Peritoneal lavage cytology under local anesthesia for detection of peritoneal recurrence after surgery

Gastric cancer with positive peritoneal lavage cytology shows a very poor prognosis due to frequent peritoneal recurrence after surgery. Therefore, we have introduced neoadjuvant intra-peritoneal and systemic chemotherapy( NIPS) for gastric cancer with peritoneal microscopic and/or microscopic dissemination before surgery. In patients subjected to the strategy, we have experienced two cases of advanced gastric cancer with CY1, which had been treated with NIPS and curative surgery, had been performed with second peritoneal lavage cytology two years after surgery. In those two cases, S-1 was discontinued due to the negative results of peritoneal lavage cytology. We will present the cases.     

Neoadjuvant chemotherapy for gastric cancer with peritoneal dissemination

An early detection and treatment of gastric cancer with peritoneal dissemination are rather difficult so that a clinical trial has been neglected. Therefore, we introduced a pre-operative peritoneal lavage diagnosis for gastric cancer patients with serosa-invaded tumors. Neoadjuvant chemotherapy was introduced to patients with positive cytology and with no non-curative factors except peritoneum. The neoadjuvant chemotherapy followed by surgery was done safely. The patients with the disappearance of CY and P factors due to neoadjuvant chemotherapy had a better prognosis than those with positive results of CY or R However, many of the patients with negative results from peritoneum eventually suffered a peritoneal recurrence. We started another protocol study with S-1 and an intra-peritoneal chemotherapy using docetaxel. The efficacy in the protocol result will be expected.     

Treatment strategy for marginally resectable gastric cancer

It has been postulated that preoperative chemotherapy might promote tumor regression, eradicate nodal metastases, and improve resectability in patients with marginally resectable gastric cancer.For a marginally resectable tumor of gastric cancer, we selected the advanced gastric cancer patients with metastases and recurrences to the abdominal para-aortic lymph node (PAN), liver and invasion to the pancreas head and/or the duodenum.Patients with positive peritoneal cytology(P0, CY1)or localized peritoneal metastasis(P1), and Stage IV gastric cancer patients, were also considered candidates in this category. The strategy and results of surgical treatment for marginally resectable gastric cancer were explained as the dissection of PAN, hepatic resection, pancreaticoduodenectomy, perioperative chemotherapy for P0CY1 or P1, and neoadjuvant chemotherapy for Stage IV gastric cancer, which was still considered an experimental approach, although its use may be justified in unresectable or marginally resectable GC.The result of the resection of a marginally resectable gastric cancer is poor, but when there are no other non-curative factors, extended surgical resection should be performed because complete response is difficult at present with chemotherapy alone.In conclusion, there was no evidence suggesting that extended surgical procedures are effective, but a strategy of multidisciplinary treatment including extended surgical approach should be verified based on randomized controlled trials.     

Treatment strategy for the type IV gastric cancer--from the standpoint of the surgery

From the standpoint of the surgery, the treatment strategy for the type IV gastric cancer (GC) was studied. Recently, the resected rate of type IV GC has been increasing, though the number of operated GC patients is decreasing. The five-year survival rate was about 20% in all and around 30% in the curatively resected pts. As a result of examination of our pts with type 4 GC, multimodality therapy including neoadjuvant chemotherapy and extended surgery is recommended for pts with P 0/CY 0 or P 0/CY 1 but without other remaining GC lesions. Palliative gastrectomy and postoperative chemotherapy are recommended if performed safely to prevent such symptoms in spite of unresectable metastasis for pts with urgent symptoms such as bleeding, stricture, pain or malnutrition. For pts with P 2/P 3 but without passage disturbance, intensive chemotherapy is selected. But the propriety for selection of reduction surgery for pts with P 2/P 3 is controversial. The results of the prospective randomized controlled study of reduction surgery in non-curative advanced gastric cancer by the Gastric Cancer Surgical Study Group in Japan Clinical Oncology Group (JCOG) are expected.     

Postoperative chemotherapy with a novel oral anticancer drug composed of tegafur, gimeracil and oteracil potassium to curability C scirrhus type gastric cancer

We report the a case of 60-year-old male whose final finding was curability C and stage IV scirrhus type gastric cancer because of N3, CY1 and DM (+) treated with a novel oral anticancer drug composed of tegafur (FT), Gimeracil (CDHP) and Oteracil Potassium (Oxo) in a molar ratio of 1:04:1 after operation. This drug was administered orally twice daily after meals at a dose of 80 mg/body/day. One cycle consisted of consecutive administration for 28 days and 14 days rest, and this treatment cycle was repeated twice. Postoperative abdominal CT showed swollen paraaortic lymph nodes regarded as metastasis. However, they were reduced after 1 cycle and remained so. The serum carcinoembryonic antigen (CEA) level had decreased after 1 cycle. The patient's performance status (PS) had also recovered without severe side effects. It was considered that this anticancer drug composed of FT, CDHP and Oxo was effective to scirrhus type gastric cancer and useful as an adjuvant chemotherapy in view of the patient's living quality.     

Preoperative combination chemotherapy with TS-1 is effective in a case gastric cancer with peritoneal dissemination

We report a case of peritoneal cancer dissemination with Type 4 gastric cancer, successfully treated with combination chemotherapy with TS-1. The patient was a 59-year-old female, who complained of abdominal distension with pain, weight loss, and poor appetite. She was diagnosed as unresectable Type 4 gastric cancer, T3N2MOHOP1CY1M0, Stage IV with massive ascites (cytology: Class V). After 2 courses of combined chemotherapy with TS-1 and cisplatin (CDDP), primary tumor reduction was confirmed and no cancer cells were detected from a pathological investigation with biopsied specimens by endoscopy. As additional therapy for remained ascites, intraperitoneal administration of paclitaxel and docetaxel was performed, resulting in a remarkable decrease of ascites with cytological disappearance of cancer cells. The patients underwent total gastrectomy with lymph node dissection, pathological diagnosis of primary site and lymph nodes showed grade 2 effect, and no cancer cells were detected in ascites and peritoneum, microscopically. While she died of peritoneal recurrence after the surgery, the case suggested the clinical advantage of controlling the advanced cancer-bearing state by combination chemotherapy with TS-1, instead of surgery.     

Two elderly patients with advanced gastric cancer responding to chronomodulation chemotherapy with tegafur + cisplatin + isovorin followed by oral administration of S-1

Recently, as society ages there have become more elderly gastric cancer patients with/without several complications(cerebrovascular diseases, cardiac diseases, atherosclerosis, DM, etc.), that were non-resected and require highly effective chemotherapy and good QOL. We report two elderly gastric cancer patients responding to chronomodulation chemotherapy (tegafur + cisplatin + Isovorin) based on circadian rhythms plus a new antitumor drug, S-1. The treatment protocol was tegafur 800 mg/body, days 1-7 (continuing 16 h, intravenously with 500 mg/body from 16 to 0 h, 300 mg/body from 0-8 h, for non-uniform administration), cisplatin 10 mg/body, days 1-5, (16 h), Isovorin 25 mg/body, days 1-5, (16 h, oneshot infusion, for 4 courses followed by a week rest. Next was S-1 120 mg/body x 2 times orally for 28 days, followed by 2 weeks rest, the administered for another 28 days. The first patient was 74 years of age, with advanced type 3 plus early type IIc gastric cancers with liver metastasis (H1). After chemotherapy the liver metastasis disappeared, there was a 70% reduction in the advanced cancer and the early cancer disappeared. The second patient was 84 years of age, with advanced type 3 gastric cancer invading the esophagus. After chemotherapy, the primary lesion was reduced 80% and the esophageal invasion mass shrunk. The only adverse effect was grade 2 pancytopenia. In conclusion this regimen resulted in good intrachemotherapeutic QOL and highly effective performance in elderly advanced gastric cancer patient.     

Evaluation of positive cases with peritoneal lavage cytology in gastric cancer

Peritoneal dissemination with advanced gastric cancer is of significant problem. Peritoneal lavage cytology has been an effective method for the detection of early peritoneal dissemination since 1999. The accurate evaluation of peritoneal lavage cytology is unclear except for the same prognosis of peritoneal dissemination. We examined the clinical findings and the prognosis with positive cases in peritoneal lavage cytology. The prognosis of cases with P1CY1 or P2P3 group was poorer than in the P0CY1 or P0, CY1 group. We thus review the evaluation of peritoneal lavage cytology with gastric cancer in the Japanese and English literature. In addition, we describe the diagnosis of early peritoneal dissemination using peritoneal lavage tumor markers or molecular markers of peritoneal lavage.     

A case of recurrent pleural effusion and positive cytology of advanced gastric cancer treated by TS-1 plus weekly taxane as second-line chemotherapy

A second-line chemotherapy for advanced gastric cancer has not been established. We report a case of good response in a 39-year-old woman who had recurrent pleural effusion and positive cytology of type 4 gastric cancer and was treated with TS-1, a DPD inhibitory fluoropyrimidine, in combination with weekly taxane. After a partial response for type 4 gastric cancer from the treatment with 2 courses of TS-1 plus low-dose cisplatinum (CDDP), followed by outpatient chemotherapy with TS-1 alone or TS-1 plus weekly CDDP, left pleural effusion appeared and CA19-9 increased during the 7th course of the chemotherapy. Cytology of the effusion was class IV. The patient was treated with a course of TS-1 (120 mg/day, day 1-21) plus paclitaxel (50 mg/m2, day 1, 8) followed by 2 week washout. In the following courses, paclitaxel was replaced with docetaxel (30 mg/m2, day 1 and 8) and the course was continued in the outpatient setting. After 2 courses, the left pleural effusion disappeared and remained absent after 6 courses. Gastric biopsy showed no cancer cells and abdominal CT showed no recurrence. Serum CA19-9 doubled 1 week after taxane treatment and decreased gradually week by week during the course. This case suggests that a combination of TS-1 and taxane is effective against recurrent pleural effusion of advanced gastric cancer and useful as a second-line chemotherapy.     

Preoperative diagnostic laparoscopy with local anesthesia and lavage telomerase activity for advanced gastric cancer

A pretherapeutic staging system to design operative or neoadjuvant treatments in gastric cancer is needed. In this study, a simple staging system based on diagnostic laparoscopic findings under local anesthesia to define a treatment was developed. This study was conducted with 68 patients with advanced gastric cancer. All the patients had been diagnosed as more than T3, or were suspected to have peritoneal seeding. Preoperative diagnostic laparoscopy under local anesthesia was performed in the operation room. After insertion of the trocars, the abdominal cavity was inspected, and biopsy and/or abdominal lavage sampling was performed. Patients were allocated into three stages based on laparoscopic and histopathologic findings. Twenty-eight out of 68 patients were diagnosed as P1, 34 patients as P0CY0 and 6 as P0CY1. Based on these results, 57 patients underwent operation. The accuracy rate of diagnosis was 95% in the P category, and 93% in the CY category. Lavage telomerase activity was examined on 10 patients with P0CY0 gastric cancer. Two out of 10 were positive for this activity, and both of them had died due to peritoneal recurrence within a year after operation. In conclusion, the proposed diagnostic laparoscopic staging system is a simple and reproducible method for selection of a suitable therapy. It is considered that diagnostic laparoscopy under local anesthesia is a useful preoperative examination in cases of advanced gastric cancer. Moreover lavage telomerase activity may be a more sensitive predictor of peritoneal recurrence than lavage cytology.     

Pathological Features of Gastric Cancer in Zhuanghe High-risk Area in China during 1992-2005

Objective:To investigate the pathological features and chronological changes of 1003 cases with gastric cancer in Zhuanghe high-risk area during 1992-2005 and the relationship between the changes and etiology factors in order to make a clue for gastric cancer prevention.Methods:A total of 1003 gastric cancer specimens resected surgically between 1992-2005 in Zhuanghe Center Hospital were studied.The specimens were fixed in formalin and diagnosed by routine pathology. Results:The incidence of patients wit...     

替吉奥治疗晚期胃癌临床观察

目的观察替吉奥治疗晚期胃癌的近期疗效及毒副反应。方法对20例具有可测量指标的晚期胃癌患者采用替吉奥胶囊治疗:替吉奥胶囊80 mg.m-2.d-1,分2次口服,连服14 d,21 d为1周期,连用3周期,休息1个月评价疗效及毒副反应。结果 20例患者中,CR 1例,PR 8例,SD 8例,PD 3例,总有效率45%。主要毒副反应为厌食、恶心、呕吐、皮肤色素沉着、白细胞减少等。结论替吉奥治疗晚期胃癌具有较好疗效,毒副反应轻,特别适宜于年老体弱患者。     

A case of advanced gastric cancer responding to paclitaxel/CDDP neoadjuvant chemotherapy leading to pathologically complete response

A 74-year-old male with advanced gastric cancer(cT3N1M0H0P0CY0, cStage III A)was treated with paclitaxel/ CDDP as neoadjuvant chemotherapy. Paclitaxel (80 mg/m(2)) and CDDP (25 mg/m(2)) were administered on days 1, 8 and 15 as one cycle. After the second course, a significant tumor reduction was obtained. Total gastrectomy, splenectomy, and D2 type nodal dissection were performed. The histological diagnosis revealed complete disappearance of cancer cells in the stomach and all of the lymph nodes, a so-called pathologically complete response. The patient has now been in good health without any recurrence for 9 months after surgery. This case suggests that neoadjuvant chemotherapy with paclitaxel/CDDP is a potential regimen for advanced gastric cancer.     

A feasibility study of sequential paclitaxel and S-1 (PTX/S-1) chemotherapy as postoperative adjuvant chemotherapy for advanced gastric cancer

Background The most frequent recurrence pattern of advanced gastric cancer is peritoneal dissemination. We investigated the safety of and compliance with sequential chemotherapy consisting of paclitaxel and S-1, both of which are effective in the treatment of peritoneal dissemination. Methods The patients in the study all had histologically proven gastric cancer, classified according to the TNM and the Japanese criteria for gastric cancer as T3–4, N0–2, P0, H0 M0, and CY0–1. In all patients, standard gastrectomy of more than a D2 dissection was performed. A dose of 80 mg/m² of paclitaxel was administered for three courses. One course comprised weekly administration for 3 weeks, followed by a 1-week rest, except for the first course (following S-1 administration at 80 mg/m² body surface area), in which paclitaxel was administered for only 2 weeks, followed by a 1-week rest. S-1 was administered from day 78 for four courses, with one course comprising 2 weeks' administration followed by a 1-week rest. Fifty patients received paclitaxel chemotherapy. The median age was 62.5 years overall; among the 34 male patients it was 65.5 years, and among the female patients it was 48.0 years. Results The patient compliance rate was 84%. There were no cases of grade 4 hematological toxicity during either paclitaxel or S-1 treatment. With respect to nonhematological toxicities, there was one case of grade 3 neuropathy during the course of paclitaxel treatment and one case of grade 3 diarrhea during the course of S-1 treatment. These patients recovered and completed the scheduled treatment regimen. Conclusion Sequential chemotherapy of paclitaxel and S-1 as postoperative adjuvant chemotherapy for advanced gastric cancer is feasible.     

Low-dose paclitaxel therapy as second-line chemotherapy for patients who previously received TS-1 therapy

TS-1 is often used as first-line chemotherapy for treatment of advanced or recurrent gastric cancer, but there is no definite therapeutic policy for patients for whom TS-1 is not effective, or to whom it cannot be administered. We have treated 6 patients with low-dose weekly paclitaxel therapy as second-line chemotherapy after initial treatment with TS-1. These patients consisted of 3 males and 3 females with a mean age of 56 years. Four patients had recurrent gastric cancer and two had unresectable advanced gastric cancer. Paclitaxel was administered in doses of 80 or 100 mg weekly. Adverse events more severe than grade 3 were not observed, but there were 2 cases of leukopenia (grade 1) and 2 cases of decreased hemoglobin (grade 2). Mean survival time after the administration of paclitaxel was 139 days. Five patients died of their cancer, and one is still alive 382 days after the paclitaxel administration. The one-year survival rate after administration was 16.7%. Low-dose weekly paclitaxel therapy is therefore safe and effective for patients with advanced and recurrent gastric cancer who previously received TS-1 therapy.     

Successful downstaging by a low-dose, fractional administration of irinotecan hydrochloride (CPT-11) in combination with cisplatin in peritoneal lavage cytology positive, 5-fluorouracil refractory advanced gastric cancer patients

A 46-year-old Japanese female with advanced gastric cancer with positive peritoneal cytology and who was refractory to methotrexate plus 5-FU sequential chemotherapy received low-dose, fractional irinotecan hydrochloride (CPT-11) in combination with cisplatin. This regimen could be repeated biweekly on an outpatient basis and was well tolerated. After 8 cycles of administration, a negative change in peritoneal cytology subsequently enabled a total gastrectomy, splenectomy, and cholecystectomy with a D3 lymph node dissection. The rationale for a low-dose, fractional administration of CPT-11 in combination with cisplatin is the synergistic antitumor activity obtained through the ability of SN-38 to potentiate cisplatin-induced cytotoxicity, as well as the increased therapeutic efficacy of a protracted CPT-11 administration over more intense treatment schedules. As far as we are aware, this case report demonstrates for the first time that a low-dose, fractional administration of CPT-11 with cisplatin can successfully produce a negative change in peritoneal lavage cytology, and potentiates a R0 resection in a 5-FU resistant advanced gastric cancer patient. This suggests that this combination could be an effective regimen for potentially disseminated, 5-FU resistant patients.     

Three cases of advanced gastric cancer resected after successful treatment with the novel oral anticancer drug TS-1

We operated on 3 patients with advanced gastric cancer after successful treatment with novel oral 5-fluorouracil derivatives (TS-1). In all 3 patients, gastrointestinal fiberscopy revealed a considerable reduction in the tumor after oral administration of TS-1 in our clinic. Case 1 underwent surgery after an interval of 1 day following oral administration of TS-1 for 18 days. Pathologically, no cancer cells were found in the resected stomach and a few cancer cells were found only in resected lymph nodes. In case 2, who underwent surgery after an interval of 7 days following oral administration of TS-1 for 14 days, a few cancer cells were found only in the submucosal layer of the stomach and no viable cancer cells remained in the metastasized lymph nodes. In case 3, who underwent surgery after an interval of 11 days following administration of TS-1 for 26 days, scattered cancer cells, mostly fibrotic, were found as far as the subserosal layer. The pathological effectiveness of chemotherapy was grade 2 or 3 in each case. Case 2 and 3 followed a satisfactory postoperative course; however, case 1 suddenly had endotoxinemia on the 7th postoperative day. Although the patient had temporary multiple organ failure, he recovered eventually. All 3 patients have been well without any signs of recurrence for more than a year after surgery.     

热疗联合顺铂与多西他赛化疗治疗晚期胃癌腹水的临床观察

为了探讨热疗联合化疗治疗晚期胃癌腹水的临床疗效,对9例伴有腹水的晚期胃癌患者,利用内生场局部热疗仪治疗腹部转移病灶,加温至41℃,持续1h,配合顺铂40 mg/m2腹腔给药,多西他赛30 mg/m2静脉滴入化疗,均每周1次,连续3周为1个周期.观察腹水疗效、腹部实体病灶缓解程度和热化疗后的不良反应.结果热化疗后9例患者中有3例腹水消退,6例腹水得到控制;腹部可测量病灶部分缓解4例,稳定2例;没有出现热化疗不良反应叠加.初步研究结果提示,热疗联合顺铂腹腔给药与多西他赛静脉滴入能够较好控制晚期胃癌腹水,并可获得较好的局部病灶缓解.     

A case of gastric cancer with multiple liver metastases responding to TS-1

We report the case of a 58-year-old male with Stage IV gastric cancer accompanied by multiple liver metastases, which responded to chemotherapy using TS-1. The patient was treated with daily oral administration of 120 mg TS-1 for 4 weeks followed by 2 weeks rest as 1 cycle. After 4 cycles, most of the liver metastases had disappeared and serum CEA level was reduced from 140 to 53.9. The patient received chemotherapy at our outpatient clinic for 9 months during which time there was no regrowth after the first treatment. The current case suggests that TS-1 may have a potent therapeutic efficacy in cases of advanced gastric cancer.     

Analysis of four patients with advanced gastric cancer undergoing gastrectomy after pre-operative combination chemotherapy using docetaxel, cisplatin and S-1

We analyzed the clinical efficacy of pre-operative combination chemotherapy using docetaxel, cisplatin and S-1 for advanced gastric cancer. Four patients were enrolled and staging laparoscopy was performed. Patients received intravenous docetaxel and cisplatin (35 mg/m2) on day 1 and 15, and oral S-1 80 mg/m2 on day 1-14 every 4 weeks. Two patients received two courses of chemotherapy and two patients received three courses of chemotherapy. Neutropenia of more than grade 3 was found in 3 cases. All cases were PR on preoperative imaging. Curative operation was performed on three cases. Histological anti-tumor effect was judged to be grade 2 in 1 case and grade 1a in 3 cases. In the postoperative period, all patients received S-1-based adjuvant chemotherapy. The combination chemotherapy using docetaxel, cisplatin and S-1 plus operation was a candidate for the standard treatment strategy for advanced gastric cancer.