Four long-surviving cases of gastric cancer with peritoneal dissemination treated by intraperitoneal administration of mitomycin C adsorbed on activated carbon particles

A new dosage format (MMC-CH) of mitomycin C, which is composed of mitomycin C on activated carbon particles, was efficacious for prevention of peritoneal recurrence of gastric cancer. However, it had no such excellent therapeutic effect on the survival of patients with peritoneal dissemination. Out of 50 patients with peritoneal dissemination of gastric cancer treated by intraperitoneal administration of MMC-CH, 4 patients have survived for long periods of time (39-80 months). However, all of the other 50 patients, who did not receive intraperitoneally administered MMC-CH, died of peritoneal carcinomatosis within two years.     

Clinical result of intraperitoneal hyperthermic chemoperfusion for gastric cancer with serosal invasion to prevent peritoneal recurrence

In order to evaluate clinical effects of intraperitoneal hyperthermic chemoperfusion (IHCP) to prevent peritoneal recurrence in gastric cancer patients with serosal invasion, the clinical outcome was studied in 126 gastric cancer patients with macroscopic serosal invasion. Results of 59 patients who had surgery combined with IHCP (IHCP group) were compared with those of 67 patients who had surgery alone (control group). IHCP was performed for 120 minutes just after surgery under hypothermic general anesthesia with perfusate containing 10 micrograms/ml of mitomycin C. The inflow temperature and the outflow temperature of the perfusate were controlled to be 44.5 approximately 45 degrees C, and 43 approximately 44 degrees C, respectively. The 2-, 4- and 8-year survival rates for the IHCP group were 86%, 74% and 66%, respectively, against 78%, 59% and 50%, respectively, in the control group. The survival rates of the IHCP group were significantly better than those of the control group. Peritoneal recurrences after surgery were encountered in one of 59 patients in the IHCP group and 17 of 67 patients in the control group. The peritoneal recurrence rate of the IHCP group was significantly lower than that of the control group. These results suggest that IHCP treatment is effective in prevention of peritoneal recurrences after surgery for gastric cancer patients with serosal invasion.     

Limitations in medicine. Challenge and threat

Intraoperative chemohyperthermia is a new method in the treatment of peritoneal seedings from digestive cancers, which combines surgery, intraperitoneal chemotherapy (mitomycin C and/or cisplatyl) and peritoneal hyperthermia. After a brief reminder on the general principles concerning high temperature action, a review of literature is made: 5 teams have performed this technique. We differentiate the indications, design features and results of each team. The results show a mean survival after 2 years of 35% (in peritoneal carcinomatosis) up to 78% (in gastric serosal invasion, peritoneal seeding free). The best result of the method is the drying up of cancerous ascites, allowing a more comfortable survival.     

Postoperative chemotherapy including intraperitoneal and intradermal administration of the streptococcal preparation OK-432 for patients with gastric cancer and peritoneal dissemination: a prospective randomized study

We studied the effects on survival time of postoperative immuno-chemotherapy, including the streptococcal preparation OK-432, in patients with gastric cancer and synchronous peritoneal dissemination. The patients were prospectively randomized and a valid statistical assessment could be made for 109. Patients randomized to group B received therapy that is widely used in Japan to treat patients with gastric cancer: mitomycin C (MMC) and UFT, a combination of tegafur and uracil in a molar ratio of 1:4, for 1 year. Patients randomized to group A received the same drugs as were given to group B patients plus OK-432 i.p. for 7 days, beginning on postoperative day 0, and OK-432 by intradermal injection for 1 year, at 2-week intervals. There were no differences between the two groups in any known prognostic factor or in the dose of any drug administered except for OK-432. There was no difference in the toxicity rate between the groups. In this negative trial, there was no improvement in survival time with the addition of OK-432 to MMC and UFT for patients with gastric cancer and peritoneal dissemination.     

Experimental and clinical studies on the intraperitoneal administration of cis-diamminedichloroplatinum (II) for peritoneal carcinomatosis caused by gastric cancers

The effectiveness of the intraperitoneal administration of cis-diamminedichloroplatinum (II) (DDP) on peritoneal carcinomatosis caused by gastric cancers was evaluated. Seventeen patients were treated with one of three protocols, consisting of the intraperitoneal injection (ip) of DDP at doses of 70 and 110 mg/m2, with or without sodium thiosulfate (STS) rescue. The area under the curve (AUC) of DDP for sufficient anticancer activities against cultured human cell lines in vitro was estimated at 240 micrograms h/ml, which was equivalent to the AUC gained by 110 mg/m2 ip DDP in the clinical studies. The cytotoxic activity of DDP was reduced by approximately 50% with 100-fold STS in the AUC in the experimental studies. However, this was achieved only in urine, and not in either the peritoneal cavity or in plasma in the clinical studies. Three cases of a partial response against peritoneal carcinomatosis were seen from a total of four evaluable cases treated with 110 mg/m2 DDP, and no renal toxicities were observed in those treated with the STS rescue. The results of this study led us to conclude that high-dose ip DDP treatment combined with the STS rescue would be useful chemotherapy against peritoneal carcinomatosis caused by gastric cancers.     

Intraoperative lymph nodes dissection guided by preoperative endoscopical injection of mitomycin C absorbed activated carbon (MMC-CH40) at pericancerous gastric mural in patients with gastric cancer

22 patients with gastric cancer underwent preoperative endoscopical MMC-CH injection before radical resection. Lymph nodes resected in MMC-CH40 group averaged 47.0 vs. 28.1 in the control group (P < 0.05). Positive nodes were found 15 of 22 cases (68%) in MMC-CH40 group vs. 22 out of 26 cases (77%) in the control group (P > 0.05). Positive nodes totalled up to 166 of all 1033 dissected in the former (16%) vs. 162 of 730 (23%) in the latter (P < 0.01). Positive nodes found in 15 of 22 cases in MMC-CH40 group averaged 11.07 per lymph-node-metastasized patient vs. 7.36 in the control group (P < 0.01). The results showed that this procedure is of assistance to thorough dissection of lymph node during surgery.     

Potential of the histoculture drug-response assay to contribute to cancer patient survival

The histoculture drug-response assay (HDRA) was recently evaluated in a retrospective clinical trial and was found to correlate to drug sensitivity, resistance, and patient survival. To further investigate the potential of HDRA to contribute to patient survival, 215 patients with gastric cancer from 45 medical centers were tested with the HDRA in a blinded study after resection of the primary lesion. One hundred sixty-eight patients received at least 20 mg/m2 of mitomycin C and a minimum of 30 g UFT, a mixture of tegafur and uracil at a molar ratio of 1:4, thereby making them eligible for the study. Of these cases 128 were evaluable by the HDRA. The evaluable patient tumors were tested by the HDRA with the [3H]thymidine incorporation end point measured by microautoradiography to be drug "sensitive" or "resistant." The in vitro conditions for distinguishing sensitivity and resistance that matched the response rates for historical controls for gastric carcinoma were 90% inhibition rate and 0.12 microgram/ml for mitomycin C and 70% inhibition rate and 1 microgram/ml for 5-fluorouracil, respectively. Most importantly in the blinded study, the overall and disease-free survival rates of the HDRA-sensitive group were found to be significantly higher than those of the HDRA-resistant group tested under the above conditions. The data further indicate the importance of three-dimensional tumor culture for obtaining accurate clinical information. The results demonstrate that the HDRA response correlates to patient survival, which suggests the potential of the HDRA to contribute to patient survival in gastric cancer when used prospectively.     

Complete omentectomy and extensive lymphadenectomy with gastrectomy improves the survival of gastric cancer patients with metastases in the adjacent peritoneum

BACKGROUND/AIMS: The omentum is the site where peritoneal metastases occur most frequently. It has not been shown whether complete resection of the omenta during gastrectomy improves the survival of gastric cancer patients with macroscopic peritoneal metastases. METHODOLOGY: We retrospectively analyzed 126 patients who underwent gastrectomies for gastric cancer with peritoneal metastases but without hematogenous metastases. The 126 patients were stratified according to their grade of peritoneal metastases into three groups: the P1 patients (patients with peritoneal metastases in the adjacent peritoneum but not in the distant peritoneum); the P2 patients (patients with a few peritoneal metastases in the distant peritoneum); and the P3 patients (patients with many metastases in the distant peritoneum). In each group, the survival and clinicopathological characteristics were compared between patients treated by complete resection of the greater omentum and the lesser omentum plus extensive lymphadenectomy during gastrectomy, versus patients treated by incomplete resection of the omenta and non-extensive lymphadenectomy during gastrectomy. RESULTS: Complete omentectomy and extensive lymphadenectomy during gastrectomy improved survival significantly only in the P1 patients. Other clinicopathological characteristics did not differ between them. CONCLUSION: Complete omentectomy and extensive lymphadenectomy is recommended in patients with peritoneal metastases in the adjacent peritoneum but not in the distant peritoneum.     

Intraperitoneal chemo-hyperthermia with mitomycin C in cancer of the stomach with peritoneal carcinosis

We report 42 cases of gastric cancer with peritoneal carcinosis treated with intraperitoneal chemohyperthermia. Intraperitoneal chemohyperthermia was achieved with a closed sterile circuit containing mitomycin C, 10 mg/l producing an input temperature varying from 46 to 49 degrees C for 90 minutes. There were three postoperative deaths: one pulmonary embolism at day 4, one multiple organ failure et day 4, and one septic shock at day 25 due to a colonic fistula. Two patients suffered complications: one opening of the duodenal stump requiring reoperation on day 5, and one prolonged postoperative ileus lasting to day 10. Of the 12 patients with ascites, resorption was achieved in 8. In patients with early-stage peritoneal carcinosis (granulations less than 5 mm) survival at 1, 2 and 3 years was 90%, 61% and 41% respectively. For those with more extensive carcinosis, survival at 1 year was 10%. Five patients survived more than 30 months, three have survived to 34, 43 and 73 months. Intraperitoneal chemohyperthermia is a new treatment for carcinosis of gastric origin. These early results must be assessed further with larger controlled.     

Fast MR imaging and the detection of small-bowel obstruction

Between 1/1986 and 6/1996, 37 consecutive patients affected by node-positive gastric cancer (GC) were treated with radical surgery and received 5-fluorouracil, epirubicin and mitomycin C (FEM) as adjuvant treatment. Only 57% of the patients received all six cycles and the reasons for treatment withdrawal were mainly related to concomitant pathologies and prolonged leukopenia. After a median follow-up of 39 months, the 3-year disease-free survival, disease-related survival and overall survival were 75.8%, 83.7% and 78.6% respectively. A statistically significant difference in survival was found in the subgroup of patients receiving more than three courses of treatment.     

Nonepileptic posttraumatic seizures

BACKGROUND: The aim of this experimental study was to evaluate the risk of tumor recurrence after laparoscopic cecal resection (LCR) of colonic carcinoma in the rat. METHODS: The experimental cancer consisted of one million cells (DHK/K12), incorporated in an extracellular matrix, placed and secured to the cecal serosa in 110 BD9 rats. Four weeks later, all animals were reoperated through a laparotomy to control tumor growth, and animals with diffuse carcinomatosis were excluded. Eligible animals were randomized either to laparoscopic cecal resection (group LCR, n = 10), to open resection (group OCR, n = 13), or to a control group without resection (group C, n = 13). Resection was always considered as macrocopically complete. All animals were killed 4 weeks after the resection to determine the tumor recurrence and quantify carcinomatosis. RESULTS: We noted diffuse carcinomatosis in 70% of rats in groups C and LCR versus 23% in group OCR (p = 0.038). For tumors noted as S- (not extending outside the serosa), diffuse carcinomatosis was observed in all animals of group C (3 of 3), in 6 of 8 in group LCR, and 0 of 6 in group OCR (p = 0.004). The rate of port site or incisional metastases was not significantly different between groups. CONCLUSIONS: These preliminary results demonstrated the deleterious impact of the laparoscopy for resection of large bowel malignancy. LCR increased significantly the incidence of a diffuse carcinomatosis even when performed for locally noninvasive tumors (S-).     

Single intraoperative application versus postoperative mitomycin C eye drops in pterygium surgery

PURPOSE: To determine the minimum effective dosage, most effective route of administration and long-term effects of mitomycin C for prevention of recurrence after pterygium surgery. METHODS: In a prospective, masked study, 227 patients undergoing surgery for primary pterygia were assigned randomly to five groups: group 1 received a single intraoperative application of 0.2 mg/ml mitomycin C for 3 minutes; group 2 received a single intraoperative application of 0.4 mg/ml mitomycin C for 3 minutes; group 3 received mitomycin C eye drops 0.2 mg/ml three times daily for 7 days; group 4 received mitomycin C eye drops 0.4 mg/ml three times daily for 14 days; group 5 acted as a control (surgery alone). RESULTS: After a mean follow-up time of 28 months, recurrence rates of 6.66%, 4.08%, 4.26%, 4.44%, and 29.27%, respectively, were observed. Statistical analysis showed significant differences between groups receiving mitomycin C and the control (P < or = 0.001). There was no statistical difference among treated groups (P > or = 0.0681). No complications of therapy were observed. CONCLUSION: These results support the efficacy and relative safety of a single, low-concentration, intraoperative application of mitomycin C in pterygium surgery together with the use of a conjunctival flap, avoiding excessive cauterization of the sclera and leaving bare sclera.     

Mercury-induced renal immune complex deposits in young (NZB x NZW)F1 mice: characterization of antibodies/autoantibodies

PURPOSE: To observe the effect of intraoperative mitomycin C on the size of the osteotomy site after dacryocystorhinostomy.: METHODS: A total of 15 eyes of 14 patients diagnosed with primary acquired nasolacrimal duct obstruction were assigned randomly to either a mitomycin C group or a control group. The surgical procedures in both groups were exactly the same, except that in the patients in the mitomycin C group, a piece of neurosurgical cottonoid soaked with 0.2 mg/ml mitomycin C was applied to the osteotomy site and then after 30 minutes was removed transnasally. Nasoendoscopic findings were recorded at the completion of the surgery and at 1 month, 3 months, and 6 months after surgery for the two groups. A computer-aided digitizer was used to calculate the surface area of the osteotomy site, and a Student's t test was used to compare the difference between the two groups. RESULTS: All patients in the mitomycin C group remained symptom free after removal of their silicone tube (100% success), and there was one patient in the control group who had recurrent epiphora (87.5% success). Septo-osteotomy adhesion was found in two patients in the control group (25%), but there was no such adhesion found in the patients in the mitomycin C group. In the mitomycin C group, the average final surface area of the osteotomy at the end of the sixth postoperative month was 27.10 +/- 5.78 mm2, whereas that of the control group was only 10.83 +/- 3.37 mm2. Although the immediate postoperative surface area of the osteotomy showed no significant difference between the two groups, a statistically significant difference was noted at 6 months. CONCLUSION: Intraoperative mitomycin C is effective in maintaining a larger osteotomy size. This modification may possibly improve success rates over the traditional dacryocystorhinostomy procedure.     

Results of a randomized phase III trial of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin versus mitomycin C alone in patients with superficial bladder cancer

PURPOSE: We study toxicity and efficacy of sequential intravesical therapy with mitomycin C and bacillus Calmette-Guerin (BCG) in patients with intermediate or high risk superficial bladder cancer compared to the use of intravesical mitomycin C alone. MATERIALS AND METHODS: Patients with intermediate and high risk papillary superficial bladder cancer and carcinoma in situ were randomized after transurethral resection between 4 weekly instillations with 40 mg. mitomycin C followed by 6 weekly instillations with BCG (group 1, 90 patients) or 10 weekly instillations with mitomycin C (group 2, 92 patients). RESULTS: The frequency of bacterial and chemical cystitis, and other local side effects was similar in both groups. Allergic reactions, including skin rash, were more frequent in the mitomycin C only group (12 of 92 patients versus 5 of 90, p = 0.08), and other systemic side effects were more frequent in the sequential group (16 of 90 versus 8 of 92, p = 0.07). After a median followup of 32 months the number of recurrences (sequential 35 of 90 patients versus mitomycin C only 42 of 92, p = 0.36) and progression (5 of 90 versus 4 of 92 respectively, p = 0.70) were similar in both groups. CONCLUSIONS: We did not find any major differences in toxicity or treatment efficacy with intravesical mitomycin C and the sequential use of BCG or mitomycin C for intermediate and high risk superficial papillary bladder cancer.     

Adjuvant intraperitoneal chemotherapy with carbon-adsorbed mitomycin in patients with gastric cancer: results of a randomized multicenter trial of the Austrian Working Group for Surgical Oncology

PURPOSE: Previous studies have demonstrated a beneficial effect of intraperitoneally applied mitomycin bound to activated carbon particles (M-CH) in preventing intraabdominal recurrence following curative surgery for gastric cancer. The Austrian Working Group for Stomach Cancer, a subgroup of the Austrian Working Group for Surgical Oncology, initiated a multicentric phase III trial to evaluate the safety and efficacy of this treatment regimen. PATIENTS AND METHODS: A total of 91 patients with a radically resected gastric cancer infiltrating the serosal surface were randomly assigned to receive either 50 mg mitomycin bound to a solution of 375 mg carbo adsorbens intraperitoneally before closure of the abdominal wound (n = 46) or served as a surgical control group (n = 45). Postoperative complications and recurrence-free and overall survival were evaluated to analyze the risks and benefits of this treatment. RESULTS: After a median observation period of 597 days (range, 72 to 1,096), a significantly higher postoperative complication rate was observed in the M-CH group (35%) compared with the control group (16%) (P < .02). In accordance with this finding, the postoperative (60 days) mortality rate was also significantly elevated in the M-CH group (11% v 2% in the control group). Since analysis of overall and recurrence-free survival failed to show any beneficial effect of M-CH therapy, the protocol committee decided to stop further recruitment of patients onto this study. CONCLUSION: Adjuvant intraperitoneal therapy of gastric cancer by mitomycin bound to activated carbon particles is associated with an increased rate of postoperative complications. However, no benefit for prognosis following radical resection of locally advanced tumors was observed in this multicenter phase III trial.     

Type-oriented intraoperative and adjuvant chemotherapy and survival after curative resection of advanced gastric cancer

Recent observations and our experience that histologic types of gastric cancer related significantly to patterns of recurrence prompted us to develop intraoperative and postoperative chemotherapy based on the preoperatively diagnosed histologic types of cancer and to evaluate its effectiveness by a prospective randomized trial. This chemotherapy regimen consisted of the intraoperative administration of mitomycin C (MMC) and postoperative administration of cisplatin (80 mg/patient, day 14), and tegaful and uracil (UFT) (300-600 mg/day for 2 years). Patients with a diffuse type of cancer were randomly assigned to one of three treatment groups: no intraoperative chemotherapy and UFT 300 mg/day (P0 group, n = 16); intraoperative chemotherapy and UFT 300 mg/day (P1 group, n = 13); or UFT 600 mg/day (P2 group, n = 17). Patients with an intestinal type of cancer were randomly assigned to one of three treatment groups: H0 (n = 17), H1 (n = 12), and H2 (n = 12); each group was subjected to the same protocols as the P0, P1, and P2 groups, respectively, except for the MMC administration route. MMC (10 mg/patient) was administered intraoperatively into the intraperitoneal cavity (P1 and P2 groups) or the portal vein (H1 and H2 groups). All patients underwent curative resection. Background factors did not differ significantly among the treatment groups. The overall survival rates were progressively worsened in the order of P2, P1, and P0 or H2, H1, and H0, respectively. The survival rate of the P2 group was statistically higher than that of the P0 group (p < 0.05). The intermediate-term survival rate of the P2 group or H2 group was significantly higher than that of the P0 group (p < 0.05) or H0 group (p < 0.05), respectively. These results suggest the effectiveness of this therapy and the possible eradication of potential micrometastatic foci outside the surgical field by the direct administration of chemotherapeutic agents to the predicted recurrence site.     

Palliative treatment of adenocarcinoma of the cardia: is there a role for surgery?

OBJECTIVES: The value of palliative surgery for adenocarcinoma of the cardia (AC) is controversial, and specific studies are lacking. The aim of this study was to report the results of a palliative resection for AC in 69 patients. METHODS: From 1980 to 1993, 69 patients (mean age 59 +/- 10 years) underwent a palliative resection for AC. Palliative resection was defined by macroscopically incomplete resection, tumoral involvement of resection margins, visceral or serosal metastasis, or N3 metastatic nodes. Patients were classified according to the diagnosis of palliation established preoperatively (group A, n = 26), peroperatively (group B, n = 35), or postoperatively (group C, n = 8) respectively. RESULTS: Six patients (8.7%) died postoperatively. Mortality rates were 3.8%, 8.6% and 25% in groups A, B and C, respectively. Twenty one patients (30%) had postoperative non-fatal complications. Median global survival was 9 months (mean 11 +/- 7 months) without significant difference between groups A, B and C. Forty-four out of 51 patients (86%) followed until death did not have dysphagia. The other patients were free of dysphagia during an average of 70% of the follow-up duration. Among the 14 patients surviving postoperatively with a tumoral esophageal margin, none experienced dysphagia from anastomotic recurrence during follow-up. CONCLUSIONS: In selected patients with AC, a palliative resection can be achieved with an acceptable mortality and a very good functional result. This result can justify a prospective comparison between palliative surgery and alternative treatments.     

Unification of protein families

OBJECTIVE: To evaluate the prognostic significance of isolated tumor cells detected by a panel of various monoclonal antibodies. SUMMARY BACKGROUND DATA: Previously, we showed by using immunocytology that cancer cells are frequently found in bone marrow and peritoneal cavity samples of gastrointestinal cancer patients. METHODS: Findings in bone marrow and peritoneal cavity samples were compared and correlated with the 4-year survival rate of 84 gastric and 109 colorectal patients with cancer. RESULTS: Although positive results in the bone marrow showed little prognostic significance, the peritoneal cavity results correlated with the 4-year survival rate (gastric cancer: p = 0.0038; colorectal cancer: p = 0.0079). Additionally, in subgroups of patients with early (gastric cancer: p = 0.02, colorectal cancer: p = 0.48) and advanced (gastric cancer: p = 0.02, colorectal cancer: p < 0.0001) tumor stages, a correlation of immunocytologic findings and the survival rate was seen. CONCLUSIONS: The detection of minimal residual disease in the peritoneal cavity serves as a new prognostic marker.     

鸦胆子、丝裂霉素和卡介苗膀胱灌注预防浅表性膀胱癌术后复发的前瞻性临床研究

Objective: The aim of this study was to evaluate the effects and safety of brucea javanica oil, mitomycin and BCG for preventing postoperative relapse of superficial bladder cancer through perfusion. Methods: From July 2000 to May 2006, 178 patients with primary superficial bladder cancer (Ta-1, G1-2) were divided into three groups after operation in random: 57 pa-tients in group A received perfusion of 60 mL 10% brucea javanica oil, and 66 patients in group B received perfusion of 20 mg mitomycin while 55 patients in group C received perfusion of 120 mg BCG. Eighteen perfusions per patient were carried out regularly a week after operation. Patients were followed up for clinical, analytical and cystoscopic evaluations every 3 months for 2 years. The tumor relapse rates and side effects after treatment were evaluated. Results: The relapse rate was 14.04% (8/57), 34.85% (23/66) and 18.18% (10/55) in group A, B and C respectively. The relapse rate in group A was obviously lower than that in group B (χ2 = 6.17, P < 0.05). Disease free interval in group A was significantly different from that in group B (F = 7.03, P < 0.05). Side effect in group A (12.28%) was observably lower than that in group B (43.94%) and group C (83.64%) (χ2AB = 15.72, P < 0.01; χ2AC = 55.34, P < 0.01). Conclusion: Perfusion of 10% brucea javanica oil after operation is safer and more effective in preventing superficial bladder tumour relapse and worth for popularizing.     

Results of resection of gastric cancer with distant metastases

BACKGROUND/AIMS: The present study was carried out in order to examine the outcome of resection in cases of gastric cancer with distant metastases. METHODOLOGY: The survival rates of two hundred and eighty-one patients who had undergone resection for primary carcinomas of the stomach, and who had distant metastases according to the TNM classification, were studied. RESULTS: The 5-year survival rates for patients with metastasis to the peritoneum or group 3 nodes were 8.9% and 15.3% respectively and were significantly higher than the survival rates for patients with metastasis to the liver (0%), to group 4 nodes (2.2%) or to more than one site among the liver, lymph nodes and peritoneum (3.5%). Moreover, the 5-year survival rates for patients with metastasis to the peritoneum and N3 nodes increased significantly to 29.4% and 24.2%, respectively, when curative surgery was performed. CONCLUSIONS: The findings of the present study suggests that metastases to the adjacent peritoneum or group 3 nodes have a greater chance of being cured using radical surgery, and that gastrectomy with extended lymphadenectomy (D2-D3) may be used for advanced gastric cancer if there is no gross evidence of metastasis to the distant peritoneum, liver or group 4 nodes.