Curative Resection Of Gastric Carcinoma Research Articles

Comparative Analysis of Immediate Postoperative Complications Following Total Gastrectomy

Total gastrectomy (TG), despite disrupting the continuity of the alimentary tract and accounting for significant postoperative complications, is the procedure of choice for curative resection of gastric carcinoma. The objectives of this study were to report the rate of postoperative complications following TG, to analyze adverse postoperative outcomes, and to determine which of the two techniques - the Roux-en-Y esophagojejunostomy and Omega-Braun TG, is safer. A retrospective, observational study was conducted among patients diagnosed with gastric carcinoma who underwent TG between January 1st, 2010 and December 31st, 2012 in the Surgery Department of the Bucharest Clinical Emergency Hospital. Descriptive and analytical statistical analysis with parametric and non-parametric tests was carried out using GraphPad, with statistical significance set at p <0.05. Seventy-seven patients, aged 37-91 years (average age 64.1 ± 11.59 years), were enrolled in this study. A total of 84 immediate postoperative complications were encountered in 35 patients (47.5%), classified into local (n=21, 25%) and general complications (n=63, 75%). Reoperation was necessary in five cases (6.2%), all after Roux-en-Y end-side esophagojejunostomy. Two deaths (n=2, 2.5%), one after Roux-en-Y and one after Omega-Braun TG, were reported. The Roux-en-Y technique had a higher number of complications, both local and general. Omega-Braun TG was associated with a lower number of local complications; however, it was associated with life-threatening complications including hemodynamic instability and multisystem organ failure. The study deemed Roux-en-Y Esophagojejunostomy the overall safer procedure. A statistically significant correlation between manual anastomosis and mortality was observed. Total Gastrectomy is a complex procedure with numerous potential complications which calls for an improved surgical technique to reduce postoperative risk.

Concurrent involved-field radiotherapy and XELOX in gastric cancer patients with postoperative oligometastatic recurrence.

The aim of this study was to retrospectively observe gastric adenocarcinoma patients with postoperative oligometastatic recurrence and investigated the effects of concurrent involved-field radiotherapy (RT) and XELOX on progression-free survival (PFS). From 2008 to 2011, 246 patients underwent curative resection of gastric carcinoma was enrolled. A retrospective review was performed on 34 patients with distant recurrence. Among them, 19 patients were oligometastases patients, where 13 patients received involved-field RT with a dose of 40-60 Gy by an intensity-modulated RT technique and concurrent XELOX chemotherapy, four patients were treated with XELOX chemotherapy alone (oxaliplatin 130 mg/m2, capecitabine 1000 mg/m2, twice daily, 3 week each cycle), and two patients with only brain metastasis were not included in the analysis. The median PFS was 11 months in the 13 oligometastatic patients who received concurrent involved-field RT and XELOX. The oligometastatic patients receiving concurrent radiochemotherapy trended toward a better median PFS when compared with those receiving chemotherapy alone. For patients with postoperative oligometastatic recurrence, concurrent involved-field RT and XELOX showed better responses and was a choice for first-line treatment.

Preoperative elevation of serum C-reactive protein as an independent prognostic indicator for gastric cancer

Preoperative elevation of serum C-reactive protein (CRP) is a prognostic indicator for some malignant tumors. We investigated the clinicopathologic importance of an elevated preoperative serum CRP value in gastric carcinoma patients. We studied the relationship between the preoperative serum CRP value and clinicopathologic characteristics in 204 patients who underwent curative resection of gastric carcinoma. The patients with preoperative CRP elevation had significantly poorer survival than those without CRP elevation (P < 0.0001). According to multivariate analysis, the factors independently associated with an unfavorable prognosis were a high preoperative CRP value (P = 0.024), lymphatic invasion (P = 0.017) and advanced tumor stage (P = 0.016). Preoperative serum CRP elevation can be an independent prognostic indicator in patients with gastric carcinoma.

Expression of c-erbB2 andp53in Curatively Resected Gastric Cancer: Correlation with Clinicopathologic Features and Prognosis

Purpose: We investigated the correlation between expression of c-erbB-2 and p53 proteins and clinicopathologic features of gastric cancer to reveal prognostic factors. Methods: 125 patient records under going curative resection for gastric carcinoma at our institution from January 2000 to June 2003 were collected. Surgical specimens embedded in paraffin block were evaluated for p53 and c-erbB-2 protein as detected by immunohistochemistry. Results: Samples from 30 cases (24.0%) of 125 patients with gastric adenocarcinomas demonstrated positive staining for c-erbB-2 and 72 patients (57.6%) showed positive nuclear staining for p53 protein. c-erbB-2 stained tumors were significantly associated with the depth of tumor invasion (P=0.022), lymph node metastasis (P=0.004) and lymphatic invasion (P=0.019). In a subgroup of patients with gastric carcinoma not exposed to serosa (n=91), expression of both c-erbB-2 and p53 significantly related with poor disease-free survival (OR=5.107) and survival (OR=4.449) in multivariate analysis. Conclusion: When patients with gastric adenocarcinoma showed expression of c-erbB-2 with p53, they were associated with aggressive pathologic features. In the subgroup of patients with gastric adenocarcinoma that did not involve serosa, expression of c-erbB-2 combined with p53 could become a predictive factor for recurrence and survival in multivariate analysis.

Prognostic significance of free peritoneal tumor cells in the peritoneal cavity before and after neoadjuvant chemotherapy in patients with gastric cancer undergoing a potentially curative resection.

4156 Background: Free peritoneal tumor cells (FPTCs) are an independent prognostic factor in patients undergoing curative resection for gastric carcinoma. Whether neoadjuvant chemotherapy (NAC) can eliminate FPTCs in the peritoneal lavage remains unclear. The aim of the study was to determine the effect of NAC on FPTCs. Methods: From 1994-2000, a total of 61 patients with resectable gastric cancer were reviewed. Peritoneal cytology was performed before NAC and at tumor resection. A minimum of six weeks of NAC, consisting of cisplatin, folinic acid and fluorouracil was administered. FPTCs were detected immunhistochemically using Ber-EP4 antibody. Median follow-up was 7.3 years. Results: FPTCs could be detected in 19 (31%) patients before NAC. Positive cytology changed to be negative in 7 patients after NAC. Those patients showed a trend towards an improved median survival (36 months) and a longer 2-year survival (71%) compared to FPTC positive patients at staging and after chemotherapy (n = 12), with a median survival of 9.2 months and a 2- year survival rate of 25%. Median survival of all patients was 29 months. Patients with negative cytology after NAC (n = 39) survived significantly longer survival (37.9 months) compared to patients with positive cytology (n = 22) (13.3 months; p < 0.001). The presence of FPTCs at resection was associated with advanced ypT, ypN- and R-category, but not with clinical or histopathological response to NAC. Multivariate analysis identified ypN category, clinical response and the evidence of FPTCs as independent prognostic factors. All patients underwent gastrectomy, which resulted in 46 R0 (78%), and 15 R1/2 resections. In R0 resected patients (n = 46), multivariate analysis elucidated that both, ypN and clinical response were independent prognostic factors, but FPTCs before or after therapy were not. Conclusions: NAC for patients with positive cytology could lead into FPTC negativity in a subset of patients and to improve their prognosis. The detection of FPTCs at any time is associated with poor prognosis and could be used for risk-group stratification. No significant financial relationships to disclose.

Prognostic Significance of Free Peritoneal Tumor Cells in the Peritoneal Cavity Before and After Neoadjuvant Chemotherapy in Patients with Gastric Carcinoma Undergoing Potentially Curative Resection

Free peritoneal tumor cells (FPTCs) are an independent prognostic factor in patients undergoing curative resection for gastric carcinoma. Whether neoadjuvant chemotherapy (NAC) can eliminate FPTCs in the peritoneal lavage remains unclear. The aim of the study was to determine the effect of NAC on FPTCs. From 1994 to 2000, data from a total of 61 patients with resectable gastric cancer were analyzed. Peritoneal cytology was performed before NAC at laparoscopy and at tumor resection. A minimum of 6weeks of NAC, consisting of cisplatin, folinic acid, and fluorouracil, was administered. FPTCs were detected immunohistochemically with Ber-EP4 antibody. No FPTCs could be detected in 42 patients (69%), compared to 19 (31%) with FPTCs before NAC. During chemotherapy, 10 (24%) of 42 patients developed FPTCs, and 7 (37%) of 19 patients reverted from positive to negative. Patients who became FPTC negative (n=7) showed an improved median survival (36.1months) and a longer 2-year survival (71.4%) compared to FPTC-positive patients before and after NAC (n=12), with a median survival of 9.2months and a 2-year survival rate of 25%. In contrast, patients who reverted from FPTC negative to positive during NAC (n=10) had a median survival of 18.5months and a 2-year survival of only 20%. Multivariate analysis identified ypN category and FPTC change as independent prognostic factors. NAC for patients with positive cytology could lead to FPTC negativity in a subset of patients and improve their prognosis. However, NAC might be a risky strategy for almost one-quarter of patients whose disease develops positive cytology.

Low rates of loco-regional recurrence following extended lymph node dissection for gastric cancer

Aim The study by MacDonald et al. [Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med 2001;345:725–30] has reported low loco-regional recurrence rates (19%) after gastric cancer resection and adjuvant radiotherapy. However, the lymph node dissection was often “inadequate”. The aim of this retrospective study is to analyse if an extended lymph node dissection (D2) without adjuvant radiotherapy may achieve comparable loco-regional recurrence rates. Methods A prospective database of 200 patients who underwent a curative resection for gastric carcinoma from January 2000 to December 2006 was analysed. D2 lymph node dissection was standard. Recurrences were categorized as loco-regional, peritoneal, or distant. No patients received neoadjuvant or adjuvant radiotherapy. Results The in-hospital mortality rate was 1% (2 patients). The mean number of dissected lymph nodes was 25.9. Overall and disease-free survival at 5 years were 60.7% and 61.2% respectively. During the follow-up, 60 patients (30%) have recurred at 76 sites: 38 (50%) distant metastases, 25 (32.9%) peritoneal metastases, and 13 (17.1%) loco-regional recurrences. The loco-regional recurrence was isolated in 6 patients and associated with peritoneal or distant metastases in 7 patients. The mean time to the first recurrence was 18.9 (95% confidence interval: 15.0–21.9) months. Conclusions Extended lymph node dissection is safe and warrants low loco-regional recurrence rates.

Large Metastatic Lymph Node Size, Especially More Than 2 cm: Independent Predictor of Poor Prognosis in Node‐Positive Gastric Carcinoma

The presence of metastatic lymph nodes (MLNs) is the most important prognostic factor for gastric carcinoma, with the number of MLNs thought to be predictive of the prognosis. However, there have been long-standing debates on how to classify node-positive patients into prognostic groups appropriately. Recent findings in patients with colon and esophageal cancer have suggested that MLN size, more than MLN number, is an important prognostic factor; but less is known about the impact of MLN size on the prognosis of patients with gastric carcinoma. We therefore assessed the prognostic impact of large MLNs, especially those>or=2 cm, in patients with gastric carcinoma. A total of 1190 patients who underwent curative resection for gastric carcinoma between 2001 and 2003 and had lymph node metastases were divided into two groups according to the size of the largest MLN:>or=2 cm (n=51) vs. <2 cm (n=1139). Clinicopathologic data, including tumor recurrence and survival, were reviewed retrospectively. The median follow-up for living patients was 47 months (range 30-80 months). Age, sex ratio, type of surgery, and histologic classification did not correlate with MLN size. The depth of invasion did correlate with MLN size (T1-2 vs. T3-4, p=0.045) but not with the number of MLNs (N stage, p=0.311). The two groups showed similar distribution of stage according to the UICC/AJCC TNM staging system. Disease-free survival (34% vs. 53%, p<0.001) and overall survival (40% vs. 63%, p=0.011) were significantly worse in the large MLN group. Univariate analysis with the log-rank test showed that MLN>or=2 cm, type of surgery, T stage, N stage, and histologic classification had a significant impact on overall survival. Multivariate analysis with the Cox proportional hazard model showed that MLN>or=2 cm was an independent prognostic factor (hazard ratio 1.76, p=0.006), along with T stage and N stage. MLN>or=2 cm is an independent additional predictor of poor prognosis in patients with node-positive gastric carcinoma.

The Effectiveness of Intravenous 5-Fluorouracil-Containing Chemotherapy after Curative Resection for Gastric Carcinoma: A Systematic Review of Published Randomized Controlled Trials

This is a review of randomized controlled trials of intravenous 5-flurorouracil (5- FU)-containing chemotherapy after curative resection versus surgery alone in patients with gastric carcinoma to determine the impact on survival rate, safety and economics. Data sources were the Cochrane Library (2006, Issue 2), Pub-Medline and Chinese Biomedical Database. We included 22 randomized controlled trials comparing 4501 patients. Intravenous 5-FU-containing chemotherapy after curative resection had a slightly significant improvement in 3-, 5- and 7-year overall survival rate (OR 1.49, 1.41 and 1.32). No benefit of postoperative disease-free survival rate was induced by 5-FU-containing chemotherapy. Sensitivity analysis was restricted to trials with the highest methodological quality, and the result was similar when the studies with Jadad score less than 3' were excluded. Subgroup analyses found borderline improved overall survival rate in both Western and Eastern countries but the statistical significance was stronger in the Eastern subset. The combinations of 5-FU plus mitomycin C, 5-FU plus cytosine arabinoside and 5-FU plus adriamycin or epidoxorubicin induced potentially more improvement of 3- and 5-year overall survival rates. Severe toxicities were reported in 1629 patients from 15 included trials, and hematological and gastrointestinal toxicities were the most remarkable side effects, around 5%-15% respectively. The chemotherapy-related overall mortality was 1.1%. No trials mentioned cost-effectiveness analysis. Although the results provide some evidence of a beneficial effect of adjuvant chemotherapy with 5-FU-containing regimens, they are inconclusive due to the limitations of methodological quality of including randomized controlled trials. Large scale randomized controlled trials with a positive result are still mandatory before postoperative chemotherapy are recommended.

Adjuvant chemotherapy with 5-fluorouracil, doxorubicin and mitomycin-C (FAM) for 6 months after curative resection of gastric carcinoma

Aim This study aimed to evaluate the efficacy and safety of 5-fluorouracil (5-FU), doxorubicin and mitomycin-C (FAM) adjuvant chemotherapy in patients who had undergone curative resection of gastric carcinoma. Methods From Nov 1999 to Jan 2002, 291 consecutive patients with stage IB–IIIB gastric adenocarcinoma were given FAM adjuvant chemotherapy. Chemotherapy comprised intravenous 5-FU 600 mg/m 2 (days 1, 8, 29 and 36), doxorubicin 30 mg/m 2 (days 1 and 29) and mitomycin-C 10 mg/m 2 (day 1), every 8 weeks for 6 months. Results The median follow-up time was 60.6 months, 92 patients died, and 93 patients had recurrent disease. The 5-year overall survival (OS) rates were 85.9% for stage IB, 72.1% for stage II, 58.0% for stage IIIA, and 48.2% for stage IIIB ( p = 0.002). The 5-year relapse-free survival (RFS) rates were 85.2% for stage IB, 71.2% for stage II, 53.3% for stage IIIA, and 39.2% for stage IIIB ( p < 0.001). A total of 769 cycles of chemotherapy were delivered, and 15 patients experienced grade 3 or higher leukopenia. The most common grade 3 or higher non-hematologic toxicity was nausea/vomiting (11 patients), followed by stomatitis (3 patients). Conclusions Adjuvant chemotherapy with FAM for 6 months for gastric carcinoma indicated comparable RFS and OS with an acceptable toxicity profile.

Helicobacter pylori in gastric cancer: Friend or foe?

Helicobacter pylori in gastric cancer: Friend or foe?

Helicobacter pylori as a prognostic indicator after curative resection of gastric carcinoma: a prospective study

The effect of Helicobacter-pylori status on survival after curative resection for gastric adenocarcinoma is unknown. We aimed to follow-up patients who were positive or negative for infection with H pylori who had curative (ie, R0) resection for gastric adenocarcinoma to assess differences in relapse-free survival and overall survival. Before surgery, we assessed the H pylori status of 166 patients who had R0 resection for gastric adenocarcinoma between 1992 and 2002 with bacterial culture, histological analyses (ie, staining with haematoxylin and eosin and with Warthin-Starry), and serological analyses. At a median follow-up of 53.0 months (range 1-146), relapse-free survival was 56.7 months (95% CI 4.7-108.7) and overall survival was 61.9 months (13.0-110.9) in patients positive for H pylori, compared with 19.2 months (12.7-25.6) and 19.2 months (7.1-31.3), respectively, in patients negative for H pylori (p=0.0009 for difference in relapse-free survival between groups, and p=0.0017 for difference in overall survival between groups). In multivariate analyses, H pylori was an independent prognostic factor for relapse-free survival (hazard ratio 2.16 [95% CI 1.33-3.49]) and overall survival (2.00 [1.22-3.27]). Depth of tumour invasion (2.60 [1.66-4.08]), lymph-node metastasis (2.11 [1.25-3.57]), and patient age 67.5 years or older (1.75 [1.11-2.75]) were also independent prognostic factors for overall survival. Tumour-specific immune responses might be downregulated in patients who are negative for H pylori, and these patients should be followed up carefully because of a poor outlook.

Does the Intraoperative Peritoneal Lavage Cytology Add Prognostic Information in Patients With Potentially Curative Gastric Resection?

Peritoneal recurrence is the foremost pattern of failure after potentially curative resection for gastric cancer. Our aim was to evaluate the prognostic value of intraperitoneal free cancer cells (IFCCs) in peritoneal lavage of patients who underwent potentially curative resection for gastric carcinoma. Two hundred twenty patients with gastric cancer stage I, II, or III were prospectively evaluated with peritoneal lavage and cytologic examination. Aspirated fluid from the abdominal cavity was centrifuged and subjected to Papanicolaou staining. The mean age was 60.9 years (range, 21-89 years), and 63.6% were men. IFCCs were detected in 6.8% of the patients; suspicious in 2.7%, and negative in 84.5%. No judgment could be given in 5.9% of the cases. Invasion of the gastric serosa (pT3) was observed in all positive cytology patients. Patients with IFCCs had a mean survival time of 10.5 months, while those with negative IFCC had a mean survival time of 61 months (P = 0.00001). There was no correlation between the presence of IFCCs and tumor size, histology, pN, or tumor site. Our conclusions are that (1) positive cytology indicates a poor prognosis in patients who underwent potentially curative gastric resection and (2) peritoneal lavage cytology improves staging in assessing these patients and may alter their therapeutic approach.

Early prediction of tumor recurrence after curative resection of gastric carcinoma by measuring soluble E‐cadherin

Currently, to the authors' knowledge, there is no serum marker to predict disease recurrence after patients undergo curative resection for gastric carcinoma. Previous reports have indicated that serum levels of soluble E-cadherin had prognostic value in these patients. The objective of the current study was to determine whether soluble E-cadherin levels could predict disease recurrence in patients with gastric carcinoma who underwent curative surgery. Sixty-nine patients who underwent curative surgery for gastric carcinoma after December 1997 were followed prospectively. Venous blood samples were collected preoperatively, 1 month after surgery, and every 3 months thereafter. The blood samples were assayed for soluble E-cadherin and for carcinoembryonic antigen (CEA) using commercial enzyme-linked immunosorbent assay kits. Receiver operating characteristic (ROC) curves were used to define a cut-off level of E-cadherin for the optimal sensitivity and specificity for predicting disease recurrence. The median follow-up was 21 months for patients with recurrent disease (n = 17 patients) and 36 months for patients without recurrent disease (n = 52 patients; P = 0.007). The optimal cut-off level of E-cadherin was 10,000 ng/mL. The sensitivity for predicting prediction disease recurrence using this cut-off level at 3 months and at 6 months postsurgery was 47% and 59% respectively, which was significantly better compared with the sensitivity of CEA using the conventional cut-off level (6% at 3 months postsurgery and 6% at 6 months postsurgery; P = 0.004 and P < 0.0001, respectively). The median time between the elevated E-cadherin level and documented disease recurrence was 13 months (range, 3-20 months), compared with 4 months (range, 1-20 months) for CEA. Serum soluble E-cadherin was a good marker for predicting disease recurrence in the first 3-6 months after surgery, with a median of 13 months before clinical recurrence. The use of this marker may allow time for vigilant surveillance and consideration of adjuvant therapy.

Time to Death and Pattern of Death in Recurrence following Curative Resection of Gastric Carcinoma: Analysis Based on Depth of Invasion

It is difficult to predict recurrence in patients who undergo curative gastrectomy for gastric carcinoma. If the timing and site of recurrence can be predicted, it becomes easier to detect recurrent disease. Records of 290 patients who died of tumor recurrence after curative gastrectomy for gastric carcinoma were retrospectively analyzed to determine whether the depth of carcinoma invasion is independently correlated with the time to death due to tumor recurrence. Additionally, the relation between the pattern of recurrence and the depth of invasion of the gastric wall was examined. Postoperative survival in patients with tumors with deep invasion was shorter than that of patients with tumors with shallow invasion. Depth of invasion was a predictor of survival on multivariate analysis. When carcinoma invaded into deeper layers, the incidence of peritoneal metastasis and local recurrence rose and that of hematogenous metastasis fell. In conclusion, the timing of death and the site of recurrence after gastrectomy for gastric carcinoma might be predicted by the depth of invasion of the gastric wall.

Minimum number of lymph nodes that should be examined for the International Union Against Cancer/American Joint Committee on Cancer TNM classification of gastric carcinoma.

The classification of lymph node metastasis based on the number of positive nodes has been adopted in the International Union Against Cancer/American Joint Committee on Cancer (UICC/AJCC) TNM classification of gastric carcinoma. However, the N classification (for condition of the regional lymph nodes) would be underestimated when the number of examined nodes were too small. To determine the minimum number of lymph nodes to examine for a correct classification, we analyzed 926 patients undergoing curative resection for gastric carcinoma. The number of metastatic lymph nodes correlated significantly with the number of examined lymph nodes. The pN0 patients with 10 to 14 examined nodes showed a significantly higher survival rate than did those with 5 to 9 examined nodes, and they had as good a prognosis as those with 15 or more examined nodes. In the pN1 and pN2 categories, patients with 29 or fewer examined nodes tended toward lower survival rates than did patients with 30 or more examined nodes. Among the patients who were classified as stage IA, the survival rate for those with 5 to 9 examined nodes was significantly lower than that for patients with 30 or more examined nodes. Among the patients classified as stage III, those with 10 to 19 examined nodes and those with 20 to 29 examined nodes had lower survival rates than did patients with 30 or more examined nodes. In conclusion, the minimum number of lymph nodes examined for a correct pN0 classification can be reduced from 15 to 10. For pN1-3 classifications, 20 or more nodes should be examined, and examining 30 or more lymph nodes may be desirable.

Predictive factors and timing for liver recurrence after curative resection of gastric carcinoma

Background Advanced and reliable diagnostic methods in order to identify the site of recurrence of gastric cancer in an early stage are needed. Methods One hundred twenty patients whose recurrence was confirmed after curative resection for gastric cancer were enrolled in this study. Results Liver recurrence was evident in 41 patients. Advanced age, tumor invasion into subserosa, intestinal and mixed type of histology, Borrmann type 0 to 2, tumor diameter (<6.5 cm), and tumor marker (carcinoembryonic antigen and alpha-fetoprotein) elevation were related to liver recurrence. By logistic regression analysis, independent risk factors for liver recurrence included Borrmann’s classification, histology, and tumor marker elevation. The median time from the primary operation to liver recurrence was shortest in the tumor marker elevation group when compared with other independent predictors. Conclusions This information may help to design a better follow-up program and appropriate treatment strategy for gastric cancer patients with liver metastasis.

Prognostic Factors of Krukenberg's Tumor

Objective. The aim of this study was to determine prognostic factors of metachronous Krukenberg's tumors of gastric origin, thereby helping to establish a therapeutic plan for this rare entity.Methods. Thirty-four female patients who underwent curative resection of gastric carcinoma from 1987 through 1996 and subsequently developed Krukenberg's tumors were identified. The covariates used for survival analysis were patient age at the time of ovarian relapse (categorized as <50 years or ≥50 years), size of Krukenberg's tumor (categorized as ≤5, 5–10, or >10 cm), initial AJCC stage of gastric carcinoma, relapse-free interval (categorized as <1, 1–2, or ≥2 years), extent of recurrent disease, and the presence of gross residual disease after treatment for Krukenberg's tumors. The influence of all covariates on the survival period was assessed using the Cox proportional hazards model.Results. At a median follow-up of 32.3 months (range, 2.2–83.1), the median survival period of 34 study patients was estimated to be 7.7 months (95% confidence interval (CI), 5.8–9.6) after the diagnosis of metachronous Krukenberg's tumor. Cox-model-based survival analysis demonstrated that the absence of residual disease after treatment and limited disease extent were favorable prognostic factors. The median survival period of patients without gross residual disease was longer (10.9 months (95% CI, 4.6–17.1)) than that of patients with gross residual disease (7.5 months (95% CI, 6.6–8.3)) [P = 0.036]. Median survival periods according to the extent of metastasis were 10.9 months (95% CI, 0–23.0) for patients with disease confined to the ovaries, 13.1 months (95% CI, 5.9–20.3) for patients with disease confined to the pelvis, 7.5 months (95% CI, 6.8–8.1) for patients with intraabdominal disease, and 3.6 months (95% CI, 3.4–3.7) for patients with disease spread outside the abdomen and pelvis [P = 0.003]. In contrast, patient age, size of ovarian tumor, initial stage of gastric adenocarcinoma, and relapse-free interval were not prognostic indicators for survival after the development of ovarian metastases.Conclusion. The absence of residual disease after treatment and limited disease extent were favorable prognostic factors of metachronous Krukenberg's tumors of stomach origin. Our data suggestthat resection might have a role in the management of Krukenberg'stumors of stomach origin if it could render patients free of gross residual disease.

Immunohistochemically detected micrometastases of the lymph nodes in patients with gastric carcinoma.

Lymph node status is a major determinant of disease recurrence after patients undergo curative resection for gastric carcinoma. A proportion of patients without lymph node metastasis develop systemic recurrences. Recent studies in a range of solid tumors have found a high incidence of micrometastases in the regional lymph nodes of patients with apparently negative lymph nodes. In patients with breast and colorectal carcinoma, the presence of micrometastases has been associated with a poorer prognosis. In patients with gastric carcinoma, the significance of micrometastases in lymph nodes remains controversial. Most published reports on this subject suffer from the problems of small sample size and selection bias. One hundred seven patients with pathologic T2N0M0 (tumor invades muscularis propria or subserosa [T2], no regional lymph node metastasis [N0], and no distant metastasis [M0]; pT2N0M0) gastric carcinoma who underwent gastric resection between 1984 and 1990 at the National Cancer Center Hospital were studied. Two consecutive sections were newly prepared from each lymph node for hematoxylin and eosin staining and immunohistochemical staining (IHC) with antibody against cytokeratin. Associations between clinicopathologic factors and the presence of micrometastases as well as micrometastases and survival were sought. Micrometastases were identified in 38 of 107 patients (35.5%) and in 87 of 4484 lymph nodes (1.94%) by IHC. The incidence of micrometastases was significantly higher in patients with infiltrative tumors than in patients with expansive, growing tumors (P = 0.02). Other clinicopathologic findings had no statistically significant correlation with the incidence of micrometastases. The 5-year survival rates of patients with and without micrometastases were 94% and 89%, respectively. Similarly, the 10-year survival rates were 79% and 74%, respectively. The survival curves of patients with or without micrometastasis were nearly superimposed (P = 0.86). The presence of immunohistochemically detected micrometastases in the regional lymph nodes did not affect the survival of Japanese patients with pT2N0M0 gastric carcinoma who had undergone gastrectomy with D2 lymph node dissection.

Significant correlation between expression of interleukin-1alpha and liver metastasis in gastric carcinoma.

Interleukin (IL)-1 has been reported to augment the hematogeneous metastasis of some cancers by inducing the expression of adhesion molecules on vascular endothelial cells and also increasing the expression of proteases from tumor cells in vitro. The purpose of this study was to determine the clinical significance of the IL-1alpha expression in primary tumors of gastric carcinoma. Paraffin embedded sections of the tumors obtained from 109 patients who underwent a gastrectomy for gastric carcinoma with subserosal invasion were stained for IL-1alpha by using the streptavidin biotin method. Staining was considered positive when 10% or more of the malignant cells displayed cytoplasmic staining. Sixty (55.0%) tumors expressed IL-1alpha. Positive staining for IL-1alpha was more likely in patients with differentiated tumors than in those with undifferentiated tumors. The expression of IL-1alpha showed a significant correlation with liver metastasis. Of the 84 patients receiving a curative resection, those with tumors expressing IL-1alpha had a significantly higher incidence of liver recurrence than those without. A logistic regression analysis revealed positive staining for IL-1alpha to be the best predictive factor of patients who develop liver recurrence. The authors' results suggest that the immunohistochemical expression of IL-1alpha is a useful predictor of liver recurrence in patients undergoing a curative resection for gastric carcinoma with subserosal invasion.