Curative Resection For Gastric Cancer Research Articles

Impact of perioperative hemoglobin levels on postoperative outcomes in gastric cancer surgery

The aim of this study was to evaluate the association of postoperative blood transfusion and anemia with postoperative outcomes in gastric cancer surgery. We enrolled 588 patients who had undergone curative resection for gastric cancer. Input variables for risk assessment consisted of 3 categories: patient demographics, surgical and pathological factors, and anemia-related factors. Postoperative outcomes included 30-day morbidity and mortality. Univariate and multivariate analyses were performed to identify risk factors influencing postoperative complications. The rate of total complications was 19.0%. Comorbidity, lowest hemoglobin (Hb) level from the operative day up to postoperative day 7 (LOW-Hb), the percentage of drop in Hb level on postoperative day 2 (POD2-Hb change), and postoperative transfusion were independent risk factors in the multivariate analysis, with LOW-Hb and postoperative transfusion found to be the most significant factors. When LOW-Hb was ≥9.0 g/dL, postoperative complications were higher in the transfused group than in the non-transfused group (60.0 vs. 14.2%, respectively, p = 0.024), but when LOW-Hb was <9.0 g/dL, postoperative complications were not different between the 2 groups (44.6 vs. 37.5%, p = 0.525). The lowest postoperative Hb level and postoperative transfusion were the most significant risk factors for postoperative complications in gastric cancer surgery.

Bone recurrence after curative resection of gastric cancer

Standard follow up for bone recurrence has not yet been established for gastric cancer after surgical resection. The aim of this study was to investigate the incidence of and related risk factors for bone recurrence after surgical resection of gastric cancer. A cohort of 3035 gastric cancer patients after curative resection was reviewed. We analyzed the patients who had bone scintigraphy before the surgery as well as during the follow-up period. The incidence of and the risk factors for bone recurrence after surgical resection of gastric cancer were investigated. In a total of 1683 patients analyzed, bone recurrence was detected in 30 patients (1.8%). The incidence of bone recurrence was significantly higher in advanced gastric cancers than in early lesions (3.5 vs. 0.4%, p < 0.01). The most common recurrence site was the spine, followed by pelvic bone and rib. Most patients had multiple bone metastases. The median time for recurrence was 28 months (range 4-111) from the surgery. In univariate analysis, the recurrence rate was higher in the tumors with large size, undifferentiated pathology, location in the body, and advanced stage. In multivariate analysis, lymph node metastasis (N2/N3 vs. N0/N0I) was the most predictable risk factor for bone recurrence [hazard ratio [HR] 1.44 (95% confidence interval [CI] 1.217-1.694)] and depth of invasion (T2-4 vs. T1) was also independently associated with bone recurrence. The incidence of bone recurrence was low after curative surgery in patients with gastric cancer. Intensive follow up with bone scintigraphy seems to be unnecessary in these patients.

Updated Analysis of SWOG-Directed Intergroup Study 0116: A Phase III Trial of Adjuvant Radiochemotherapy Versus Observation After Curative Gastric Cancer Resection

Surgical resection of gastric cancer has produced suboptimal survival despite multiple randomized trials that used postoperative chemotherapy or more aggressive surgical procedures. We performed a randomized phase III trial of postoperative radiochemotherapy in those at moderate risk of locoregional failure (LRF) following surgery. We originally reported results with 4-year median follow-up. This update, with a more than 10-year median follow-up, presents data on failure patterns and second malignancies and explores selected subset analyses. In all, 559 patients with primaries ≥ T3 and/or node-positive gastric cancer were randomly assigned to observation versus radiochemotherapy after R0 resection. Fluorouracil and leucovorin were administered before, during, and after radiotherapy. Radiotherapy was given to all LRF sites to a dose of 45 Gy. Overall survival (OS) and relapse-free survival (RFS) data demonstrate continued strong benefit from postoperative radiochemotherapy. The hazard ratio (HR) for OS is 1.32 (95% CI, 1.10 to 1.60; P = .0046). The HR for RFS is 1.51 (95% CI, 1.25 to 1.83; P < .001). Adjuvant radiochemotherapy produced substantial reduction in both overall relapse and locoregional relapse. Second malignancies were observed in 21 patients with radiotherapy versus eight with observation (P = .21). Subset analyses show robust treatment benefit in most subsets, with the exception of patients with diffuse histology who exhibited minimal nonsignificant treatment effect. Intergroup 0116 (INT-0116) demonstrates strong persistent benefit from adjuvant radiochemotherapy. Toxicities, including second malignancies, appear acceptable, given the magnitude of RFS and OS improvement. LRF reduction may account for the majority of overall relapse reduction. Adjuvant radiochemotherapy remains a rational standard therapy for curatively resected gastric cancer with primaries T3 or greater and/or positive nodes.

Long-term outcome of surgical treatment for ampullary carcinoma.

We aimed to clarify the surgical indication and describe the long-term surgical outcome for ampullary carcinoma. The long-term outcomes of 23 patients who underwent pancreaticoduodenectomy were retrospectively reviewed. The prognostic factors for cancer-specific survival and overall survival after surgery were investigated. The cancer-specific 5-, 10- and 20-year survival rates after resection of the ampullary carcinoma were 52%, 43% and 43%, respectively, while the corresponding overall survival rates were 52%, 32% and 24%, respectively. Ten of the 11 patients with recurrent ampullary carcinoma died within 5 years after surgery. Four patients died because of pancreatic cancer, colon cancer, old age after curative resection of gastric cancer, and pneumonia at later than 5 years after the surgery. The risk factors for the short cancer-specific survival period were pancreatic invasion and lymph node metastasis, while those for the short overall survival period were pancreatic invasion and the tumor grade. Our study indicates that recurrence of ampullary carcinoma within 5 years after its resection, especially in patients with pancreatic invasion or lymph node metastasis and development of other diseases after more than 5 years after the surgery should be carefully investigated.

P-0064 ERCC1 Overexpression Predicts Poor Prognosis in Patients with Gastric/GE Junction Adenocarcinoma Treated with Adjuvant Cisplatin-Based Chemotherapy

IntroductionAdjuvant chemotherapy is gaining an increasing role after curative resection for gastric cancer. Novel molecular markers could guide treatment decision-making, in order to better select candidates for adjuvant chemotherapy. The objective of our study was to analyze the status of excision repair cross-complementing gene 1 (ERCC1), thymidylate synthetase (TS) e p53, and correlate with outcome of patients who underwent adjuvant chemotherapy after curative resection for locally advanced gastric/GE junction adenocarcinoma. MethodsWe retrospectively evaluated patients with locally advanced gastric/GE junction adenocarcinoma (stage≥IB according to UICC classification), who underwent curative gastrectomy with D2 dissection, followed by adjuvant chemotherapy consisting of 4 to 6 courses of the ECF regimen (epirubicin 50 mg/m2 day 1, cisplatin 60 mg/m2 day 1, 5FU 200 mg/m2 protracted continuous infusion). Molecular analyses were performed on formalin-fixed paraffin-embedded tissues collected from surgical specimens. p53 mutations were analyzed by sequencing exons 4-10. Protein expression of ERCC1 and TS was assessed by immunohistochemistry (IHC), using specific monoclonal antibodies from Neomarkers. Real-time PCR (TaqMan assay) was performed to quantify mRNA ERCC1 expression. Statistical analyses were carried out using both Fisher'exact and Log Rank tests. ResultsSixty-eight patients were eligible for the study. There were 32 women (47%) and 36 men (53%). The median age was 69 (range: 30-74); UICC stage was III in 44 patients (65%). The median number of delivered chemotherapy cycles was 5.1 (range 4-6). With a median f-up was 40.5 months, disease-free and overall survival were 18.0 (95%CI: 13.4-22.76) and 56 months (95%CI: 44.87-67.13), respectively. We identified mutations in p53 in 21 out of 66 (32%) cases. ERCC1 expression was negative (score 0) in 14 out of 67 (21%) cases, whereas a positive score (score 1-3+) was observed in 53 (79%) cases. TS expression was negative (score 0) in 17 out of 67 (25%) cases, while a positive (score 1-3+) was found in 50 (75%) cases. High ERCC1 mRNA level was found in 19 out of 33 (57%) evaluable cases. Median overall survival was significantly longer in patients with ERCC1 negative tumors (p=0.04) by IHC, whilst TS, p53 and ERCC1 mRNA were not significantly associated with survival. ConclusionIn gastric/GE junction cancer patients after curative resection, ERCC1 by IHC might predict who is more likely to benefit from adjuvant platinum-based chemotherapy, according to the better overall survival observed in ERCC1 negative patients. In those exhibiting ERCC1 positive tumors, alternative chemotherapy regimens should be considered.

Adjuvant Therapy for Gastric Cancer: Revisiting the Past to Clarify the Future

The initial publication in 2001 of the Intergroup trial 0116 (INT0116) was a watershed moment in the treatment of gastric and gastroesophageal junction adenocarcinoma, offering the first high-level evidence for improved survival from any adjuvant therapy in gastric cancer. Since that time, however, the evolution of adjuvant therapy for gastric cancer has been far from linear. No adjuvant regimen has definitively supplanted fluorouracil-based chemoradiotherapy, although alternative approaches have proliferated without direct comparison to the approach established by INT-0116. Five years after the initial publication of INT-0116, the British MAGIC (MRC Adjuvant Gastric Infusional Chemotherapy Trial) trial demonstrated the superiority of epirubicin, cisplatin, and fluorouracil (ECF) administered before and after surgical resection when compared with surgery alone. Despite the omission of radiotherapy, perioperative ECF conferred a statistically and clinically significant reduction in death and cancer recurrence, establishing perioperative chemotherapy, without radiation therapy, as an alternative, reasonable standard in the adjuvant treatment of gastric cancer. More recently, clinical trials from Asia demonstrate the efficacy of adjuvant chemotherapy alone after curative resection for gastric cancer. Among 1,059 patients with resected gastric cancer, the Japanese ACTS-GC (Adjuvant Chemotherapy Trial of TS-1 for Gastric Cancer) study demonstrated a 33% improvement in overall survival (OS) for patients receiving 1 year of postoperative adjuvant S-1, an oral fluoropyrimidine not commercially available in the United States, when compared with surgery alone. Among 1,035 resected gastric cancer patients in South Korea, Japan, and Taiwan, the CLASSIC (Adjuvant Capecitabine and Oxaliplatin for Gastric Cancer After D2 Gastrectomy) study reported a 44% improvement in diseasefree survival (DFS) for patients randomly assigned to postoperative capecitabine and oxaliplatin (XELOX) when compared with observation. Of note, both ACTS-GC and CLASSIC limited enrollment to patients who had undergone a D2 lymph node dissection, commonplace in Asia, which contrasts to the limited D0 or D1 dissections more widespread in the United States. As such, the generalizability of both the ACTS-GC and CLASSIC trials to patients undergoing a D0 or D1 dissection is less certain. Moreover, the striking epidemiologic and prognostic differences in gastric cancer between Asian and Western populations further confound the application of these well-conducted Asian trials to Western patient populations. With a growing body of evidence supporting adjuvant approaches in resectable gastric cancer, it becomes critical to establish the relative contribution of individual components of adjuvant therapy. Two recently completed trials have directly compared distinct postoperative adjuvant regimens. Among 458 South Korean patients who had undergone a curative gastrectomy with D2 dissection, the ARTIST (Adjuvant Chemoradiation Therapy in Stomach Cancer) trial compared postoperative capecitabine and cisplatin (XP) to chemoradiotherapy (XP plus radiotherapy with capecitabine). Although the addition of radiotherapy to postoperative chemotherapy did not significantly improve DFS among all enrolled subjects (P .09), patients with node-positive disease (87% of the study population) did experience a superior DFS (P .04). On the other end of the spectrum, the North American Cancer and Leukemia Group B 80101 trial examined whether the benefit of postoperative chemoradiotherapy with fluorouracil and leucovorin (as shown in INT-0116) could be improved by utilizing a more intensive systemic therapy (ECF) with chemoradiotherapy. Interim results, however, find no survival benefit when comparing postoperative ECF chemotherapy before and after chemoradiotherapy to fluorouracil and leucovorin before and after chemoradiotherapy. Into this maelstrom of clinical reports, the INT-0116 investigators offer another critical contribution, featured in this issue of Journal of Clinical Oncology. The investigators report an updated analysis of their findings, now with 10-year median follow-up. Eleven years after the initial publication, is there more that we can learn from INT-0116 today? And, with half a dozen key trials reported since that initial publication, can we improve our understanding of adjuvant therapy in gastric cancer by going back to square one? The report by Smalley et al updates OS and recurrence-free survival (RFS) for the INT-0116 trial. It is reassuring to find that these survival outcomes are largely unchanged, with significant benefits in both OS and RFS. This finding perhaps comes as no surprise, given that the median survival time in both arms had been well surpassed at the time of the original report. Nevertheless, this latest update highlights the durable benefit of postoperative fluorouracil-based chemoradiotherapy in patients with resected gastric and gastroesophageal junction adenocarcinoma. Longer follow-up to confirm the results of a previously reported landmark clinical trial has certain merit in medical science. Beyond supplying confirmatory updated results of the primary treatment hypothesis, completed clinical trials can represent exceptional, well-designed prospective cohorts with detailed clinical data and biospecimens to explore critical questions that arise in the JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L VOLUME 30 NUMBER 19 JULY 1 2012

Only Surgical Resection Can Identify the Second Primary Lung Cancer out of the Metastasis after Gastric Cancer Surgery

Solitary pulmonary lesions (SPLs) in patients with a history of malignancy require not only the distinction between benign and malignant, but also that between metastatic and primary lesions. We aim to establish the clinical strategy for the treatment of a solitary pulmonary lesion that is detected during the postoperative surveillance for gastric cancer. We retrospectively examined the clinical records of the patients who underwent curative resection for gastric cancer between January 1999 and December 2009. Patients who were diagnosed with solitary pulmonary lesion during the postoperative surveillance underwent pulmonary resection, and were reviewed with regard to their histological diagnosis and prognosis. Out of a total of 1017 patients who underwent gastric resections during this period, 13 patients with solitary pulmonary lesion underwent pulmonary resection. These tumors were shown to be eight primary lung cancers, four metastatic tumors (three from gastric cancer) and one benign nodule. Of the eight patients with primary lung cancer, seven remained alive after pulmonary resection, including one liver metastasis case, and the other died without recurrence. In contrast, the other three patients with metastasis from gastric cancer died with distant metastasis, despite undergoing curative pulmonary resection. One of these three metastatic patients was misdiagnosed as primary lung cancer by transbronchial biopsy before surgery. Solitary pulmonary lesions detected during postoperative gastric cancer surveillance should undergo surgical resection to distinguish between primary and metastatic disease because of the quite different prognosis of these two entities.

Comparison of the prognostic value of tumour and patient related factors in patients undergoing potentially curative resection of gastric cancer

BackgroundThere is increasing evidence that the patient-related systemic inflammatory response is a powerful prognostic factor. The aim of the present study was to compare the prognostic value of selected markers of the systemic inflammatory response in patients undergoing resection of gastric cancer. MethodsOne hundred twenty patients undergoing resection of gastric cancer, had measurements of various systemic inflammatory markers in addition to tumor-related factors. From these, the modified Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and metastatic lymph node ratio were calculated. ResultsOn multivariate analysis, only the ratio of positive to total lymph nodes (hazard ratio, 2.29%; 95% confidence interval, 1.57%–3.33%; P < .001) and the mGPS (hazard ratio, 2.23%; 95% confidence interval, 1.40%–3.54%; P = .001) were independently associated with cancer-specific survival in patients with gastric cancer. An increase in the mGPS was associated with a higher neutrophil/lymphocyte ratio (P < .05) and poorer survival (P < .001). ConclusionsThe present study indicates that the mGPS, an acute-phase, protein-based prognostic score, is a superior predictor of cancer survival compared with the cellular components of the systemic inflammatory response in patients undergoing resection of gastric cancer.

Clinical implication of an insufficient number of examined lymph nodes after curative resection for gastric cancer

The seventh edition of the tumor, lymph node (LN), metastasis (TNM) staging system increased the required number of examined LNs in gastric cancer from 15 to 16. However, the same staging system defines lymph node-negative gastric cancer regardless of the number of examined LNs. In this study, the authors evaluated whether gastric cancer can be staged properly with fewer than 15 examined LNs. The survival rates of 10,010 patients who underwent curative gastrectomy from 1987 to 2007 were analyzed. The patients were divided into 2 groups according to the number of examined LNs, termed the "insufficient" group (≤15 examined LNs) and the "sufficient" group (≥16 examined LNs). The survival curves of patients from both groups were compared according to the seventh edition of the TNM classification. Three hundred sixteen patients (3.2%) had ≤15 examined LNs for staging after they underwent standard, curative lymphadenectomy. Patients who had T1 tumor classification, N0 lymph node status, and stage I disease with an insufficient number of examined LNs after curative gastrectomy had a significantly worse prognosis than patients who had ≥16 examined LNs. Moreover, having an insufficient number of examined LNs was an independent prognostic factor for patients who had T1, N0, and stage I disease. Lymph node-negative cancers in which ≤15 LNs were examined, classified as N0 in the new TNM staging system, could not adequately predict patient survival after curative gastrectomy, especially in patients with early stage gastric cancer.

Tobacco Use Is Associated with Increased Recurrence and Death from Gastric Cancer

Tobacco use increases the risk of developing gastric cancer. We examined the hypothesis that gastric cancer developing in patients with a history of tobacco use may be associated with increased risk of cancer-specific death after curative surgical resection. From the Memorial Sloan-Kettering Cancer Center Gastric Cancer prospective surgical database, we collected baseline demographic data and tumor characteristics from all patients who had undergone curative resection for gastric cancer between 1995 and 2009 and who had not received pre- or postoperative chemo- or radiotherapy. A smoking history was defined as >100 cigarettes' lifetime use. The primary end point was gastric cancer disease-specific survival (DSS); secondary end points were 5-year disease-free survival (DFS) and overall survival (OS). Gastric cancer-specific hazard was modeled by Cox regression. A total of 699 eligible patients were identified with a median age of 70 years (range 25-96 years); 410 (59%) were current or previous smokers. Smoking was associated with gastroesophageal junction/cardia tumors and white non-Hispanic ethnicity. Multivariate analysis included the following variables: tumor stage, age, performance status, diabetes mellitus, gender, and tumor location. In this analysis, the hazard ratio for gastric cancer DSS in smokers was 1.43 (95% confidence interval 1.08-1.91, P=0.01). Smoking was also an independent significant risk factor for worse 5-year DFS (hazard ratio 1.46, P=0.007) and OS (hazard ratio 1.48, P=0.003). Among 516 patients for whom tobacco pack-year usage was available, both heavy (≥20 pack-years) and light (<20 pack-years) tobacco use was significantly associated with DSS, DFS, and OS. Smoking history appears to be an independent risk factor for death from gastric cancer in patients who have undergone curative surgical resection.

Adjuvant Chemoradiation for Gastric Cancer: Multicentric Study of the Anatolian Society of Medical Oncology

The aims of this study were to report the clinical outcomes of adjuvant chemo-radiotherapy after curative resection in 637 patients with gastric cancer. The retrospective analysis included 637 patients with resectable gastric cancer and stage IB-IV (M0) from 8 medical centers between 2003 and 2010. The patients were treated with 5FU-leucovorin and radiotherapy according to Schema for INT-0116. Of the 637 patients, the median of overall survival (OS) was 43.7 months and relapse free survival (RFS) was 36.6 months. OS rates were 84%, 45%, 40% while RFS rates were 81%, 45% and 35% at 1, 3 and 5-years, respectively. Hematological and gastrointestinal toxicities (grade 1-4) were observed in 35% and 36.5% of patients, respectively. In univariate analysis, according to the Lauren classification, tumor grade, T stage, N stage, type of operation (total gastrectomy or subtotal) and surgery resection margin (R0 or R1) were found as prognostic factors on RFS and OS (p<0.05). In multivariate analysis, T stage, N stage and surgical margins were found as effective factors on OS. T stage, N stage and Lauren classification were factors affecting RFS. Adjuvant chemo-radiotherapy after curative resection of gastric cancer was feasible, with acceptable toxicities in the Turkish population.

Changing pattern of postoperative body weight and its association with recurrence and survival after curative resection for gastric cancer.

The aim of this study was to assess the pattern of body weight change after gastrectomy for gastric cancer and its association with prognosis. From February 2001 to June 2005, 1554 patients who underwent gastrectomy for gastric cancer were included. The pattern of body weight change according to the preoperative body mass index was analyzed and compared with recurrence, survival. Body weight in 1057 (68.0%) patients stabilized before 6 months. As preoperative BMI is low, weight was stabilized on early time after surgery (p<0.001). There were 228 (14.7%) recurrences of 1554 patients. One hundred and fifty three (9.8%) patients experienced recurrence within 2 years after gastric cancer surgery whereas 75 (4.8%) patients experienced recurrence 2 years after operation. Weight loss was associated with poor prognosis and weight loss more than 30% at postoperative 6 months was significantly associated with early recurrence (p=0.020, OR=6.524). Body weight measure after gastric cancer surgery would be a simple but important method during follow-up period. Physician should pay attention to patients if they experience severe weight loss at 6 months after gastrectomy for gastric cancer due to the possibility of early recurrence.

Hyperthermic intraperitoneal chemotherapy following gastrectomy for the prevention of carcinomatosis in advanced gastric cancer: Nonrandomized phase II prospective trial.

116 Background: About half of patients with serosa-invasive gastric cancer develop peritoneal recurrence and die of this disease even if curative resections performed. This prospective phase II study was performed to assess the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) with three anticancer drugs in patients with curative resection of clinically T3 or T4 serosa-invasive advanced gastric cancer. Methods: Patients age 75 years or younger with curative resection of clinically T3 or T4 advanced gastric cancer were eligible for this nonrandomized phase II trial. After the curative resection of gastric cancer with D2 lymph node dissection, HIPEC was carried out for 30 minutes with 50mg of CDDP, 10mg of MMC, and 1000mg of 5-FU in 5 L saline maintained at 42-43C°. Patients were given an adjuvant S-1 treatment after surgery. Primary endpoint of this study was overall survival. Second end points included safety and recurrence rate. Results: A total of 50 patients were eligible between January 2002 and December 2010. Pathologically, 12 patients had sub-serosal invasion (pT2(ss)), 35 patients had serosal invasion (pT3), and 3 patients had adjacent organ invasion (pT4). Median follow-up period was 52 months (12-104 months). Overall 5-year survival rate in all eligible patients was 89.9%. Overall 5-year survival rate in patients with stage IB (n=4), stage II (n=12), stage IIIA (n=18), or stage IIIB (n=16) was 100%, 100%, 90.9%, or 76.2%, respectively. Only one patient (2.0%) had peritoneal recurrences. Four patients (8.0%) with pN2 had lymphatic recurrences. A total of 13 patients had postoperative complications such as minor pancreatic fistula (Grade A) (10.0%), abdominal abscess (4.0%), leakage of the anastomosis (8.0%), and pneumonia (6.0%). All patients recovered without any surgical interventions. None of patients needed for the treatment in the Intensive Care Units after HIPEC. Conclusions: Intra-operative HIPEC with three anticancer drugs following curative resection of advanced gastric cancer improves overall survival with an inhibition of peritoneal recurrence and an acceptable morbidity.

Infectious complication and recurrence after surgery for gastric cancer.

85 Background: There are many known prognostic indicators following surgery for gastric cancer. However, the impact of infectious complication on prognosis is less clear. The aim of the present study was to evaluate the relationship between infectious complication and relapse-free survival in patients undergoing potentially curative resection of gastric cancer. Methods: A consecutive series of 657 patients who underwent macroscopically curative resection between 2000 and 2005 in Kanagawa Cancer Center were retrospectively studied. Five-year relapse-free survival rates in each stages (TNM7th) were calculated. Infectious complications (≥Grage2 by Clavien-Dindo classification) were classified as pneumonia, anastomotic leakage, intra-abdominal abscess, septicaemia, colitis, pancreatic-fistula, and wound infection. Results: Mean age was 61 years; male-female ration was 4:1; the number of patients in TNM7th stages were I :389, II :93, III :116, and IV :59. Infectious complications occurred in 57 patients (8.7%) including 8.5% in stage I, 3.2% in stage II, 12.1% in stage III, and 11.9% in stage IV, respectively. Five-year relapse-free survival rates in patients without infectious complications and with infectious complications were 93.1% vs 81.6% in stage I, 84.4% and 100% in stage II, 55.8% and 28.6% in stage III, and 9% and 0% in stage IV, respectively. In stage III, patients with infectious complication had significantly poorer outcome in relapse-free survival compared with those without one (p&lt;0.05). Conclusions: This study indicates a correlation between infectious complications and cancer recurrence in advanced but localized gastric cancer. Immunologic response of the host against postoperative infection could influence the viability of microscopic residual disease. Further clinical and basic study are needed to improve outcome for this category of patients.

Cumulative Radiation Exposure during Follow-Up after Curative Surgery for Gastric Cancer

ObjectiveTo quantify the cumulative effective dose (cED) of radiation due to repeated CT and PET/CT examinations after curative resection of gastric cancer and to assess the lifetime attributable risk (LAR) estimates based on Biological Effects of Ionizing Radiation VII models.Subjects and MethodsPatients who underwent a curative resection for gastric cancer between January 2006 and December 2006 and were followed-up until May 2010 were included in this study. The cED was calculated by using the dose-length product values and conversion factors for quantitative risk assessment of radiation exposure. cED and LAR were compared between early and advanced gastric cancer patients and among American Joint Committee on Cancer TNM stage groups (stage I, II, and III). The nonparametric Mann-Whitney U and Kruskal-Wallis tests, followed by a post-hoc analysis with Bonferroni adjustment, were employed as part of the statistical analysis.ResultsThe overall median cED was 57.8 mSv (interquartile range [IQR], 43.9-74.7). The cED was significantly higher in the advanced (median, 67.0; IQR, 49.1-102.3) than in the early gastric cancer group (median, 52.3; IQR, 41.5-67.9) (p < 0.001), and increased as the TNM stage increased. For radiation exposure, 62% of all patients received an estimated cED of over 50 mSv, while 11% of patients received over 100 mSv. The median LAR of cancer incidence was 0.28% (IQR, 0.20-0.40) and there were significant differences between the early gastric cancer and advanced gastric cancer group (p < 0.001) as well as among the three TNM stage groups (p = 0.015). The LAR of cancer incidence exceeded 1% in 2.4% of the patients.ConclusionThe cED increases proportionally along with tumor stage and, even in early gastric cancer or stage I patients, cED is much higher than that found among the general population. Considering the very good prognosis of early gastric cancer after curative surgery, the cED should be considered when designing a postoperative follow-up CT protocol.

Correct Evaluation of the 7th Edition of the TNM Classification for Gastric Cancer?

TO THE EDITOR: We read with great interest the article by Warneke et al, which reported that the seventh edition of the International Union Against Cancer (UICC)/American Joint Committee on Cancer (AJCC) TNM classification for gastric cancer has not improved the assessment of patient prognosis compared with the fifth and sixth editions of the UICC/AJCC TNM classification. In contrast, other investigators demonstrated that the seventh edition of the TNM classification for gastric cancer was more suitable for predicting the prognosis of patients after surgery than the previous editions. After a careful analysis of this article’s results, we found several obvious defects which could give rise to bias in the conclusions and which should be addressed in detail. In comparison with patients with gastric cancer, patients with esophagogastric junction tumors could have a more distinctive prognosis, given that these patients were classified as having esophageal cancer according to the seventh edition of the UICC/AJCC TNM classification. In addition, the authors did not provide detailed information to show the number of dissected lymph nodes, which is considered a requirement for curative resection of gastric cancer and radical lymphadenectomy. Actually, 15 or more lymph nodes should be required to determine the accurate pN stage and inhibit stage migration. Lastly, we found that some patients described in this article as having advanced stage cancer only underwent palliative resection and had distant metastasis. These patients must have had a poorer prognosis and could not be evaluated precisely for TNM classification. Strictly speaking, patients with distant metastasis should be excluded from the study.

Efficacy of pre‐operative chemotherapy with docetaxel, cisplatin, and S‐1 (DCS therapy) and curative resection for gastric cancer with pathologically positive para‐aortic lymph nodes

The prognosis of gastric cancer with para-aortic lymph node (PAN) metastasis is poor. We applied triple combination chemotherapy with docetaxel, cisplatin, and S-1 (DCS therapy) as pre-operative chemotherapy and investigated the outcome of the combination of this therapy and gastrectomy with para-aortic lymph node dissection (PAND). We retrospectively identified 44 patients with pathologically positive PAN who underwent curative surgery at Kanazawa University Hospital between 1990 and 2008. Among the 44 patients, 16 received pre-operative DCS therapy and subsequent surgical resection after two courses of the therapy. Pre-operative DCS therapy showed high clinical response ratio (68.8%) and disease control ratio (100%). The pathological response ratio of resected specimen was 87.5%. At 2 years after surgery, the overall survival ratio was 93.8% and relapse-free survival was 75.0%. Pre-operative DCS therapy was only independent prognostic factor in multivariate analysis. Grade 3/4 toxicity was observed only in 25.0% of patients who underwent DCS therapy. Surgical complication was observed in 31.3% of patients, and this ratio was equal to that of patients who did not receive DCS therapy. Multimodal therapy comprising combined pre-operative DCS therapy and gastrectomy with PAND was extremely effective and feasible for advanced gastric cancer with PAN metastasis.

Prognostic Significance of Morphological Distribution of Metastatic Foci in Lymph Nodes with Gastric Cancer

Background/Aims: The morphological distribution of tumor cells in metastatic lymph nodes has been investigated in positive sentinel lymph nodes in several solid cancers. The aim of this study was to clarify the effect of the distribution of metastatic foci in lymph nodes on the prognosis in gastric cancer. Methods: The distribution of metastatic foci in the 100 node-positive patients who had undergone curative gastrectomy were classified into two groups: (1) massive type, in which the tumor occupied the entire lymph node, and (2) non-massive type, in which the tumor did not occupy the entire lymph node. Results: There were 38 patients in the massive type group and 62 patients in the non-massive type group. The 10-year survival rate was significantly poorer in the massive type group (p = 0.001). Multivariate analysis showed that distributional type and nodal status were independent prognostic factors. UICC N stage was subcategorized by distributional type, and survival was shown to be significantly worse in the massive type in the N1 group (p = 0.035). Conclusion: It seems necessary to take the morphological distribution of metastatic foci into consideration when dealing with node-positive patients who had received curative resection for gastric cancer.

Factors Associated with Recurrence Within 2 Years After Curative Surgery for Gastric Adenocarcinoma

Despite curative surgery for gastric cancer, many patients die of recurrent cancer. Few studies have investigated the time to recurrence after curative resection for gastric cancer. Data were collected prospectively between December 1987 and December 2006. A total of 1,549 patients underwent curative resection of adenocarcinoma of the stomach at Taipei Veterans General Hospital. Among them, 419 patients had recurrence; they were divided into early recurrence (<2years) and late recurrence (≥2years). The clinicopathological characteristics, survival time after recurrence, and recurrence patterns were compared between the two groups. Multivariate analysis showed that stage III gastric cancer patients with early recurrence had larger tumors and more lymph node metastasis than patients with late recurrence, while no difference between early and late recurrence was observed in stage I and II patients. Early recurrence was associated with more distant metastasis than was late recurrence. Patients with advanced TNM stage tended to die within 2years after recurrence. Gastric cancer patients with larger tumors and more lymph node metastasis tended to have early recurrence, especially stage III patients. Advanced TNM stage was associated with early cancer death after recurrence.

Impact of Lymphatic Vessel Invasion on Survival in Curative Resected Gastric Cancer

BackgroundLymphatic vessel invasion (LV) has been regarded as a prognostic factor in some solid tumors. The aim was to clarify the impact of lymphatic vessel invasion on survival in curative resected gastric cancer. MethodsIn this retrospective study, we reviewed the records of 1,024 patients who underwent curative resection for gastric cancer. Among all of the studied patients, 285 of them (27.8%) had lymphatic vessel invasion. ResultsThere were significant differences in tumor size, tumor location, depth of invasion, and lymph node metastasis (LN) between the patients with lymphatic vessel invasion and those without. The 5-year survival rates in patients were 80.1%, 59.2%, 40.9%, and 30.5% for LN−LV−, LN−LV+, LN+LV−, and LN+LV+ group, respectively. Multivariate analysis revealed that age, tumor location, the depth of invasion, and lymph node metastasis were independent prognostic factors for curative resected gastric cancer. Lymphatic vessel invasion was not an independent prognostic factor in node-positive gastric cancer; however, it was true in node-negative gastric cancer. ConclusionLymphatic vessel invasion is one of the independent prognostic factors for node-negative gastric cancer after curative resection.