Analysis Of Clinical Features And Prognostic Factors Of Krukenberg Tumor

Background and purpose:Generalized Krukenberg tumor refers to all sources of metastatic ovarian cancer, and narrow Krukenberg tumors are defined from ovarian metastases of gastrointestinal cancer. In this study, the Krukenberg tumors originated from gastrointestinal metastatic ovarian cancer. Krukenberg tumors have poor prognosis. It is considered the median survival time is less than 1 year. It is onset occult, clinical manifestations and imaging characteristics of the lack of specificity,easy to cause missed diagnosis, misdiagnosis, and poor treatment effect, poor prognosis, causing great difficulties to the diagnosis and treatment of the disease. In this study,we analyse the clinical features, treatment options and prognosis related factors of Krukenberg tumor patients in our hospital, aim to summarize the clinical and pathological features of the Krukenberg tumors and differential diagnosis with primary ovarian cancers, explore method of treatment and improve the prognosis, in order to improve the knowledge of clinical doctors of Krukenberg tumors, reduce misdiagnosis and missed diagnosis rate.Materials and Methods:In this study, we retrospectively analyse the Krukenberg tumor patients who met the inclusion criteria admitted to our hospital in 2010 January to 2015 December,count up the clinical, pathological and follow-up data.Clinical data includes the age of primary tumor, ovarian metastasis,menopause,symptoms, tumor markers of CEA, CA125, image feature, sequential diagnosis,primary tumor and metastatic ovarian cancer operation time, operation mode,treatment.Pathological data includes tumor differentiation degree of tissue types,unilateral or bilateral, TNM staging, immunohistochemistry.Follow-up data includes subsequent survival and survival period.We use SPSS 17.0 statistical software to have statistical analysis of the above data. Survival curve analysis uses Kaplan-Meier method. Log-rank test is used to compare the single factor that may affect the survival. we apply Cox proportional hazard regression model for multivariate analysis.The differences of each group are compared using chi square test. P<0.05 is statistically significant.Results:From 2010 January 1st to 2015 December 31 st,we enrolled 88 cases of Krukenberg tumor patients, which originated from gastric patients 28 cases,intestinal patients 48 cases, primary unknown patients 12 cases. Simultaneite patients with Krukenberg tumor is 43 cases(12 cases of gastric, intestinal 31cases),heterochrony Krukenberg tumor patients is 33 cases(16 cases of gastric source, intestinal 17 cases). Patients are with a median age of 51 years,premenopausal accounted for 56.8%. For primary tumor surgery is 63 cases(20cases of stomach,intestine 43 cases), and the primary tumor chemotherapy is 50cases(21 cases of stomach, 29 cases of intestine). 55 patients(stomach derived in7 cases, intestinal 36 cases, unidentified 12 cases)had the metastatic ovarian cancer surgical treatment. Systemic chemotherapy has 54 cases(21 cases of gastric origin,intestinal in 27 cases, 6 cases of unknown origin).Intraperitoneal chemotherapy has12 cases, 4 cases of radiation therapy,and target treatment has 8 cases, biological treatment in 9 cases, untreated 8 cases. The follow-up time is 1-60 months,and median follow-up time is 11 months. At the end of follow-up, the survival is 18 cases(gastric source in 7 cases, intestinal in 10 cases, unknown origin 1 cases) and death in patients with with 51 cases(16 cases of gastric source, intestinal 28 cases,unidentified 7 cases), 19 is lost to follow-up(5 cases of gastric source, intestinal in10 cases, unknown origin 4 cases). The overall 1 year,2 year,3 year survival rate is51.2%, 31.6%, and 4.6%. The 1year, 2years and 3years survival rates of patientswith gastric origin are 35.4%,17.7%and 0%.Patients with intestinal origin are 60.3%,38.9% and 8.1%. Patients with unknown origin are 44.4%, 29.6% and 0%.The clinical and pathological data of the patients were as follows.1.The incidence rate in our hospital: Krukenberg tumor incidence accounted for13.1% of ovarian cancer,and 2.8% of the female patients with gastrointestinal cancer.The incidence rates of gastric and intestinal origin were 2.7% and 2.9% respective in female patients with gastric cancer and intestinal cancer.2.Clinical characteristics: the median age is 51 years old, and 56.8% of them is not menopause. The highest incidence of the site are ileocecus(19.7%) and gastric antrum(17.1%). The most common initial symptoms are abdominal pain(51.1%),abdominal distension(31.8%), and abdominal mass(25%). Tumor marker CEA positive rate is 59.5%,and CA125 positive rate is 71.3%. The median CA125 value is73.85U/ml.The median CEA value is 7.72ng/ml.CA125 within the 200u/ml accountes for 71.9%; CA125/CEA ratio between 0 and 20 is 72.5%. The median ratio of CA125/CEA is 9.6.Ovarian metastatic lesions imaging characteristics include adnexal mass in 30 cases and abnormal density(36.4%), ovarian cystic mass in 28 cases(34.1%), cystic mass in 22 cases(27.3%).The proportion of the cystic mass is high, and the missed diagnosis or misdiagnosis of primary ovarian carcinoma is very easy.3.Pathological features: the primary tumor pathological types are adenocarcinoma(75%), mucinous adenocarcinoma(23.7%), and ring cell carcinoma(17.1%). Primary tumors of adenocarcinoma(59.6%) and mucinous carcinoma(88.9%) originated from intestinal. Signet ring cell carcinoma originated from the stomach(61.5%).Ovarian metastases of adenocarcinoma(70.6%) and mucinous carcinoma(73.7%) originated from intestinal and signet ring cell carcinoma of the source without significant differences(21.4%, 21.4%, 28.6%). The primary tumor was 86% of the pathological types of ovarian metastatic carcinoma, and the other 6were not(14%). There were 3 cases with ovarian metastasis, the cell component of the ring cell and mucinous adenocarcinoma. The proportion of mucinous adenocarcinoma was increased, and the proportion of adenocarcinoma was decreased, considered the degree of malignancy after ovarian metastasis was increased. Analysis of patients with gastric origin, whether the primary tumor is printed ring cell carcinoma and diagnostic order has correlation(p=0.03). gastric ring cell carcinoma invasion, is easy to occur at the same time.The differentiation degree of primary carcinoma are mainly differentiated carcinoma(64.9%) and poorly differentiated carcinoma(45.6%). Among them, 90.9% of patients with gastric cancer were poorly differentiated, and 88.6% of the patients with intestinal origin were moderately differentiated. Bilateral ovarian metastasis accounte for65.9%. Unilateral ovarian metastases to the right side is the main(73.7%).Sources in the right colon of Krukenberg tumor prone to metastasis in the right ovary.In this group of intestinal source with depth of invasion for T4 is 58.3 %, and lymph node metastasis number for 0-6 pieces of 87.2%.The evidence does not support lymph node metastasis route, considers transfer pathway may exist direct invasion and metastasis. There was a significant correlation between the number of lymph node metastasis and the primary site, and the lymph node metastasis(p=0.000) was easy to occur in the patients with gastric origin. In this group, the infiltration depth of gastric origin was 84.2% with the exception of T4,which considered combination of planting metastasis. There were 5 cases of gastric origin with immunohistochemical results, including 3 cases of CK7+CK20+, accounting for60%; CK7+CK20- were 1 cases, accounting for 20%; CK7-CK20+ had 1 cases,accounting for 20%. There were 27 cases of intestinal origin in patients with immunohistochemical results, including 18 cases of CK7-CK20+, accounting for66.7%; CK20+ CK7+ in 9 cases, accounting for 33.3%. Other immunohistochemical positive rates: PR:5%, ER:0%, CEA:92.3%, CA125:3.7%.4.Survival:patients’ overall 1year,2years,3years survival rate are 51.2%, 31.6%,4.6%. 1 years, 2 years and 3 years survival rates of patients with intestinal origin were higher than those in patients with gastric origin.The median survival time is 13 months, originated from gastric and intestinal, unknown origin with a survival period of 12 months, 15 months, and 12 months, respectively.5.Prognostic factors: single factors:The pathologic types of mucinous adenocarcinoma(p=0.013), ovary solitary metastasis(p=0.023), primary tumor pathological lymph node metastasis(p= 0.000), surgery after ovarian metastasis(p=0.021), chemotherapy for metastatic ovarian tumor(p=0.041),operation of primary tumor and metastatic ovarian tumor(p=0.030),operation and chemotherapy of primary foci and metastatic ovarian tumor(p=0.021). Independent prognostic factor from multivariate COX regression analysis:mucinous adenocarcinoma(p=0.005),the number of lymph node metastasis of primary tumor after operation(p=0.000). The median survival time of primary tumor pathological type of mucous adenocarcinoma is 10 months, which is significantly shorter than other types of 15 months(P=0.013).Primary tumor surgery pathology shows lymph node metastasis number from 0 to 6, 7 and above a survival are 26 months and 12 months(P = 0.000),which suggests primary tumor resection lymph node metastasis and prognosis in patients with pathological correlation,and transfer number is greater than equal to seven short survival time.The median survival of ovarian metastases for solitary metastasis is 21 months, more than 12 months with other parts of the transfer(P=0.023).The median survival time was 15 months and 12 months(p=0.021), suggested that the surgical resection of ovarian metastases could prolong the survival time. For ovarian metastasis of systemic chemotherapy and without chemotherapy in patients with a survival time was 22 months and 11 months(P = 0.041), suggesting that systemic chemotherapy can prolong the Krukenberg tumor patients survival. The median survival time was 16 months, and 12 months(p=0.030) in the patients with primarytumor and ovarian metastases were longer than the other months. Primary tumors and ovarian metastases surgery and twice after operation were performed in systemic chemotherapy in patients with a survival time was 35 months significantly, longer than that of without the median survival of patients with the treatment of 12 months(P = 0.021), tips for Krukenberg tumor standardized treatment can prolong the Krukenberg tumor patient survival.6.The median interval between the primary tumor and the occurrence of ovarian metastasis is 12 months in patients with different time.The median interval time was1 months in 43 patients with simultaneous ovarian metastasis..Conclusions:1.Adenocarcinoma and mucinous adenocarcinoma are derived from the gut, and the cell carcinoma of the ring cell carcinoma are derived from the stomach.2.The malignant degree of gastrointestinal cancer cells after the occurrence of ovarian metastasis is increased.3.Enterogenous ovarian Krukenberg tumors metastasis pathway may exist directing invasion and metastasis.4.Gastrogenic Krukenberg tumor metastasis pathway may have lymph node metastasis, except with metastasis.5.Gastric ring cell carcinoma has higher invasion, easy to occur at the same time transfer.6.Patients with intestinal origin 1 years, 2 years, 3 years survival rates are higher than those of patients with gastric origin.7.The differential diagnosis of primary ovarian cancer are: CA125/CEA median ratio, cystic mass of ovarian lesions, immunohistochemistry CK7CK20.8.Single factors in favour of prognosis :pathological types of non mucinous adenocarcinoma, primary tumor lymph node metastasis number less than or equal to6 pieces, ovary solitary metastasis, ovarian metastasis tumor surgery, chemotherapyfor metastatic ovarian tumor, operation of primary tumor and metastatic ovarian tumor, operation and chemotherapy primary tumors and ovarian metastases. The pathological type of mucinous adenocarcinoma of the primary tumor, postoperative lymph node metastasis are independent prognostic factors for the number of Krukenberg tumor..