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.     

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.     

Survival outcomes and prognostic indicators for gastric cancer patients with positive peritoneal wash cytology but no peritoneal metastasis after radical gastrectomy

BACKGROUNDPositive peritoneal wash cytology with no peritoneal metastasis (CY1P0) is a special type of distant gastric cancer metastasis, which describes a patient with positive peritoneal lavage cytology, but no definitive peritoneal metastasis, and there are no widely accepted treatment guidelines. We enrolled 48 primary CY1P0 gastric cancer patients treated by radical gastrectomy in this study. Our study illustrated the efficacy of radical gastrectomy for CY1P0 gastric cancer patients, and suggested that the pathological N factor and vascular invasion were significant independent risk factors for overall survival (OS). AIMTo assess the survival of CY1P0 gastric cancer patient post-radical gastrectomy, and to identify factors associated with long-term prognosis.METHODSOur study included 48 patients with primary CY1P0 gastric cancer who had radical gastrectomies at the Cancer Hospital, Chinese Academy of Medical Sciences, Beijing, China between 2013 and 2018. R0 resection was achieved in all 48 patients. Twelve patients received neoadjuvant chemotherapy. Thirty patients received adjuvant chemotherapy and four received adjuvant chemoradiotherapy. OS statistics were available for 48 patients. Follow-up continued through March 2020. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify prognostic factors. RESULTSMedian OS was 22.0 mo (95% confidence interval: 13.366-30.634 mo) post-surgery. Univariate analyses demonstrated that tumor site (P = 0.021), pathological N factor (P = 0.001), pathological T factor (P = 0.028), vascular invasion (P = 0.046), and the level of CA199 prior to initiating therapy (P = 0.002) were significant risk factors for OS. Multivariate analyses demonstrated that pathological N factor (P = 0.001) and vascular invasion (P = 0.031) were significant independent risk factors for OS.CONCLUSIONThis study suggested that radical gastrectomy may be efficient for CY1P0 gastric cancer patient post-radical gastrectomy and the pathological N factor and vascular invasion are significant independent risk factors for OS.     

Neoadjuvant chemotherapy for patients with positive cytology from advanced gastric cancer

Free cancer cells from advanced gastric cancer are associated with a poor prognosis. The aim of this study was to clarify the role of neoadjuvant chemotherapy (NAC) for patients with positive cytology from advanced gastric cancer. Thirty four patients with positive cytology and no macroscopic peritoneal deposits from advanced gastric adenocarcinoma at staging laparoscopy were studied. Gastrectomy after staging laparoscopy was performed in 9 patients (Surgery group). NAC following gastrectomy after staging laparoscopy was performed in 25 patients (NAC group). The overall response rate was 24% (CR in none, PR in 6, NC in 15, PD in 4). Two of the 4 patients with PD did not undergo surgical resection. Twenty three patients in the NAC group (resection rate 92%) underwent gastrectomy, which resulted in 17 R0, four R1, and two R2 resections. Eighteen of the 23 patients (78%) in the NAC group revealed no free cancer cells at operation. There was no significant deference in the overall survival curves between Surgery and NAC groups. Five of the 17 patients performed curative operation developed recurrence (peritoneum in 1, liver in]1, brain in 1, local and peritoneum in 1, paraaortic lymph node and peritoneum in 1). NAC for patients with positive cytology could lead into no free cancer cells at a high rate, but not to improve their prognoses. An intensive chemotherapy after gastrectomy should be necessary for these patients.     

The treatment strategy for type 4 gastric cancer with positive lavage cytology--a decision making of the therapeutic strategy by the change of the result of the lavage cytology

It has been difficult to improve the prognosis of the type 4 advanced gastric cancer because the peritoneal dissemination develops frequently. In the present study, the therapeutic strategy, an administration of chemotherapy followed by gastrectomy, for the type 4 advanced gastric cancer with positive lavage cytology (CY) was discussed. CY has changed to negative in 3 of 6 cases (50%) at the surgery and in 1 of another 3 cases during the post operative chemotherapy. MST was 1487 days (966-2354 days) in cases with negative CY after pre-operative treatment, while 193 and 395 days in another 2 cases remained in positive CY, respectively. It may be important to perform re-staging laparoscopy with the evaluation of CY after preoperative chemotherapy for the type 4 advanced gastric cancer with positive CY, because the survival was comparatively better in cases with the change from positive CY to negative CY after the treatment. In conclusion, the treatment strategy for the type 4 advanced gastric cancer with positive CY was to administer chemotherapy followed by curative intent surgery for the case with negative CY after pre-operative treatment, while the other regimen of chemotherapy administration for the case with positive CY remained.     

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.     

Surgery after intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology findings

Background

Despite recent progress in systemic chemotherapy, the prognosis of gastric cancer patients with peritoneal metastasis (P1) or positive peritoneal cytology findings (CY1) is still poor. We developed a regimen combining intraperitoneal (IP) paclitaxel (PTX) with S-1 and PTX, which can produce notable efficacy with regard to peritoneal lesions. Surgery after response to combination chemotherapy is a promising option for P1 or CY1 gastric cancer. A retrospective study was performed to evaluate the safety and efficacy.

Methods

This study enrolled 100 primary P1 or CY1 gastric cancer patients treated with IP PTX plus S-1 and PTX at the University of Tokyo Hospital between 2005 and 2011. Radical gastrectomy was performed when peritoneal cytology findings became negative, and the disappearance or obvious shrinkage of peritoneal metastasis was confirmed by laparoscopy. The same chemotherapy regimen was restarted after surgery and repeated with appropriate dose reduction.

Results

Gastrectomy was performed in 64 (P1 56, P0CY1 8) of 100 (P1 90, P0CY1 10) patients. R0 resection was achieved in 44 patients (69%). The median survival time was 30.5 months [95% confidence interval (CI) 23.6–37.7 months] from the initiation of intraperitoneal chemotherapy and 34.6 months (95% CI 26.8–39.4 months) from the diagnosis of gastric cancer. Postoperative complications included anastomotic leakage and pancreatic fistula, each in two patients, which were cured conservatively. There were no treatment-related deaths. The median survival time of the 36 patients who did not undergo surgery was 14.3 months (95% CI 10.0–17.8 months).

Conclusions

Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.

     

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.     

Surgery after intraperitoneal and systemic chemotherapy for gastric cancer with peritoneal metastasis or positive peritoneal cytology findings

Background

Despite recent progress in systemic chemotherapy, the prognosis of gastric cancer patients with peritoneal metastasis (P1) or positive peritoneal cytology findings (CY1) is still poor. We developed a regimen combining intraperitoneal (IP) paclitaxel (PTX) with S-1 and PTX, which can produce notable efficacy with regard to peritoneal lesions. Surgery after response to combination chemotherapy is a promising option for P1 or CY1 gastric cancer. A retrospective study was performed to evaluate the safety and efficacy.

Methods

This study enrolled 100 primary P1 or CY1 gastric cancer patients treated with IP PTX plus S-1 and PTX at the University of Tokyo Hospital between 2005 and 2011. Radical gastrectomy was performed when peritoneal cytology findings became negative, and the disappearance or obvious shrinkage of peritoneal metastasis was confirmed by laparoscopy. The same chemotherapy regimen was restarted after surgery and repeated with appropriate dose reduction.

Results

Gastrectomy was performed in 64 (P1 56, P0CY1 8) of 100 (P1 90, P0CY1 10) patients. R0 resection was achieved in 44 patients (69%). The median survival time was 30.5 months [95% confidence interval (CI) 23.6–37.7 months] from the initiation of intraperitoneal chemotherapy and 34.6 months (95% CI 26.8–39.4 months) from the diagnosis of gastric cancer. Postoperative complications included anastomotic leakage and pancreatic fistula, each in two patients, which were cured conservatively. There were no treatment-related deaths. The median survival time of the 36 patients who did not undergo surgery was 14.3 months (95% CI 10.0–17.8 months).

Conclusions

Surgery after response to intraperitoneal and systemic chemotherapy is safe and may prolong the survival of P1 and CY1 gastric cancer patients.

     

Optimizing outcomes for patients with gastric cancer peritoneal carcinomatosis

Peritoneal carcinomatosis (PC) from gastric cancer has traditionally been considered a terminal progression of the disease and is associated with poor survival outcomes. Positive peritoneal cytology similarly worsens the survival of patients with gastric cancer and treatment options for these patients have been limited. Recent advances in multimodality treatment regimens have led to innovative ways to care for and treat patients with this disease burden. One of these advances has been to use neoadjuvant therapy to try and convert patients with positive cytology or low-volume PC to negative cytology with no evidence of active peritoneal disease. These strategies include the use of neoadjuvant systemic chemotherapy alone, using neoadjuvant laparoscopic heated intraperitoneal chemotherapy (NLHIPEC) after systemic chemotherapy, or using neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) in a bidirectional manner. For patients with higher volume PC, cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been mainstays of treatment. When used together, CRS and HIPEC can improve overall outcomes in properly selected patients, but overall survival outcomes remain unacceptably low. The extent of peritoneal disease, commonly measured by the peritoneal carcinomatosis index (PCI), and the completeness of cytoreduction, has been shown to greatly impact outcomes in patients undergoing CRS and HIPEC. The uses of NLHIPEC and NLHIPEC plus NIPS have both been shown to decrease the PCI and thus increase the opportunity for complete cytoreduction. Newer therapies like pressurized intraperitoneal aerosol chemotherapy and immunotherapy, such as catumaxomab, along with improved systemic chemotherapeutic regimens, are being explored with great interest. There is exciting progress being made in the management of PC from gastric cancer and its’ treatment is no longer futile.     

A population-based study on treatment and outcomes in patients with gastric adenocarcinoma diagnosed with distant interval metastases

BackgroundIn patients with gastric or gastroesophageal junction (GEJ) cancer treated with curative intent, distant interval metastases may be detected after start of neoadjuvant chemotherapy or during surgery. The aim of this study was to explore characteristics, allocated treatment and overall survival (OS) in gastric/GEJ cancer patients with interval metastases, and to compare OS with synchronous metastatic gastric/GEJ cancer patients who started palliative chemotherapy.MethodsPatients with interval metastases were selected from the Netherlands Cancer Registry by including patients with potentially curable gastric/GEJ adenocarcinoma (2010–2018) who started chemotherapy without concurrent radiotherapy. The OS since start of neoadjuvant treatment of patients with interval metastases was compared with a propensity score-matched cohort of patients with synchronous metastases who received palliative systemic treatment.Results164 patients with interval metastases diagnosed in 2010–2018 were included. Metastases were most frequently detected during surgery (83%) and most frequently located in the peritoneum (77%). Peritoneal interval metastases were observed in 63% and 80% of the patients who did and did not have a diagnostic laparoscopy prior to neoadjuvant treatment, respectively (P = 0.041). Median OS was 8.9 months (IQR 5.5–13.4), compared to 8.0 months (IQR 4.1–14.1) in matched synchronous metastatic patients calculated from start of neoadjuvant and palliative systemic treatment, respectively (P = 0.848).ConclusionThis population-based study shows that gastric/GEJ cancer patients who started neoadjuvant treatment and were diagnosed with interval metastases most frequently suffered from peritoneal metastases detected during (exploratory) surgery, even when a diagnostic laparoscopy was performed before start of treatment. OS was comparable to patients with synchronous metastatic gastric/GEJ cancer.     

Neoadjuvant chemotherapy with S-1 and surgical resection for a mucinous gastric cancer with peritoneal dissemination

We herein report the case of a patient with mucinous gastric carcinoma with peritoneal dissemination that disappeared after neoadjuvant chemotherapy with S-1 alone. The patient has survived for over 23 months after surgery, without recurrence. A 60-year old man was referred to our hospital because of an advanced gastric cancer, detected by upper gastrointestinal endoscopy at another hospital. Staging laparoscopy was performed on October 25, 2002, and revealed massive peritoneal dissemination. Two courses of neoadjuvant chemotherapy with S-1 were administered, at 120mg/day for 28 days, as one course. Total gastrectomy, with D2 lymph node dissection, was performed on January 24, 2003. The peritoneal dissemination had macroscopically disappeared and the cytology of the peritoneal lavage fluid was class III. His final diagnosis was gastric carcinoma, MLU, type 3, T2(SS), P0, H0, M0, N3, CY0, stage IV.     

Neoadjuvant treatment of gastric cancer with peritoneal dissemination.

AIMS: To report our experience of neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) for patients having a complete resection of the primary gastric cancer and peritoneal carcinomatosis (PC). PATIENTS AND METHODS: Patients with advanced peritoneal dissemination of primary gastric cancer had the placement of a peritoneal port system. For intraperitoneal chemotherapy, 40 mg of docetaxel and 150 mg of carboplatin were introduced in 1000 ml of saline on a weekly basis. Simultaneously, 100 mg/m2 of methotrexate and 600 mg/m2 of 5-fluorouracil were infused via a peripheral vein. A minimum of two cycles and up to six cycles of NIPS were used prior to cancer resection. At surgery a complete removal of the primary gastric cancer and the peritoneal implants by peritonectomy was attempted. RESULTS: Sixty-one patients were enrolled in the study. Thirty-nine had positive intraperitoneal cytology which reverted to negative cytology after treatment in 22. Thirty-eight showed a partial response. Thirty patients came to resection and 14 patients could be made disease-free. Median survival time of all patients was 14.4 months. Patients who received a complete resection had a median survival time of 20.4 months. Grade III/IV toxicities were not found after two courses of NIPS, but did develop in seven patients after more than three courses of NIPS. CONCLUSION: NIPS can downstage large volume peritoneal dissemination of gastric cancer. When combined with gastrectomy including peritonectomy a complete surgical resection was possible in one-quarter of the patients and resulted in a prolonged survival. This combined intraperitoneal and systemic chemotherapy for PC from gastric cancer is worthy of consideration for phase III clinical investigations.     

TEM1表达与胃癌患者新辅助化疗疗效相关性研究

  目的  检测胃癌组织中P53、人表皮生长因子受体2（HER-2）、肿瘤内皮标记物1（TEM1）的表达情况,结合新辅助化疗后临床疗效进行相关性分析,探讨其作为新辅助化疗疗效生物学标志物的可能性。  方法  选取2015年5月至2017年5月于兰州大学第一医院就诊以氟尿嘧啶为基础行新辅助化疗的63例胃癌患者,对新辅助化疗前的胃癌标本行免疫组织化学法检测P53、HER- 2、TEM1的表达情况,通过影像学评估新辅助化疗疗效,分析各肿瘤指标与新辅助化疗疗效之间的关系。  结果  63例进展期胃癌患者新辅助化疗后总有效率为69.8%,其中完全缓解（complete response,CR）2例,部分缓解（partial response,PR）7例,疾病稳定（stable disease,SD）35例,疾病进展（progressive disease,PD）19例;单因素分析结果显示TEM1阳性、T分期较高的患者新辅助化疗疗效较差（均P < 0.05）;病变部位、分化程度、病灶大小、P53（P=0.488）阳性及HER-2（P=0.106）阳性表达与胃癌新辅助化疗疗效无相关。多因素分析结果显示TEM1阳性、T分期高可能是进展期胃癌患者新辅助化疗疗效差的预测因素。  结论  TEM1作为肿瘤基质的标志物,其阳性表达可能成为预测胃癌新辅助化疗疗效差的重要分子生物学指标。      

A successfully treated case of type 4 gastric cancer with intraperitoneal free cancer cells undergoing a curative resection followed by neoadjuvant chemotherapy with S-1 plus cisplatin

A 41-year-old female complained of epigastric pain and was referred to our hospital. Gastrofiberscopy revealed that type 4 gastric cancer located at the whole gastric body. Although abdominal computed tomography showed that no distant metastasis but regional lymph node metastasis existed, staging laparoscopy and cytological diagnosis revealed that there were intraperitoneal free cancer cells without overt peritoneal metastasis(P0CY1). She received neoadjuvant chemotherapy with S-1 plus cisplatin for consecutive 21 days followed by 7 days of rest as a course. After 3 courses of the chemotherapy, intraperitoneal free cancer cells were not found, and she underwent curative gastrectomy. Pathological examination showed that the therapeutic effect was Grade 2. S-1 as postoperative chemotherapy had been prescribed for 10 months without relapse. However, she suffered from anorexia and abdominal distension and peritoneal metastasis was confirmed on the 575th day after curative operation. She has received a weekly paclitaxel therapy as second-line chemotherapy.     

Significance of laparoscopy for response assessment of chemotherapy in gastric cancer

We performed laparoscopy before and after chemotherapy in two patients with relapsed and advanced gastric cancer, whose major metastatic sites had been diagnosed as being in the peritoneum. A change in tumor responses when assessed by laparoscopy was found. Case 1: A 63-year-old man presented with an umbilical metastasis and suspected peritoneal metastases after gastrectomy. Laparoscopy revealed peritoneal metastases before chemotherapy. After one course of chemotherapy the umbilical tumor disappeared (CR). Laparoscopy after two courses of chemotherapy revealed increasing peritoneal metastases (PD). The overall response was PD. Case 2: A 67-year-old woman was referred to our hospital with a diagnosis of type 4 gastric cancer. Staging laparoscopy revealed massive lymph node metastases and the patient was positive in peritoneal washing cytology. After four courses of chemotherapy, the primary tumor and the metastatic lymph nodes had decreased in size (PR). In contrast, laparoscopy revealed increasing peritoneal metastases (PD). The overall response was PD. CONCLUSION: In patients with peritoneal and other modes of metastasis, tumor response to chemotherapy may be misjudged by conventional imaging alone. Intraperitoneal examination by laparoscopy provides accurate information, including the tumor response to chemotherapy.     

Neoadjuvant chemotherapy with CDDP and 5-fluorouracil for gastric cancer with serosal invasion

Many gastric cancer patients who recur peritoneally are initially diagnosed with serosal invasion. To clarify the usefulness of neoadjuvant chemotherapy with 5-fluorouracil (5-FU) +/- cisplatin (CDDP), neoadjuvant versus no preoperative chemotherapy for gastric cancer with preoperative serosal invasion was investigated. The patients were treated preoperatively with 5-FU 300 mg/m(2)/day for 2 weeks (F group; n=40), 5-FU 300 mg/m(2)/day for 2 weeks + CDDP 15 mg/m(2)/day for 2 days (FP group; n=80) or nothing (C group; n=100). A total of 78% of patients in C, 65.0% in F and 67.5% in FP group were classified as T3 or higher surgically. In patients without peritoneal metastasis, the positive peritoneal lavage cytology was 29.2% in C, 11.8% in F, and 12.2% in FP patients (p=0.0279). Serosal invasion was found histologically in 60.0% of C, 30.0% of F, and 33.8% of FP patients (p=0.001). There were no serious drug reactions and no increases in morbidity or mortality using either regimen. The 5-year survival rate was 47.0% in F and 50.9% in FP patients, but only 33.2% in C patients (p=0.0042). In conclusion, neoadjuvant chemotherapy with 5-FU +/- CDDP for gastric cancer patients with serosal invasion may reduce positive peritoneal cytology, eliminate cancer cells from the serosal surface, and improve prognosis.     

Pharmacokinetics of S-1 in patients with peritoneal dissemination of gastric cancer

The response of gastric cancer with peritoneal dissemination to systemic chemotherapy may be negatively affected by poor drug delivery due to the blood-peritoneal barrier. However, S-1 has been reported to be effective. We examined the pharmacokinetics of S-1 in 14 patients who had gastric cancer with peritoneal dissemination. S-1 was given from the morning of the day before surgery to the morning of surgery. Concentrations of 5-fluorouracil (5-FU) and gimeracil (CDHP) were measured in the serum, ascites, disseminated peritoneal nodes, and normal peritoneum. There was a strong correlation between 5-FU and CDHP concentrations in peritoneal tissues. The concentrations of 5-FU and CDHP in the serum were similar to those in ascites. The concentration of 5-FU was significantly higher in disseminated nodes than in the normal peritoneum. After administration of S-1 to gastric cancer patients with peritoneal dissemination, 5-FU and CDHP in the serum linearly pass through the peritoneum and enter the ascites. High concentrations of 5-FU selectively penetrate disseminated peritoneal cells.     

Neoadjuvant chemotherapy with S-1 for scirrhous gastric cancer: a pilot study

We conducted a pilot study using S-1 (TS-1^®), a novel oral derivative of 5-fluorouracil, as neoadjuvant chemotherapy for potentially resectable scirrhous gastric cancer. The neoadjuvant chemotherapy consisted of two courses (each, 4-week administration and 2-week withdrawal) of S-1 at 100–120?mg/body per day. Five patients were enrolled in this pilot study and underwent resection. The response rate for the neoadjuvant chemotherapy was 60% (three partial response [PR]; two stable disease [SD]). Three of the five patients received curative resection; the other two patients received noncurative resection because of localized peritoneal dissemination and positive results on cytological examination of the abdominal washing. No toxicity of grade 3 or more was exhibited during the two courses of chemotherapy. Pathological examination of the resected specimens revealed a marked reduction in the distribution of viable cancer cells in the stomach in the three patients with PR. In one of these patients, pathological findings suggestive of the possibility of disappearance of the cancer cells in the perigastric and paraaortic lymph nodes were noted. Because of the unexpectedly high response to S-1, we consider that the efficacy of S-1 as neoadjuvant chemotherapy for scirrhous gastric cancer should be verified by phase II and III trials.     

Regional therapy trials in peritoneal metastases: The path to standardization of care for gastric cancer

As the peritoneum is the most common site of metastatic disease at diagnosis, disease identified at staging laparoscopy, and site of recurrence for patients with gastric cancer, intraperitoneal therapy has been an area of interest for many investigators. There are several ways to categorize the existing trials and studies. One is by indication, which includes palliative, neoadjuvant, adjuvant, and prophylactic. Another is by treatment modality which includes approaches such as hyperthermic intraperitoneal chemotherapy, pressurized intraperitoneal aerosol chemotherapy, intraperitoneal normothermic chemotherapy, and bidirectional combinations of systemic and intraperitoneal therapy. Recently completed and ongoing trials of peritoneal therapy in gastric cancer may be improving on the historically dismal survival rates for patients with carcinomatosis or disease at high risk of peritoneal recurrence. All completed randomized trials are from outside the United States, and additional studies of peritoneal therapy in Western populations are needed to clarify survival outcomes. Cooperative group trials and multi-institutional registry study efforts are ongoing to help address this clear area of unmet need.