Macroscopic Peritoneal Carcinomatosis Research Articles

Looking for a strategy in treating peritoneal gastric cancer carcinomatosis: an Italian multicenter Gastric Cancer Research group\u2019s analysis

BackgroundThe present study provides a snapshot of Italian patients with peritoneal metastasis from gastric cancer treated by surgery in Italian centers belonging to the Italian Research Group on Gastric Cancer. Prognostic factors affecting survival in such cohort of patients were evaluated with the final aim to identify patients who may benefit from radical intent surgery.MethodsIt is a multicentric retrospective study based on a prospectively collected database including demographics, clinical, surgical, pathological, and follow-up data of patients with gastric cancer and synchronous macroscopic peritoneal metastases. Patients were surgically treated from January 2005 to January 2017. We focused on patients with macroscopic peritoneal carcinomatosis (PC) treated with upfront surgery in order to provide homogeneous evidences.ResultsOur results show that patients with peritoneal carcinomatosis cannot be considered all lost. Strictly selected cases (R0/R1 and P1 patients) could benefit from an aggressive surgical approach performing an extended lymphadenectomy and HIPEC treatment.ConclusionThe main result of the study is that GC patients with limited peritoneal involvement can have a survival benefit from a surgery with “radical oncological intent”, that means extended lymphadenectomy and R0 resection. The retrospective nature of this study is an important bias, and for this reason, we have started a prospective multicentric study including Italian stage IV patients that hopefully will give us more answers.

Cirugía de second look más HIPEC en pacientes sin evidencia de recidiva con alto riesgo de desarrollar carcinomatosis tras resección de cáncer colorrectal

IntroductionTo analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor, in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). MethodsBetween 2012-2016, 33 patients without any sign of peritoneal recurrence on imaging studies were prospectively included in the study and underwent second-look surgery aimed at treating limited PC earlier and were prospectively recorded. They were selected based on 5 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 10), synchronous ovarian metastases (n = 2), positive peritoneal cytology (n = 2), pT4 primary tumors (n = 15) and perforation (n = 4). ResultsPC was found and treated by cytoreduction plus HIPEC in 10 of the 33 (30.3%) patients, although it was detected in only 2/15 patients of the pT4 subgroup (13.3%). The patients without PC underwent complete abdominal exploration plus HIPEC. Median follow-up was 14.5 months. One patient died postoperatively at day 55. Severe morbidity rate (Clavien-Dindo III-V) was low (15.2%). The 3-year overall survival rate was 93% and the 3-year disease-free survival rate was 33%. Peritoneal recurrences occurred in 4 patients (12.1%), 2 of whom had macroscopic PC discovered at the second-look (20%), while the other 2 patients had no macroscopic PC (8.7%) (P = .04). ConclusionsThe second look + HIPEC strategy in our series of patients at high risk of developing PC, allows its early detection and its treatment in 30.3% of cases, with a very low rate of peritoneal recurrence. It is important to continue evaluating the results to increase the accuracy of the inclusion criteria, especially the pT4 criterion that in this series has a low predictive power for the occurrence of PC.

Systematic Second-look Surgery Plus HIPEC in Patients Without Evidence of Recurrence, at High Risk of Carcinomatosis After Colorectal Cancer Resection

IntroductionTo analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor, in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). MethodsBetween 2012 and 2016, 33 patients without any sign of peritoneal recurrence on imaging studies were prospectively included in the study and underwent second-look surgery aimed at treating limited PC earlier and were prospectively recorded. They were selected based on 5 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n=10), synchronous ovarian metastases (n=2), positive peritoneal cytology (n=2), pT4 primary tumors (n=15) and perforation (n=4). ResultsPC was found and treated by cytoreduction plus HIPEC in 10 of the 33 (30.3%) patients, although it was detected in only 2/15 patients of the pT4 subgroup (13.3%). The patients without PC underwent complete abdominal exploration plus HIPEC. Median follow-up was 14.5 months. One patient died postoperatively at day 55. Severe morbidity rate (Clavien–Dindo III–V) was low (15.2%). The 3-year overall survival rate was 93% and the 3-year disease-free survival rate was 33%. Peritoneal recurrences occurred in 4 patients (12.1%), 2 of whom had macroscopic PC discovered at the second-look (20%), while the other 2 patients had no macroscopic PC (8.7%) (P=.04). ConclusionsThe second look+HIPEC strategy in our series of patients at high risk of developing PC, allows its early detection and its treatment in 30.3% of cases, with a very low rate of peritoneal recurrence. It is important to continue evaluating the results to increase the accuracy of the inclusion criteria, especially the pT4 criterion that in this series has a low predictive power for the occurrence of PC.

Microscopic peritoneal carcinomatosis in gastric cancer: Prevalence, prognosis and predictive factors.

Peritoneal carcinomatosis (PC) is typically identified in advanced stage gastric cancer and is frequently considered to be an incurable disease. Along with macroscopic PC, microscopic PC may be diagnosed through pathological examination of tissue specimens and is not detectable during surgical intervention. The present study aimed to analyse the prevalence, prognostic value and predictive factors for microscopic PC. In the present retrospective study, data from patients with epithelial gastric cancer that were treated with curative intent surgery were examined. Patients with macroscopic PC were excluded. Additionally, the study population was divided into two groups based on the presence or absence of microscopic PC. The prevalence of microscopic PC was 5.5%. Microscopic PC exhibited a significant negative effect on overall survival. In addition, multivariate analyses revealed that the significant predictive factors for the presence of microscopic PC were adenocarcinoma of a diffuse type, lymphatic and vascular invasion, cancer location at the site of previous gastric surgery and a tumour extent >T2. In particular, the presence of lymphatic and vascular invasion was the most significant predictive factor. These results indicate that ≥5.5% of patients with gastric cancer who undergo surgery with a curative intent may benefit from more aggressive loco-regional treatment against microscopic PC at the time of surgery.

Yield of Staging Laparoscopy and Lavage Cytology for Radiologically Occult Peritoneal Carcinomatosis of Gastric Cancer.

This study aimed to identify the yield of staging laparoscopy with peritoneal lavage cytology for gastric cancer patients and to track it over time. The medical records of patients with gastric or gastroesophageal adenocarcinoma who underwent pretreatment staging laparoscopy at the authors' institution from 1995 to 2012 were reviewed. The yield of laparoscopy was defined as the proportion of patients who had positive findings on laparoscopy, including those with macroscopic carcinomatosis, positive cytology, or other clinically important findings. To compare the yield of laparoscopy over time, the patients were divided into three 6-year ranges based on the date of diagnosis. Associations between clinicopathologic factors and peritoneal disease were examined using uni- and multivariate analyses. The study included 711 patients. Among these patients, 43.5 % had gastroesophageal junction tumors, 72.9 % had poorly differentiated adenocarcinoma, and 53 % had signet ring cell morphology. Endoscopic ultrasound had most commonly identified T3 (83.9 %) and N-positive (66.4 %) tumors. At laparoscopy, 148 (20.8 %) patients had been found to have macroscopic peritoneal carcinomatosis. Among 514 macroscopically negative patients who underwent peritoneal lavage cytologic analysis, 68 (13.2 %) had positive cytology results for malignancy. The total laparoscopy yield was 36 %, which did not change over time (p = 0.58). Multivariate analysis demonstrated that positive cytology or carcinomatosis was associated with poorly differentiated histology, linitis plastica, and equivocal computed tomography findings. Laparoscopy remains a useful staging procedure to evaluate for peritoneal spread when treatment or surgery is considered, even with the current availability of high-quality imaging.

Staging laparoscopy with cytology analysis in gastric cancer.

35 Background: The purpose of this study was to identify clinicopathologic factors associated with the identification of peritoneal disease in patients with gastric cancer and to compare the yield of laparoscopy over time. Methods: The medical records of 7,404 patients with gastric or gastroesophageal adenocarcinoma presenting to our institution (1/1995 to 12/2012) were reviewed to identify patients who underwent diagnostic laparoscopy as a staging procedure before treatment. Associations between clinicopathologic factors and peritoneal disease were examined with chi square and logistic regression analysis. The yield on laparoscopy was stratified according to time. Results: We identified 880 patients who underwent staging laparoscopy for gastric adenocarcinoma. Excluded patients included those with recurrent gastric cancer, those who underwent prior chemotherapy and/or radiation therapy, those with known distant metastatic disease (except for equivocal radiological findings), and those who underwent procedures not for staging purposes, leaving 711 patients in this study: 43.5% with gastroesophageal junctional tumors, 72.9% with poorly differentiated adenocarcinoma, and 53.0% with signet ring cell morphology. Endoscopic ultrasound (EUS) most commonly identified T3 (83.9%) and N-positive (66.4%) tumors. As results of laparoscopy, 148 patients (20.8%) were found to have macroscopic peritoneal carcinomatosis. Among 514 macroscopically negative patients who had peritoneal lavage cytology analysis, 68 (13.2%) were found to have positive. Of the 711 study patients, 42 (5.9%) had other unexpected clinically important findings (e.g., distant metastasis, cirrhosis). Multivariate analysis showed a high positive rate of laparoscopy in patients with poorly differentiated pathology, linitis plastica, or equivocal CT scan, after adjusting race, signet ring cell, and tumor location. The yield of laparoscopy did not change over time when divided into three 6-year periods (p = 0.58). Conclusions: Laparoscopy remains an important staging procedure to evaluate for peritoneal spread when considering treatment or surgery, even in the current era of high-quality imaging evaluation.

Surgical second-look in high risk gastrointestinal stromal tumor of small intestine: A case report

INTRODUCTIONThe peritoneum is one of the most common sites of distant gastrointestinal stromal tumor (GIST) metastases. In particular, GIST arising from the small intestine with resected minimal synchronous macroscopic peritoneal carcinomatosis or with primary tumor rupture has a higher risk of developing peritoneal recurrence. Current clinical practice does not envisage second-look surgery in GIST patients at high risk of developing peritoneal recurrence, and no literature data are available. PRESENTATION OF CASEWe describe a 45-year-old woman who underwent emergency surgical resection of jejunal GIST presenting with spontaneous tumor rupture, synchronous ovarian and minimal macroscopic peritoneal involvement, and subsequent second-look surgery after 13 months of imatinib treatment. DISCUSSIONSecond-look surgery confirmed a 2.6cm lesion close to the mesenteric border of the fourth jejunal loop, and 11 peritoneal lesions with a macroscopic necrotic aspect related to treatment response. After conversion to an open procedure, a segmental jejunal resection was performed with removal of all peritoneal lesions and macroscopic radical cytoreduction. CONCLUSIONSecond-look surgery in selected GIST patients may be performed after at least 12 months of medical treatment with tyrosine-kinase inhibitors to identify those patients with limited peritoneal disease not disclosed by instrumental imaging who could undergo radical cytoreduction of peritoneal lesions.

Long-Term Results and Prognostic Factors of Gastric Cancer Patients with Microscopic Peritoneal Carcinomatosis

BackgroundClinical significance of microscopic peritoneal carcinomatosis remained unclear. The aim of this study was to evaluate the prognostic value of microscopic peritoneal carcinomatosis in gastric cancer.MethodsFrom 1996 to 2007, 4426 patients underwent gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. The clinical and pathological data were reviewed to identify patients with microscopic peritoneal carcinomatosis (group 1). The clinicopathological features and prognosis were examined. Additionally, 242 stage-matched gastric cancer patients without microscopic peritoneal carcinomatosis (group 2) and 118 with macroscopic peritoneal carcinomatosis (group 3) were selected as control groups.ResultsMicroscopic peritoneal carcinomatosis was found in 121 patients. There were 85 males and 36 females (2.36:1). There was a higher incidence rate of large size tumor (≥5 cm) (P = 0.045), Borrmann IV (P = 0.000), and serosal invasion (P = 0.000) in gastric cancer with microscopic peritoneal carcinomatosis compared with the control group. The 5-year survival rate of gastric cancer with microscopic peritoneal carcinomatosis was 24%, significantly poorer than that of the stage-matched control group but better than that of patients with macroscopic peritoneal carcinomatosis. The independent prognostic factors identified included pathological stage and operative curability.ConclusionsThe presence of microscopic peritoneal carcinomatosis was associated with worse prognosis for gastric cancer, but curative surgery showed potential to improve prognosis.

Ascites as a Presenting Sign of Disseminated Tuberculosis in an Immunocompetent Patient

Purpose: A 39 year-old black male presented with a two-month history of abdominal distension, weight loss (28 Kg), anorexia and fever. On physical examination he was found to have ascites and hepatomegaly. A paracentesis was performed revealing an exsudate with elevated adenosine deaminase (259 U/L). He also had anemia (hemoglobin 11.6 g/dL); high erythrocyte sedimentation rate (45 mm/hr), aspartate aminotransferase (155 U/L), alanine transaminase (106 U/L), alkaline phosphatase (732 U/L), ADA (144 U/L) and elevated C-reactive protein (116 mg/L) levels. Human immunodeficiency virus (HIV) 1 and 2, Hepatitis A, B and C serologies were negative. A thoracic abdomino-pelvic computed tomography (CT) scan showed epiploic adipose densification suggesting peritoneal inflammatory features or peritoneal carcinomatosis and bilateral micronodular pattern in the pulmonary intersticium. Polymerase chain reaction (PCR) for Mycobacterium tuberculosis and Ziehl-Neelsen stain for acid-fast bacilli in the peritoneal fluid, bronchoalveolar lavage (BAL), and urine (3 samples) were negative. Blood cultures were negative. Laparoscopy was performed, with absence of macroscopic peritoneal carcinomatosis and hepatic, intestinal and peritoneal biopsies were retrieved. Histology showed epithelioid hepatic granulomas and peritoneal granulomas with central necrosis. Antituberculous therapy were started (isoniazid, rifampicin, pyrazinamide, and ethambutol), although there has no laboratory confirmation of mycobacterial infection. The cultures from the peritoneal fluid, BAL, and urine were positive. He was discharged with no symptoms and with early recovery, under antituberculous therapy for disseminated tuberculosis (hepatic, renal, peritoneal and pulmonary). Workup for HIV was negative; immunoglobulin levels, lymphocyte subsets, and complement levels were normal. Disseminated tuberculosis is rare, particularly in immunocompetent host and is secondary to hematogenic dissemination of Mycobacterium tuberculosis. The estimated frequency is 2.8% of all cases of tuberculosis and 7.3% of extrapulmonar cases. Predisposing factors for the development of disseminated tuberculosis include advanced age, alcoholism, immunosuppressive therapy, neoplasm, hematologic malignancy or HIV infection. Our patient did not have any of these conditions.

Intraperitoneal docetaxel combined with S‐1 for advanced gastric cancer with peritoneal dissemination

Our previous phase I study indicated that combination chemotherapy with intraperitoneal docetaxel and S-1 was well tolerated by gastric cancer patients with peritoneal carcinomatosis (PC). This study evaluated the benefits of this combination chemotherapy and subsequent surgery. Neoadjuvant Intra-Peritoneal and Systemic chemotherapy (NIPS) was introduced to gastric cancer patients with positive cytology or with PC. Two cycles of intraperitoneal chemotherapy with docetaxel combined with S-1, were administrated and gastrectomy with lymph node dissection was performed in cases without macroscopic PC at post-NIPS staging laparoscopy. Eighteen patients were enrolled in this study. Eight patients had measurable lymph node metastases by the RECIST criteria and computed tomography (CT) showed that five (62.5%) displayed a major response to the treatment. Out of 18 patients, 14 (78%) showed negative results on peritoneal cytology and no macroscopic PC, while the remaining four were cancer cell positive on peritoneal cytology or showed macroscopic PC even after NIPS. The median survival time of the entire group was 24.6 months. No treatment-related mortality was observed during NIPS and surgery. This study indicated that the NIPS combined with surgery was highly active and well tolerated by advanced gastric cancer patients with PC.

Results of Systematic Second-look Surgery Plus HIPEC in Asymptomatic Patients Presenting a High Risk of Developing Colorectal Peritoneal Carcinomatosis

To analyze the impact of systematic second-look surgery plus hyperthermic intraperitoneal chemotherapy (HIPEC) performed 1 year after resection of the primary tumor in asymptomatic patients at high risk of developing peritoneal carcinomatosis (PC). From 1999 to 2009, 41 patients without any sign of recurrence on imaging studies underwent second-look surgery aimed at treating limited PC earlier and more easily. They were selected based on 3 primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 25), synchronous ovarian metastases (n = 8), and perforation (n = 8). PC was found and treated with complete surgery plus HIPEC in 23 of the 41 (56%) patients. The other patients underwent complete abdominal exploration plus systematic HIPEC. Median follow-up was 30 (9-109) months. One patient died postoperatively at day 69. Grade 3-4 morbidity was low (9.7%). The 5-year overall survival rate was 90% and the 5-year disease-free survival rate was 44%. Peritoneal recurrences occurred in 7 patients (17%), 6 of whom had macroscopic PC discovered during the second-look (26%), and one patient had no macroscopic PC (6%). In the univariate analysis, the presence of PC at second-look surgery was a significant risk factor for recurrence (P = 0.006). Selection criteria for high-risk patients appear to be accurate. In these patients, the second-look strategy treated peritoneal carcinomatosis preventively or at an early stage, yielding promising results. This study has allowed us to design a multicentric randomized trial (comparing the second-look + HIPEC approach versus standard follow-up alone), which is beginning.

Lymph Node-Positive Stage IIIC Ovarian Cancer: A Separate Entity?

Ovarian cancer spreads via the retroperitoneal lymphatics, and these lymph nodes frequently contain metastasis. A subset of patients whose disease was classified as stage IIIC has retroperitoneal lymph node metastases in the pelvic and/or para-aortic lymph nodes without intraperitoneal carcinomatosis and was upstaged from stage I to IIIB diseases based on these findings. Patients undergoing cytoreductive surgery for advanced-stage ovarian cancer undergo concomitant retroperitoneal lymphadenectomy in an effort to improve their survival. Stratification of patients with stage IIIC ovarian cancer by lymph node status and presence and extent of metastatic disease in the peritoneal cavity has been performed. Studies have determined the impact on disease-free and overall survivals of the resection of retroperitoneal lymph nodes as part of primary and secondary cytoreductive operations. The overall survival of patients with stage IIIC ovarian cancer based on retroperitoneal lymph node metastasis without peritoneal carcinomatosis is 58% to 84% compared with 18% to 36% for those with macroscopic peritoneal carcinomatosis. Although the performance of a pelvic and para-aortic lymphadenectomy in patients with stage IIIC to IV diseases has been reported to prolong survival, an international randomized study did not confirm this finding. Patients who undergo secondary resection of isolated recurrent lymph node metastasis have a better survival than those with more extensive recurrent disease. These data support the stratification of patients with stage IIIC ovarian cancer based on the finding of metastasis to the retroperitoneal lymph nodes without peritoneal carcinomatosis versus those who have peritoneal carcinomatosis. The International Federation of Gynecology and Obstetrics Committee should consider modifying the ovarian cancer staging system by further stratifying stage III disease. Although systematic lymphadenectomy during primary cytoreductive surgery does not appear to improve overall survival, resection of isolated lymph node metastasis and recurrences in lymph nodes may be associated with a survival benefit.

Results of Systematic Second-Look Surgery in Patients at High Risk of Developing Colorectal Peritoneal Carcinomatosis

The aim of this prospective study was to analyze the impact of second-look surgery in an attempt to treat peritoneal carcinomatosis (PC) at an early stage in a series of patients at high risk of developing PC from colorectal cancer. The prognosis of colorectal PC has recently been improved with hyperthermic intraperitoneal chemotherapy (HIPEC) after complete cytoreductive surgery (CCRS), and could be further improved if PC could be treated at an early stage. But, currently, the diagnosis of early PC is not accessible to imaging. From 1999 to 2006, 29 patients without any sign of recurrence on imaging studies underwent second-look surgery 13 months after resection of the primary tumor. Patients were selected according to primary tumor-associated criteria: resected minimal synchronous macroscopic PC (n = 16), synchronous ovarian metastases (n = 4), perforated primary tumor (n = 9). PC was found and treated with CCRS plus HIPEC in 16 of 29 (55%) cases, corresponding to 10 of 16 patients with initial PC, 3 of 4 patients with synchronous ovarian metastases and 3 of 9 patients with a perforated primary tumor. There was no postoperative mortality, and morbidity (grade III/IV) occurred in 14% of cases. After a median follow-up of 27 months (range, 6-96), 8 of 16 patients treated with CCRS and HIPEC are free of disease, 4 relapsed in the peritoneum, and 4 developed isolated visceral metastases. Performing second-look surgery at 1 year in selected patients at high risk of developing PC allowed the early detection and treatment of PC in 55% of cases. Our preliminary results have encouraged us to pursue this strategy and to evaluate it in a prospective multicenter trial.

Intraperitoneal Treatment With Dimethylthioampal (DIMATE) Combined With Surgical Debulking Is Effective for Experimental Peritoneal Carcinomatosis in a Rat Model

The goal was to evaluate the efficiency of intraperitoneal administration of dimethylthioampal (DIMATE), a cellular apoptosis inducer, combined, or not, with cytoreductive surgery on rats with peritoneal adenocarcinomatosis. Peritoneal carcinomatosis was induced in rats by intraperitoneal injection of adenocarcinoma cell line DHD/K12/pro B. Intraperitoneal DIMATE was given at 17.3 mg/kg. Rats were randomized into five groups of eight animals, regarding the day of treatment (2 days or 20 days after peritoneal carcinomatosis induction) and the combination with cytoreductive surgery. All rats were killed at 30 days to evaluate carcinomatosis extent (quantitative score) and ascites volume. The quantitative score of carcinomatosis and the ascites volume were significantly reduced in the groups treated with DIMATE at day 2 (P = 0.005 and P < 0.001, respectively) and when DIMATE was used with cytoreductive surgery at day 20 (P = 0.009 and P < 0.001, respectively). Cytoreductive surgery or DIMATE used alone at day 20 had no significant influence. The intraperitoneal DIMATE administration at day 20, when not combined with surgery, had no significant influence on carcinomatosis extent or on ascites volume. Intraperitoneal DIMATE appeared to be an efficient drug in the prevention or treatment of peritoneal carcinomatosis when combined with cytoreductive surgery or when it was given by intraperitoneal route, before the development of macroscopic peritoneal carcinomatosis. It appears to be a promising therapeutic agent to be investigated in a human phase I trial in peritoneal carcinomatosis.

A phase I trial of intraperitoneal (IP) chemohyperthermia (CH) with oxaliplatin (L-OHP) and irinotecan (CPT-11) in patients (pts) with peritoneal carcinomatosis (PC): Pharmacokinetic (PK),tissue distribution and tolerance

3672 Background: The complete resection of macroscopic PC followed by intraoperative IPCH to treat residual microscopic disease enables curing some patients (pts). Methods: Pts with PC from gastrointestinal or other origin underwent complete cytoreductive surgery followed by intraoperative IPCH with a fixed dose of L-OHP (460 mg/m2) and one of the 7 increasing doses of CPT-11 (from 300 to 700 mg/m2). IPCH was performed using an open procedure for 30 min at an IP temperature of 43°C with 2l/m2 of 5% dextrose instillation in a closed continuous circuit. Just before IPCH, pts received systemic IV leucovorin (LV) 20mg/m2 and 5FU 400mg/m2 to maximize the effect of L-OHP and CPT-11. Results: From May 2002 to June 2003, 39 pts were included with: M/F: 13/26; median age: 46y[26–60]; primary tumor was: 20 colorectal,11 appendix pseudomyxoma,3 endocrine tumors,3 mesothelioma, 2 small bowel. The PK of IP L-OHP was not modified by increasing doses of IP CPT-11, and the drug concentration was 17.8 higher in bathed tumor tissue that in non-bathed tissue. The PK of IP CPT-11 showed an exponential decrease in the peritoneal perfusion and a peak of plasma concentration at 30 min. SN-38 was present in peritoneal instillation immediately after the beginning of IPCH. CPT concentration in tumor tissue increased until the step of 400 mg/m2, and then remained stable. It was 16 to 23 higher than in non-bathed tissues. Half of the L-OHP and CPT-11 was absorbed during the procedure. The hospital mortality rate was 2.5% and the non hematological grade 3 to 5 complication rate (abdominal and intraabdominal) was 25%. At the recommended dose of 400mg/m2, 5/6 pts had grade ½ hematological toxicity: 2 anemia, 5 neutropenia, 1 thrombopenia.The hematological toxicity was correlated to the extent of PC (p=0.017) and duration of surgery (p=0.046). Conclusions: This trial demonstrated a dose related exposure and efficient intratumoral penetration of the 2 drugs. The recommended dose of IP CPT-11 was 400 mg/m2, for phase 2. This phase 2 trial is ongoing. Author Disclosure Employment or Leadership Consultant or Advisory Stock Ownership Honoraria Research Funding Expert Testimony Other Remuneration AstraZeneca; Aventis Pharmaceutical Co. Aventis Pharamceutical Co. Aventis Pharamceutical Co. Aventis; Sanofi-Synthelabo

Preoperative staging of gastric cancer by endoscopic ultrasound: the prognostic usefulness of ascites detected by endoscopic ultrasound.

Endoscopic ultrasound (EUS) is the standard modality in local preoperative staging of gastric cancers and is reputedly able to detect ascites. However, the association between ascites detected by EUS and local tumor staging, peritoneal carcinomatosis, or survival after surgery is not well documented. To assess the accuracy, sensitivity, and specificity of EUS in the preoperative staging and detection of ascites in gastric cancers. We also try to correlate ascites with histologic staging, tumor differentiation, and survival rate of gastric carcinoma after surgery. The retrospective analysis was made in 57 consecutive patients with histologically confirmed gastric adenocarcinomas that underwent EUS before surgery. The accuracy of EUS was compared with the final surgical-pathologic findings. We estimated the prognostic usefulness by analyzing the clinicopathologic features of gastric adenocarcinomas and following up their survival rates. The overall T staging was 88% accurate by EUS. The accuracy for T staging was as follows: T1, 100%; T2, 33%; T3, 93%; and T4, 100%. About 50% of T2 cases were overstaged. The overall accuracy, sensitivity, and specificity of detecting lymph node metastasis by EUS were 79%, 79%, and 80%, respectively. One of the seven T1 cancers had regional lymph node metastasis, and it was missed by EUS, although the T classification was precisely staged based on finding submucosal invasion. A total of 22 patients (39%) had ascites detected by EUS; both the sensitivity and specificity of EUS in demonstrating ascites were 100% in our study. Ascites was significantly correlated with the depth of tumor invasion ( = 0.036), lymph node metastasis ( = 0.008), and poor cellular differentiation ( = 0.007), but it was not significantly correlated with macroscopic peritoneal carcinomatosis. The survival rate after surgical treatment was poor in those with gastric cancers with lymph node metastasis, ascites, or poorly differentiated tumors ( < 0.05). However, multivariate analysis showed that lymph node metastasis was the only significant prognostic predictor ( = 0.004). Endoscopic ultrasound is a valuable diagnostic tool in the local staging of gastric cancers and demonstration of ascites. Although the surgical treatment of gastric cancers with lymph node metastasis, ascites, or poor differentiation had poorer survival rate, only lymph node metastasis was proved to be a significant prognostic predictor in multivariate analysis.

Description of two new human ovarian carcinoma models in nude rats suitable for laparoscopic experimentation.

Experimental laparoscopic trials require relevant models of ovarian carcinomatosis. Female nude rats were inoculated intraperitoneally either with the IGR-OV1 or the NIH:OVCAR-3 human adenocarcinoma cell lines. Serial clinical checks and sacrifices were used to evaluate the rates of tumor take, survival, and patterns of tumor spread. Finally, laparoscopies with various pneumoperitoneum pressures were performed to verify the "surgical" relevancy of out models. The learning curve was measured. The best results were obtained when twenty-seven 106 IGR-OV1 cells and thirty-six 106 NIH:OVCAR-3 cells were injected in 28-day-old rats. The IGR-OV1 model provided a mean survival of 17.8 days (range, 13-22 days), with a high take rate (94%). The NIH:OVCAR-3 model resulted in a longer mean survival (59 days; range, 49-77) and also a high take rate (83%). The two models differed in their patterns of tumor spread: solid bulky omental metastasis having a diffuse microscopic peritoneal carcinomatosis with the IGR-OV1 line (the weight of the omental cake correlated significantly with the stage of development) and diffuse macroscopic peritoneal carcinomatosis having no large solid tumor, but visceral and paraaortic metastases, with the NIH:OVCAR-3 line. In both models, CA125 was high. Anesthesia could be performed and repeated in healthy and tumor-bearing rats. Laparoscopy was feasible, with pneumoperitoneum pressures as high as 8 mmHg lasting 1 h. Laparoscopy provided a reliable evaluation of the tumor spread into the peritoneal cavity. The plateau of the learning curve was soon obtained for take rate and survival after laparoscopy. We report two new human ovarian carcinoma xenografts in nude rats suitable for laparoscopy. The IGR-OV1 model mimics an advanced stage of the disease, and the NIH:OVCAR-3 model presents an earlier stage. These two models appear useful for experiments involving laparoscopy.

Combined suicide and cytokine gene therapy for peritoneal carcinomatosis

BACKGROUNDGene therapy is a novel approach for the treatment of cancers, and tumours disseminated in the peritoneal cavity are suitable for in situ delivery of a therapeutic gene.AIMSThe efficacy of...

Role of peritoneal lymphatics for peritoneal metastasis and chemotherapy with mitomycin C bound to activated carbon particles

Background Based on the knowledge that omental milky spots take up cancer cells seeded in the peritoneal cavity as well as carbon particles, mitomycin C bound to activated carbon particles (MMC-CH) was examined in patients with advanced gastric cancer in a prospective randomized study. Methods 104 patients who underwent gastrectomy for gastric cancer with definite serosal involvement were entered in this trial. Patients in the MMC-CH group were given 50 mg mitomycin C as MMC-CH dispersed throughout the peritoneal cavity just before surgical closure. Results 3-year survival rates for all-over patients treated with MMC-CH was 48% and for patients without MMC-CH was 28%, the differences between these 2 groups being significant (p<0.05). In the patients with macroscopic peritoneal carcinomatosis, there was no difference in survival between these 2 groups. There were no operative deaths in this series but bowel fistula developed in 2 patients given MMC-CH. Conclusions Chemotherapy with MMC-CH improves the survival of patients with gastric cancer involving the serosa, but does not improve the survival of patients with evidence of macroscopic peritoneal carcinomatosis.