Peritoneal Metastasis In Patients Research Articles

Preferential HER2 expression in liver metastases and EGFR expression in peritoneal metastases in patients with advanced gastric cancer.

Despite recent clinical trials, the sensitivity and resistance of metastatic gastric cancer to anti-HER2 and anti-EGFR therapy are still unclear. To clarify the HER2 and EGFR expression status in the metastatic sites, we immunohistochemically compared HER2 and EGFR expression between primary and metastatic tumors from 52 gastric cancer patients with liver metastases and 85 patients with peritoneal metastases. The HER2 positivity rate of primary and metastatic tumors in patients with liver metastases, especially with intestinal-type histology (70.6 and 80.0 %, respectively), was significantly higher than in primary and metastatic tumors (22.4 and 16.4 %, respectively) in patients with peritoneal metastases. HER2 positivity of the primary tumor and liver metastases showed good concordance (87.5 %) in patients with liver metastases. In contrast, the EGFR positivity rate of metastatic tumors (70.1 %) in patients with peritoneal metastases was significantly higher than that of metastatic tumors (37.5 %) in patients with liver metastases. HER2 and EGFR expression tended to be mutually exclusive, and HER2/EGFR double-positive cases were rare in patients with liver or peritoneal metastases. In four such patients with HER2/EGFR double-positive primary tumors, the HER2- and EGFR-positive areas were separate, and corresponding liver metastasis was only positive for HER2 and peritoneal metastasis only positive for EGFR. These results indicate that HER2 and EGFR are preferentially expressed in the liver and peritoneal metastases, respectively, which would be potential targets for anti-HER2 and anti-EGFR molecular therapy in metastatic gastric cancer patients.

Update on the prevention of local recurrence and peritoneal metastases in patients with colorectal cancer.

The prevention of a disease process has always been superior to the treatment of the same disease throughout the history of medicine and surgery. Local recurrence and peritoneal metastases occur in approximately 8% of colon cancer patients and 25% of rectal cancer patients and should be prevented. Strategies to prevent colon or rectal cancer local recurrence and peritoneal metastases include cytoreductive surgery and hyperthermic perioperative chemotherapy (HIPEC). These strategies can be used at the time of primary colon or rectal cancer resection if the HIPEC is available. At institutions where HIPEC is not available with the treatment of primary malignancy, a proactive second-look surgery is recommended. Several phase II studies strongly support the proactive approach. If peritoneal metastases were treated along with the primary colon resection, 5-year survival was seen and these results were superior to the results of treatment after peritoneal metastases had developed as recurrence. Also, prophylactic HIPEC improved survival with T3/T4 mucinous or signet ring colon cancers. A second-look has been shown to be effective in two published manuscripts. Unpublished data from MedStar Washington Cancer Institute also produced favorable date. Rectal cancer with peritoneal metastases may not be so effectively treated. There are both credits and debits of this proactive approach. Selection factors should be reviewed by the multidisciplinary team for individualized management of patients with or at high risk for peritoneal metastases.

Cytoreductive Surgery Under Aminolevulinic Acid-Mediated Photodynamic Diagnosis Plus Hyperthermic Intraperitoneal Chemotherapy in Patients with Peritoneal Carcinomatosis from Ovarian Cancer and Primary Peritoneal Carcinoma: Results of a Phase I Trial

BackgroundWe conducted a phase I clinical trial to evaluate the sensitivity, specificity, and safety of cytoreductive surgery (CRS) under aminolevulinic acid-mediated photodynamic diagnosis (ALA-PDD) plus hyperthermic intraperitoneal chemotherapy (HIPEC) on 20 patients with peritoneal carcinomatosis (PC) from ovarian cancer and primary peritoneal carcinoma (PPC).Patients and MethodsPatients took 5-aminolevulinic acid (5-ALA) at a dose of 20 mg/kg orally with 50 mL of water 2 h before surgery. During surgery, the abdominal cavity was observed under blue light (wavelength of 440 nm) before and after CRS plus HIPEC. Specimens were excised and submitted for pathological examination to evaluate the specificity of ALA-PDD. Postoperative course was closely monitored and detailed information was recorded.ResultsCRS under ALA-PDD plus HIPEC was performed 21 times in 20 patients with PC (16 ovarian cancer, 4 PPC) between June 2011 and October 2013. With the exception of 1 (5 %) patient, strong red fluorescence was detected in 19 patients with ovarian cancer, with a sensitivity of 95 %. All specimens from red fluorescent lesions were invaded by cancer cells, with a specificity of 100 %. No severe adverse events occurred during the perioperative period, with the exception of some abnormal laboratory results and mild complications. All patients were alive until the last follow-up.ConclusionALA-PDD provided a high sensitivity and specificity in detecting peritoneal metastasis in patients with PC from ovarian serous carcinoma and PPC. CRS under ALA-PDD plus HIPEC was a feasible and safe treatment option for patients with PC from ovarian cancer and PPC.

Usefulness of the neutrophil/lymphocyte ratio measured preoperatively as a predictor of peritoneal metastasis in patients with advanced gastric cancer.

The prognosis for gastric cancer patients with peritoneal metastasis is poor. Many studies have reported that the neutrophil/lymphocyte ratio (NLR) might be useful to predict the degree of progression of gastric cancer. In this study, we attempted to evaluate whether the NLR and other related laboratory parameters might be reliable predictors of the presence of peritoneal metastasis in patients with advanced gastric cancer. The data of 359 patients who underwent gastric surgery between June 2008 and December 2011 were reviewed. A retrospective analysis of the preoperative blood data in relation to the presence of peritoneal metastasis was carried out. An increased serum C-reactive protein level (P = 0.022), APTT (P = 0.017) and NLR (P < 0.001), and a decreased serum Alb (P = 0.014) were significantly related to the presence of peritoneal metastasis. A multivariate analysis showed that a NLR >2.37 (OR = 2.59, 95 % CI = 1.38-4.93, P = 0.003) and clinical T4 stage (OR = 4.36, 95 % CI = 2.33-8.24, P < 0.001) were independent predictors of the presence of peritoneal metastasis. Our results suggest that the preoperative NLR was a significant independent predictor of the presence of peritoneal metastasis in patients with advanced gastric cancer.

Value of peritoneal cytology in potentially resectable pancreatic cancer

Peritoneal lavage cytology (CY) is used in the diagnosis and staging of various cancers. The clinical significance of positive cytology results in patients with pancreatic cancer is yet to be determined. Peritoneal washing samples were collected from consecutive patients with pancreatic cancer between July 1991 and December 2012. The correlations between cytology results, clinicopathological parameters and recurrence patterns were evaluated. The prognostic impact of CY status, regarding resectability and the effectiveness of adjuvant chemotherapy, were analysed. Of 523 included patients, 390 underwent resection. Patients with tumours at least 2 cm in diameter were more likely to have CY+ status than patients with tumours smaller than 2 cm (48 of 312 versus 3 of 78 respectively; P = 0·005) and there was a significant correlation between CY+ status and tumour invasion of the anterior pancreatic capsule (43 of 276 versus 8 of 113 with no invasion of the capsule; P = 0·030). Although the overall survival of patients with resected CY+ tumours was worse than that of patients with resected CY- tumours, it was significantly better than the survival of unresected patients regardless of CY status. Multivariable analysis of all patients who had pancreatectomy did not identify CY+ as an independent prognostic factor. Patients with CY+ tumours tended to develop peritoneal metastasis more often than those with CY- tumours, although not significantly so. The median survival time of 34 patients with resected CY+ tumours who received adjuvant chemotherapy was better than that of 17 patients who had surgery alone, although this was not statistically significant (15·3 versus 10·0 months; P = 0·057). CY+ status is not clinically equivalent to gross peritoneal metastasis in patients with pancreatic cancer. Curative resection is still recommended regardless of CY status.

386. The Role of Diagnostic Laparoscopy in Detecting Minimal Peritoneal Metastasis in Patients with Pancreatic Cancer Scheduled for Curative Resection

386. The Role of Diagnostic Laparoscopy in Detecting Minimal Peritoneal Metastasis in Patients with Pancreatic Cancer Scheduled for Curative Resection

Predictors of survival in patients with high-grade peritoneal metastases undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Peritoneal metastases in patients with high-grade adenocarcinoma have been typically associated with a poor outcome. Recent literature has suggested that cytoreduction surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may improve survival. We examined this subset of patients in an effort to better delineate those factors which contribute to improved survival. A retrospective review was performed looking at patients who had undergone CRS/HIPEC. Patients were identified as high-grade histology on the basis of pathology reports indicating their lesion as high grade, moderately, or poorly differentiated and/or associated with signet ring or goblet cell carcinoid features. Peritoneal cancer index and completeness of cytoreduction (CC) were used to define disease burden. Survival analysis was performed by the method of Kaplan-Meier with the log-rank test used to determine significance. Of the 250 patients who underwent CRS/HIPEC between 1999 and 2011, 36 (14%) were identified as having peritoneal metastases from a high-grade gastrointestinal primary. Actual overall survival from the time of diagnosis was 11.1% at 5 years. Median survival from time of surgery was 21.6 months. Survival advantage was conferred to those patients who underwent a CC0/CC1 resection, had a peritoneal cancer index score at time of surgery ≤20, appendiceal primary, or moderately differentiated histopathology. Receipt of neoadjuvant chemotherapy and nodal status was not significantly predictive of improved survival. Patients with signet ring cell histology had a particularly poor prognosis. For those patients with high-grade peritoneal metastases and historically a poor prognosis, prolonged survival may be achieved through CRS/HIPEC, optimally with a CC0/CC1 resection.

Resection of peritoneal metastases in patients with hepatocellular carcinoma

Peritoneal metastases from hepatocellular carcinoma are common; they are found in as many as 18% of autopsy cases. Effective treatment for peritoneal metastases, however, has not yet been established. We resected peritoneal metastases 12 times in 9 patients with hepatocellular carcinoma. We assessed the clinical course and outcome of these patients to determine the effectiveness of resecting peritoneal metastases and the factors related to survival. The 1-, 3-, and 5-year survival rates were 58%, 52%, and 42%, respectively. Four patients survived for longer than 2 years without recurrence or with controlled recurrence confined to the liver. Three patients receiving palliative resection had a poor prognosis, with survivals of only 4, 9, and 12 months. Operative resection should be an option for selected patients with peritoneal metastases from hepatocellular carcinoma. Resection of peritoneal metastases should be considered in patients whose primary liver neoplasm is under control and who have no metastases in other organs.

Increased metastases are associated with inflammation and matrix metalloproteinase-9 activity at incision sites in a murine model of peritoneal dissemination of colorectal cancer

BackgroundPro-inflammatory processes associated with the early postoperative state are known to contribute to peritoneal metastases in patients with advanced diseases. This study aimed to determine whether the wound healing response after an abdominal incision leads to increased matrix metalloproteinase (MMP)-9 activity locally, contributing to peritoneal metastasis. Materials and methodsMetastatic tumors were initiated in C57bl/6J male mice (8wk of age) using a peritoneal injection model with syngeneic MC38 murine colon cancer cells; appropriate control mice also were studied. Injections were performed into the peritoneum in the right lower quadrant. We then observed the occurrence and rate of peritoneal metastasis for each group. ResultsBy making an incision into the abdominal wall of mice, an inflammatory response was induced at the wound site. The inflammatory response initiated by the wound, in turn, increased the proliferation of mesothelial cells and increased inflammatory cell numbers locally, which contributed to an increase in parietal peritoneal metastases. In addition, the wound healing process increased the expression of pro-inflammatory cytokines and the number of inflammatory cells in the peritoneum. Moreover, MMP-9 in the modeled postoperative injury setting increased the number and severity of peritoneal metastases. ConclusionsThus, we conclude that wound-associated inflammation enhances pro-MMP-9 expression, which plays a key role in the growth and progression of cancer cells associated with peritoneal metastases.

Identification and Quantification of Peritoneal Metastases in Patients With Ovarian Cancer With Multidetector Computed Tomography

The purpose of the study was to determine the performance of a 64-row multidetector computed tomography (MDCT) in identifying peritoneal metastases in ovarian cancer patients undergoing surgical staging or cytoreduction. This retrospective study included 76 patients who underwent surgical staging (n = 11) or cytoreduction (n = 65). Patients had MDCT before surgery (mean, 24 [SD, 16.9] days) as well as correlative surgicopathologic data. For the imaging analysis, the peritoneal cavity was divided to 28 segments, which were assessed for absence or presence of disease. Rate of optimal cytoreduction at the time of surgery was recorded. The standard of reference for this study was surgery, unless there was proof of metastasis as assessed by follow-up imaging. Sensitivity and predictive accuracy of CT and surgery compared with the standard of reference were calculated. The overall sensitivity and accuracy were 81.2% and 94.3% for MDCT and 87.4% and 97.2% for surgery (P = 0.14, P = 0.007), respectively. There was no difference in the detection of lesions 1 cm or greater between MDCT and surgery (89.3% and 84.9%, respectively; P = 0.31); however, MDCT was less sensitive than surgery in detecting disease sites of less than 1 cm (65.5% and 92.3%, respectively; P = 0.001). For the subgroup of patients undergoing cytoreduction after neoadjuvant chemotherapy (NAC) (n = 30), sensitivities for MDCT and surgery were similar (80% and 76.9%, respectively [P = 0.71]). Although sensitivity of CT was not altered by NAC (P = 0.92), there was a significant decrease in sensitivity of surgical assessment after NAC (94% vs 76.9%; P = 0.003). Multidetector computed tomography (MDCT) has similar sensitivity as surgery for peritoneal metastases of 1 cm or greater. The maintained sensitivity of MDCT in detecting peritoneal disease after NAC, which is underestimated at surgery, may help surgical planning and may improve optimal cytoreduction rate in this group of patients.

Clinicopathologic characteristics of gastric cancer patients who underwent noncurative gastrectomy with long-term survival

To demonstrate clinicopathologic characteristics of gastric cancer patients who underwent noncurative gastrectomy with long-term survival. We retrospectively reviewed 202 advanced gastric cancer patients who underwent noncurative gastrectomy. The long-term survivors who survived for more than 3 years comprised four of 65 patients with a residual tumor in the peritoneum, one of 50 patients with a residual tumor from lymph node metastasis, three of 41 patients positive for the resected margin (M-factor) and 17 of 153 patients with free intraperitoneal cancer cells (Cy-factor). Multivariate analysis indicated that independent indicators affecting survival were lymph node metastasis and peritoneal metastasis in patients with the Cy-factor and histology in patients with the M-factor. Long-term survival can only be expected in patients with the Cy-factor who have neither macroscopic peritoneal metastasis nor lymph node metastasis or in patients with the M-factor who have a well-differentiated tumor.

The Usefulness of Serum Tumor Markers as a Predictor of Peritoneal Metastasis in Patients with Gastric Carcinoma: CA 19-9 and CEA

The Usefulness of Serum Tumor Markers as a Predictor of Peritoneal Metastasis in Patients with Gastric Carcinoma: CA 19-9 and CEA

Comparison of CT and 18F-FDG PET for Detecting Peritoneal Metastasis on the Preoperative Evaluation for Gastric Carcinoma

ObjectiveThe aim of our study was to compare the accuracy of CT and 18F-FDG PET for detecting peritoneal metastasis in patients with gastric carcinoma.Materials and MethodsOne-hundred-twelve patients who underwent a histologic confirmative exam or treatment (laparotomy, n = 107; diagnostic laparoscopy, n = 4; peritoneal washing cytology, n = 1) were retrospectively enrolled. All the patients underwent CT and 18F-FDG PET scanning for their preoperative evaluation. The sensitivities, specificities and accuracies of CT and 18F-FDG PET imaging for the detection of peritoneal metastasis were calculated and then compared using Fisher's exact probability test (p < 0.05), on the basis of the original preoperative reports. In addition, two board-certified radiologists and two board-certified nuclear medicine physicians independently reviewed the CT and PET scans, respectively. A receiver-operating characteristic curve analysis was performed to compare the diagnostic performance of CT and 18F-FDG PET imaging for detecting peritoneal metastasis.ResultsBased on the original preoperative reports, CT and 18F-FDG PET showed sensitivities of 76.5% and 35.3% (p = 0.037), specificities of 91.6% and 98.9% (p = 0.035), respectively, and equal accuracies of 89.3% (p = 1.0). The receptor operating characteristics curve analysis showed a significantly higher diagnostic performance for CT (Az = 0.878) than for PET (Az = 0.686) (p = 0.004). The interobserver agreement for detecting peritoneal metastasis was good (κ value = 0.684) for CT and moderate (κ value = 0.460) for PET.ConclusionFor the detection of peritoneal metastasis, CT was more sensitive and showed a higher diagnostic performance than PET, although CT had a relatively lower specificity than did PET.

Experimental radioimmunoguided surgery for peritoneal metastases of gastric cancer using anticarcinoembryonic antigen-specific T84.66 F(ab’)2

In gastric cancer, peritoneal dissemination is the most frequent cause of the noncurative resection and recurrence after curative resection. We therefore evaluated the feasibility of radioimmunoguided surgery (RIGS) in the treatment of peritoneal metastases of gastric cancer and the use of anti-CEA-specific T84.66 F(ab')2 as an efficient immune agent. Two human gastric cancer cell lines, MKN45 and RF48, were intraperitoneally xenografted into nude mice, which were later injected with 125I-labeled T84.66 F(ab')2. Peritoneal tumors were localized by RIGS 5 days after antibody injection. The minimum number of cells detected by a gamma probe was assayed by in vitro tumor cell localization. We observed 37 peritoneal metastases: 8 invisible (long diameter, <1 mm), 6 small (1- < 5 mm), and 23 large (> or =5 mm) tumors. The accuracy, sensitivity and specificity of RIGS in detecting peritoneal metastasis were 82% (69/84), 76% (28/37), and 87% (41/47), respectively. RIGS accuracy did not differ with respect to tumor diameter. Mean labeling indices over minimal and maximal normal counts were 6.1+/-1.2 (mean +/- SEM) and 4.7+/-1, respectively. Mean scores of CEA immunostaining and silver grains in tumors were significantly higher than those in the nontumor-bearing peritoneum (P < 0.001). There was a close correlation among radioactivity, immunostaining and microautoradiography (P < 0.001-0.005). We observed six false-positive and nine false-negatives which may have been due to high blood background and negative radioimmune reactivity, respectively. 125I-labeled T84.66 F(ab')2 efficiently targeted peritoneally disseminated gastric cancer cells, suggesting that RIGS using this immune agent may accurately detect occult peritoneal metastases in patients with gastric cancer.

Predictive value of preoperative serum CEA, CA19-9 and CA125 levels for peritoneal metastasis in patients with gastric carcinoma.

Peritoneal metastasis is a crucial factor for the prognosis in gastric cancer, but its diagnosis is difficult before laparotomy. This study analyzed the usefulness of diagnostic imaging and various tumor markers in the detection of peritoneal metastasis in gastric cancer. The sera from 768 patients with gastric cancer were measured for CEA, CA19-9 and CA125 levels using a commercial immunoradiometric assay. All the patients underwent diagnostic imaging with computed tomography (CT) and ultrasound (US) before laparotomy. Preoperative levels of CEA, CA19-9 and CA125 were above the cut-off levels in 15.4%, 8.7% and 5.7% of all cases, respectively. Eighty-eight patients were diagnosed with peritoneal metastasis by laparotomy. CT and US revealed peritoneal dissemination in 15 of 88 patients (17%). Among the three tumor markers, CA19-9 and CA125 showed similar detection rates of peritoneal metastasis (37.5% and 38.6%, respectively). In particular, the serum CA125 levels showed the best sensitivity (38.6%), specificity (98.4%), and diagnostic accuracy (91.5%), and the highest odd ratio (24.46, 95% CI: 11.17 approximately 53.57) for predicting peritoneal metastasis among the markers tested. CEA did not add significant predictive information (p=0.471). Preoperative serum CA19-9 and CA125 levels may provide a predictable value in determining peritoneal metastasis in patients with gastric cancer.

Thin section dual-phase multidetector-row computed tomography detection of peritoneal metastases in gynecologic cancers.

To determine the sensitivity, specificity, and accuracy of multidetector-row computed tomography (CT) using thin sections and multiplanar reconstruction for the detection of peritoneal implants in patients with ovarian cancer. Seventeen thin section dual-phase multidetector-row CT scans were performed on 17 women with potential peritoneal metastases from ovarian cancer, which scans were then followed by surgery. Axial and multiplanar images from the CT scans were reviewed by 2 observers, and the results were compared with the operative and clinical notes. Peritoneal metastases were detected by both readers in all 7 patients presenting with ovarian cancer and disease at laparotomy. Metastases were detected in 5/6 patients with recurrent tumor by observer 1 and in 4/6 patients by observer 2. Sensitivity, specificity, and accuracy for detecting peritoneal metastases at individual sites in the abdomen and pelvis were improved when both axial and multiplanar images were reviewed. Sensitivities were highest for the paracolic gutters and infracolic omentum (>70%). Approximately 50% of liver and diaphragmatic lesions were detected. Specificities approached 100% for all sites and accuracies were >80% for most sites of disease. The sensitivity, specificity, and accuracy of CT for peritoneal metastases in patients is high using thin slices and axial and multiplanar review of the data.

Regional lymph node metastasis as a predictor of peritoneal carcinomatosis in patients with Borrmann type IV gastric carcinoma

Objective: Postoperative survival of patients with Borrmann type IV gastric carcinoma is significantly worse than that in patients with other Borrmann types of gastric carcinomas. The most common pattern of recurrence in patients with Borrmann type IV gastric carcinoma is peritoneal metastasis. We examined the predictors of developing peritoneal metastasis. Methods: We retrospectively analyzed the relationship between peritoneal metastasis and Borrmann type IV gastric carcinoma. We also examined the dependence of the peritoneal metastasis on clinicopathological findings. Results: Borrmann type IV was an independent prognostic factor of survival by multivariate analysis, and regional lymph node metastasis was an independent predictor of peritoneal metastasis in patients with Borrmann type IV gastric carcinoma. Conclusion: Because type of lymph node dissection was not associated with developing peritoneal metastasis, early detection of cancer without lymph node metastasis may be the only means of improving survival in patients with Borrmann type IV gastric cancer.

Regional lymph node metastasis as a predictor of peritoneal carcinomatosis in patients with Borrmann type IV gastric carcinoma.

Postoperative survival of patients with Borrmann type IV gastric carcinoma is significantly worse than that in patients with other Borrmann types of gastric carcinomas. The most common pattern of recurrence in patients with Borrmann type IV gastric carcinoma is peritoneal metastasis. We examined the predictors of developing peritoneal metastasis. We retrospectively analyzed the relationship between peritoneal metastasis and Borrmann type IV gastric carcinoma. We also examined the dependence of the peritoneal metastasis on clinicopathological findings. Borrmann type IV was an independent prognostic factor of survival by multivariate analysis, and regional lymph node metastasis was an independent predictor of peritoneal metastasis in patients with Borrmann type IV gastric carcinoma. Because type of lymph node dissection was not associated with developing peritoneal metastasis, early detection of cancer without lymph node metastasis may be the only means of improving survival in patients with Borrmann type IV gastric cancer.

Serum CA 125 level as a predictor of peritoneal dissemination in patients with gastric carcinoma.

Prediction of peritoneal dissemination is very difficult using current diagnostic tools such as computed tomography, ultrasonography, or various tumor markers. The predictive value of serum CA 125 levels for peritoneal metastasis from gastric carcinoma was studied. The sera from 384 patients with gastric carcinoma were measured for CA 125 titer using an immunoradiometric assay. Carcinoembryonic antigen, carbohydrate antigen 19-9, and sialyl-Tn antigen were measured in the same samples. The serum CA 125 level was elevated according to the degree of peritoneal dissemination. The reference value for peritoneal dissemination was determined to be 35 U/mL, resulting in a sensitivity of 39.4%, specificity of 95.7%, and diagnostic accuracy of 90.8%. The diagnostic ability was more reliable than the other imaging modalities including computed tomography and ultrasonography and the other useful tumor markers for gastric carcinoma. The serum CA 125 level was elevated after gastrectomy for approximately 2 months, most likely due to the continuous inflammation of the peritoneum and lost predictive significance for peritoneal dissemination during this period. Measurement of the serum CA 125 titer may be a powerful predictor of peritoneal metastases in patients with gastric carcinoma.