Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy improves survival of patients with peritoneal carcinomatosis from gastric cancer: final results of a phase III randomized clinical trial.

BACKGROUND: This randomized phase III study was to evaluate the efficacy and safety of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal carcinomatosis (PC) from gastric cancer. METHODS: Sixty-eight gastric PC patients were randomized into CRS alone (n = 34) or CRS + HIPEC (n = 34) receiving cisplatin 120 mg and mitomycin C 30 mg each in 6000 ml of normal saline at 43 ± 0.5°C for 60-90 min. The primary end point was overall survival, and the secondary end points were safety profiles. RESULTS: Major clinicopathological characteristics were balanced between the 2 groups. The PC index was 2-36 (median 15) in the CRS + HIPEC and 3-23 (median 15) in the CRS groups (P = 0.489). The completeness of CRS score (CC 0-1) was 58.8% (20 of 34) in the CRS and 58.8% (20 of 34) in the CRS + HIPEC groups (P = 1.000). At a median follow-up of 32 months (7.5-83.5 months), death occurred in 33 of 34 (97.1%) cases in the CRS group and 29 of 34 (85.3%) cases of the CRS + HIPEC group. The median survival was 6.5 months (95% confidence interval 4.8-8.2 months) in CRS and 11.0 months (95% confidence interval 10.0-11.9 months) in the CRS + HIPEC groups (P = 0.046). Four patients (11.7%) in the CRS group and 5 (14.7%) patients in the CRS + HIPEC group developed serious adverse events (P = 0.839). Multivariate analysis found CRS + HIPEC, synchronous PC, CC 0-1, systemic chemotherapy ≥ 6 cycles, and no serious adverse events were independent predictors for better survival. CONCLUSIONS: For synchronous gastric PC, CRS + HIPEC with mitomycin C 30 mg and cisplatin 120 mg may improve survival with acceptable morbidity.

Postoperative recurrence in gastric cancer: analysis of 59 cases.

BACKGROUND/AIMS: Gastric cancer (GC) is the leading cause of death in China. Although surgery based comprehensive treatment is the best approach to improve survival, postoperative recurrence is a major problem. This study was aimed to find out the relationship of cancer recurrence with major clinico-pathological factors, with special attention focused on time of recurrence. METHODOLOGY: Data of 59 recurrences after surgery among 286 GC patients were systemically collected and analyzed. Time of recurrence, the relationship between clinical stages and time of recurrence, and between number of adjuvant chemotherapy cycles and time of recurrence were evaluated. RESULTS: 76.3% (45/59) recurrence happened within 1 year after surgery. Median time to recurrence was 7 months. Most recurrences were locoregional recurrence (57.6%). The differences in time of recurrence among stage I, stage II, stage III and stage IV were statistically not significant (p > 0.05, Kruskal-Wallis Test). There were significant differences among different adjuvant chemotherapy cycles for time to recurrence (p = 0.014, Kruskal-Wallis Test). CONCLUSION: Close monitoring and active followup of patients with GC should be conducted over the first 2 years after operation. Adjuvant chemotherapy could prolong recurrence-free survival.

Expression of cyclooxygenase-2 in colorectal cancer and its clinical significance.

AIM: To clarify the clinicopathologic significance of COX-2 expression in human colorectal cancer. METHODS: A total of 128 surgically resected colorectal cancer specimens were immunohistochemically analyzed with the use of anti-COX-2, anti-VEGF and anti-MMP-2 antibodies. The relationship between the cyclooxygenase-2 expression in primary lesions of colorectal cancer and clinicopathologic parameters was evaluated by chi-square test. RESULTS: Among 128 cases of colorectal cancer, 87 (67.9%) were positive for cyclooxygenase-2. The expression of cyclooxygenase-2 was significantly correlated with the depth of invasion, stage of disease, and metastasis (lymph node and liver). Patients in T3-T4, stages III-IV and with metastasis had much higher expression of cyclooxygenase-2 than ones in T1-T2, stages I-II and without metastasis (P<0.05). Among 45 cases of colorectal cancer with lymph node metastasis, the COX-2- positive rate was 86.7% (39/45) for primary lesions and diffuse cytoplasmic staining for COX-2 protein was detected in cancer cells in 100% of metastatic lesions of the lymph nodes. VEGF expression was detected in 49 tumors (38.3%), and VEGF expression was closely correlated with COX-2 expression. The positive expression rate of VEGF (81.6%) in the cyclooxygenase-2-positive group was higher than that in the cyclooxygenase-2- negative group (18.4%, P<0.05). MMP-2 expression was detected in 88 tumors (68.8%), and MMP-2 expression was closely correlated with COX-2 expression. The positive expression rate of MMP-2 (79.6%) in the positive COX-2 group was higher than that in the negative COX-2 group (20.4%, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by modulating the angiogenesis and cancer cell motility and invasive potential in colorectal cancer and it can be used as a possible biomarker.

[Clinical significance of detecting lymph node micrometastasis of colorectal cancer by reverse transcriptase-polymerase chain reaction (RT-PCR)].

BACKGROUND & OBJECTIVE: It remains controversial whether lymph node micrometastasis has impact on staging and prognosis of colorectal cancer. This study was to compare the sensitivity of reverse transcriptase- polymerase chain reaction (RT-PCR) in detecting lymph node micrometastasis of colorectal cancer with pathological morphology and immunohistochemistry, and assess the impact of lymph node micrometastasis on clinical staging and prognosis of colorectal cancer. METHODS: Lymph nodes from 56 cases of colorectal cancer radical resection specimens were studied by RT-PCR to detect the expression of cytokeratin 20 (CK20) mRNA, and compared with routine pathology detection using hematoxylin and eosine (HE) staining, and immunohistochemistry using monoclonal antibody specifically against CK20. The patients had been followed up for 5 years. RESULTS: A total of 432 lymph nodes in 56 patients were analysed by pathological morphology, immunohistochemistry, and RT-PCR, the detected positive lymph node numbers were 247 (57.2%), 269 (62.3%), and 316 (73.1%), respectively. The difference in metastatic lymph node numbers was significant between pathological morphology and RT-PCR method (P< 0.05). Five-year disease- free survival rates of PN0,PN1, and PN2 stages detected by RT-PCR method were 100%, 61.9%, and 55.6%, respectively, significantly higher than those obtained by pathological morphology method, which were 80.0%, 60.0%, and 50.0%, respectively (P< 0.05). CONCLUSIONS: Detecting lymph node micrometastasis of colorectal cancer with RT-PCR method is more sensitive than pathological morphology. RT-PCR method could define the TNM stage and make accurate prognosis for patients with colorectal cancer.

Cyclooxygenase-2 expression and angiogenesis in colorectal cancer.

AIM: Cyclooxygenase-2 is involved in a variety of important cellular functions, including cell growth and differentiation, cancer cell motility and invasion, angiogenesis and immune function. However, the role of cyclooxygenase-2 as an angiogenic factor in colorectal cancer tissue is still unclear. We investigated the relationship between cyclooxygenase-2 and angiogenesis by analyzing the expression of cyclooxygenase-2 in colorectal cancer tissue, as well as its association with vascular endothelial growth factor (VEGF) and microvascular density (MVD). METHODS: The expression of cyclooxygenase-2, VEGF, as well as MVD was detected in 128 cases of colorectal cancer by immunohistochemical staining. The relationship between the cyclooxygenase-2 and VEGF expression and MVD was evaluated. Our objective was to determine the effect of cyclooxygenase-2 on the angiogenesis of colorectal cancer tissue. RESULTS: Among 128 cases of colorectal cancer, 87 were positive for cyclooxygenase-2 (67.9 %), and 49 for VEGF (38.3 %), respectively. The microvessel counts ranged from 23 to 142, with a mean of 51.7 (standard deviation, 19.8). The expression of cyclooxygenase-2 was correlated significantly with the depth of invasion, stage of disease, metastasis (lymph node and liver), VEGF expression and MVD. Patients in T3-T4, stage III-IV and with metastasis had much higher expression of cyclooxygenase-2 than patients in T1-T2, stage I-II and without metastasis (P<0.05). The positive expression rate of VEGF (81.6 %) in the cyclooxygenase-2 positive group was higher than that in the cyclooxygenase-2 negative group (18.4 %, P<0.05). Also, the microvessel count (56+/-16) in cyclooxygenase-2 positive group was significantly higher than that in cyclooxygenase-2 negative group (43+/-12, P<0.05). The microvessel count in tumors with positive cyclooxygenase-2 and VEGF was the highest (60+/-18, 41-142, P<0.05), whereas that in tumors with negative cyclooxygenase-2 and VEGF was the lowest (39+/-16, 23-68, P<0.05). CONCLUSION: Cyclooxygenase-2 may be associated with tumor progression by madulating the angiogenesis in colorectal cancer tissue and used as a possible biomarker.