Baojun Huang

Prognostic significance of microscopic positive margins for gastric cancer patients with potentially curative resection.

BackgroundMost 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.MethodsClinicopathologic and prognostic data were compared between 110 patients with positive margins and 2,159 patients with negative margins who underwent R0 surgery (D2/D3 lymphadenectomy). Multivariate analysis was performed to identify independent factors correlated with positive margins. Cox’s proportional hazard model was applied to investigate whether a positive margin was an independent factor predicting poor outcome. Overall survival rates and the incidence of recurrence were compared between patients with positive and negative margins, stratifying by pT, pN, and TNM stage.ResultsTumor size, pT stage, and pN stage were independent factors associated with positive margins. Although the overall survival rate of patients with positive margins was significantly poorer than that of patients with negative margins, margin status was not an independent prognostic factor on multivariate analysis. Significant differences in survival between patients with negative and positive margins could be observed for those in pT1-2, pN0-1, and I–II stage, but not for those in pT3-4, pN2-3, and III–VI stage. Although locoregional recurrence was more frequently observed for patients with positive margins, the incidence of any recurrence was significantly higher only for patients in pT1-2, pN0-1, and I-II stage, but not for those in pT3-4, pN2-3, and III–VI stage.ConclusionA positive margin results in a significantly worse outcome for pT1-2, pN0-1, and I–II stage gastric cancer patients who undergo D2/D3 lymphadenectomy, but not for those in pT3-4, pN2-3, and III–IV stage.

Evaluation of the seventh edition of American Joint Committee on Cancer TNM staging system for gastric cancer: results from a Chinese monoinstitutional study.

BackgroundTo investigate the validity of the 7th edition of American Joint Committee on Cancer (AJCC) TNM staging system for gastric cancer with special attention paid to pT2/pT3, pN1/pN2, and pN3a/pN3b category.Materials and MethodsClinicopathologic data of 1998 patients underwent R0 surgery for histologically proven gastric cancers with >15 lymph nodes retrieved were retrospectively reviewed.ResultsPrognoses were significantly different between pT2 and pT3 categories, between pN1 and pN2 categories, or between pN3a and pN3b categories. Each stage in the 6th edition was divided into the 7th edition stage with different survival rates. Moreover, stage IIIA, IIIB, and IIIC in the 7th edition system was divided into the 6th edition stage with different survival rates. Prognoses for patients in 7th edition T4aN1M0/T3N2M0/T2N3aM0, T4bN0-1M0/T4aN2M0/T3N3aM0, and T4aN3aM0/T4bN2M0 were similar to that of patients in T1N3bM0, T2N3bM0, and T3N3bM0, respectively, but significantly better than that of patients in T2N3bM0, T3N3bM0, and T4aN3bM0, respectively. However, no significant difference could be observed among patients in T4bN3aM0, T4aN3bM0, T4bN3bM0, and stage IV. A revised TNM system was proposed, in which T1N3bM0 was incorporated into stage IIIA, T2N3bM0 into stage IIIB, T3N3bM0 into stage IIIC, T4bN3aM0/T4aN3bM0/T4bN3bM0 into stage IV. Further analyses revealed the revised TNM system had better homogeneity, discriminatory ability, and monotonicity of gradients than the 6th and the 7th edition system.ConclusionsIt is reasonable to subclassify the 6th edition pT2 category and pN1 category into the 7th edition pT2/pT3 category and pN1/pN2 category, respectively. However, for better prognostic stratification, it might be more suitable for pN3a and pN3b categories to be considered individual determinants of the 7th edition TNM staging system.

Early gastric cancer with signet-ring cell histologic type: Risk factors of lymph node metastasis and indications of endoscopic surgery

BACKGROUND To clarify the biologic behavior of the early signet-ring cell cancers (SRCs) by comparing the clinicopathologic features and the incidence of lymph node metastasis between different histologic types of early gastric cancer (EGC) and to propose the indications of endoscopic surgery for SRCs. METHODS Clinicopathologic features and the incidence of lymph node metastasis of 422 EGCs were retrospectively reviewed and compared according to the histologic type. RESULTS Clinicopathologic features, incidence of node metastasis, prognosis, as well as the incidence of recurrence for SRCs, were similar to those of differentiated cancers (DCs), however, significantly different from those of undifferentiated cancers (UDCs). Tumor size, histologic type, lymphatic and/or blood vessel invasion (LBVI), and depth of invasion were independent factors predicting node metastasis for EGCs. For DCs and SRCs with mucosal invasion and ≤ 2 cm in diameter without LBVI, no metastatic lymph node was detected (95% CI, 0-5.0). Also, for DCs and SRCs with mucosal invasion and >2 cm in diameter without LBVI, or with submucosal invasion and ≤ 2 cm in diameter without LBVI, no metastatic lymph node was detected (95% CI, 0-3.0). CONCLUSION Clinicopathologic features of SRCs were similar with DCs, but different from other UDCs. Consequently, the treatment strategy for SRCs might be similar with that for DCs. According to the incidence of node metastasis, we propose SRCs with mucosal invasion without LBVI, or with submucosal invasion and ≤2 cm in diameter without LBVI, might be suitable for endoscopic surgery.

A novel subclassification of pT2 gastric cancers according to the depth of muscularis propria invasion: superficial muscularis propria versus deep muscularis propria/subserosa.

Purpose:To propose a novel subclassification of pT2 gastric cancers according to the depth of muscularis propria (MP) invasion (superficial MP vs. deep MP/subserosa [SS]) and to investigate its impact in prognostic assessment. Summary Background Data:The major change in the sixth edition of the International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification concerned the pT (primary tumor) category. Specifically, pT2 lesions were divided into pT2a (invading the MP) and pT2b (invading the SS) to discriminate these intramural locations. However, the value of the modification is still debated. Methods:One thousand two hundred fifty-six patients with pT2 cancers classified according to the UICC/AJCC pT staging system were reviewed. Among them, 214 (17.0%) were classified as invasion of the superficial MP (sMP) or inner circular muscle, 163 (13.0%) as invasion of the deep MP (dMP) or outer longitudinal muscle, and 879 (70.0%) as invasion of SS. Clinicopathologic features were compared between patients with sMP, dMP, and SS invasion. Overall survival rates were compared between the pT2a and pT2b stage cancers, according to the UICC/AJCC and the novel pT2 system. Two-step multivariate analysis was performed to identify the significantly important prognostic factors. Results:There was significant difference in most of the clinicopathologic features between sMP and SS cancers. Although, only 5 factors (tumor location, tumor size, Borrmann type, metastasis number, and metastasis ratio) were significantly different between dMP and SS cancers. In step 1 of the multivariate analysis, the UICC/AJCC pT2 system was an independent factor that correlated with prognosis, but was substituted by the novel pT2 system in step 2 of the multivariate analysis. With a certain metastasis ratio of lymph nodes, the novel pT2 system discriminated 2 subsets of patients with significantly different prognoses, whereas the UICC/AJCC pT2 system did not. Conclusions:The novel pT2 staging system, which was subclassified as sMP and dMP/SS cancers, had more potential to identify the different prognoses for patients with pT2 gastric cancers.

Macroscopic Serosal Classification Predicts Peritoneal Recurrence for Patients with Gastric Cancer Underwent Potentially Curative Surgery

BackgroundPrevious studies revealed serosal invasion as one of the most important predictors of peritoneal micrometastasis. However, even for cancers with serosal invasion, the macroscopic serosal appearance is highly heterogeneous. The aim of the present study was to propose a macroscopic serosal classification (MSC) and to investigate the validity of this classification as a predictor of peritoneal recurrence.Materials and MethodsClinicopathologic features including MSC of 1528 patients with pT3/pT4a stage gastric cancers who underwent potentially radical surgery were retrospectively reviewed. MSC was classified as reactive type, nodular type, tendonoid type, and color-diffused type according to the macroscopic serosal appearance.ResultsThere were significant differences in tumor size, location, Bormann type, Lauren grade, lymphatic and/or blood vessels invasion (LBVI), width of serosa changes, depth of invasion, number of nodes metastasis, lymph node metastasis ratio, pN stage, and peritoneal cytology between patients with different types of serosa. Multivariate analysis revealed MSC, as well as depth of invasion, Lauren grade, and pN stage, significantly predicted the presence of peritoneal-free cancer cells. Both MSC and peritoneal cytology significantly correlated with patient survival. However, only MSC significantly predicted peritoneal recurrence on multivariate analysis, but peritoneal cytology did not, indicating MSC was more sensitive than cytologic examination. Further investigation suggested MSC and pN stage were also independent predictors of peritoneal recurrence for patients with negative peritoneal cytology.ConclusionsThe MSC sensitively predicts the presence of peritoneal micrometastasis for pT3/pT4a-stage gastric cancer patients who underwent potentially radical surgery. Consequently, it might be considered a good indicator to guide perioperative adjuvant therapy for patients with high risk of peritoneal recurrence.

Splenic hilar lymph node metastasis independently predicts poor survival for patients with gastric cancers in the upper and/or the middle third of the stomach

Effectiveness of splenectomy for advanced gastric cancers occupying the upper and/or the middle third of the stomach is still in debate. The aim of the present study is to elucidate the impact of splenectomy on patient survival by investigating the pathological characteristics and prognostic significance of splenic hilar lymph node metastasis.

Factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer: a retrospective study of a prospectively-collected database

BackgroundPeritoneal dissemination is the most common type of recurrence in advanced gastric cancer. The main mechanism is thought to be via the exfoliation of free cancer cells (FCCs) from tumor in the gastric serosa. The frequency of recurrence thus increases once the tumor cells penetrate the serosa. However, this type of recurrence also occurs in patients without serosal invasion, though the mechanisms responsible for have not been fully established. We therefore investigated the factors associated with peritoneal dissemination in patients with non-serosa-invasive gastric cancer.MethodsA total of 685 patients with non-serosa-invasive gastric cancer who underwent curative resection with retrieval of more than 15 nodes were selected. The associations between clinicopathological features and peritoneal dissemination were analyzed. Among them, the tumor infiltrating growth pattern (INF) were classified into α, β and γ according to the Japanese Classification of Gastric Carcinoma (JCGC).ResultsThe overall incidence of peritoneal metastasis was 20% (137/685). Age, Borrmann type, differentiation, INF, nodal status and free cancer cells (FCCs) were correlated with peritoneal dissemination using univariate analysis. However, only INF, Borrmann type and TNM node stage were identified as independent correlated factors with peritoneal metastasis by multivariate analysis when FCCs were excluded, and these were also prognostic factors. Peritoneal dissemination was more common in patients with INFγ, Borrmann III/IV and N3 stage. Among patients without FCCs, nodal involvement or vessel invasion, only INF remained an independent associated factor according to multivariate analysis.ConclusionsTumor infiltrating growth pattern (INF), together with Borrmann type and TNM node stage, are important factors associated with peritoneal metastasis in non-serosa-invasive gastric cancer.

A novel insight of sentinel lymph node concept based on 1-3 positive nodes in patients with pT1-2 gastric cancer

BackgroundSentinel node (SN) biopsy has been practiced in gastric cancer in recent years, and many studies focused on the distribution of solitary lymph node metastasis (SLM) to assess the pattern of SN. In fact, there is usually more than one SN existing in gastric cancer. The distribution of SNs needs to be further re-evaluated.MethodsA total of 289 patients in pT1-2 stage with 1-3 positive nodes confined to same compartment were included in this study with informed consents. The primary lesion was solitary (≤ 5.0 cm in diameter) and D2 or D3 lymph node dissection had been performed. The location of metastatic lymph nodes was analyzed retrospectively.ResultsMost positive nodes occurred in N1 compartment, with frequency of 79.6% to 85.7% based on site of tumor. In the lower third of stomach, no. 6 was the most common metastatic site and no. 3 was the second; the order was reversed for SLM. With increasing depth of tumor invasion, a progressively augmented nodal involvement was shown. Nearly a half appeared transverse metastasis when the tumor located at the lesser or greater curvature. Among skip metastasis, no. 7, 8a, 9 and 11p were the most common metastatic sites and the prognosis was as similar as that of patients with N1 involved only.ConclusionsThe 1-3 positive nodes in the same compartment should be possible SNs, and most of which are restricted in N1 in pT1-2 gastric cancer. Transversal and 2 stations lymph node metastasis are common.

Advanced Gastric Cancer with Early Cancer Macroscopic Appearance: Is It Worthy of D2 Lymphadenectomy?

BackgroundPrevious studies report that 5.9–22.2% of patients with preoperatively diagnosed early gastric cancers were eventually proven to have advanced gastric cancers by postoperative pathological examination. Such misdiagnosed cases commonly had cancers with macroscopic appearance like early gastric cancer and consequently can be recognized as a subgroup of cancer, namely advanced gastric cancer with early cancer macroscopic appearance (eAGC). Theoretically eAGCs might require D2 lymphadenectomy, but frequently undergo limited lymphadenectomy. However, the validity of the limited surgery is still unclear.MethodsClinicopathologic features of 134 patients with eAGC were retrospectively reviewed and compared with those of patients with early gastric cancers and advanced gastric cancers, respectively.ResultsClinicopathologic features of eAGCs were similar to those of submucosa cancers, but significantly different from those of mucosa cancers and other muscularis propria cancers. Tumor size, lymphatic and/or blood vessels invasion (LBVI), and depth of invasion were identified as independent factors predicting lymph node metastasis; however, postoperative stage was not. All patients with eAGCs were proven to have lymph node metastasis restricted to the perigastric lymph nodes and lymph nodes at stations 7, 8a, and 9. Age, LBVI, and depth of invasion were independent prognostic factors for patients with preoperatively diagnosed early gastric cancers; however, the misdiagnosis of early cancer and the option of lymphadenectomy (D2 or not D2) had no impact on patient survival. The incidence of recurrence of eAGCs was similar to that of submucosa cancers, but significantly different from that of mucosa cancers and other muscularis propria cancers.ConclusionsModified gastrectomy B (dissection of perigastric lymph nodes and nodes at stations 7, 8a, and 9) might be recommended for patients with eAGCs.

Silence of cancer susceptibility candidate 9 inhibits gastric cancer and reverses chemoresistance

Cancer Susceptibility Candidate 9 (CASC9) is a novel gene generating long non-coding RNA (lncRNA) with oncogenic potential that was first identified in esophageal cancer. In this study, we have found that CASC9 was overexpressed in gastric cancer (GC) compared to normal gastric tissue. A higher expression level was associated with aggressive pathological characteristics, including deep invasion, poor differentiation and lymph node metastases. In two gastric cancer cell lines, BGC823 and SGC7901, CASC9 were both overexpressed compared to that of normal gastric epithelial cell (GES-1). Moreover, the expression of CASC9 was even higher in BGC823/DR and SGC7901/DR cells that are resistant to paclitaxel or adriamycin. CASC9 knockdown inhibited proliferation and promoted cell apoptosis In BGC823/DR and SGC7901/DR cells. The invasion potential was also significantly inhibited measured by Transwell assay. In addition, CASC9 knockdown in BGC823/DR and SGC7901/DR cells restored chemosensitivity to paclitaxel and adriamycin. This was associated with decreased expression of multidrug resistance 1 (MDR1) protein. Taken together, our data suggest that expression of lncRNA CASC9 correlated with aggressive pathological characteristics of GC, it may serve as a potential oncogene to regulate proliferation, invasion, and chemoresistance of GC cells.