Meningeal metastases, also known as meningeal metastases or leptomeningeal metastases (LM), are serious complications involving the central nervous system caused by extensive metastatic infiltration of malignant tumor cells into the meninges and subarachnoid space. Its incidence accounts for about 5-10% of all complications in tumor patients, and increases year by year with the prolongation of the survival of tumor patients.The prognosis of LM patients is very poor, and even after treatment the survival of patients is still low, with a median survival of only 2-4 months [1-2]. In order to alleviate symptoms, prolong survival and improve quality of life, we have treated some LM patients with ventriculoperitoneal shunt (VP shunt) and intracerebroventricular chemotherapy via Ommaya capsule on the basis of radiotherapy. These cases are now retrospectively analyzed to explore the value and significance of neurosurgery in the treatment of LM of lung adenocarcinoma origin. 1, DATA AND METHODS 1.1 General information The clinical data of patients with LM of lung adenocarcinoma origin diagnosed in our hospital between June 2006 and February 2012 were collected, and the follow-up data were improved, and a total of 39 patients were included. Among them, 16 cases were male and 23 cases were female; age ranged from 33 to 67 years old, with a median age of 54 years; 20 cases were accompanied by intracranial parenchymal metastases. The interval between diagnosis of the primary focus and detection of meningeal metastases ranged from 3 to 28 months, with a median time of 13 months. Headache was the most common symptom (71.8%, 29/39), accompanied by different degrees of nausea and vomiting, optic papillae edema, limb weakness, and cranial nerve involvement was detected in some patients (12.8%, 5/39). The differences in gender, age, KPS score, clinical symptoms, metastatic characteristics and duration of lung adenocarcinoma between the two groups before receiving treatment were not statistically significant (all P>0.05) and were comparable. 1.2 Diagnostic criteria Patients with a clear history of lung adenocarcinoma, accompanied by newly appeared neurological symptoms and signs, and any one of the following two conditions can be diagnosed as meningeal metastasis of lung adenocarcinoma: ① Malignant tumor cells are detected in the cerebrospinal fluid. (2) There is a single clear CT or MRI imaging manifestation. 1.3 Imaging manifestations: CT plain scan cannot detect meningeal metastasis, but enhanced scan can show meningeal enhancement, which provides value for diagnosis. However, enhanced MRI is still preferred for the imaging diagnosis of LM [3], which typically shows direct signs such as meningeal thickening or accompanied by nodules, meningeal linear or striated enhancement, diffuse meningeal enhancement, and sometimes caudate signs, and is accompanied by secondary changes such as reduced brain parenchymal volume, cerebral edema, periventricular edema, and so on. 1.4 Treatment methods A retrospective analysis of the clinical data showed that: 16 patients were treated with VP shunt + Ommaya capsule placement; 8 patients were treated with simple Ommaya capsule placement, and all of them were treated with simultaneous radiotherapy + adjuvant chemotherapy + intracerebroventricular chemotherapy after the operation; 15 patients were treated with only simultaneous radiotherapy + adjuvant chemotherapy, and among them, 7 patients were treated with intrathecal chemotherapy. Whole brain radiotherapy was performed with 6MVX linear gas pedal external irradiation, DT40Gy/20 times/4 weeks, and temozolomide 75mg/(m2・d) synchronous chemotherapy was used during the radiotherapy period, which lasted until the end of radiotherapy. Adjuvant chemotherapy was performed with temozolomide (300mg/m2, d1-5), nedaplatin (80mg/m2, d1), and vincristine (1.4mg/m2, d1) regimen, repeated every 4 weeks. Intrathecal and intracerebroventricular chemotherapy was administered with cytarabine 50mg/m2 twice weekly until complete cytologic and marker remission. 1.5 Statistical methods The SPSS16.0 statistical software package was used for data analysis, and the Kaplan-Meier method was used for survival analysis and plotting of survival curves; Log-rank test was used for the analysis of differences between groups, and the t-test for independent samples was used for the changes in the KPS of patients before and after surgery. The test level was set as a=0.05 (two-sided), and P<0.05 was regarded as statistically significant difference. 2, Results 39 patients with lung adenocarcinoma LM were followed up until July 9, 2012, 1 patient developed shunt obstruction after surgery, 1 patient developed encapsulated fluid in the abdominal shunt, the physical condition of the patients improved significantly after VP shunt + Ommaya capsule placement, and the KPS was raised on average in the first 2 weeks after surgery compared with the preoperative period. The average number of cycles of adjuvant chemotherapy completed in the whole group was 3. All patients died of tumor progression. The overall survival time of the patients ranged from 0.6 to 26 months, with a median overall survival of 5.1 months and a 1-year survival rate of 12.8% (5/39). Thirty-nine patients with meningeal metastases from lung adenocarcinoma were divided into: the VP shunt + Ommaya bursa group, the Ommaya bursa alone group, and the non-surgical group according to the treatment modality. It was found that the median survival of the VP shunt + Ommaya capsule group and the non-surgical group were 7.8 months and 3.2 months, respectively, and the difference between the groups was statistically significant (2=8.450, P=0.015); the median survival of the VP shunt + Ommaya capsule group and the simple Ommaya capsule group were 7.8 months and 5.8 months, respectively, and the difference between the groups was statistically non-significant (2=1.5, P=1.5). There was no statistically significant difference between the groups (2=1.355,P=0.244); the difference between the Ommaya bursa group and the non-surgical group was not statistically significant. Figure 2 Influence on patients' survival rate with different treatment methods 3.Discussion With the prolongation of the survival period of tumor patients and the progress of imaging technology, the incidence of meningeal metastasis is increasing year by year. The incidence rate of meningeal metastasis is increasing year by year. Traditional treatments mainly include radiotherapy, systemic and intrathecal chemotherapy, etc. Since meningeal metastasis is an advanced stage of malignant tumors, the physical condition of patients is poor, coupled with the toxic side effects associated with the treatment, the therapeutic effect is unsatisfactory [1,2,4]. Neurosurgery gives intracerebroventricular chemotherapy to patients through ventriculoperitoneal shunt and placement of Ommaya capsule, which can rapidly alleviate clinical symptoms, improve or stabilize neurological function, and improve patients' quality of life [4]. In this study, we showed that the KPS of patients was significantly increased 2 weeks after VP shunt (P=0.000), and this significant improvement in the physical condition of patients in a short period of time is often brought about by the rapid relief of intracranial hypertension condition after VP shunt. Reviewing the clinical data of this group of patients, it was found that the whole group of patients had different degrees of increased intracranial pressure, and the possible mechanisms were as follows: malignant tumor cells blocked the arachnoid granules when returning with cerebrospinal fluid, which impaired the absorption of cerebrospinal fluid and led to the occurrence of traffic hydrocephalus; in addition, cancer cells and their metabolites were accumulated in the cerebrospinal fluid and stimulated the plagiocephaly and brain tissues to produce tumor inflammation, which caused widespread or focal cerebral swelling, and the cerebral tissue was also affected. In addition, the accumulation of cancer cells and their metabolites in the cerebrospinal fluid stimulates the soft cerebral membrane and brain tissues to produce tumor inflammation, which leads to widespread or focal brain swelling and increases intracranial pressure. Shunt can flush and transfer cancer cells in cerebrospinal fluid, reduce the stimulation of meninges and nerves due to the wide spread and planting of cancer cells, and more importantly, ventriculoperitoneal shunt can buy valuable time for further radiotherapy treatment. Therefore, in clinical work, we should closely observe the symptoms of high cranial pressure of patients, and under the premise of ensuring safety, timely perform lumbar puncture to measure cerebrospinal fluid pressure and cerebrospinal fluid cytology [5], in order to clarify the diagnosis and take effective treatment. For patients who are not relieved by internal medicine treatment, VP shunt should be performed in time to prevent the occurrence of cerebral hernia. Of course, it is undeniable that by shunting, the risk of abdominal implantation metastasis in patients is increased, however, none of our 16 patients who underwent abdominal shunting had malignant ascites and other serious complications of abdominal implantation metastasis. A search of the relevant national and international literature also revealed only one case report of malignant ascites reported by Lee [6]. It was also found that the median survival of patients in the VP shunt + Ommaya capsule placement group (7.8 months) was significantly higher than that of the non-surgical group (3.2 months). In addition to the important role of VP shunt in rapidly relieving the symptoms of the patients, intracerebroventricular chemotherapy through the Ommaya capsule was also an important reason for the prolongation of the overall survival of the patients. Compared with the traditional intrathecal drug delivery method, drug delivery through the Ommaya capsule is more effective, which is analyzed for the following possible reasons: intracerebroventricular chemotherapy can better distribute the drug uniformly in the cerebrospinal fluid and improve the therapeutic efficacy, and intracerebroventricular chemotherapy through the Ommaya capsule is relatively mildly painful, convenient, and safe [7]. Malignant tumor cells often invade the choroid plexus through the blood circulation and then enter the cerebrospinal fluid, and lumbar puncture intrathecal injection is difficult to make the drug retrograde into the lateral ventricle and act on the source of tumor cells, while the Ommaya capsule can make chemotherapeutic drugs uniformly distributed in the ventricles of the brain and the subarachnoid space of the various parts of the cerebral spinal fluid [8,9]. However, in our study, we showed that there was no significant difference (P>0.05) between the overall survival of patients in the intracerebroventricular chemotherapy group with Ommaya capsule alone (median survival of 5.8 months) and that of patients in the non-surgical group (median survival of 3.2 months), and the main reason for this may be due to the fact that the number of patients in the Ommaya capsule group was too small (n=8), which only accounted for 20.5% of the total number of patients in the group. Therefore, we combined the VP shunt + Ommaya bursa placement group with the Ommaya bursa placement group alone and compared it with the non-surgical group, and found that the difference between the two groups was statistically different (2=7.586,P=0.006), and the difference was significantly greater after combination than the difference between the VP shunt + Ommaya bursa placement group and the non-surgical group (P=0.006 VSP=0.015), so intracerebroventricular chemotherapy via Ommaya capsule is still considered an effective treatment, but still needs to be confirmed by a large-sample multicenter randomized controlled study. Of course since studies have shown that chemotherapeutic agents injected into the cerebrospinal fluid can only penetrate the brain parenchyma to a distance of 3 mm outside the ventricular meninges. Therefore patients with intra-parenchymal brain metastases should still be treated with a combination of local radiotherapy and systemic chemotherapy [10,11]. Current empirical treatment confirms that most patients with meningeal metastases can benefit from systemic chemotherapy, mainly considering that: the blood-brain barrier and blood-cerebrospinal fluid barrier of patients with meningeal metastases are disrupted; systemic chemotherapy is able to control foci that are not penetrated by intrathecal chemotherapeutic agents; and it can also benefit patients whose primary foci are not controlled. In a retrospective study by Oechsle et al [12], systemic chemotherapy was found to be an important factor affecting the survival time of meningeal metastases, and its role was even more important than that of local chemotherapy. Temozolomide is a new oral alkylating agent that crosses the blood-brain barrier and enters the cerebrospinal fluid, and has a low toxic effect, making it more suitable for patients with advanced malignancies [13]. A recent study found that the molecularly targeted drug erlotinib had an outstanding effect in the treatment of meningeal metastases from lung adenocarcinoma [14], which opens up a new way of thinking about the treatment of meningeal metastases, but it still needs to be confirmed by a large number of clinical trials. In conclusion, in our study, we realized that the treatment of ventriculoperitoneal shunt and intracerebroventricular chemotherapy via Ommaya sac can improve the quality of survival and prolong the survival time of patients to a certain extent, based on the combination of whole-brain radiotherapy and temozolomide-based chemotherapy according to the specific conditions of patients.