Non-curative Factor Research Articles

Long-term outcomes of endoscopic submucosal dissection and surgery for undifferentiated intramucosal gastric cancer regardless of size.

BACKGROUNDThe clinical outcomes of endoscopic submucosal dissection (ESD) for undifferentiated (UD) intramucosal early gastric cancer (EGC) compared with those of surgery, regardless of lesion size, are not well known. Furthermore, there is a concern regarding the treatment plan before and after ESD in cases of UD intramucosal EGC within expanded indications.AIMTo evaluate clinical outcomes of ESD compared with those of surgery in UD intramucosal EGC patients regardless of tumor size. METHODSWe enrolled patients with UD intramucosal EGC after ESD with complete resection or surgery from January 2005 to August 2020 who met the within or beyond expanded indications with lesion size > 2 cm (the only non-curative factor). Overall, 123 and 562 patients underwent ESD and surgery, respectively. After propensity-score matching, clinical and long-term outcomes, i.e., recurrence-free survival (RFS) and overall survival (OS), were analyzed. The multivariable Cox proportional hazard model with treatment modality and ESD indication was used to evaluate the recurrence risk.RESULTSAfter matching, 119 patients each were finally enrolled in the ESD and surgery groups. The median length of hospital stay was shorter in the ESD group than surgery group (4.0 vs 9.0 days, P < 0.001). Four cases of recurrence after ESD were local recurrences, all of which occurred within 1 year. Total recurrence was seven (5.9%) and two (1.7%) in the ESD and surgery groups, respectively. No difference was observed between the two groups with respect to OS (P = 0.948). However, the ESD group had inferior RFS compared with the surgery group (P = 0.031). ESD was associated with the risk of recurrence after initial treatment in all enrolled patients (hazard ratio, 5.2; 95% confidence interval: 1.0-25.8, P = 0.045).CONCLUSIONAlthough OS was similar between the two groups, surveillance endoscopy was important for the ESD than for the surgery group because RFS was inferior and local recurrence was an issue.

Long-term Outcomes of Additional Endoscopic Treatments for Patients with Positive Lateral Margins after Endoscopic Submucosal Dissection for Early Gastric Cancer.

Background/AimsIt is uncertain whether additional endoscopic treatment may be chosen over surgery in patients with positive lateral margins (pLMs) as the only non-curative factor after endoscopic submucosal dissection (ESD) for early gastric cancer (EGC). We aimed to compare the long-term outcomes of additional endoscopic treatments in such patients with those of surgery and elucidate the clinicopathological factors that could influence the treatment selection.MethodsA total of 99 patients with 101 EGC lesions undergoing additional treatment after non-curative ESD with pLMs as the only non-curative factor were analyzed. Among them, 25 (27 lesions) underwent ESD, 29 (29 lesions) underwent argon plasma coagulation (APC), and 45 (45 lesions) underwent surgery. Clinicopathological characteristics and long-term outcomes were compared.ResultsResidual tumor was found in 73.6% of cases. The presence of multiple pLMs was associated with higher risk of residual tumor (p=0.046). During a median follow-up of 58.9 months, recurrent or residual lesions after additional ESD and APC were found in 4% (1/25) and 6.8% (2/29) of patients, respectively. However, all were completely cured with surgery or repeated ESD. There were no extragastric recurrences after additional endoscopic treatment. Lymph node metastasis was identified after additional surgery in one (2.2%) patient with an EGC showing histological heterogeneity.ConclusionsGiven the favorable long-term outcomes, additional ESD or APC may be an acceptable choice for patients with pLMs as the only non-curative factor after ESD for EGC. However, clincopathological characteristics such as multiple pLMs and histological heterogeneity should be considered in the treatment selection.

Long-term Outcomes of Undifferentiated-Type Early Gastric Cancer with Positive Horizontal Margins after Endoscopic Resection

Background/AimsThis study examined the long-term outcomes of undifferentiated-type early gastric cancer (UD EGC) with positive horizontal margins (HMs) after endoscopic resection (ER) and compared them between additional surgery and nonsurgical management.MethodsFrom 2005 to 2015, a total of 1,124 patients with UD EGC underwent ER at 18 tertiary hospitals in Korea. Of them, 92 patients with positive HMs as the only noncurative factor (n=25) or with both positive HMs and tumor size >2 cm (n=67) were included. These patients underwent additional surgery (n=40), underwent additional endoscopic treatment (n=6), or were followed up without further treatment (n=46).ResultsNo lymph node (LN) metastasis was found in patients who underwent additional surgery. During a median follow-up of 57.7 months (interquartile range, 27.6 to 68.8 months), no LN or distant metastases or gastric cancer-related deaths occurred in the overall cohort. At baseline, the residual cancer rate was 57.8% (26/45) after additional surgery or ER. The 5-year local recurrence rate was 33.6% among patients who were followed up without additional treatment. The 5-year overall survival rates were 95.0% and 87.8% after additional surgery and nonsurgical management (endoscopic treatment or close follow-up), respectively (log-rank p=0.224). In the multivariate Cox regression analysis, nonsurgical management was not associated with an increased risk of mortality.ConclusionsUD EGC with positive HMs after ER may have favorable long-term outcomes and a very low risk of LN metastasis. Nonsurgical management may be suggested as an alternative, particularly for patients with old age or chronic illness. (Gut Liver 2021;15-731)

Risk-Scoring System for Prediction of Non-Curative Endoscopic Submucosal Dissection Requiring Additional Gastrectomy in Patients with Early Gastric Cancer

PurposeWhen patients with early gastric cancer (EGC) undergo non-curative endoscopic submucosal dissection requiring gastrectomy (NC-ESD-RG), additional medical resources and expenses are required for surgery. To reduce this burden, predictive model for NC-ESD-RG is required.Materials and MethodsData from 2,997 patients undergoing ESD for 3,127 forceps biopsy-proven differentiated-type EGCs (2,345 and 782 in training and validation sets, respectively) were reviewed. Using the training set, the logistic stepwise regression analysis determined the independent predictors of NC-ESD-RG (NC-ESD other than cases with lateral resection margin involvement or piecemeal resection as the only non-curative factor). Using these predictors, a risk-scoring system for predicting NC-ESD-RG was developed. Performance of the predictive model was examined internally with the validation set.ResultsRate of NC-ESD-RG was 17.3%. Independent pre-ESD predictors for NC-ESD-RG included moderately differentiated or papillary EGC, large tumor size, proximal tumor location, lesion at greater curvature, elevated or depressed morphology, and presence of ulcers. A risk-score was assigned to each predictor of NC-ESD-RG. The area under the receiver operating characteristic curve for predicting NC-ESD-RG was 0.672 in both training and validation sets. A risk-score of 5 points was the optimal cut-off value for predicting NC-ESD-RG, and the overall accuracy was 72.7%. As the total risk score increased, the predicted risk for NC-ESD-RG increased from 3.8% to 72.6%.ConclusionsWe developed and validated a risk-scoring system for predicting NC-ESD-RG based on pre-ESD variables. Our risk-scoring system can facilitate informed consent and decision-making for preoperative treatment selection between ESD and surgery in patients with EGC.

Histological Differentiated/Undifferentiated Mixed Type Should Not Be Considered as a Non-Curative Factor of Endoscopic Resection for Patients With Early Gastric Cancer.

BackgroundHistological differentiated/undifferentiated mixed-type adenocarcinomas are frequently found in patients with early gastric cancer (EGC). Yet it is unclear whether these mixed-type adenocarcinomas can be treated by endoscopic resection (ER) in EGC patients.AimsTo evaluate the lymph node metastasis (LNM) rate and long-term outcomes in mixed-type EGC patients and assess the feasibility of ER in these patients.MethodsClinicopathological features, risk factors of LNM, and overall survival (OS) and progression-free survival (PFS) rates of EGC patients were analyzed according to different histological types.ResultsPatients with mixed-type EGC had higher LNM rates than patients with non-mixed-type EGC (11.4 vs. 6.2%, P = 0.044). In the multivariate analysis, larger tumor diameter, presence of an ulcer, submucosal invasion, histological undifferentiated type, histological mixed type, and lymphovascular invasion resulted as independent risk factors for LNM in EGC patients (all P < 0.05). The LNM rate in mixed-type patients who met the Japanese ER criteria was 3.3%, including fulfilling the absolute criteria 0%. The 5-year OS and PFS rates in mixed-type patients were 94.59 and 91.47%, respectively. There was no statistical significance in the OS (P = 0.870) and PFS (P = 0.705) between mixed-type and non-mixed-type EGC patients fulfilling the Japanese ER criteria.ConclusionHistological differentiated/undifferentiated mixed type in EGC patients meeting the Japanese absolute criteria for ER are associated with low risk of LNM and favorable prognosis, and thus, it should not be considered as a non-curative factor for ER.

Clinical outcomes of endoscopic resection for undifferentiated intramucosal early gastric cancer larger than 2cm.

This study investigated the long-term clinical outcomes of endoscopic resection (ER) for undifferentiated-type (UD) early gastric cancer (EGC), with tumor size > 2cm as the only non-curative factor. From among 1123 patients who underwent ER for UD EGC at 18 tertiary hospitals in Korea between 2005 and 2014, we identified 216 patients with UD intramucosal EGC > 2cm, which was completely resected, with negative resection margins, and absence of ulceration and lymphovascular invasion. The patients were divided into the additional surgery (n = 40) or observation (n = 176) groups, according to post-ER management and were followed up for a median duration of 59months for recurrence and 90months for overall survival. Lymph node (LN) or distant metastasis or cancer-related mortality was not observed in the surgery group. In the observation group, two (1.1%) patients developed LN or distant metastasis with a 5-year cumulative risk of 0.7%, and one (0.6%) patient died of gastric cancer. The 5-and 8-year overall survival rates were 94.1% and 89.9%, respectively, in the observation group and 100.0% and 95.2%, respectively, in the surgery group (log-rank P = 0.159). Cox regression analysis did not reveal an association between the observation group and increased mortality. The risk of LN or distant metastasis was not negligible, but as low as 1% for patients undergoing non-curative ER for UD EGC, with tumor size > 2cm as the only non-curative factor. Close observation may be an alternative to surgery, especially for older patients or those with poor physical status.

Long-term outcomes after endoscopic submucosal dissection for differentiated-type early gastric cancer that fulfilled expanded indication criteria: A prospective cohort study.

Background and AimEndoscopic resection for early gastric cancer (EGC) is widely performed. However, there is still a paucity of strong evidence regarding long‐term outcomes after endoscopic submucosal dissection (ESD) for the expanded indication criteria of the Japanese guidelines (ver. 2010).MethodsEndoscopic submucosal dissection was performed in patients with EGC that met the expanded indication criteria: (i) cT1a, differentiated‐type EGC of 2 to 5 cm, ulcer negative or (ii) cT1a, differentiated‐type EGC of ≤3 cm, ulcer positive. Patients whose pathological examination fulfilled the curative resection criteria were then enrolled in this cohort study: negative vertical margin, negative lymphovascular invasion, and (i) pT1a, differentiated‐type, and ulcer negative; (ii) pT1a, differentiated‐type, ≤3 cm, and ulcer positive; or (iii) pT1b1 (<500‐μm submucosal invasion), differentiated‐type, and ≤3 cm. Patients with only a positive horizontal margin as a noncurative factor were included for follow‐up.ResultsFrom September 2003 to February 2012, a total of 356 patients underwent ESD, and 214 were enrolled in the survival analysis. One hundred twenty patients (56%) had >2 cm in diameter and ulcer‐negative lesions, and 94 (44%) had ≤3 cm and ulcer‐positive lesions. The vital status at 5 years after ESD was confirmed in all (100%) patients. No local or metastatic recurrence was detected; however, 26 metachronous gastric cancers developed, and 1 patient died of metachronous gastric cancer. The 5‐year disease‐specific and overall survival rates were 99.5% (95% confidence interval [CI], 97.2%–100%) and 93.9% (95% CI, 89.8%–96.4%), respectively.ConclusionESD for EGC that fulfills the expanded criteria is feasible and shows favorable long‐term outcomes.

Prognostic Significance of Conversion Surgery Following First- or Second-line Chemotherapy for Unresectable Gastric Cancer.

Advances in chemotherapy for gastric cancer have encouraged surgeons to perform conversion surgery following a response to first-line chemotherapy in patients with initially unresectable gastric cancer. In this study we evaluated the efficacy of conversion surgery following first- or second-line chemotherapy for unresectable gastric cancer. We retrospectively analyzed clinicopathological and survival data of 94 patients with unresectable gastric cancer treated with first- (n=94) or second-line (n=43) chemotherapy. Patients who converted to surgery following first- (n=26) or second-line (n=5) chemotherapy had significantly longer survival times than those treated with chemotherapy alone (n=63) (p<0.01). Survival length did not differ significantly between patients converted to surgery following first- and second-line chemotherapy. Among 31 patients who underwent conversion surgery, one initial non-curative factor (odds ratio(OR)=0.49; 95% confidence interval (95%CI)=0.22-0.95; p=0.03) was the only significant independent predictor of longer survival in multivariate Cox regression analysis. Patients with unresectable gastric cancer initially exhibiting one noncurative factor may obtain survival benefit from conversion surgery after a response to both first- and second-line chemotherapy.

Clinical significance and efficacy of conversion surgery for patients with stage IV gastric cancer

Gastric cancer is the second most common malignancy and the one of the leading causes of cancer-related death in China. In particular, the survival rate of patients with stage IV or unresectable gastric cancer is very poor. Conversion therapy for stage IV gastric cancer has been the main subject with much attention recently. It is defined to achieve an R0 surgical resection after chemotherapy for originally unresectable cancer due to technical and/or oncological reasons. However, the optimal indications for conversion surgery are still controversial, and how to select the most appropriate candidates for conversion therapy remains to be clarified. A new biological category for stage IV gastric cancer proposed by K Yoshida from Gifu University has been tested out in some trials, from which stage IV gastric cancer can be divided into two different classifications based on the absence (category 1: potentially resectable metastasis and category 2: marginally resectable metastasis) or presence (category 3:incurable and unresectable metastasis and category 4: non-curable metastasis) of macroscopic peritoneal dissemination. The optimal indications for conversion therapy mainly include the patients with category 2, and partially for patients with categories 3 and 4. A surgery-oriented classification proposed by Peking University Cancer Hospital tried to classify the stage IV gastric cancer for conversion therapy. It would be classified as resectable and unresectable categories, depending on uhether R0 resection is available by preoperative evaluation. In this classification, unresectable cancer can be further classified as conversed, partly conversed and non-conversed types based on extent of cancer metastasis. The resection of primary and metastatic lesion in unscreened stage IV gastric cancer was not testified to improve survival. REGATTA trial has identified no significant difference in survival rate between the chemotherapy only and palliative gastrectomy with postoperative chemotherapy for stage IV gastric cancer with a single non-curable factor. With development of conversion therapy, a consensus has been reached that the patients with unresectable gastric cancer initially exhibiting one non-curative factor, if having clinical response to chemotherapy, may obtain a survival benefit from subsequent R0 radical gastrectomy. Several novel combined chemotherapy regimens occasionally allow for conversion of an initially unresectable gastric cancer to resectable cancer in clinical practice. Conversion surgery may result in long-term survival in selected patients who respond to chemotherapy. Several previous studies have evaluated the positive prognostic role of surgery after chemotherapy in stage IV gastric cancer patients with one non-curative factor, such as peritoneal metastasis, para-aortic lymph node metastasis or liver metastasis. Gastric cancer is a highly heterogeneous tumor in nature, consisting of varying aggressive biological characteristics. Oncologically stage IV gastric cancer is a systemic disease, and the complete response to any therapy is really very rare, so that conversion therapy is a great clinical challenging problem for gastric cancer patients. Due to the multi-pathway metastasis, perioperative systemic chemotherapy is the most important in conversion therapy for stage IV gastric cancer, and a radical surgical resection is the key to improve prognosis. A good local control does not necessarily lead to prolonged survival in patients with stage IV gastric cancer, in which other sites metastases often emerge even after successful local-regional cancer-oriented treatment. To date, most reports of conversion therapy for gastric cancer were from single-center or retrospective study. If more reliable evidences are to be obtained, more multi-center and prospective RCT studies must be carried out.

Phase II trial of conversion surgery after apatinib in combination with S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (Ahead-BG301 trial).

TPS203 Background: Recent study has showed that selected patients with unresectable gastric cancer could benefit from surgical resection after achieving response following induction chemotherapy. We speculated that apatinib, an inhibitor of VEGFR-2, in combination with chemotherapy could increase response rate and resection rate following systemic therapy. This trial is designed to investigate the efficacy and safety of conversion surgery after apatinib plus S-1/oxaliplatin (SOX) for patients with unresectable gastric cancer (NCT03007446). Methods: This is a prospective, single-arm and open-label Phase II clinical trial. The primary outcome is resection rate after induction chemotherapy for patients with unresectable gastric cancer. The secondary outcomes include objective response rate and overall survival. Main eligibility criteria include patients with at least single non-curative factor confirmed by CT, MRI, PET-CT or staging laparoscopy: unresectable diseases with locally advanced gastric cancer (T4b); hepatic metastasis (H1; less than five lesions, total diameter ≤ 8 cm); peritoneal metastasis (CY1, P1). An estimated enrollment of 20 patients was planned. After receiving two cycles of apatinib (500 mg, oral, qd) plus SOX (S-1: 40mg bid, d1-14 q3W; oxaliplatin: 130 mg/m2, d1 q3W), patients will be subject to multidisciplinary team evaluation for surgery. First patients were enrolled in Dec 2016. Data analysis was planned in Nov 2018. Clinical trial information: NCT03007446.

Long-term outcomes after noncurative endoscopic resection of early gastric cancer: the optimal time for additional endoscopic treatment

We aimed to evaluate long-term outcomes with noncurative endoscopic submucosal dissection (ESD) for early gastric cancer (EGC) and surveillance strategies such as the optimal time for additional endoscopic treatment in patients with noncurative ESD. Of 2527 patients who underwent gastric ESD for EGC, 512 (20.3%) patients with noncurative resection were reviewed. Noncurative resection is defined as positive resected margins on histology, lymphovascular infiltration, or beyond the expanded criteria for ESD. The mean ± standard deviation follow-up duration was 79.0 ± 55.7 months. A total of 264 patients (51.6%) and 50 patients (9.8%) underwent surgery and endoscopic treatment after noncurative resection, respectively, whereas 198 patients (38.7%) were observed. Cancer-specific survival and disease-free survival rates were significantly different among the surgery, other endoscopic treatment, and observation groups (96.7%, 86.8%, and 86.2%, respectively; P=.030; and 92.5%, 73.6%, and 63.0%, respectively; P< .001). When patients who underwent surgery were excluded, the disease-free survival rate of recurrence was not significantly different between the endoscopic treatment and observation groups (73.6% vs 63.0%; P= .548). To exclude the potential for the presence of lymph node metastasis, we further analyzed disease-free survival of local recurrence by comparing the patients with only a positive lateral resection margin. The disease-free survival rate was higher in the endoscopic treatment group than in the observation group (89.2% vs 69.1%; P= .023). Moreover, additional endoscopic treatment within 3 months showed significant associations with lower risk of local recurrence on multivariate analysis (hazard ratio, 0.017; 95% confidence interval, 0.002-0.260; P= .003). In patients with noncurative ESD, additional surgery showed a better long-term outcome; moreover, when a positive lateral resection margin was the only noncurative factor, additional endoscopic treatment within 3 months could be considered to improve disease-free survival.

Conversion surgery for unresectable gastric cancer following complete response of distant metastasis by systemic chemotherapy.

152 Background: In case of gastric cancer (GC), conversion surgery (CS) can be defined as resection of the primary cancer by gastrectomy which had not been originally planned but was indicated after confirming complete response (CR) in the distant metastasis (DM) by chemotherapy. In the present study, we looked at prognostic significance of CS, which is intended to cure originally unresectable GC. Methods: From 2004 to Feb in 2016, 24 GC patients who were treated by chemotherapy and achieved CR in DM underwent CS among 909 patients with gastrectomy in our department. 10 out of 24 patients who had peritoneal metastases (P) as a single non-curative factor underwent intraperitoneal chemotherapy (IP) in addition to systemic chemotherapy. CR was confirmed by CT and/or laparoscopic examination. Results: 15 patients had P, 13 had distant lymph node metastases (LYM), 2 had liver metastases, and 2 had lung metastases. Chemotherapeutic regimens consisted of systemic chemotherapy plus IP of taxane in 10 patients, S-1/CDDP in 7, capecitabine/CDDP/trastsuzumab in 3, and others in 4. Median duration of chemotherapy before surgery was 7.3 months (2.3-17.5). Total gastrectomy was performed in 18 patients and distal gastrectomy in 6, achieving R0 resection in 21 patients and R1 in 3. 10 patients with P who underwent IP relapsed within 12 months postoperatively except for 2 and had significantly shorter overall survival time than those with other DM except for P (median: 20 vs. 42 months, P = 0.004). Among 14 patients who had DM other than P as target lesions, 9 are disease-free with postoperative median follow up time of 35 months (6.8-82), and 5 patients had recurrence (LYM in 4 and P in 1) with postoperative median survival time of 25 months (4.8-45). DM of the patients without recurrence had achieved CR within shorter period (median: 3.6 vs. 6.7 months) and had higher pathological response rate of the primary lesion (89% vs. 40%) compared to patients with recurrence. Conclusions: Outcome of GC patients who underwent CS after achieving CR in DM was promising, especially in those without P. Further issues such as appropriate chemotherapeutic period, and prognostic factors to decide on the indication for CS need to be solved.

Additional surgery for non-curative resection after endoscopic submucosal dissection for gastric cancer: a retrospective analysis of 200 cases.

Endoscopic submucosal dissection is recommended for early gastric cancer with a low risk of lymph node metastasis. When the pathological findings do not meet the curative criteria; then, an additional gastrectomy with lymph node dissection is recommended. However, most cases have neither lymph node metastasis nor a local residual tumor during an additional surgery. This was a single-institutional retrospective cohort study, analyzing 200 patients who underwent an additional gastrectomy after non-curative endoscopic submucosal dissection from January 2005 to October 2015. We reviewed the patients' clinicopathological data and evaluated the predictors for the presence of a residual tumor. Histopathology revealed lymph node metastasis in 15 patients (7.5%) and a local residual tumor in 23 (11.5%). A multivariable analysis revealed macroscopic findings (flat/elevated type) (p=0.011, odds ratio=4.63), lymphatic invasion (p<0.0001, odds ratio=14.2), and vascular invasion (p=0.04, odds ratio=4.00) to be predictors for lymph node metastasis. A positive vertical margin (p=0.0027, odds ratio=3.26) and horizontal margin (p=0.0008, odds ratio=5.74) were predictors for a local residual tumor. All cases with lymph node metastasis had lymphovascular invasion with at least one other non-curative factor. The risk of a residual tumor can, therefore, be estimated based on the histopathology of endoscopic submucosal dissection samples. Lymphovascular invasion appears to be a pivotal predictor of lymph node metastasis.

Prognostic Role of Conversion Surgery for Unresectable Gastric Cancer

The prognosis of unresectable gastric cancer is poor. Chemotherapy occasionally converts an initially unresectable gastric cancer to a resectable cancer. The responses of noncurative factors to initial chemotherapy and the outcomes of additional (conversion) surgery were retrospectively evaluated in 151 patients with unresectable gastric cancer receiving combination chemotherapy with S-1 plus cisplatin or paclitaxel from February 2003 to December 2013. Forty (26 %) of 151 patients underwent conversion surgery. After chemotherapy, R0 resection was accomplished in 32 patients (80 %). The 5-year overall survival (OS) rate among the 40 patients who underwent conversion surgery was 43 % (median survival time, 53 months). The 5-year OS rate in the 111 patients treated with chemotherapy alone was 1 % (median survival time, 14 months). Patients who underwent conversion surgery had significantly longer OS times than patients who underwent chemotherapy alone (P < 0.01). The 5-year OS rate among patients who underwent R0 resection was 49 % (median survival time, 62 months). Patients who underwent R0 resection had significantly longer OS times than those who underwent R1 and R2 resection (P = 0.03). Among patients who underwent conversion surgery, multivariate Cox regression analysis showed that one noncurative factor (odds ratio 0.49; 95 % confidence interval 0.28-0.88; P = 0.02) and R0 resection (odds ratio 0.52; 95 % confidence interval 0.28-0.95; P = 0.03) were significant independent predictors for favorable OS. Patients with unresectable gastric cancer initially exhibiting one noncurative factor may obtain a survival benefit from chemotherapy and subsequent curative surgery.

Risk of recurrent gastric cancer after endoscopic resection with a positive lateral margin

After noncurative endoscopic submucosal dissection (ESD) for differentiated-type early gastric cancer (EGC), close observation is often preferred when a cancer-positive lateral margin is the only noncurative factor. However, sometimes recurrence is found during the observation period. This study aimed to examine risk factors for recurrent cancer based on the long-term clinical outcomes after noncurative ESD in which the only noncurative factor was a cancer-positive lateral margin. Among 3784 EGCs (3316 patients) treated by ESD between 1997 and 2010, 77 noncurative differentiated-type EGCs (75 patients) were retrospectively analyzed after meeting the following inclusion criteria: 1) the only noncurative factor was a cancer-positive lateral margin; 2) close observation was selected after the ESD; and 3) > 1 year follow-up after ESD. Locally recurrent cancer was found in 10 lesions within a median follow-up period of 59.8 months; no metastasis or gastric cancer-related death occurred. The cumulative incidence of local recurrence 5 years after ESD was 11.9 %. All locally recurrent cancers were mucosal differentiated-type adenocarcinomas. Multivariate analysis indicated that a cancer-positive lateral margin length of ≥ 6 mm was significantly associated with local recurrence (hazard ratio 20.8; 95 % confidence interval 5.2 % - 82.9 %; P < 0.001). The cut-off value of 6 mm was determined by the receiver operating characteristic curve; the sensitivity and specificity for 5-year risk of developing local recurrence were 66.7 % and 95.6 %, respectively. A cancer-positive lateral margin length of ≥ 6 mm was an independent risk factor for local recurrence, and this may be a useful criterion for selecting high-risk cases for stricter management.

Favorable long-term outcomes of endoscopic submucosal dissection for locally recurrent early gastric cancer after endoscopic resection

Close observation after noncurative endoscopic resection for early gastric cancer (EGC) is an acceptable option if a positive horizontal margin or piecemeal resection of differentiated-type adenocarcinoma is the only noncurative factor. When locally recurrent EGC is subsequently detected, endoscopic submucosal dissection (ESD) may be performed, although only limited research has been reported regarding the outcomes. We aimed to evaluate the effectiveness, safety, and long-term clinical outcomes of ESD performed for locally recurrent EGC. Endoscopic resection was performed in 3704 patients with a total of 4216 EGC lesions between January 1997 and December 2011 at our institution. During this period, 95 patients with 95 locally recurrent EGCs following their endoscopic resection underwent ESD performed by experts, which we retrospectively reviewed. The prior endoscopic resection procedures were endoscopic mucosal resection in 75 cases and ESD in 20. Of the 95 cases, en bloc resection was achieved in 90.5 %, R0 resection in 84.2 %, and curative resection in 81.1 %. Median procedure time was 70 minutes; no bleeding requiring blood transfusion was seen. There were six perforations (6.3 %), with one necessitating emergency surgery. Within a median follow-up period of 76.4 months (range, 10.5 - 170.0 months), second local recurrences occurred in three patients. Five-year overall and disease-specific survival rates were 92.8 % and 100 %, respectively. ESD was safe and effective with favorable long-term clinical outcomes for locally recurrent EGC following endoscopic resection.

58 Management of Differentiated-Type Early Gastric Cancer After Non-Curative Endoscopic Submucosal Dissection With a Positive Lateral Margin or Piecemeal Resection: a Retrospective Analysis

After non-curative endoscopic submucosal dissection (ESD) for differentiated-type early gastric cancer (EGC), if a positive lateral margin (LM) or piecemeal resection is the only non-curative factor, non-surgical management (close observation or immediate additional endoscopic treatment) can be performed instead of gastrectomy due to the negligible risk of metastasis. However, the most appropriate management is unknown because of limited research.

Impact of Intraperitoneal Chemotherapy after Gastrectomy with Positive Cytological Findings in Peritoneal Washings

Background: There is no standard treatment available for gastric cancer patients whose sole ‘non-curative factor’ is positivecytological findings in peritoneal washings (CFPW). The aim of this study was to examine the safety, pharmacokinetics and efficacy for free intraperitoneal cancer cells of intraperitoneal chemotherapy with paclitaxel after gastrectomy with en bloc D2 lymph node dissection in cases of gastric cancer with positive CFPW. Methods: Ten patients with gastric cancer who underwent gastrectomy and systemic lymphadenectomy with D2 dissection, without any other non-curative factors besides positive CFPW, were treated with early postoperative intraperitoneal paclitaxel. Intra-chemotherapeutic toxicity and operative complications were measured using NCI-CTC version 3.0. Intraperitoneal and plasma paclitaxel concentrations were measured using a high-performance liquid chromatographic assay. Results: Grade 3/4 toxic effects included anemia (20%) and neutropenia (10%) that required no treatment. Operative complications were, for example, superficial surgical site infections (10%) that were treated with antibiotics. No viable cancer cells were observed in the intra-abdominal fluid 24 h after intraperitoneal administration of paclitaxel. The intraperitoneal/plasma area under the drug concentration-time curve ratio was 2,003.3:1. Conclusion: Intraperitoneal chemotherapy with paclitaxel is a safe and effective treatment modality for free intraperitoneal cancer cells.

Significance of volume-reduction surgery for far-advanced gastric cancer during treatment with novel anticancer agents

We retrospectively assessed the survival benefit of novel anticancer agents (NACA) after volume-reduction surgery for far-advanced gastric cancer (FAGC). From 1995 to 2005, 41 patients with FAGC underwent chemotherapy after volume-reduction surgery. Those treated since 2000 who received NACA were referred to as group A, and those treated before 2000, who received anticancer agents other than NACA, were referred to as group B. In addition, 21 patients with unresectable gastric cancer treated since 2000 who received NACA were referred to as group C. We investigated the significance of volume-reduction surgery during treatment with NACA. The median survival time (MST) was significantly prolonged in group A (626 days) compared to group B (364 days; P = 0.0156). Multivariate analysis showed that having one noncurative factor (NCF), and the use of NACA, were factors that contributed to survival time. Comparison between the subgroup of group A that had one NCF and the subgroup that had two or more NCFs revealed MSTs of 700 days and 180 days, respectively, with a significantly longer MST among the patients with one NCF (P = 0.0021). In addition, no difference from the MST of 333 days in group C was seen among the group A patients with two or more NCFs. The postoperative survival time of patients with one NCF was prolonged by the advent of NACA, but no significant prolongation was observed in the patients with two or more NCFs.

Neoadjuvant chemotherapy followed by salvage surgery: effect on survival of patients with primary noncurative gastric cancer.

The prognosis for gastric cancer patients who undergo noncurative resection is extremely poor. This study evaluated the effects of neoadjuvant chemotherapy for primary noncurative gastric cancer. Thirty-four patients with biopsy-proven noncurative gastric cancer were treated with either of two neoadjuvant chemotherapies: FEMTXP (5-fluorouracil, epirubicin, methotrexate, cisplatin) or THP-FLPM (pirarubicin, 5-fluorouracil, leucovorin, cisplatin, mitomycin C). Noncurability was determined by conventional staging procedures, staging laparoscopy, and exploratory laparotomy. After chemotherapy the resectability of the tumors was reassessed. Patients who were judged to be candidates for curative resection underwent salvage surgery. Of the final 33 patients, 8 (24.2%) showed a major response [0 complete response (CR), 8 partial response (PR)]. In three patients the second laparoscopy revealed disappearance of the peritoneal metastasis. Of the 33 patients, 14 (42.4%) underwent salvage surgery, including 8 curative resections (2 curability A, 6 curability B). Pathologic examinations revealed a grade 2 response in eight patients but no grade 3 response. Univariate analysis showed the following to be significant prognostic factors: histology type (differentiated type vs. undifferentiated type; p = 0.035), T4 as a noncurative factor (T4 vs. T3 or less; p = 0.025), clinical response (PR + no change vs. progressive disease; p = 0.002), and salvage surgery (resected vs. unresected; p = 0.001). Among these factors, salvage surgery was found to be the only independent prognostic factor by multivariate analysis, with a relative risk of 0.253 and a 95% confidence interval of 0.066 to 0.974. The treatment was well tolerated. Major toxicities of WHO grade 3 or more were leukopenia in 20 (60.6%), gastrointestinal toxicities in 5 (15.2%), renal toxicities in 2 (6.1%), and alopecia in 1 (3.0%). In conclusion, neoadjuvant chemotherapy is effective for primary noncurative gastric cancer when salvage surgery can be performed. A chemotherapy regimen with a higher complete response rate would improve the prognosis of this dismal disease even more.