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.     

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.     

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.

     

Evaluation of peritoneal cytology in colorectal carcinoma

We investigated the incidence of free cancer cells in the peritoneal washings of 278 patients who had undergone surgery for colorectal cancer to evaluate its influence as a prognostic factor of the disease. Twenty-two cases (7.9%) were found to have malignant positive cytology (CY(+)). The rate of CY(+) in the cases with peritoneal dissemination (P(+)) was significantly higher than that in P(-) (66.7% vs 3.8%). In 244 cases, those who had tumors exposing to the peritoneum, both CY(+) and P(+) were observed highly in poorly differentiated adenocarcinoma. Among 18 P(+) cases, the rates of CY(+) were higher in both P3 and cur C than in P1, 2 and cur B. When restricted to 260 P(-) cases, CY(+) was observed more often in stage IV cases (14.3% vs 1.8%). Rate was significantly high in M+ (66.7%). Prognosis of 4 P(-) CY(+) cur A cases was as follows; 2 survived for a long time with no recurrence (20 and 60 months), 1 had curable liver metastases after half a year and obtained a 2 year disease free period after surgery, and another one died with brain, liver, and peritoneal recurrence one year later. The incidence of CY(+) is correlated with P(+); CY(+) increased when P(+) is extended more highly and incurable. CY(+) alone doesn't become a prognostic factor for peritoneal recurrences, because CY(+) is found rarely in curable P(-) cases. However, CY(+) is also associated with far advanced cancer with remote metastases, therefore we should consider the risk of such metastases for CY(+) cases with curable colorectal cancer.     

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.

     

The effect of extensive intraoperative peritoneal lavage therapy (EIPL) on stage III B + C and cytology-positive gastric cancer patients

Background

The aim of this study was to investigate the effects of extensive intraoperative peritoneal lavage (EIPL) therapy on stage III B + C and CY1/P0 gastric cancer patients after potentially curative surgery.

Methods

The study included 37 patients with CY1/P0 and 23 patients with stage III B + C gastric cancer who were treated with potentially curative gastrectomy and EIPL therapy between March 1995 and May 2013. D2 lymphadenectomy, R0 resection, and EIPL therapy were performed for all cases.

Results

Multivariate analysis revealed that male gender (P = 0.01) and lymph node metastasis (P = 0.03) were independent prognostic factors, while positive cytology was not (P = 0.21). There was no significant difference in overall survival rates between the CY1/P0 and stage III B + C groups (P = 0.93). There was also no significant difference in peritoneal recurrence rates, i.e., 13 (35.1%) in the CY1/P0 group and 5 (21.7%) in the stage III B + C group (P = 0.39).

Conclusions

EIPL therapy combined with complete resection and sufficient (D2) lymphadenectomy could improve the prognosis of CY1/P0 gastric cancer and, to a similar extent, that of stage III B + C.

     

Depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis

Objective:Diagnostic laparoscopy is recommended for the pretherapeutic staging of gastric cancer to detect any unexpected or unconfirmed intra-abdominal metastasis.The aim of this study was to evaluate the role and indications of diagnostic laparoscopy in the detection of intra-abdominal metastasis.Methods:Standard diagnostic laparoscopy with peritoneal cytology examination was performed prospectively on patients who were clinically diagnosed with primary local advanced gastric cancer (cT≥2M0).We calculated the rate of intra-abdominal metastases identified by diagnostic laparoscopy,and examined the relationship between peritoneal dissemination (P) and cytology results (CY).Split-sample method was applied to find clinical risk factors for intra-abdominal metastasis.Multivariate logistic regression analysis and receiver-operator characteristic (ROC) analysis were performed in training set to find out risk factors of intra-abdominal metastasis,and then validate it in testing set.Results:Out of 249 eM0 patients,51 (20.5％) patients with intra-abdominal metastasis were identified by diagnostic laparoscopy,including 20 (8.0％) P1CY1,17 (6.8％) P0CY1 and 14 (5.6％) P1CY0 patients.In the training set,multivariate logistic regression analysis and ROC analysis showed that the depth of tumor invasion on computer tomography (CT) scan ≥21 mm and tumor-occupied ≥2 portions of stomach are predictive factors of metastasis.In the testing set,when diagnostic laparoscopy was performed on patients who had one or two of these risk factors,the sensitivity and positive predictive value for detecting intra-abdominal metastasis were 90.0％ and 32.1％,respectively.Conclusions:According to our results,depth of tumor invasion and tumor-occupied portions of stomach are predictive factors of intra-abdominal metastasis.     

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.     

The survival and prognosticators of peritoneal cytology-positive gastric cancer patients who received upfront gastrectomy and subsequent S-1 chemotherapy

Background

Upfront surgery and subsequent S-1 chemotherapy is frequently selected for peritoneal cytology-positive (CY1) gastric cancer patients without other distant metastases (CY1-only). The objective of this study was to confirm the efficacy of this strategy in clinical practice and to identify the risk factors associated with survival.

Methods

Overall survival (OS) and recurrence-free survival (RFS) were examined in 36 CY1-only patients who underwent macroscopic curative resection followed by postoperative S-1 chemotherapy between January 2000 and June 2015. Univariate and multivariate analyses were performed using a Cox proportional hazards model to identify risk factors.

Results

The median OS was 22.3 months (95% confidence interval 18.7–31.0). When the OS was compared by a log-rank test, significant differences were observed in the status of lymph node metastasis of pathological N3b (pN3b). Moreover, the univariate and multivariate analyses demonstrated that the status of pN3b was a significant independent risk factor for OS and RFS. The median OS in patients with pathological N0–N3a (pN0–N3a) was 31.0 months, while that in patients with pN3b was 18.2 months (P = 0.002). The median RFS in patients with pN0–N3a was 16.4 months, while that in patients with pN3b was 7.9 months (P = 0.007).

Conclusions

The present study confirmed the efficacy of postoperative S-1 chemotherapy for CY1-only gastric cancer patients who received upfront surgery. This strategy might be recommended as clinical practice for patients with CY1 disease but a more effective treatment should be established for CY1-positive patients, especially for those who are diagnosed with CY1 and pN3b disease.

     

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.     

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.     

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.     

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.     

Successful treatment of advanced gastric cancer by surgical resection following combination chemotherapy with oral S-1 and biweekly paclitaxel

We report on the successful treatment of advanced gastric cancer by surgical resection following neoadjuvant chemotherapy. A 67-year-old man was referred to our hospital with a diagnosis of pancreatic cancer. Meticulous examination, however, revealed the presence of gastric cancer with ascites and large lymph node metastasis adjacent to the pancreas. We selected combination chemotherapy with oral S-1 and biweekly paclitaxel. After two courses, both the primary tumor and metastatic lymph nodes were greatly reduced, and the ascites had disappeared. Using laparoscopy, there was no evidence of peritoneal metastases, and the cytological examination was negative. The patient underwent distal gastrectomy with D2 lymph node dissection. Histological examination revealed that the cancer cells were still present in part, but no lymph node metastases were found. The tumor was pathologically diagnosed as pT2, pN0, P0, M0, CY0, and p-stage II. The patient is healthy over 4 years after surgery without recurrence.     

A case of gastric cancer with bilateral ovarian metastasis after gastrectomy performed ovarian resection

The patient was a 51-year-old female, who underwent radical surgery for cancer of remnant stomach in May 2006 (f-T4N0M0P0H0CY0, por 2, Stage IIIA, Cur B). Bilateral ovarian resection was performed in March 2009 for bilateral ovarian metastasis, so called "Krukenberg tumor" with peritoneal dissemination detected with CT scan after one-year adjuvant chemotherapy with S-1 (80 mg/m2, 4 weeks on and 2 weeks off). As of June 2010, she is alive and maintain her status quo after 6 courses of S-1 plus CDDP combination therapy (S-1 80 mg/m2, 3 weeks on, CDDP 60 mg/m2, started at day 8, ended 35 days later) followed by S-1 for residual peritoneal dissemination detected at operation. In ovary metastasis of gastric cancer, even if accompanied by peritoneum metastasis, ovarian resection as a reduction surgery followed by chemotherapy may improve survival.     

Prospective study to validate the clinical utility of DNA diagnosis of peritoneal fluid cytology test in gastric cancer

The clinical efficacy of DNA cytology test (CY) in gastric cancer (GC) has been retrospectively proposed using cancer-specific methylation of cysteine dioxygenase type 1 (CDO1). We confirmed the clinical utility of DNA CY in a prospective cohort. Four hundred GC samples were prospectively collected for washing cytology (UMIN000026191), and detection of the DNA methylation of CDO1 was assessed by quantitative methylation-specific PCR in the sediments. Endpoint was defined as the match rate between conventional CY1 and DNA CY1 (diagnostic sensitivity), and the DNA CY0 rate (diagnostic specificity) in pStage IA. DNA CY1 was detected in 45 cases (12.5%), while CY1 was seen in 31 cases (8.6%) of 361 chemotherapy-naïve samples, where the sensitivity and specificity of the DNA CY in the peritoneal solutions were 74.2% and 96.5%, respectively. The DNA CY was positive for 3.5/0/4.9/11.4/58.8% in pStage IA/IB/II/III/IV, respectively (P < .01). In the multivariate analysis, DNA CY1 was independently correlated with pathological tumor depth (pT) (P = .0012), female gender (P = .0099), CY1 (P = .0135), P1 (P = .019), and carcinoembryonic antigen (CEA) (P = .036). The combination of DNA CY1 and P factor nearly all covered the potential peritoneal dissemination (P1 and/or CY1 and/or DNA CY1) (58/61:95.1%). DNA CY1 had a significantly poorer prognosis than DNA CY0 in GC patients (P < .0001). DNA CY1 detected by CDO1 promoter DNA methylation has a great value to detect minimal residual disease of the peritoneum in GC clinics, representing poor prognosis as a novel single DNA marker.     

Re-irradiation after salvage mastectomy for local recurrence after a conservative treatment: a retrospective analysis of twenty patients (Nancy: 1988-2001)]

PURPOSE: To retrospectively assess the efficacy of post-mastectomy re-irradiation for local relapse of breast cancer. PATIENTS AND METHODS: Twenty patients, initially treated by conservative surgery and radiotherapy (50 Gy in 25 fractions over 5 weeks) were treated from 1998 to 2001 for a local relapse by salvage mastectomy and re-irradiation (either electron or photon beams). Mean age was 53 years (31-71). Reasons for re-irradiation were that the local relapses were inflammatory (4 pts), multifocal (5 pts), cutaneous (5 pts), involved the nipple (3 pts) or because the surgical margins (either muscle or skin) were involved (3 pts). The median dose of re-irradiation was 45 Gy (33-65) in 15 fractions over 33 days. Mean follow-up was 48 months (5-97). RESULTS: Fifteen patients remained free of a second local recurrence and 10 were still alive, without metastasis. Neither the dose of re-irradiation nor the irradiated surfaces were prognostic factors of local control (P = 0.877 and P = 0.424). Five patients developed radiation-induced pneumonitis without functional respiratory impairment. The incidence of pneumonitis seemed to be related to the biological dose of re-irradiation (P = 0.037). Other late complications occurred such as pigmentation changes (12 pts), telangiectasia (8 pts), chondritis (2 pts), parietal fibrosis (7 pts), rib fractures (4 pts), severe pain (11 pts) and lymphedema (2 pts). The increase in biological equivalent dose was highly statistically linked with the occurrence of disabling pain (P = 0.0123). CONCLUSION: Parietal re-irradiation achieves good and lasting local control with an acceptable rate of acute complications but with a risk of disabling late sequelae such as severe pain.     

Repeated intraperitoneal chemotherapy for peritoneal dissemination from gastric carcinoma

Repeated intraperitoneal chemotherapy (RIC) via an i.p. port system was carried out in 16 patients with peritoneal dissemination (P1) and in 10 with positive washing cytology (P0.CY1) from gastric carcinoma. CDDP dissolved in 500-1,000 ml of physiological saline solution was periodically administered via the i.p. port system. The change of washing cytology (CY), which was obtained from i.p. port, was examined before each administration as a indicator of the response. The average number of administrations was 5.7 and the average total dose was 301.7 mg. As a result, a negative change of CY after RIC was found in 74% of patients, and also more than 80% of the response occurred within three administrations. The prognosis tended to be better in P0.CY1 patients than in P1 patients. In particular, the median survival time of the CY responders markedly improved as compared with non-responders (27.8 months versus 7.1 months). Although diarrhea and anorexia of grade 3 developed once in each patient, serious toxicities were not found. In conclusion, we consider RIC to be an effective therapy for P0.CY1 among cases with peritoneal dissemination from gastric carcinoma.     

VEGF significance in peritoneal recurrence from gastric cancer

Background In gastric cancer, the management of peritoneal dissemination in the Peritoneal cavity is extremely important; however, peritoneal dissemination in the final stage of gastric cancer remains untreatable. Peritoneal dissemination involves several steps, including tumor-cell attachment, invasion, and growth in the peritoneum. Many cytokines, growth factors, matrix metalloproteinases (MMPs), and angiogenic factors play important roles in these steps. So far, few studies have investigated the correlation, if any, between peritoneal dissemination and the angiogenic factor, vascular endothelial growth factor (VEGF).Methods Immunohistochemical staining, using the avidin-biotin peroxidase complex method, was performed on slides of surgical specimens from 40 patients with stage II gastric cancer with serosal invasion, who underwent surgery at our hospital between 1990 and 2000. Anti-human VEGF rabbit polyclonal IgG was used as the primary antibody. VEGF expression was classified in one of four categories depending on the percentage of tumor-cell staining (P). VEGF expression was also classified in one of three categories depending on the staining intensity (I). The VEGF expression score was calculated as P × I.Results There were ten patients with peritoneal recurrence. Of these, seven had macroscopic type-4 scirrhous-type gastric carcinoma. In the immunohistochemical study, the VEGF score of patients with peritoneal recurrence was 9.40 ± 2.46; on the other hand, that of patients without peritoneal recurrence was 3.47 ± 2.36. The VEGF score of patients with peritoneal recurrence was significantly higher than that of patients without peritoneal recurrence. In patients with macroscopic type 4, the VEGF score of those with peritoneal recurrence was 9.14 ± 2.19, while on the other hand, that of the patients without peritoneal recurrence was 3.80 ± 3.03. The VEGF score of these patients with peritoneal recurrence was significantly higher than that of those without peritoneal recurrence. The survival rate in the VEGF low-expression group was significantly higher than that in the VEGF high-expression group. Multivariate analysis showed that the VEGF score was a significant parameter of peritoneal recurrence.Conclusion These results suggested that VEGF was correlated with peritoneal metastasis from gastric cancer, and that VEGF was a useful indicator of peritoneal recurrence.     

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.