Su-Shun Lo

Nodal dissection for patients with gastric cancer: a randomised controlled trial

BACKGROUND The survival benefit and morbidity after nodal dissection for gastric cancer remains controversial. We aimed to do a single-institution randomised trial to compare D1 (ie, level 1) lymphadenectomy with that of D3 (ie, levels 1, 2, and 3) dissection for gastric cancer in terms of overall survival and disease-free survival. METHODS From Oct 7, 1993, to Aug 12, 1999, 335 patients were registered. 221 patients were eligible, 110 of whom were randomly assigned D1 surgery and 111 of whom were randomly assigned D3 surgery, both with curative intent. Three participating surgeons had done at least 25 independent D3 dissections before the start of the trial, and every procedure was verified by pathological analyses. The primary endpoints were 5-year overall survival and 5-year disease-free survival. We also analysed risk of recurrence. Main analyses were done by intention to treat. This trial is registered at the US National Institute of Health website . FINDINGS Median follow-up for the 110 (50%) survivors was 94.5 months (range 62.9-135.1). Overall 5-year survival was significantly higher in patients assigned D3 surgery than in those assigned D1 surgery (59.5% [95% CI 50.3-68.7] vs 53.6% [44.2-63.0]; difference beteween groups 5.9% [-7.3 to 19.1], log-rank p=0.041). 215 patients who had R0 resection (ie, no microscopic evidence of residual disease) had recurrence at 5 years of 50.6% [41.1-60.2] for D1 surgery and 40.3% [30.9-49.7] for D3 surgery (difference between groups 10.3% [-3.2 to 23.7], log-rank p=0.197). INTERPRETATION D3 nodal dissection, compared with that of D1, offers a survival benefit for patients with gastric cancer when done by well trained, experienced surgeons.

Randomized clinical trial of morbidity after D1 and D3 surgery for gastric cancer

A randomized comparison of D1 (level 1 lymphadenectomy) and D3 (levels 1, 2 and 3 lymphadenectomy) dissection was performed to evaluate morbidity and effects on survival from gastric cancer.

Surgical mortality, survival, and quality of life after resection for gastric cancer in the elderly.

Abstract. Although there were some studies on clinicopathologic characteristics, operative morbidity, and mortality in elderly patients with gastric cancer, no reports have specifically focused on survival and quality of life after resection. A total of 433 patients aged ≥ 65 years (1987–1994) who underwent gastric resection for gastric adenocarcinoma were studied. Two groups were considered: patients aged 65 to 74 years and those > 74 years. Most of the patients (78.1%) had advanced diseases, and nearly half (41.3%) had associated chronic disease(s). Resections with curative intention were performed in 362 patients (83.6%). The overall operative morbidity rate was 21.7% and mortality rate 5.1%. Although operative procedures were similar in both groups, patients aged >74 years had a higher mortality rate than those aged 65 to 74 years (10.1% vs. 3.5%; p= 0.034). Age and extent of gastric resection were two independent factors negatively affecting mortality. The cumulative survival rates for patients who underwent curative resection were 86.2%, 72.4%, 67.2%, 62.9%, and 60.0% at 1, 2, 3, 4, and 5 years, respectively. Nearly all patients (96%) after surgery had normal work and daily activities. Some patients appeared to lack energy (16%) or experienced a period of anxiety or depression. There was no statistical difference in survival and quality of life assessed by the Spitzer index after curative resection between the two groups. Therefore resection with curative intention can be performed for the elderly with acceptable morbidity and mortality rates, possible long-term survival, and good quality of life, but a limited operation should be considered in the very elderly patients.

Incidence and factors associated with recurrence patterns after intended curative surgery for gastric cancer

Recurrence after curative resection for gastric cancer remains high. We examined its incidence and factors related to recurrence pattern, while trying to avoid the interaction of various factors. A total of 611 gastric cancer patients after resection for curative intent (1988–1995) were analyzed. The result showed that 245 patients had recurrence (40.1%). Cumulative recurrence rates were 53.5%, 80%, 89.0%, 94.7%, 96.3%, 98%, and 99.5% at 1, 2, 3, 4, 5, 6, and 7 years, respectively. Over half of patients with recurrence (123; 50.2%) had an initial single recurrence. Taking single and multiple recurrence together, most recurrences (213; 86.9%) were distant metastases, 110 recurrences (44.9%) were local relapses, and 78 recurrences (49.8%) were both local and distant. Among the distant metastases, 131 patients (53.5%) had peritoneal dissemination, 106 patients (43.3%) had hematogenous metastases, and 70 patients (28.6%) had distant lymphatic spread. Scirrhous-type stromal reaction, serosa invasion, and female gender were factors negatively related to peritoneal recurrence. Medullary-type stromal reaction and male gender showed a preference for locoregional recurrence, and expanding growth tumor commonly led to hematogenous metastasis. Patients who had paraaortic lymph node metastasis were at high risk of developing distant lymphatic recurrence. It is conceivable that the patterns of recurrence and the times to recurrence provide a biological basis for clinical monitoring of patients with the aim of modifying therapeutic modalities.

Relation of number of positive lymph nodes to the prognosis of patients with primary gastric adenocarcinoma.

BACKGROUND--No nodal grouping category of gastric cancer has been universally accepted for the grading of the effectiveness of therapeutic regimens. AIMS--To establish an appropriate nodal grouping as a forecaster of distant disease and test its validity as a determinant in survival. PATIENTS--Five hundred and ten patients who underwent curative resections for gastric cancer were studied. METHODS--Retrospectively analyse the prognostic significance of the number of metastatic lymph nodes. RESULTS--A total of 17 176 lymph nodes with an average of 34 per specimen were removed, of which 2811 (16%) showed metastases. Among the 510 patients, 287 (56%) had lymph node metastases, with an average of 9.8 per metastatic case. The survival of all patients was related to their nodal status, an abrupt decrease in survival was seen between 0 and 1 and 4 compared with 5 or more modes while little difference in survival existed among 1, 2, 3, and 4, and among 5, 6, 7, and 8 positive nodes. Multivariate analysis showed that the number of positive nodes (1-4, 5-8 versus > or = 9; relative risk 2.2) and depth of cancer invasion (three levels; relative risk 1.9) were independently correlated with survival. The current nodal stage was not a prognostic factor. CONCLUSIONS--Gastric cancer patients with 0, 1 to 4, 5 to 8, and > 9 positive nodes may represent four appropriate prognostic groups and should be adopted for classification of nodal stage in gastric cancer.

Initial Experience of Robotic Gastrectomy and Comparison with Open and Laparoscopic Gastrectomy for Gastric Cancer

BackgroundRobotic gastrectomy has become more popular in the treatment of gastric cancer, especially in Asian countries. Until now, few studies have compared robotic surgery with open or laparoscopic surgery for gastric cancer patients.MethodsData were prospectively collected between January 2006 and February 2012. A total of 689 patients underwent curative resection of adenocarcinoma of the stomach. Patients were separated into three groups according to the different surgical approaches used (586 open, 64 laparoscopic, and 39 robotic). The clinicopathological characteristics and surgical outcomes of the three groups were compared.ResultsThe open group was associated with a larger tumor size, more D2 dissection, more advanced tumor stage, and more blood loss than the groups treated with laparoscopic and robotic methods. Robotic gastrectomy was associated with female predominance, less blood loss, shorter hospital stay, and longer operative time than open and laparoscopic gastrectomy. The retrieved lymph node numbers were similar between the open and robotic groups. Postoperative morbidity rates were similar among the three groups. In terms of the learning curve of robotic gastrectomy, operative time and docking time were significantly reduced in the recent robotic group (n = 14) compared to the initial robotic group (n = 25).ConclusionRobotic gastrectomy could achieve extended lymph node dissection similar to open surgery. Our results showed a significant learning curve effect in the initial 25 cases of the robotic group.

Quality of Life of Patients with Gastric Adenocarcinoma after Curative Gastrectomy

Abstract. Quality of life (QOL) was evaluated in 162 patients having radical gastrectomy for cancer. The results showed that more than half of the patients had a good appetite; they consumed a normal diet and a normal volume of food. Approximately 60% of the patients had weight loss of more than 5 kg. Patients who underwent a total gastrectomy had poor tolerance of normal food and frequent eating and body weight loss versus those who had a subtotal gastrectomy. Patients who underwent Billroth II reconstruction after a distal subtotal gastrectomy lost more body weight than those with a Billroth I anastomosis. The extent of lymphadenectomy did not influence the QOL. Patients under 65 years of age had a better QOL. Nearly all patients had normal work and daily living activities. Some patients appeared to lack energy or had a period of anxiety or depression. These data indicate that radical gastrectomy can be performed with an acceptable QOL for a potentially curable gastric carcinoma.

Prognostic indicators for survival after curative resection for patients with carcinoma of the stomach

This study aims to determine prognosticindicators among patient-, tumor-, and treatmentrelatedfactors of gastric cancer patients. A total of 510patients who underwent curative gastric resection were studied. Univariate analysis of patient-relatedfactors showed a significantly lower survival inpatients with a history of obstruction, hypoalbuminemia,and anemia. Tumor-related factors including gross appearance, location, and size of tumor; depthof cancer invasion; level, number, and frequency oflymph node metastasis; stromal reaction and tumor growthpattern; and histological classification allsignificantly affected survival. Surgical treatment relatedfactors such as total or distal subtotal gastrectomy,extent of lymphadenectomy, and combined resection ofadjacent organ(s) showed a statistically significant adverse influence on survival. Multivariateanalysis identified only four tumor-related factors— number of metastatic lymph nodes, depth ofcancer invasion, stromal reaction, and gross appearanceof the tumor — as independently affectingsurvival. These findings suggest that only fourtumor-related factors were prognostic indicators inpatients with gastric cancer.

Heme Oxygenase-1 Gene Promoter Polymorphism is Associated with Risk of Gastric Adenocarcinoma and Lymphovascular Tumor Invasion

PurposeHeme oxygenase-1 (HO-1) gene, which encodes an oxidative response protein, plays a role in cytoprotection. A (GT)n dinucleotide repeat in HO-1 promoter is polymorphic and modulates the transcriptional activity of the gene. A HO-1 gene promoter polymorphism was reported to be associated with the risks of lung adenocarcinoma and oral squamous cancer. In this study, the correlation between the HO-1 gene promoter polymorphism and the clinicopathological characteristics, along with the risk of gastric cancer, was analyzed.Experimental designWe examined the genotypic frequencies of (GT)n repeats in 183 gastric cancer patients and 250 control subjects by PCR-based genotyping and DNA sequencing. The length polymorphisms of (GT)n repeats were classified into short (S) component (n ≤ 25), medium (M) component (26 ≤ n ≤ 30) and long (L) component (n ≥ 31). The distribution of S, M and L components in patient and control groups were evaluated to determine the correlation with susceptibility and clinicopathological characteristics of gastric adenocarcinoma.ResultsHigher frequencies of L-allele, L-allele carrier (S/L, M/L, L/L) and S/L genotype were found in gastric cancer patients. The frequencies of M-allele, M-allele carrier (M/M, M/L, M/S) and M/M genotype were significantly lower in patients with gastric cancer than controls. Furthermore, the frequency of lymphovascular tumor invasion was significantly lower in M-allele carriers compared to non-M-allele carriers (S/S, S/L, L/L) (p = 0.009).ConclusionsThese findings suggest that the long (GT)n repeat of HO-1 gene promoter was associated with a higher frequency of gastric adenocarcinoma, and the medium (GT)n repeat might possess protective effect against gastric adenocarcinoma with a lower frequency of lymphovascular invasion in tumors.

Quality of life after curative gastrectomy for gastric cancer in a randomised controlled trial

Quality of life (QOL) was studied in gastric cancer patients treated on a randomised, controlled trial comparing D1 (level 1) with D3 (levels 1, 2 and 3) lymphadenectomy. A total of 221 patients were randomly assigned to D1 (n=110) and D3 (n=111) surgery. Quality-of-life assessments included functional outcomes (a 14-item survey about treatment-specific symptoms) and health perception (Spitzer QOL Index) was performed before and after surgery at disease-free status. Patients suffered from irrelative events such as loss of partners was excluded thereafter. Main analyses were done by intention-to-treat. Thus, 214 D1 (106/110=96.4%) and D3 (108/111=97.3%) R0 patients were assessed. Longitudinal analysis showed that functional outcomes decreased at 6 months after surgery and increased over time thereafter, while health perceptions increased over time in general. On the basis of linear mixed model analyses, patients having total gastrectomy, advanced cancer and hemipancreaticosplenectomy, but not complications had poorer QOL than those without. D1 and D3 patients showed no significant difference in QOL. The results suggest that changes of QOL were largely due to scope of gastric resection, disease status and distal pancreaticosplenectomy, rather than the extent of lymph node dissection. This indicates that nodal dissection can be performed for a potentially curable gastric cancer.