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.     

A case of recurrent gastric cancer patient with peritoneal dissemination who obtained a long-term survival and QOL by multi-modality therapy

We report a case of recurrent gastric cancer patient with peritoneal dissemination who obtained a long-term survival and QOL by multi-modality therapy. A 54-year-old woman underwent a total gastrectomy against type 4 gastric cancer (por 2 ss ly1 v1 n0, pT2 pN0 sH0 sP0 sCY0 sM0, fStage IB). After two years, multiple stenoses due to peritoneal dissemination occurred consecutively. Multi-modality therapy combining operation, chemotherapy, and IVR was applied. Symptoms due to stenoses were decreased and a long-term survival was successfully acquired.     

A case of type 4 gastric cancer with peritoneal dissemination treated with intra-aortic chemotherapy]

A 45-year-old woman was admitted to our hospital because of lower abdominal pain and anorexia. A barium gastrography and gastroscopy showed a type 4 gastric cancer in the upper gastric body. Histologic study on biopsy specimens from the tumor revealed poorly differentiated adenocarcinoma. Computed tomography revealed bilateral hydronephrosis, and barium enema showed diffuse stenosis of the sigmoid colon because of peritoneal dissemination. This patient was treated by intra-aortic infusion therapy with sequential MTX and 5-FU. After five courses of the administration, barium enema revealed reexpansion of the lumen of sigmoid colon with normalization of the tumor markers. The patient was discharged without symptoms. Intra-aortic infusion therapy with sequential MTX and 5-FU was considered an effective treatment for unresectable gastric cancer.     

A case of long-term survival of 5 years after operation and chemotherapy for type 4 gastric cancer with peritoneal dissemination

We report a case of long-term survival of 5 years after operation and chemotherapy for type 4 gastric cancer with peritoneal dissemination. A 41-year-old woman underwent total gastrectomy for type 4 gastric cancer with peritoneal dissemination and pancreas invasion. After operation, chemotherapy with S-1 plus PSK therapy, S-1 plus CDDP, and S-1 plus DOC was performed. The regimen of S-1 plus CDDP included S-1 on day 1-5, 8-12, 15-19, 22-26 and 2 weeks rest and PSK daily. After S-1 plus PSK therapy(34th course), peritoneal recurrence caused ileus, so a right hemicolonectomy was performed. Now the patient is undergoing weekly paclitaxel. The S-1 plus PSK therapy is able to prolong time to progression and has fewer adverse effects.     

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves the survival of gastric cancer patients with ovarian metastasis and peritoneal dissemination

The prognosis for ovarian metastasis of gastric cancer is poor. There is no currently available treatment for this disease. The purpose of this study was to evaluate the efficacy and safety of hyperthermic intraperitoneal chemotherapy (HIPEC) after cytoreductive surgery (CRS) in female gastric cancer patients with metachronous ovarian metastasis. From January 2000 to December 2010, 62 patients developed ovarian metastasis after undergoing gastrectomy with D2 lymphadenectomy. Thirty-two patients underwent CRS plus HIPEC, and 30 patients underwent CRS alone. The median age of all 62 patients was 44 years (range 19–71 years). Metastatic carcinoma involving bilateral ovaries was observed in 50 patients (80.6 %). The median survival time in the CRS?+?HIPEC group was 15.5 months (95 % confidence interval [CI] 12.1–18.9 months) but was only 10.4 months (95 % CI 8.5–12.2 months) in the CRS group (P?=?0.018). Among the 32 patients with pelvic peritoneal metastasis, a stratified analysis revealed that the median survival period for the 15 patients treated with CRS?+?HIPEC was significantly higher than that for the patients treated with CRS alone (P?=?0.046). Among the 30 patients who suffered from ovarian metastasis alone, the median survival times were similar in both groups (P?=?0.141). A multivariate analysis revealed that CRS?+?HIPEC and a low Peritoneal Cancer Index (PCI) were independent predictors for improved survival. In conclusion, our study indicates that employing the HIPEC procedure after CRS could improve the survival time of patients with ovarian metastasis with few complications; however, we do not recommend HIPEC treatment for ovarian metastasis alone.     

Intraperitoneal chemotherapy in gastric cancer patients with peritoneal dissemination

Peritoneal dissemination is one of the non-curative factors in gastric cancer and colon cancer. Although many treatments have been conducted for peritoneal dissemination, no standard chemotherapy has yet been established. For sometime we had used continuous hyperthermic peritoneal perfusion (CHPP)for peritoneal dissemination in gastric cancer and colon cancer. CHPP has a marked survival benefit for scirrhous type gastric cancer patients without liver metastasis. Patients with prophylactic CHPP have significantly better prognoses than those without prophylactic CHPP, and therapeutic CHPP has a survival benefit for gastric cancer patients with slight to moderate peritoneal dissemination (P 1-2). But CHPP has no significant prognostic benefit for gastric cancer patients with severe peritoneal dissemination (P 3). Therefore, a new cancer treatment is needed for those patients. On the other hand, many kinds of anticancer agents, including cisplatin, via intraperitoneal (ip) administration have been tried thus far for peritoneal dissemination therapy. Especially, intraperitoneal taxane anticancer agent is very effective for the treatment and local control of severe peritoneal dissemination in gastric cancer. A phase I/II study of taxane anticancer agents via ip administration should be tried in gastric cancer patients with peritoneal dissemination.     

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.     

ARAP3 inhibits peritoneal dissemination of scirrhous gastric carcinoma cells by regulating cell adhesion and invasion

During the analysis of phosphotyrosine-containing proteins in scirrhous gastric carcinoma cell lines, we observed an unusual expression of Arf-GAP with Rho-GAP domain, ankyrin repeat and PH domain 3 (ARAP3), a multimodular signaling protein that is a substrate of Src family kinases. Unlike other phosphotyrosine proteins, such as CUB domain-containing protein 1 (CDCP1) and Homo sapiens chromosome 9 open reading frame 10/oxidative stress-associated Src activator (C9orf10/Ossa), which are overexpressed and hyperphosphorylated in scirrhous gastric carcinoma cell lines, ARAP3 was underexpressed in cancerous human gastric tissues. In this study, we found that overexpression of ARAP3 in the scirrhous gastric carcinoma cell lines significantly reduced peritoneal dissemination. In vitro studies also showed that ARAP3 regulated cell attachment to the extracellular matrix, as well as invasive activities. These effects were suppressed by mutations in the Rho-GTPase-activating protein (GAP) domain or in the C-terminal two tyrosine residues that are phosphorylated by Src. Thus, the expression and phosphorylation state of ARAP3 may affect the invasiveness of cancer by modulating cell adhesion and motility. Our results suggest that ARAP3 is a unique Src substrate that suppresses peritoneal dissemination of scirrhous gastric carcinoma cells.     

Cytoreductive surgery and sandwich therapy with chemohyperthermic peritoneal perfusion and intra-aortic chemotherapy for peritoneal dissemination in gastric cancer

Cytoreductive resection (RST), chemohyperthermic peritoneal perfusion (CHPP) and/or intra-aortic chemotherapy (IA-chemo) were performed for peritoneal dissemination in gastric cancer. Ninety-six patients with peritoneal dissemination were grouped into tubercular (TB), 40; nodular (ND), 31; diffuse (DF) type, 19; and others, 6, respectively, by the gross findings. Sixty-three patients underwent RST. Fifty-nine patients received CHPP by 10-liter heated saline. Thirty patients underwent intra-aortic catheterization for the IA-chemo. The 1-year and 2-year survival rate (1-ysr and 2-ysr) of the RST(+) group were 47% and 10% significantly greater than the 9% and 0% of the RST(-) group (p<0.001). The 1-ysr and 2-ysr of the CHPP(+) group were 37% and 11% significantly greater than the 27% and 0% of the CHPP(-) group (p=0.04). In the TB type the 1-ysr and 2-ysr of the former was 43% and 8% significantly greater than the 15% and 0% of the latter (p=0.04). But there was no significant difference in survival time between the CHPP(+) and the CHPP(-) group in the ND type (p=0.22) or in the DF type (p=0.42). The 1-ysr and 2-ysr of the IA-chemo(+) group were 49% and 19% significantly greater than the 27% and 2% of the IA-chemo(-) group (p<0.01). In the DF type the 1-ysr and 2-ysr of the former was 50% and 33% significantly greater than the 8% and 0% of the latter (p=0.02). However, there was no significant difference in survival time between the IA-chemo(+) and the IA-chemo(-) group in the TB type (p=0.06) or in the ND type (p=0.50). Moreover, the effect of the combination therapy of CHPP and IA-chemo (the sandwich therapy, SDW) were examined. The 1-ysr and 2-ysr of the SDW(+) group were 49% and 22% significantly greater than the 24% and 0% of the SDW(-) group (p=0.002). The sandwich therapy should be performed in addition to cytoreductive surgery for improvement of prognosis in the patient with intractable peritoneal dissemination.     

A case of long survival with UFT and lentinan treatment in a patient with peritoneal metastasis of gastric carcinoma

The patient was a 50-year-old female with peritoneal metastasis of Type 4 gastric cancer. She underwent a relative curative resection with total gastrectomy and peritonectomy. Postoperative chemotherapy with 5'-DFUR following 5-FU and CDDP was performed. Thirteen months after surgery, cancer recurrence was suspected due to elevated levels of the serum tumor markers carcinoembryonic antigen (8.9 ng/ml) and alpha fetoprotein (85.8 ng/ml). She was additionally treated with UFT 300 mg/day and Lentinan 2 mg/week. The serum tumor markers decreased gradually returned to normal levels. At 5 years and 8 months after surgery, she is alive without any sign of recurrence.     

A case of gastric cancer with peritoneal dissemination responding to combination chemotherapy with oral fluoropyrimidine and weekly paclitaxel

We report a case in which combination chemotherapy with oral fluoropyrimidine and weekly paclitaxel was effective for gastric cancer with peritoneal dissemination. A 44-year-old woman suffering from advanced gastric cancer with peritoneal dissemination underwent total gastrectomy. After surgery, combination chemotherapy with doxifluridine plus weekly paclitaxel was administered on an outpatient basis, and was effective without any sign of relapse of the disease for a year. However, she complained of dull abdominal pain, and ascites was observed 13 months after surgery. She received combination chemotherapy with S-1 plus weekly paclitaxel. The ascites decreased after 3 courses of the chemotherapy. No major adverse effect was observed except for grade 1 anemia and grade 2 hair loss. She has been well with the chemotherapy on an outpatient basis 18 months after surgery.     

A case of advanced gastric cancer with peritoneal dissemination responding to S-1/CDDP neoadjuvant chemotherapy

The patient was a 72-year-old male diagnosed with type III poorly-differentiated adenocarcinoma in the lesser curvature by gastric fiberscopy. An abdominal computed tomography (CT) scan showed the thickness of the gastric wall and the enlarged lymph node around the stomach and laparoscopic examination revealed peritoneal dissemination. The patient received neoadjuvant combined chemotherapy with S-1 and CDDP. S-1 (100 mg/day) was orally administered for 3 weeks followed by 2 drug-free weeks as a course, and CDDP (100 mg/body) was administered by intravenous drip on day 8. After the third course, significant tumor reduction was obtained. Total gastrectomy, splenectomy and D2 nodal dissection were performed. Peritoneal dissemination disappeared, and the histological diagnosis revealed complete disappearance of cancer cells in the ascites and no metastasis in all lymph nodes. The patient has now been in good health with no recurrence for 22 months after surgery. The combined neoadjuvant chemotherapy with S-1 and CDDP can be an effective treatment of choice for advanced gastric carcinoma with peritoneal dissemination.     

A case of advanced gastric cancer with peritoneal dissemination effectively treated with fourth-line chemotherapy of S-1 alone

The patient was a 42-year-old female diagnosed with unresectable highly advanced gastric cancer complicated by peritoneal dissemination. We performed systemic chemotherapy with MTX+5-FU as the first-line treatment, which stabilized the disease. Since the patient initially wished a radical resection, we tried chemotherapy with weekly PTX as a second-line treatment. Her therapeutic response remained between a partial response and a stable disease for about five months, followed, however, by progressive disease. The result of the third-line treatment with CPT-11+CDDP was again a progressive disease, so we switched her regimen to single-agent S-1 as a fourth-line treatment. The ascites disappeared three months after the change in regimen. As of March 2006, the patient had survived for 17 months since diagnosis (8 months since the ongoing S-1 therapy started) and the disease is currently stabilized, and preserving a favorable performance status. However, in June 2006, the patient died of pneumonia 20 months after the diagnosis.     

A case of gastric cancer with peritoneal dissemination successfully treated by S-1/paclitaxel combination chemotherapy

A 62-year-old woman visited our hospital with diarrhea, bloating, vomiting, and black stool. Borrmann-type 3 gastric cancer with hemorrhaging was revealed by stomach endoscopy. The biopsy showed a poorly-differentiated adenocarcinoma. Moreover, peritoneal dissemination was found by computed tomography and we combined S-1 80 mg/m2(4 weeks administration and week rest)with paclitaxel(PTX)50 mg/ m2 (day 1, 8, 15, 3 weeks rest). After 2 courses, endoscopy showed tumor shrinkage. Therefore, we conducted total gastrectomy with resection of gall bladder and spleen. The final findings were Stage II .We conducted S-1/PTX combination chemotherapy(4 courses)followed by monotherapy as adjuvant chemotherapy. Recently, the woman had been living without relapse four years after operation.     

A case of recurrent gastric cancer with peritoneal dissemination successfully treated with DJ stents against bilateral hydronephrosis and chemotherapy

A 69-year-old female patient underwent total gastrectomy with a D2 lymph node dissection. Her final findings were of pT2, pN0, sP0, sH0, sM0 and Stage IB. After thirty-five months from the operation, peritoneal recurrence with ascites, bilateral hydronephrosis and stenosis of colon was found. TS-1 (80 mg/day/body) was administered for four weeks followed by a 2-week rest after DJ stents were inserted into bilateral ureters. At the end of two courses of TS-1, ascites disappeared and the decrease of tumor marker was observed. During the seventh course, symptoms such as abdominal fullness and ascites became worse. She underwent a weekly administration of paclitaxel (90 mg/body) as a second-line chemotherapy. This regimen was continued for three weeks followed by a 1-week rest. After four courses of paclitaxel, ascites disappeared and the tumor marker was gradually reduced. However, multiple bone metastases were found during the eighth course, and she died about two years after the recurrence. The toxic events were mucositis (grade 1) in TS-1, and alopecia (grade 2) and leukopenia (grade 1) in paclitaxel. No major adverse effects were observed. Although the prognosis of recurrent gastric cancer with peritoneal dissemination was extremely poor, this case might suggest a possibility that intensive therapies are useful in maintaining the quality of life and improving survival.     

A case of a nonresected gastric cancer with peritoneal dissemination maintained on TS-1 and docetaxel combination chemotherapy with good QOL

In general, treatment for gastric cancer with peritoneal dissemination or recurrent gastric cancer is outside the scope of surgery. The efficacy of new anti-cancer drugs such as TS-1 system was revealed in a controlled study by comparing treatment with non-treatment groups. We performed chemotherapy of TS-1 and docetaxel (TXT) in the outpatient clinic on a 72-year-old nonresected gastric cancer patient accompanied by peritoneal dissemination. Although no killer cell effect was recognized, the patient clinically achieved good QOL by this method for one year and seven months. In conclusion, we reported a treatment method for nonresected gastric cancer, which was treated only on an outpatient basis. The course of this case closely resembled the tumor dormancy therapy performed by Takahashi et al.     

A case of scirrhous gastric cancer with peritoneal dissemination acquiring stable disease over three years by treatment with oral anticancer drug S-1

A 71-year-old male, who complicated of abdominal distension, was diagnosed as scirrhous gastric cancer. We treated him with the oral anticancer drug S-1 and achieved long-term stable disease over three years.     

A case of advanced gastric cancer with peritoneal dissemination responding remarkably to TS-1/CDDP combination chemotherapy

A 57-year-old woman visited a physician with complaints of anorexia and pollakiuria. Because a pelvic tumor and ascites were detected, she was referred to our department. Douglas pouch puncture revealed adenocarcinoma cells. Further examination showed an advanced gastric cancer with peritoneal dissemination. The cancer was judged to be unresectable. Chemotherapy with a combination of TS-1 and CDDP was performed before the operation. After 2 courses of the chemotherapy, her complaints disappeared, although abdominal CT confirmed remaining peritoneal dissemination. After 7 courses of chemotherapy, abdominal CT showed that the peritoneal dissemination had disappeared. Total gastrectomy and lymph node dissection were performed. Histological findings of the stomach revealed complete disappearance of cancer cells in the stomach and the regional lymph nodes. We confirmed that the TS-1/CDDP therapy resulted in a complete response to advanced gastric cancer and peritoneal dissemination. We recommend that chemotherapy be continued until the peritoneal dissemination disappears.     

A case of unresectable advanced gastric cancer with peritoneal dissemination responding to UET/low-dose CDDP combination chemotherapy

We report the case of a 69-year-old female with unresectable gastric cancer (T3, N2, P3, H0, Stage IVb) accompanied by peritoneal dissemination, diagnosed on laparotomy. UFT/low-dose cisplatin (CDDP) combination chemotherapy was performed after surgery. UFT 300 mg/day was administered orally every day, and CDDP 10 mg was injected intravenously every week. Chemotherapy was continued for ten months with a total dose of CDDP of 380 mg, but was stopped after oral mucositis developed as a side effect. Seven months after the chemotherapy was started, endoscopy revealed that the gastric cancer tumors had disappeared and the gastric mucosa was intact. Gastric cancer recurrence occurred 2 years and 2 months after chemotherapy was started. Low-dose CDDP/5-FU chemotherapy and TS-1 chemotherapy were performed, but no effects were observed. The patient died 3 years and 6 months after the start of initial chemotherapy, and was treated as an outpatient for 3 years while maintaining a good quality of life. UFT/low-dose CDDP combination chemotherapy offers promise as an effective tool in the clinical management of advanced gastric cancer with peritoneal dissemination.     

胃癌腹膜种植患者手术并发症的危险因素分析及护理体会

目的 探讨胃癌腹膜种植患者姑息手术术后并发症的危险因素和相应的护理措施.方法 回顾性分析2000年1月至2014年4月在本中心诊治的464例胃癌腹膜种植患者的临床资料,分析其术后并发症的危险因素和临床护理相应措施.结果 5.82％ (27/464)的胃癌腹膜转移患者姑息性手术后出现相关并发症,包括:肠梗阻4例(0.86％)、腹腔感染7例(1.51％)、吻合口瘘3例(0.65％)、消化道出血2例(0.43％)、吻合口狭窄2例(0.43％)、急性胰腺炎2例(0.43％)、胃瘫1例(0.22％)、肺部感染4例(0.86％)、急性肾衰竭1例(0.22％)、脑血管意外1例(0.22％).姑息性胃切除是影响患者术后并发症发生的危险因素(P=0.017).结论 姑息性胃切除术是胃癌腹膜种植患者术后并发症发生的影响因素,加强临床护理可以早期发现并处理术后并发症.