Correlation Between Connexin 26 Expression and Poor Prognosis of Esophageal Squamous Cell Carcinoma

Background  Failure of gap junction formation affects the development of various types of cancer. We aimed to clarify the clinicopathologic outcome and prognostic significance of connexin (Cx) 26 in human esophageal squamous cell carcinoma (ESCC). Methods  Immunohistochemical staining for Cx26 was performed on surgical specimens obtained from 123 patients with ESCC. Results  There was no positive staining for Cx26-specific expression in normal esophageal squamous cells. Primary ESCC with Cx26-positive expression was detected in the cytoplasm of cancer cell nests in 60 cases. Cx26 expression was correlated with N (lymph node metastasis, P = 0.014) and the number of metastatic lymph nodes (P = 0.047). The 5-year survival rates of ESCC patients with Cx26-positive expression were significantly lower than those with Cx26-negative expression (positive, 39.7%; negative, 65.7%; P = 0.007). By multivariate analysis, tumor–node–metastasis (TNM) clinical classification (T, P < 0.001; N, P = 0.002; M, P = 0.046) and Cx26 (P = 0.024) were independent prognosis predictors of ESCC. Conclusions  These results suggest that abnormal expression of Cx26 participates in the progress of ESCC.     

SnoN Overexpression is Predictive of Poor Survival in Patients with Esophageal Squamous Cell Carcinoma

Background  Earlier studies have identified the minimal overlapping region of amplification at 3q26 in esophageal squamous cell carcinoma (ESCC) by comparative genomic hybridization (CGH) analysis. These include PIK3CA which encodes the p110α catalytic subunit of phosphatidylinositol (PI) 3-kinase, a telomerase RNA component (TERC), a squamous cell carcinoma-related oncogene (SCCRO), ecotropic viral integration site-1 (EVI-1), and a Ski-related novel oncogene (SnoN). In the present study, we investigated the mRNA levels of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) to determine whether genes other than PIK3CA are targets for amplification at 3q26 in ESCC. And also, we examined SnoN expression in ESCC samples. Methods  Fifty-nine representative cases with ESCC were selected from our archives. We performed quantitative RT-PCR of four candidate genes (TERC, SCCRO, EVI-1, and SnoN) and immunohistochemistry for SnoN. Finally, we correlated these findings with the clinicopathological characteristics to determine their interrelationship. Results  Among the four genes we tested, only SnoN mRNA was consistently overexpressed in primary ESCC, compared with those in corresponding nontumorous esophageal epithelia (P < 0.001). Immunoreactive SnoN was detectable in 31 of 59 (52.5%) esophageal squamous cell carcinoma specimens. The levels of SnoN expression were found to correlate with the depth of invasion and recurrence (P < 0.05). Furthermore, patients with positive staining for SnoN displayed more unfavorable outcomes than patients with negative staining (P < 0.05). Conclusion   SnoN is likely to be the target of the amplification at 3q26 in ESCC and plays an important role in the development of ESCC, influencing disease-specific survival.     

Overexpression of Sox3 is Associated with Diminished Prognosis in Esophageal Squamous Cell Carcinoma

Background

Esophageal squamous cell carcinoma (ESCC) is a lethal malignancy lacking valid prognostic biomarkers. As a member of the High Mobility Group domain-containing DNA-binding proteins, Sox3 has been reported to induce oncogenic transformation of chicken embryo fibroblasts. However, the expression and prognostic value of Sox3 in ESCC remain unclear.

Methods

A total of 30 pairs of ESCC with a corresponding non-neoplastic esophageal epithelium (NE) specimen were investigated for Sox3 expression using RT-PCR and western blot analysis. Tissue microarrays containing 118 ESCC and 30 NE samples were detected for Sox3 expression using immunohistochemical staining. The relationship of Sox3 staining with various clinicopathological characteristics and survival of patients was statistically analyzed.

Results

Sox3 expression in ESCC was 3.1- and 2.7-fold higher than in NE at mRNA (P < 0.001) and protein level (P < 0.001), respectively. Positive staining of Sox3 was observed in 77.1 % of the ESCC and 16.7 % of the NE samples (P < 0.001). High expression of Sox3 was significantly correlated with the regional lymph nodes metastasis (RLNM) (P = 0.022) and advanced TNM stage (P = 0.011). Moreover, high expression of Sox3 was significantly associated with poor overall survival (P < 0.001) and recurrence-free survival (P < 0.001) in ESCC patients. Both Sox3 expression (P < 0.001) and RLNM (P = 0.002) were independent prognostic factors for patients with ESCC.

Conclusions

Sox3 might play a positive role in tumor development and could serve as an independent predictor of poor prognosis for ESCC.

     

Overexpression of vascular endothelial growth factor-C correlates with lymph node micrometastasis in submucosal esophageal cancer

Lymph node metastasis, including lymph node micrometastasis (LMM), is one of the most important prognostic factors in esophageal squamous cell carcinoma (ESCC). Vascular endothelial growth factor C (VEGF-C) plays a key role in the process of lymphangiogenesis. We examined VEGF-C expression and tumor microvessel density of the primary tumors in ESCC and analyzed relationships between VEGF-C expression and clinicopathologic findings including LMM in submucosal ESCC. The subjects were 87 patients with submucosal ESCC. Immunohistochemical staining of VEGF-C and CD34 was performed with primary tumors, and staining of cytokeratin was performed with dissected lymph nodes. Microvessel density was calculated from CD34 expression, and LMM was detected by cytokeratin staining. VEGF-C overexpression significantly correlated with depth of tumor invasion, lymphatic invasion, and lymph node metastasis (P<0.05, P<0.0001, and P<0.0001, respectively). High microvessel density also correlated with lymphatic invasion and lymph node metastasis (P<0.005 and P<0.05, respectively). LMM was detected in 8 cases and 14 lymph nodes by cytokeratin staining. VEGF-C overexpression and high microvessel density were found in tumors with lymph node metastasis and/or LMM, compared with tumors without nodal metastasis or LMM (P<0.0001 and P<0.01, respectively). The present findings indicate that in ESCC with submucosal invasion, VEGF-C overexpression of the primary tumor is a strong high risk factor for lymph node metastasis, including LMM. Supported in Grant No. 17390373 part by grants-in-aid for scientific research from the Ministry of Education, Science, Sports and Culture, Japan. (Shoji Natsugoe, M.D., Ph.D.)     

Preoperative platelet count in esophageal squamous cell carcinoma: is it a prognostic factor?

Purpose

Platelet count is inversely related to prognosis in many cancers; however, its role in esophageal cancer is still controversial. The purpose of this study was to determine the prognostic value of preoperative platelet count in esophageal squamous cell carcinoma (ESCC).

Methods

From January 2006 to December 2008, a retrospective analysis of 425 consecutive patients with ESCC was conducted. A receiver operating characteristic (ROC) curve for survival prediction was plotted to verify the optimum cutoff point for preoperative platelet count. Univariate and multivariate analyses were performed to evaluate the prognostic parameters.

Results

A ROC curve for survival prediction was plotted to verify the optimum cutoff point for platelet count, which was 205 (×10⁹/L). Patients with platelet count ≤205 had a significantly better 5-year survival than patients with a platelet count >205 (60.7 vs. 31.6 %, P?<?0.001). The 5-year survival of patients either with platelet count ≤205 or >205 were similar (68.6 vs. 58.8 %, P?=?0.085) when the nodes were negative. However, the 5-year survival of patients with platelet count ≤205 was better than that of patients with a platelet count >205 when the nodes were involved (32.0 vs. 12.7 %, P?=?0.004). Multivariate analysis showed that platelet count (P?=?0.013), T grade (P?=?0.017), and N staging (P?<?0.001) were independent prognostic factors.

Conclusions

Preoperative platelet count is a predictive factor for long-term survival in ESCC, especially in nodal-positive patients. We conclude that 205 (×10⁹/L) may be the optimum cutoff point for platelet count in predicting survival in ESCC patients.     

Prognostic Role of PGE2 Receptor EP2 in Esophageal Squamous Cell Carcinoma

Prostaglandin E2 (PGE2), a major cyclooxygenase-2 (COX-2) product, has been shown to affect numerous tumorigenic processes. PGE2 acts through G-protein-coupled receptors designated as EPs. Recently it has been documented that PGE2 promotes colon cancer cell growth via EP2. However, the expression and the prognostic role of EP2 in esophageal squamous cell carcinoma (ESCC) remained unknown. From January 1995 to January 2001, tissue samples from 226 patients with ESCC who underwent esophagectomies at our institutions were collected and made into tissue core arrays for study. EP2 expression was examined by immunohistochemical staining and confirmed by Western blot. The clinicopathologic data were then analyzed. EP2 overexpression was observed in 43.4% (98/226) of ESCC. Overexpression of EP2 correlated positively with depth of tumor invasion (T status) (P = 0.016) and was associated with worse overall survival (P = 0.047). In patients without regional or distant lymph node metastasis (N0 or M0), EP2 overexpression was associated with worse overall survival (P = 0.033 and P = 0.003, respectively). Using Cox regression analysis, T status, N status, and M status were the independent factors of overall survival, but EP2 expression was not. However, when focusing on patients with T1-3N0M0 status, EP2 expression became an independent factor of overall survival (P = 0.048). Our results show that EP2 overexpression was associated with worse prognosis, and correlated positively with T status in ESCC. Meanwhile, among those patients at earlier stages, EP2 overexpression significantly disclosed patients at high risks for poor prognosis.     

Clinical impact of lymphadenectomy extent in resectable gastric cancer of advanced stage

Background Advanced, but potentially still curable gastric cancer (stages IIIA, IIIB, or stage IV M0) is associated with very high recurrence rates after gastrectomy. The value of an extended lymph node dissection (ELND) remains unclear in this setting. Methods A resected gastric cancer data set was created through structured queries to the SEER 1973–2000 database. Relationships between the number of lymph nodes (LNs) examined and survival outcomes were analyzed for the stage subgroups characterized by the N categories N2 or N3, and transmural tumor extension (T categories T2b or T3). Results The study group encompassed 1,377 patients, including T2b/3N2 (n = 1,076) and T2b/3N3 stage subgroups (n = 301). Total LN count (or number of negative LNs examined; P < 0.0001), number of positive LNs (P < 0.0001), age (P < 0.0001), primary site (P = 0.0002), T category (P = 0.0271), race (P = 0.0301) and gender (P = 0.0261) were independent prognostic survival predictors. A cut point analysis yielded the ability to detect significant survival differences for LN numbers up to 30 (N2) or up to 40 (N3), always in favor of the higher number of LNs examined. Best long-term survival outcomes were observed with negative LN counts of more than 15 (N2) or more than 20 (N3). Conclusions Even in transmural or serosa-positive gastric cancer with advanced nodal involvement, more extensive LN dissection and analysis influences survival. Stage-based survival prediction depends on total LN number and number of negative LNs. The mechanism remains uncertain, but is not limited to stage migration. ELND during potentially curative gastrectomy is recommended even for advanced gastric cancer.     

Dickkopf-1 Expression as a Marker for Predicting Clinical Outcome in Esophageal Squamous Cell Carcinoma

Background and Objectives  Dickkopf-1 (DKK1) is the inhibitor of the canonical Wnt signaling pathway, however it is highly transactivated in various cancers, suggesting the presence of unknown mechanism. Its implication in human esophageal squamous cell carcinoma (ESCC) has not been sufficiently investigated. Patients and Methods  We evaluated DKK1 protein expression in resected specimens from 170 patients with ESCC by immunohistochemistry. Tumors were categorized as positive or negative for DKK1. The relationships between DKK1 expression in ESCC and various clinicopathological parameters and prognosis (disease-free survival; DFS) were analyzed separately. Results  Immunohistochemically, 72 (42.4%) tumors were DKK1 positive while no significant staining was observed in the normal squamous epithelium except for few basal cells. There was no significant relationship between DKK1 expression in ESCC and any of the clinicopathological parameters tested in this study. Patients with DKK1-positive tumors had poorer DFS than those with negative ESCC (5-year DFS; 31.5% versus 53.6%, P = 0.0062). Univariate analysis showed a significant relationship between pT [hazard ratio (HR) = 2.944, 95% confidence interval (CI) = 1.713–5.059, P < 0.0001], number of pN (HR = 2.836, 95% CI = 1.866–4.309, P < 0.0001), lymphatic invasion (HR = 2.892, 95% CI = 1.336–6.262, P = 0.0070), and DKK1 expression (HR = 1.763, 95% CI = 1.167–2.663, P = 0.0071) and DFS. Multivariate analysis including the above four parameters identified pT (HR = 2.053, 95% CI = 1.157–3.645, P = 0.0140), pN number (HR = 2.107, 95% CI = 1.362–3.260, P = 0.0008), and DKK1 expression (HR = 1.813, 95% CI = 1.195–2.751, P = 0.0052) as independent and significant prognostic factors for DFS. Conclusion  Our data suggest the usefulness of DKK1 as a novel predictor of poor prognosis of patients with ESCC after curative resection and also as a therapeutic target for future tailored therapies against ESCC.     

Preoperative Serum CA19-9 and Dissected Peripancreatic Tissue Margin as Determiners of Long-Term Survival in Pancreatic Cancer

Background  Pancreatic cancer, a particularly deadly form of malignancy, has increased in the last decade worldwide. The purpose of this study is to identify markers for determining and identifying possible long-term survivors in cases of advanced pancreatic cancer. Patients and methods  117 patients with pancreatic ductal carcinoma, including 89 with invasive tubular adenocarcinoma of the pancreas, Japan Pancreas Society (JPS) stage III–IVb patients, who underwent tumor resection between 1986 and 2006. Results  Univariate prognostic analyses of the 5-year disease-specific survival (DSS) revealed that JPS stage (P < 0.0001), preoperative serum carbohydrate antigen 19-9 (CA19-9) level (preCA19-9; P < 0.0001), dissected peripancreatic tissue margin (DPM; P < 0.0001), residual tumor (R factor; P = 0.0007), lymph node metastasis density over 10% (ND10; P = 0.006), volume of the stromal connective tissue (stroma factor; P = 0.008), growth pattern (P = 0.01), and histology (P = 0.03) were all significantly associated with poor outcome in advanced pancreatic cancer. Multivariate logistic analysis confirmed that preCA19-9 [P = 0.0006, relative risk (RR) = 2.16] and DPM (P = 0.04, RR = 1.62) were prognostic factors that remained, independent of JPS stage (P = 0.001). The higher preCA19-9 was, the worse the prognosis was. Astonishingly, among JPS stage III cases, 76.9% of the patients with preCA19-9 below 37 U/ml survived more than 5 years. This, combined with an analysis of DPM, allowed us to identify those with the potentiality for long-term survival. Conclusion  Our results reveal for the first time that it is possible with JPS stage III–IVb invasive tubular adenocarcinomas of the pancreas to differentiate prognostic groups and potential survival rates, like with other cancers. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Prognostic value of recurrence pattern in locally advanced esophageal squamous cell carcinoma: Results from the phase III trial NEOCRTEC5010

ObjectivesThe prognosis of patients with locally advanced esophageal squamous cell carcinoma with different recurrence backgrounds is highly heterogeneous. This study aims to explore the effects of recurrence patterns on prognosis.MethodsThe phase III, multicenter, prospective NEOCRTEC5010 trial enrolled 451 patients with stage IIB-III esophageal squamous cell carcinoma randomly assigned to neoadjuvant chemoradiotherapy combined with surgery (NCRT group) or surgery alone (S group) and followed them long-term. We investigated the effects of recurrence patterns on survival in patients undergoing radical esophagectomy.ResultsIn total, 353 patients were included in the study. The 5-year overall survival of patients with different recurrence patterns was significantly different: recurrence versus recurrence-free (17.8% vs 89.2%; P < .001), early recurrence versus late recurrence (4.6% vs 51.2%; P < .001), and distant metastasis versus locoregional recurrence (17.0% vs 20.0%; P = .666). Patients with early recurrence had significantly shorter survival after recurrence than those with late recurrence (hazard ratio, 1.541; 95% confidence interval, 1.047-2.268, P = .028). There was no significant difference in postrecurrence survival between patients with distant metastasis and locoregional recurrence (hazard ratio, 1.181; 95% confidence interval, 0.804-1.734; P = .396). Multivariate logistic analysis showed that pN1 stage, lymph node dissection <20, and lack of response to NCRT were independent risk factors for postoperative early recurrence. Multivariate Cox regression suggested that NCRT, age ≥60 years, early recurrence, and the pN1 stage were independent risk factors for shortened survival after recurrence.ConclusionsPrerecurrence primary tumor stage is inaccurate in predicting postrecurrence survival. In contrast, recurrence patterns can guide follow-up while also predicting postrecurrence survival. NCRT prolongs disease-free survival but is associated with a worse prognosis in patients with recurrence, especially early recurrence.     

Effect of increases in tumor volume after neoadjuvant chemotherapy on the outcome of stage II osteosarcoma regardless of histological response

Background  We assessed volume changes after neoadjuvant chemotherapy and evaluated relations between tumor size changes and clinical characteristics. In addition, we sought to determine whether tumor size change influences patient outcome. Methods  The records of 127 patients with stage II osteosarcoma who showed more than a 15% volume change after chemotherapy were retrospectively reviewed. Patients were divided into two groups depending on whether tumors increased or decreased in size. Fisher’s exact test was performed to analyze correlations between tumor size changes and clinicopathological variables. Five-year metastasis-free survival and overall survival were evaluated using univariate and multivariate analyses. Results  A total of 71 patients (55.9%) showed a decrease in tumor volume, and 56 patients (44.1%) showed an increase. An increase in tumor volume after neoadjuvant chemotherapy was found to be positively correlated with a poor histological response and subsequent metastasis. Univariate analysis identified the following parameters as poor prognostic factors: age ≤15 years (P = 0.03), American Joint Committee on Cancer (AJCC) stage IIB (P = 0.02), a subtype other than osteoblastic (P < 0.01), a poor histological response (P < 0.001), and increased tumor volume after preoperative chemotherapy (P < 0.0001). Multivariate analysis revealed that AJCC stage IIB (P = 0.006) and an increase in tumor volume after preoperative chemotherapy (P < 0.001) both independently shortened metastasis-free survival. However, a poor histological response lost its prognostic significance (P = 0.34). Conclusions  Increased tumor volume after neoadjuvant chemotherapy independently shortened metastasis-free and overall survival in AJCC stage II osteosarcoma patients. Tumor volume changes may serve as a basis for risk-adapted therapy when used in combination with other prognostic factors.     

Thymidine phosphorylase as a prognostic factor in renal cell carcinoma

The purpose of the current study was to clarify further the clinicopathologic significance of thymidine phosphorylase (TP) expression in renal cell carcinoma (RCC). TP expression was evaluated with immunohistochemistry assays using monoclonal anti-TP antibody in formalin-fixed, paraffin-embedded archived specimens of 70 patients with radically operated nonmetastatic RCC (M0 by TNM classification). Semiquantitative analysis, using a scoring system for staining pattern and staining intensity was used. Univariate analysis showed that the characteristics that carried the prognostic significance for survival were age as continuous characteristic (chi-square log-rank test P = 0.0121), TP expression (P = 0.0061), histologic grade (P < 0.0001), and stage (P = 0.0244). In multivariate analysis (by Cox proportional hazards regression analysis), the factors significant for survival were age (HR 1.09; 95% CI 1.03–1.14), stage (HR 2.76; 95% CI 1.27–6.07), and histologic grade (HR 7.91; 95% CI 2.11–29.7), TP did not show independent significant value (HR 0.68; 95% CI 0.19–2.50). However, TP had strong correlation with histologic grade (P = 0.818). In conclusion, TP expression level in RCC is strongly correlated with histologic grade, which is one of well-known prognostic factors in RCC, but TP had no independent prognostic value.     

Ki-67 is an independent indicator in non–muscle invasive bladder cancer (NMIBC); Combination of EORTC risk scores and Ki-67 expression could improve the risk stratification of NMIBC

ObjectiveTo prove the predicting role of Ki-67 expression and to demonstrate that the combination of European Organization for Research and Treatment of Cancer (EORTC) risk scores and Ki-67 staining status could improve the risk stratification in a large series of patients with non–muscle invasive bladder cancer (NMIBC).Material and methodsFrom October 2002 to July 2010, in our cohort, 332 patients who were treated with transurethral resection of the bladder tumor were diagnosed with NMIBC by histopathologic analysis. Two experienced uropathologists rereviewed the slides. The EORTC risk scores for recurrence and progression were determined. Ki-67 expression was evaluated using immunohistochemical studies and scored for intensity and area of staining. We correlated Ki-67 expression scores with clinical and pathologic variables. We evaluated the prognosis role of EORTC risk scores, Ki-67 staining, and their combination on tumor recurrence-free survival and progression-free survival (PFS) by univariate analysis, multivariate analysis, and Kaplan-Meier survival curves.ResultsWith a median follow-up of 47 (range, 2–124) months, 119 patients (35.8%) had tumor recurrence and 40 patients (12%) had tumor progression. Ki-67 positivity (Ki-67>25%) was reported in 108 tumors (32.5%), and it was significantly associated with high EORTC risk scores for both tumor recurrence and progression. In univariate analysis, multifocality, tumor size, tumor stage, tumor grade, and Ki-67 staining correlated with recurrence-free survival, whereas tumor size, tumor stage, tumor grade, concomitant CIS, and Ki-67 staining correlated with PFS. In multivariable analysis, Ki-67 expression was an independent risk factor for predicting tumor recurrence (hazard ratio, 2.14; P<0.0001) and progression (hazard ratio: 2.97, P = 0.004). Kaplan-Meier curves showed that combining EORTC risk scores and Ki-67 staining led to more accurate prediction for tumor recurrence and progression (log-rank test; P<0.0001).ConclusionsKi-67 positivity is prognostic for predicting tumor recurrence and progression. Combination of EORTC risk scores with Ki-67 expression could improve the risk stratification for both recurrence and progression in NMIBC.     

Predictors of Surgical Margin Status in Breast-Conserving Surgery Within a Breast Screening Program

Background  Breast-conserving surgery (BCS) requires clear surgical margins to minimize local recurrence. We sought to identify groups of patients at higher risk of involved margins who might benefit from preoperative counselling and/or more generous excision at the first operation. Methods  We reviewed demographic, clinical, radiological and pathological records of all women diagnosed with ductal carcinoma in situ (DCIS) or invasive cancer (IC) through a population-based breast screening program in Melbourne, Australia between 1994 and 2005. Results  A total of 2,160 women were diagnosed with DCIS or IC. We excluded 199 who had mastectomy (TM) as initial procedure or had missing data. Three hundred and thirteen had a diagnostic biopsy. Of 1,648 women who had BCS after a preoperative diagnosis of DCIS or IC, 13.5% had involved margins, 16.6% had close (≤1 mm), and 69.8% clear (>1 mm) margins. Of the patients, 281/1,648 (17.1%) underwent re-excision, of whom 93 (33.1%) had residual disease identified. Mammographic microcalcifications (P < 0.0001), absence of a mammographic mass (P = 0.002), presence of DCIS (P < 0.0001), high tumour grade (P < 0.0001), large size (P < 0.0001), multifocal disease (P < 0.0001) and lobular histology (P = 0.005) were associated with involved margins. Microcalcifications (odds ratio [OR] 1.97), large size (OR 4.22) and multifocal disease (OR 2.85) were independently associated with involved margins. Residual disease was associated with involved margins (P < 0.0001), presence of DCIS (P = 0.05) and large tumour size (P = 0.01). Conclusion  After BCS, patients with mammographic microcalcifications, larger tumour size and multifocal tumours are more likely to have involved margins. Patients with involved margins, large tumour size and/or a DCIS component are more likely to have residual disease on re-excision.     

The Global Histone Modification Pattern Correlates with Cancer Recurrence and Overall Survival in Gastric Adenocarcinoma

Background  Epigenetic alterations such as DNA methylation and histone modification play important roles in carcinogenesis. It has been recently suggested that global histone modification patterns are independent predictors of cancer recurrence. In this study, we used immunohistochemistry to evaluate the patterns of histone H3 and H4 acetylation and trimethylation in gastric adenocarcinomas. Methods  Double 2-mm core tissue microarrays were made from 261 paraffin-embedded gastric adenocarcinoma samples and examined by immunohistochemistry for histone H3 lysine 9 (H3K9) acetylation and trimethylation, histone H4 lysine 16 acetylation, and histone H4 lysine 20 trimethylation. Sections were graded according to the proportion of tumor cells showing nuclear staining. Results  Trimethylation of H3K9 positively correlated with tumor stage (P = 0.043); lymphovascular invasion (P = 0.029), cancer recurrence (P = 0.043), and higher level of H3K9 trimethylation correlated with a poor survival rate (P = 0.008). Multivariate survival analysis showed that H3K9 trimethylation status is an independent prognostic factor (P = 0.014). After categorizing cases according to the dominant modification pattern, we found that methylation dominance was associated with lymphovascular invasion (P = 0.001), cancer recurrence (P = 0.001), and poor survival rate (P = 0.028). Methylation dominance was also an independent prognostic factor (P = 0.026) in multivariate survival analysis. Conclusion  The pattern of histone modification as detected by immunohistochemistry may be useful as a predictor for the recurrence of cancer and may be an independent prognostic factor in gastric adenocarcinomas.     

Borrmann Type IV: An Independent Prognostic Factor for Survival in Gastric Cancer

Background  Borrmann type IV gastric cancer has a poorer prognosis than other gastric carcinomas. This study compared the clinicopathological features of Borrmann type IV gastric cancer with those of other types of cancer and examined the significance of a Borrmann type IV carcinoma as a prognostic factor after gastrectomy. Methods  The clinicopathological features, tumor–node–metastasis (TNM) stage, and survival rates of 4,191 advanced gastric cancer patients, who had undergone a gastrectomy at the Samsung Medical Center between 1995 and 2005, were reviewed. Results  Borrmann type IV gastric cancer was found to be associated with more advanced and unfavorable clinicopathological features at diagnosis than the other cancers. The 5-year survival rate of the patients with Borrmann type IV cancer was 27.6%. In contrast, the 5-year survival rate of patients with the other types of cancer was 61.2%. The 5-year survival rate for each stage of Borrmann type IV gastric cancer and the other type gastric cancer was 61.0% and 88.8% for stage Ib (P < 0.001), 49.8% and 76.1% for stage II (P < 0.001), 36.4% and 55.1% for stage IIIa (P < 0.001), 15.2% and 38.5% for stage IIIb (P = 0.001), and 10.2% and 20.1% for stage IV (P = 0.008), respectively. Multivariate analyses revealed a Borrmann type IV carcinoma, the surgical extent, curability, tumor stage, including T, N, and M status, and adjuvant therapy to be independent prognostic factors for survival. Conclusion  A Borrmann type IV carcinoma has unique clinicopathological features compared with other types of gastric carcinomas and is an important independent prognostic factor.     

Laparoscopic Rectal Resection for Cancer: Effects of Conversion on Short-Term Outcome and Survival

Background  Laparoscopic rectal resection (LRR) is an oncologically safe procedure. The impact of conversion to open surgery on outcomes has not been fully elucidated. The aim of the study is to compare short- and long-term outcomes of converted (CR) and not converted (NCR) patients undergoing LRR. Methods  Data were drawn from a prospective database of LRR performed between 1999 and 2008. Statistical analysis employed the chi-squared or Wilcoxon test and Kaplan–Meier estimation. Results  Of 173 patients undergoing LRR, 26 (15%) required conversion. No differences in age, gender, American Society of Anesthesiologists (ASA) score, and T and N stages were observed between CR and NCR patients. Conversion was associated with higher body mass index (BMI) (27.3 versus 24.9 kg/m², P < 0.001) and American Joint Committee on Cancer (AJCC) stage IV (26.9% versus 4.8%, P < 0.001), and resulted in longer operative time (342 versus 285 min, P = 0.006) and increased intraoperative complication rate (31% versus 5%, P < 0.001). No differences were observed in postoperative outcome between CR and NCR patients. After a mean follow-up of 46 and 36 months, 5-year disease-free survival was 55.7% in CR group and 79.2% in NCR group (P = 0.007). After exclusion of stage IV patients from the analysis, 5-year disease-free survival was 71.1% in CR group and 85.3% in NCR group (P = 0.17), while the overall recurrence rate was 26.3% in CR patients and 11.4% in NCR patients (P = 0.07). Conclusions  Our study suggests that conversion to open surgery does not affect postoperative outcome, but could have a negative impact on long-term overall recurrence rate. LRR should be performed by experienced surgeons in selected patients. This study was partially presented at the 49th Annual Meeting of the Society for Surgery of the Alimentary Tract, on May 20, 2008 in San Diego, CA.