improved survival vs. a sub-mm margin (65 vs. 36 months; P?=?0.03) or an involved margin (65 vs. 33 months; P?<?0.001). No significant difference in survival was detected between patients with involved vs. sub-mm margins (P?=?0.31). A sub-mm margin and an involved margin were both independent predictors of worse OS (HR 1.66, 1.04–2.67; P?=?0.04, and HR 2.14, 1.46–3.16; P?<?0.001, respectively) in multivariable analysis. Importantly, after combining the two definitions, patients with either an involved margin or a sub-mm margin were associated with worse OS in multivariable analysis (HR 1.94, 1.41–2.65; P?<?0.001).

Conclusions

Patients with involved or sub-mm margins demonstrated a similar inferior OS vs. patients with a margin width >?1 mm. Consequently, a uniform definition of R1 as a margin width <?1 mm should perhaps be employed by future studies.

     

The Prognostic Impact of Isolated Tumor Cells in Lymph Nodes of T2N0 Gastric Cancer: Comparison of American and Japanese Gastric Cancer Patients

Background  The clinical significance of immunohistochemically detected isolated tumor cells (ITC) in lymph nodes of gastric cancer patients is controversial. This study examined the prognostic impact of ITC on patients with early-stage gastric cancer in two large volume centers in the United States and Japan. Methods  Fifty-seven patients with T2N0M0 gastric carcinoma who underwent gastric resection between January 1987 and January 1997 at Memorial Sloan-Kettering Cancer Center (MSKCC) in New York and 107 patients resected at National Cancer Center Hospital (NCCH) in Tokyo between January 1984 and December 1990 were studied. The sections were newly prepared from each lymph node for immunohistochemical staining for cytokeratin. Lymph nodes and original specimens from MSKCC were examined by pathologists in NCCH. The prognostic significance of the presence of ITC in lymph nodes was investigated in patients of both institutions. Results  ITC were identified in 30 of 57 patients (52.6%) at MSKCC and in 38 of 107 patients (35.5%) at NCCH. In both institutions, there was no significant difference in the prognosis of the studied patients with or without ITC (P = .22, .86 respectively). Conclusions  The presence of ITC detected by immunohistochemistry in the regional lymph nodes did not affect the prognosis of American and Japanese patients with T2N0M0 gastric carcinoma who underwent gastrectomy with D2 lymph node dissection.     

The Prognostic Significance of an R1 Resection in Gastric Cancer Patients Treated with Adjuvant Chemoradiotherapy

Background

A microscopically irradical (R1) resection is a well-known adverse prognostic factor after gastric cancer surgery. However, the prognostic significance of an R1 resection in gastric cancer patients who are treated with chemoradiotherapy (CRT) after the operation has been poorly studied. Therefore, the aim of this study was to evaluate the effect of an R1 resection on (recurrence-free) survival in gastric cancer patients who were treated with CRT after surgery.

Methods

Gastric cancer patients who had undergone a resection with curative intent followed by adjuvant CRT at our institute between 2001 and 2011 were included. CRT consisted of radiotherapy (45 Gy/25 fractions) combined with concurrent capecitabine (with or without cisplatin) or 5-fluorouracil/leucovorin.

Results

A consecutive series of 110 patients was studied, including 80 (73 %) patients who had undergone an R0 resection and 30 (27 %) patients with an R1 resection. Pathologic T-classification (p = 0.26), N-classification (p = 0.77), and histologic subtype according to Laurén (p = 0.071) were not significantly different between these groups. Three-year recurrence-free survival (45 vs. 35 %, p = 0.34) and overall survival (47 vs. 48 %, p = 0.58) did not significantly differ between patients who had undergone an R0 or R1 resection. In a multivariate analysis, pathologic T-classification and N-classification were independent prognostic factors for survival.

Conclusions

A R1 resection was not an adverse prognostic factor in gastric cancer patients who had undergone CRT after the operation.     

Prognostic Significance of Circumferential Resection Margin Following Total Mesorectal Excision and Adjuvant Chemoradiotherapy in Patients with Rectal Cancer

Background This study was designed to evaluate the prognostic value of circumferential resection margin (CRM) in rectal cancer patients who underwent curative resection with adjuvant chemoradiotherapy (CRT). Methods We studied 504 patients who underwent total mesorectal excision with adjuvant CRT for rectal cancer between 1997 and 2001. The patients were divided into two groups: a negative CRM group (CRM > 1 mm) and a positive CRM group (CRM ≤ 1 mm). The survival rates, local recurrence rates, and systemic recurrence rates were compared between groups. Results The negative CRM group had 460 patients and the positive CRM group had 44 patients. The 5-year local and systemic recurrence rates were 11.3 and 25.3%, respectively, in the negative CRM group and 35.2 and 60.8% in the positive CRM group, respectively. The cancer-specific 5-year survival rates for the two groups were 72.5 and 26.9% (P < .001), respectively. CRM was found to be an independent prognostic factor by multivariate analyses which were adjusted for known outcome predictors (P < .001). Conclusion Oncological outcome for patients in the positive CRM group is less favorable than for those in the negative CRM group. Adjuvant CRT is not a definite treatment modality that can be used to compensate for a positive CRM following TME and adjuvant CRT in patients with TNM stage II or III rectal cancer.     

Prognostic Significance of Tumor Size in T3 Gastric Cancer

Background  Clinical significance of tumor size remains elusive in gastric cancer. The aim of this study was to evaluate the prognostic value of tumor size in T3 gastric cancer. Methods  A total of 273 patients with T3 gastric cancer who underwent curative D2 gastrectomy between 1996 and 2005 were evaluated. In terms of average value of tumor size, patients were divided into two groups according to tumor size: small-size group (SSG, tumor ≤6 cm) and large-size group (LSG, tumor >6 cm). The prognostic value of tumor size and the correlation between tumor size and other clinicopathologic factors were investigated. Results  LSG accounted for 34.8% in all patients. Tumor size was correlated with histological type, lymphatic invasion, venous invasion, and resection type. The prognosis of LSG patients was worse than that of SSG patients. Multivariate analysis showed that type of resection, status of lymph nodes, metastatic lymph node ratio, and tumor size were defined as independent prognostic factors for patients with T3 gastric cancer. A comparison between LSG patients and SSG patients showed differences in the survival of those with stage IIIB and IV disease. Conclusions  Tumor size is a simple and reliable prognostic factor for patients with T3 gastric cancer; it might be a candidate for the gastric cancer staging system.     

Type-oriented Intraoperative and Adjuvant Chemotherapy and Survival after Curative Resection of Advanced Gastric Cancer

n = 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n= 13); or UFT 600 mg/day (P2 group, n= 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n= 17), H1 (n= 12), and H2 (n= 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.     

进展期近端胃癌根治术联合脾脏切除术适应证的选择

目的探讨进展期近端胃癌根治术联合脾脏切除术的合理适应证。方法选取我院自2005年3月至2008年2月期间50例进展期近端胃癌行全胃切除患者为研究对象,根据脾脏是否切除分为切脾组(n=18)和保脾组(n=32),比较2组患者间手术时间、住院时间、术后并发症以及脾门淋巴结转移情况。结果切脾组手术时间、住院时间和膈下感染发生率均明显高于保脾组(P0.05)。切脾组与保脾组术后病理检查出的第10、11组淋巴结转移率的差异无统计学意义(P0.05)。结论进展期近端胃癌根治术时,脾脏和脾血管受侵是联合脾脏切除的合理适应证。