Combined S-1 and cisplatin preoperative chemotherapy for patients with advanced gastric cancer: report of five cases

BACKGROUND/AIMS: A high response rate with acceptable toxicities is required in the setting of neoadjuvant chemotherapy. Five cases (3 stage IV, 2 stage IIIb) of advanced gastric cancer were successfully treated by neoadjuvant chemotherapy consisting of a combination of S-1 and cisplatin. METHODOLOGY: All 5 patients were men younger than age 60, with no severe complications. S-1 was administered orally (80 mg/m2/day) twice daily for 21 consecutive days, and cisplatin (60 mg/m2) was infused over 2 hours on day 8 with hydration. This schedule was repeated every 5 weeks. After each cycle, the clinical response evaluation was performed with endoscopy, barium meal, and spiral CT scan. Surgery was carried out about 3 weeks after chemotherapy. RESULTS: All patients were responders (100%) after one or two cycles. However, there was no patient with either complete response, or down-staging. Toxicities, according to the WHO criteria, were very mild and none required treatment. Postoperatively one patient died of aspiration pneumonia unrelated to the chemotherapy. The others were discharged within 3 weeks after operation without complications. CONCLUSIONS: S-1 plus cisplatin seems safe and effective as neoadjuvant chemotherapy in advanced gastric cancer patients.     

Hepatic sinusoidal obstruction associated with S-1 plus cisplatin chemotherapy for highly advanced gastric cancer with paraaortic lymph node metastases: report of a case

A 56-year-old man who was diagnosed with gastric cancer with multiple paraaortic lymph node metastases was treated with S-1 plus cisplatin. The spleen gradually enlarged during the therapeutic courses. After the 6th course of therapy, the primary gastric lesion and paraaortic lymphadenopathies disappeared. He underwent a curative resection, including a distal gastrectomy with regional and paraaortic lymph node dissections. Irregularly distributed congestion of the liver was noted during the surgery. Histological examinations revealed residual cancer cells in 3 regional lymph nodes and no cancer cells in the primary site and paraaortic lymph nodes. Hepatic sinusoidal obstruction syndrome (SOS) was also confirmed histologically. This is the first report of a case with SOS after S-1 plus cisplatin therapy. S-1 plus cisplatin therapy can cause SOS, although it is a promising preoperative chemotherapy for highly advanced gastric cancer.     

Neoadjuvant chemotherapy with S-1 and CDDP in advanced gastric cancer

Purpose This retrospective study evaluated the effects of neoadjuvant chemotherapy in advanced gastric cancer.Methods Between 2002 and 2005, we treated 14 patients with advanced gastric cancer (involvement of more than five nodes or tumor invasion into pancreas) and 25 patients with Stage III gastric cancer. The group of 14 patients with advanced gastric cancer received combination chemotherapy with S-1 and cis-diamminedichloroplatinum (CDDP) as a neoadjuvant chemotherapy (NAC). This regimen was repeated every 5 weeks for a total of 2–5 cycles. The 25 patients with Stage III gastric cancer was carried surgery alone (SA). All patients underwent extensive surgery, including gastrectomy, and D2 lymphadenectomy. The rate of response and overall survival in the two groups were compared.Results All patients of NAC group completed the planned regimens of chemotherapy and surgery. Patients of the NAC group had a response rate of 78.6% (95% confidence interval 57.1–100.0%). The most common adverse effect was leukocytopenia (42.9%). However, only four patients (28.6%) had upper Grade 2 leukocytopenia, and all recovered promptly. Postoperative complications were not significant differentiated between NAC and SA group of patients (7.2 vs. 4.0%). Patients in the NAC group had a significantly better survival than those in the SA group (P = 0.03). The median survival has not been reached after 26.9 months of median follow-up for patients in the NAC group. 1-, 2-, and 3-year survival rates were 92.3, 92.3, and 61.5%, respectively. NAC was identified as an independent prognostic factor in all patients (P = 0.018).Conclusion Neoadjuvant chemotherapy with TS-1 + CDDP improves the survival in patients with advanced gastric cancer.     

Efficacy and safety of docetaxel/cisplatin/5-fluorouracil preoperative combination chemotherapy in esophageal cancer patients with extended lymph node metastases

Aim

We retrospectively investigated the efficacy and safety of combination chemotherapy with 5-fluorouracil (5-FU) and cisplatin plus docetaxel (DCF) as preoperative chemotherapy.

Methods

One hundred and seven patients were diagnosed with esophageal cancer of clinical stage II and III (except T4) from March 2007 to June 2009. Among these, five patients who had extensive locoregional lymph node metastases underwent preoperative DCF chemotherapy.

Results

Median age of the five patients was 59 (51–67) years, and all were men with clinical stage III esophageal cancer. The best overall responses were 80% with partial response (PR) and 20% with stable disease (SD). Histological response of grade 1b and more was also 80%. The hematologic toxicities included grade 3 leucopenia in 80% of patients; grade 3 or 4 neutropenia was observed in all patients. Febrile neutropenia occurred in 20% of patients. Nonhematologic toxicities included grade 3 anorexia in 80% of patients. The operations were not postponed due to any adverse events. Postoperative complications included pneumonia, pneumothorax, and cervical lymphatic leakage (one case each). No chemotherapy-related postoperative complications were observed. Median follow-up of surviving patients was 51.5 (33.9–56.4) months. Disease-free survival times were 12.1, 30.9, 48.0, 49.0, and 54.0 months, respectively. Overall survival times were 28.9, 33.9, 51.0, 52.1, and 56.4 months, respectively.

Conclusions

The response rate of preoperative DCF was 80%, and toxicities were tolerated with support therapies such as granulocyte colony-stimulating factor (G-CSF) and dexamethasone. We therefore concluded that this preoperative treatment might be a promising strategy for patients who have extensive regional lymph node metastases.     

Significance of para-aortic lymph node dissection in advanced gastric cancer.

BACKGROUND/AIMS: Since surgical results in advanced gastric cancer remain poor and para-aortic lymph node dissection may contribute to survival, it is useful to determine the significance of para-aortic lymph node dissection. METHODOLOGY: Para-aortic lymph node dissection was provisionally indicated for patients with invasion depth deeper than the subserosal layer. Clinicopathologic variables were retrospectively analyzed using univariate analysis and multivariate analysis to predict para-aortic lymph node metastasis. Similarly, they were analyzed using univariate analysis and the Cox's proportional hazards regression model to estimate the prognostic factor in 120 patients who underwent para-aortic lymph node dissection. Surgical results and post-operative complications were compared between para-aortic lymph node dissection and D2 dissection. RESULTS: Univariate analysis revealed that the mean diameter, the degree of lymph node metastasis, and the invasion depth were significant predictors of para-aortic lymph node metastasis. Multivariate analysis showed that n2 was the only independent predictive factor as to para-aortic lymph node metastasis. Univariate analysis revealed tumor site, tumor diameter, lymph node metastasis, number of positive lymph nodes, INF, and stage were significantly associated with 5-year survival. The Cox's proportional hazards regression model showed that the number of positive lymph nodes and the number of positive para-aortic lymph nodes were independent prognostic factors. Patients with < or = 10 positive lymph nodes in any stage or < or = 3 positive para-aortic lymph nodes in stage IVb had significantly better surgical results. Surgical results for patients who underwent para-aortic lymph node dissection with n2 or invasion depth deeper than the exposed serosa were significantly higher than those in D2. As to post-operative complications, pancreatic fistula and respiratory complications were significantly frequent after para-aortic lymph node dissection. CONCLUSIONS: n2 is helpful in predicting para-aortic lymph node metastasis. Whereas, post-operative morbidity such as pancreatic fistula and respiratory complications after para-aortic lymph node dissection were significantly higher, they were controllable. Para-aortic lymph node dissection should be indicated in advanced gastric cancer patients in which lymph node metastasis is over n2 or invasion depth is deeper than the exposed serosa. But the number of positive para-aortic lymph nodes must be less than three.     

A case report of bi-weekly docetaxel and S-1 combination chemotherapy for gastric cancer with carcinomatous lymphangitis of the lung

A 38-year-old man with complaints of nausea, epigastralgia, cough, and decrease body weight was given a diagnosis of advanced gastric cancer (type 4) with carcinomatous lymphangitis of the lung (UM-circ cT3, N3, H0, P0, M1, stage IV, por2). He was treated with combination of docetaxel (DOC) 40 mg/m(2)/day (days 1, 15) and S-1 orally 80 mg/m(2)/day (days 1-7, 15-21), 1 week administered 1 week rest. After 2 courses of treatment, the patient achieved a partial response in the carcinomatous lymphangitis of the lung. Tumor markers decreased and symptoms improved. He experienced grade 2 peripheral neuropathy but with no grade 3 adverse events. Although the prognosis of gastric cancer with carcinomatous lymphangitis is poor. These results indicate that bi-weekly DOC and S-1 combination chemotherapy might be effective for gastric cancer with carcinomatous lymphangitis of the lung.     

The successfully curative treatment of advanced gastric adenocarcinoma with multiple liver metastases and paraaortic lymph node metastases by salvage operation following the biweekly paclitaxel and S-1 combination chemotherapy: a case report

We report the case of 67-year-old man who was given a diagnosis of advanced gastric adenocarcinoma. Complete response of multiple liver and paraaortic lymph node metastases occurred in this patient after combination chemotherapy with systemic injection of paclitaxel and oral administration of novel dihydropyrimidine- dehydrogenase- inhibitory fluoropyrimidine (S-1). Following 7 courses of the biweekly paclitaxel and S-1 combination chemotherapy, the patient underwent total gastrectomy with D3 extended lymph node dissection. According to the operative findings, the tumor was curatively removed along with the liver metastases and paraaortic lymph node metastases. Biopsy of the liver was performed and the pathological diagnosis indicated no gastric adenocarcinoma cells. The pathological report showed that the lymph node metastases had completely disappeared with single exception and minute cancerous lesions were identified in the gastric mucosa and submucosa. Therefore, the histological efficacy was evaluated as Grade 2. For postoperative chemotherapy, oral S-1 administration only was chosen. However, 6 months later, biweekly paclitaxel and S-1 combination chemotherapy was administered in sequence as a second adjuvant chemotherapy because the serum level of the tumor marker was elevated. The patient is fine and has not shown any recurrence at other sites 37 months after surgery. Salvage surgery following paclitaxel and S-1 chemotherapy may be feasible for patients with advanced gastric cancer and complete regression of distant metastases. Biweekly paclitaxel and S-1 combination chemotherapy has been used safely and its administration may be continued for a long time in an outpatient clinic setting for the treatment of advanced gastric cancer.     

Neoadjuvant chemotherapy with a combination of irinotecan and cisplatin in advanced gastric cancer--a case report

We report a case of advanced gastric carcinoma successfully treated with a combination of irinotecan and cisplatin as neoadjuvant chemotherapy. The patient, a 78-year-old man, had type 2 gastric cancer, which had metastasized to the paraaortic lymph nodes. He was treated with irinotecan, 70 mg on day 1 and day 15, and cisplatin, 80 mg on day 1. The course was repeated every 4 weeks. Two courses of treatment resulted in a marked reduction of both the primary tumor and lymph nodes. Subsequently, the patient underwent curative surgery consisting of total gastrectomy, splenectomy, and D3 lymph node dissection. No surgical complications were observed. On microscopic examination, only a few tumor cells were detected in the granulation tissues of the resected stomach and in the lymph nodes. This would be the first case to demonstrate the effectiveness and the safety of irinotecan and cisplatin used in the neoadjuvant setting for treatment of advanced gastric carcinoma.     

Successful downstaging by S-1-based chemotherapy followed by surgical resections for gastric carcinoma with extensive distant lymph node metastasis - report of two cases and a review of cases with surgical resection after downstaging by S-1-based chemotherapy

We report two cases of gastric carcinoma with successful downstaging using S-1-based chemotherapy followed by surgical resection, which enabled us to confirm the histological effect of chemotherapy. These patients were associated with extensive distant lymph node metastases for which curative resections were unlikely to be performed. We performed anticancer chemotherapy using S-1 with or without concomitant administration of cisplatin in a neoadjuvant setting. After the successful downstaging of these metastatic gastric carcinomas evaluated by imaging analyses, the patients underwent surgical resections. Effect of the chemotherapy was confirmed by the histological analyses. These cases provide further evidence, suggesting that S-1-based chemotherapy enabled downstaging of stage IV gastric carcinoma associated with distant extensive lymph node metastasis and consequently the following possible curative resections. The review of 16 cases of S-1-based chemotherapy followed by surgical resections indicated that, although downstaging may not be expected when N3 lymph node metastases are evident, the S-1-based chemotherapeutic regimens were effective in short cycles for patients in whom potential curative resection is expected. Survival benefit of downstaging followed by surgical resection, however, remains to be further elucidated.     

螺旋CT对胃癌淋巴结转移的评价

目的:探讨胃癌淋巴结转移的螺旋CT特征,从而指导临床合理地制订治疗方案和进行预后分析.方法:回顾性分析经手术病理证实的45例胃癌全阴组和全阳组淋巴结的影像资料,并与病理进行对照研究.结果:螺旋CT检出病理诊断为全阳组和全阴组的各组淋巴结共267个,其中阳性淋巴结有123个,阴性淋巴结有144个.如以平扫CT值≥25Hu或动脉期CT值≥70Hu或静脉期CT值≥80Hu为诊断阳性淋巴结标准,则阳性淋巴结的敏感性高达98.4%,阳性预测值为70.0%;特异性为69.3%,阴性预测值为97.9%.结论:螺旋CT对判断胃癌有无淋巴结转移有重要作用.如以平扫CT值≥25Hu或动脉期CT值≥70Hu或静脉期CT值≥80Hu为诊断阳性淋巴结标准,则将大大提高对淋巴结转移的诊断.     

Combination chemotherapy using TS-1, Paclitaxel and cisplatin for multiple lung metastases from AFP-producing gastric cancer: a case report

A 61-year-old male had undergone distal gastrectomy followed by right hepatectomy for alpha-fetoprotein-producing gastric cancer and liver metastasis. Subsequently, multiple lung metastases were detected by follow-up chest examinations. Despite treatment with TS-1/Irinotecan (CPT-11)/Cisplatin (CDDP) combination therapy, the metastases increased gradually in size and number. Combination therapy with TS-1/Paclitaxel (TXL)/CDDP was effective, as confirmed by marked reduction in tumor size on chest computed tomography. TS-1/TXL/CDDP chemotherapy was administered repeatedly for relapse of lung metastases. The relapse was controlled twice with this chemotherapy regimen, and the patient remains alive at 52 months after gastrectomy without pulmonary symptoms such as hemosputum. Although patients with postoperative lung metastases from AFP-producing gastric cancer have a dismal prognosis, our clinical experience suggests that TS-1/TXL/CDDP combination therapy may be a useful regimen for such conditions.     

Advanced gastric cancer with multiple lymph node metastasis successfully treated with etoposide, adriamycin and cisplatin

Gastric cancer usually shows poor sensitivity to chemotherapy, and the presence of lymph node metastases is associated with extremely poor prognosis, especially when the number of such nodes is more than 10. We report here a case of advanced gastric cancer with histopathologically confirmed metastases in 15 regional lymph nodes, in which the recurrent tumor was sensitive to combination chemotherapy. Distal gastrectomy with lymphadenectomy was performed for the primary tumor. A hard (recurrent) tumor was detected in the upper abdomen 5 months postoperatively. Abdominal CT revealed two tumors measuring 3.5 x 1.8 and 3.3 x 2 cm in diameter at the front of the pancreatic head, which suggested recurrence. Etoposide, adriamycin and cisplatin (EAP) chemotherapy (20 mg/kg adriamycin, 100 mg/kg etoposide and 50 mg/kg cisplatin (CDDP)) was administered every 6 weeks. The tumors regressed and became undetectable on CT after four cycles. At that stage, CDDP was replaced with 400 mg/kg carboplatin, which was administered every 1 or 2 months. The patient had no recurrence 8 years after surgery. For treatment of advanced gastric cancer with multiple lymph node metastases, a wide resection of the tumor should be performed followed by treatment of the residual tumor cells with a suitable combination chemotherapy taking into consideration the characteristics of the tumor and the condition of the host. We present a patient with gastric cancer and histopathologically confirmed metastases in 15 regional lymph nodes, who was successfully treated by surgery followed by EAP adjuvant chemotherapy. The patient remains alive and well at 8 years after surgery.     

胃中部癌前哨淋巴结邻近、横向和跳跃性转移的临床分析

目的探讨胃中部癌前哨淋巴结的分布规律,为合理淋巴结清除提供依据。方法从我院收治的1 825例胃癌患者中选取52例单个转移淋巴结的胃中部癌病例,分析转移淋巴结的位置分布及其与病理分级的关系。结果52例患者中N137例;N1以上15例。小弯侧癌35例,No.3（＋）17例,No.4（＋）5例,No.7（＋）8例;大弯侧癌17例,No.4（＋）7例,No.10（＋）3例。病理分级在N1组和N1以上组间无统计学差异（P〉0.05）。结论胃中部小弯侧癌术中,No.7应被切除,大弯侧癌手术时应注意探查No.10,如怀疑有转移应行脾切除。     

Sentinel lymph node concept in gastric cancer with solitary lymph node metastasis

AIM: To study the localization of the solitary metastases in relation to the primary gastric cancers and the feasibility of sentinel lymph node (SLN) concept in gastric cancer. METHODS: Eighty-six patients with gastric cancer, who had only one lymph node involved, were regarded retrospectively as patients with a possible sentinel node metastasis, and the distribution of these nodes were assessed. Thirteen cases with jumping metastases were further studied and followed up. RESULTS: The single nodal metastasis was found in the nearest perigastric nodal area in 65.1% (56/86) of the cases and in 19.8% (17/86) of the cases in a fairly remote perigastric area. Out of 19 middle-third gastric cancers,3 tumors at the lesser or greater curvatures had transverse metastases. There were also 15.1% (13/86) of patients with a jumping metastasis to N2-N3 nodes without N1 involved. Among them, the depth of invasion was mucosal (M) in 1 patient, submucosal (SM) in 2, proper-muscular (MP) in 4, subserosal (SS) in 5, and serosa-exposed (SE) in 1. Five of these patients died of gastric cancer recurrence at the time of this report within 3 years aftersurgery. CONCLUSION: These results suggest that nodal metastases occur in a random and multidirectional process in gastric cancer and that not every first metastatic node is located in the perigastric region near the primary tumor. The rate of “jumping metastasis” in gastric cancer is much higher than expected, which suggests that the blind examination of the nodal area close to the primary tumor can not be a reliable method to detect the SLN and that a extended lymph node dissection (ELND) should be performed if the preoperative examination indicates submucosal invasion.     

Conversion surgery after S-1 plus oxaliplatin combination chemotherapy for advanced gastric cancer with multiple liver metastases

Conversion therapy for gastric cancer is a new therapeutic concept. We report a case of a patient with advanced gastric cancer who underwent conversion surgery due to a remarkable regression of multiple liver metastases following chemotherapy. A 71-year-old man was referred to our hospital with gastric cancer. Esophagogastroduodenoscopy (EGD) revealed an irregular, nodular, ulcerated lesion in the lower third of the stomach. Analysis of biopsy specimens revealed a poorly differentiated adenocarcinoma. Abdominal contrast-enhanced computed tomography (CT) showed multiple liver mass lesions. The patient was clinically diagnosed with advanced gastric cancer with liver metastases and received S-1 plus oxaliplatin chemotherapy. After 6 cycles of chemotherapy, CT and magnetic resonance imaging showed complete resolution of the liver metastases, and EGD detected mucosal irregularities only. Since there was no evidence of further metastatic lesions in other organs, the patient underwent distal gastrectomy with D2 lymphadenectomy. The gross appearance of the surgically resected specimen showed a slightly elevated tumor measuring 4.5?×?3.5 cm. Pathological examination confirmed the diagnosis of a moderately differentiated gastric adenocarcinoma invading the muscularis propria with no lymph node metastases. The postoperative course was uneventful. The patient has continued to receive S-1 and oxaliplatin chemotherapy, and there has been no evidence of recurrence for 3 months following the operation. We propose that conversion therapy might be an effective treatment for patients with advanced gastric cancer; however, further studies and assessments are needed to confirm and establish this treatment strategy.     

Adjuvant chemotherapy indications for stage I gastric cancer patients with negative lymph node

PurposeWhether adjuvant chemotherapy (AC) has a survival benefit for pathological stage Ⅰ (T1N0 and T2N0) gastric cancer (GC) patients with negative lymph node (N0) remains controversial.MethodsPatients with surgically resected, histologically confirmed pT1N0 and pT2N0 GC between January 2011 and December 2017 at the National Cancer Center, China, were retrospectively reviewed.ResultsA total of 1601 patients who met the inclusion criteria were identified. Independent risk factors for reduced overall survival (OS) identified in the Cox regression analysis were male sex (hazard ratio [HR] 1.454, 95% confidence interval [CI] 1.127–1.876), age ≥ 65 years (HR 1.367; 95% CI 1.071–1.744 ), T2 stage (HR 1.283; 95% CI 1.005?1.638), tumor size > 3 cm (HR 1.704; 95% CI 1.346?2.158), examined lymph nodes (EN) ≤ 15 (HR 1.327; 95% CI 1.058–1.664), and non-signet ring cell carcinoma (Non-SRCC) (HR 1.639; 95% CI 1.123–2.392). While only T2 stage (HR 1.410; 95% CI 1.026?1.936), tumor size > 3 cm (HR 1.755; 95% CI 1.285?2.397), examined lymph nodes (EN) ≤ 15 (HR 1.489; 95% CI 1.101–2.015) were independent risk factors for cause-specific survival (CSS). We divided patients with pT2N0 into four sub-categories according to two significant prognostic factors (size and EN) and found that only patient in group 3 (EN ≤ 15, size >3 cm) with improved CSS benefit from AC (p = 0.049). More significant CSS benefit from AC was identified in Non-SRCC patients within group 3 (p = 0.034).ConclusionAn additional survival benefit related to AC is expected for selected pT2N0 patients. Non-SRCC patients with EN ≤ 15 and tumor size >3 cm may be particularly appropriate candidates for AC.     

Third-line chemotherapy with paclitaxel, irinotecan hydrochloride and cisplatin for recurrent gastric cancer: a case report

With the availability of new chemotherapeutic agents such as S-1 and paclitaxel (TXL) for advanced gastric cancer, the development of a strategy for a third-line chemotherapy is urgently needed. We treated a patient with recurrent gastric cancer using TXL, irinotecan hydrochloride (CPT-11) and cisplatin (CDDP) as a third-line chemotherapy. The patient was a 46-year-old man who had undergone total gastrectomy for advanced gastric cancer with lymph node metastases. For postoperative recurrence, he was first treated with S-1 as an outpatient; however, tumor markers increased, and para-aortic lymph node metastasis was revealed by thoracic and abdominal CT scan. A second-line therapy with weekly TXL and CDDP was then added, but resulted in PD. Therefore, combination chemotherapy with TXL, CPT-11 and CDDP was started biweekly as a third-line chemotherapy. TXL (80mg/m2) was infused over 1 hour after short premedication, followed by CPT-11 (25mg/m2) and CDDP (15mg/m2) over 30 min. After 6 courses of this therapy, the serum AFP and TPA returned to normal, and the size of the metastatic para-aortic lymph nodes reduced. The effect of this therapy was judged as PR and the toxicity of this regimen was tolerable. The patient has undergone 10 courses of this therapy and is maintaining a clinical PR. The patient was able to resume his full social activities. TXL, CPT-11 and CDDP combination chemotherapy may be useful and safe for patients with recurrent gastric cancer, even after first-or second-line therapy with S-1 or taxanes.