Recently, intracranial tumors have overtaken leukemia as the most common cancer in children aged over 14 years old[1]. GPIT is a challenging type of pediatric intracranial tumors with pessimistic prognosis, which puts forward a higher requirement in management. Previously, a study analyzed pathological features and outcomes of GPIT, and found that microsurgery is an effective way to treat GPIT[2]. Another study shared their management strategies of giant supratentorial tumors in children[4]. However, we cannot acquire the size feature of GPIT in previous researches and there is still a lack in the systematic study of GPITs. As far as we know, this study is the first one to measure and analyze the volume of GPITs, with the experience sharing of the GPIT management including diagnosis, operative strategy and postoperative treatment.
In the past literature, measurements such as length, width and height were often used to describe the size of tumors[5]. However, intracranial tumors from different locations vary dramatically in shape and volume. Thus, it was difficult to compare the sizes of tumors directly. Recently, a prospective study used quantitative sodium MR imaging to calculate cell volume fraction and volume of glioblastoma[6]. Another research got figures of brain tumor volume in rats with multimodal MRI[7]. Our study is retrospective, so we measured the volume of GPITs in this series according to preoperative MR image with 3D model reconstruction in 3D slicer software. With the accurate value of tumor volume, the sizes of GPITs could be described and compared directly. The frequency histogram of tumor volume was shown in Fig. 1. Over time, we found some characters and the connections between the size and the location of GPITs. The average volume of GPITs in this study is 107.5ml, but the majority (22/36, 61.1%) is between 40-80ml. Tumors with volume over 100ml are rare, with only 9 cases (25%), of which 7 cases occurred in cerebral hemispheres, accounting for 58.3% of GPITs in the supratentorial—hemisphere. Other two cases occurred in suprasellar region and cerebellum. The supratentorial—hemisphere and cerebellum were the most common sites of GPIT, but GPIT in the supratentorial—hemisphere was generally larger in volume than other locations. One possible reason is that the hemisphere has more space for tumor to grow, which may reduce the severity of symptoms and cause delay of diagnosis. Supratentorial tumors also have better prognosis than infratentorial tumors, which may be associated with derivation and pathologic types of tumors. However, because of the deficiency in number of cases, we did not find an exact relationship between tumor volume and histopathology, as well as the tumor volume and prognosis. Further research depends on the establishment of a database of pediatric intercranial tumor with detailed dates including tumor volume.
In histopathology outcomes, medulloblastoma, ependymoma and pilocytic astrocytoma are the most common types in this series, which was similar to the Guo et al.’s research on GPIT’s clinicopathological features[2]. However, among statistic researches of pediatric intracranial tumor, the most common ones are pilocytic astrocytoma, glioma malignant (NOS) and embryonal tumors (including medulloblastoma), while ependymal tumors are relatively rare[1, 8, 9]. In GPITs, ependymoma seems to occur more frequently, but high-grade glioma was not seen in this study and Guo et al. 's. This indicates that GPITs have certain particularity in histopathology. Different types of tumors show diverse biological characteristics in the origin location, growth speed and metastasis, leading to the difference in the size of tumors at the time of diagnosis. In high-grade malignant pathological types like AT/RT, CPC and PENT in GPIT, tumors grow and transfer rapidly, their rich blood supply and unclear boundaries also create huge obstacle for surgical treatment, which results in poor prognosis.
The most common symptoms in GPITs of this series are vomiting, headache, gait disorders, muscle weakness and hypersomnia, which are similar to intracranial tumors. However, since infants’ ability to express feelings is not fully developed, the early symptoms are difficult to be noticed by their guardians or might be misdiagnosed as other diseases in primary medical and health care institutions. Consequently, GPITs are diagnosed only after tumors grow further and symptoms aggravate. This may also be the reason why over half of patients in this study are infants under 3 years old. (19 /36, 55.9%) Most intracranial tumors lack blood biomarkers, imaging examination is the basis of diagnosis. Pediatricians should consider central nervous system diseases and perform CT or MR examination for symptoms such as unreasonable crying and vomiting when other diseases were excluded. Besides, economic and social factors are also important factors for the occurrence of GPIT. In this study, 70.6% (24/34) of patients were from rural areas. The relatively lower education level of guardians and weaker medical services delayed the discovery of tumors, and some patients even gave up surgical treatment in this series. Interestingly, the male-to-female ratio is 2:1 in our study, the number of boys dramatically surpass girls. However, though boys have a higher incidence in embryonal tumors[10], the sex difference of the incidence of pediatric brain tumors is not that obvious in other researches[2, 9, 11]. This phenomenon may attribute to "son preference" thought in economic undeveloped regions of China, some parents of GPIT girls in rural areas might have refused further treatment in upper-level hospital.
We adopted different treatment strategies according to the concrete situation of each patient and have achieved a low-mortality rate during the perioperative stage. Hydrocephalus is common in pediatric brain tumors, approximately 70–90% of posterior fossa tumors present with preoperative hydrocephalus[12, 13]. GPIT patients are more likely to have preoperative hydrocephalus because giant tumor blocks the circulation of cerebrospinal fluid. We chose Ommaya reservoir or EVD to manage obstructive hydrocephalus before the surgery for their convenience, high efficiency and low infection rate. Massive bleeding is a cardinal factor in surgery that decides the quality of the operation. Coagulation test would be done before the surgery and we estimate blood loss to prepare for blood transfusion. Researches show that GTR indicates better prognosis with the higher survival rate and lower recurrences rate[14, 15]. However, some GPITs are only feasible to STR on account of restriction of surgical space or adherence to the surrounding structure. We applied microsurgical approach in most of the cases to identify and resect deep tumors. Nevertheless, in a case of pilocytic astrocytoma in suprasellar region, we only achieved STR for unclear border between tumor and brain stem tissue, further resection may be life-threatening or cause nerve dysfunction. Besides, encasement of neurovascular structures in tumors and extensive bleeding in operation is also the significant obstacle preventing GTR. This situation occurred frequently in highly malignant tumors like CPC and AT/RT[16]. A 7-years-old boy was considered to have a choroid plexus tumor in lateral ventricles on MR image (Fig. 2). However, we underestimated the blood supply of tumor and failed to resect whole tumor due to severe bleeding in practice. Relatively small bone windows craniotomy also restricted our operation space. From then on, we enhanced the preoperative evaluation of tumor blood vessels. An 8-years-old girl had a giant ependymoma in left frontal lobe with hemorrhage necrosis and significant calcification, and the tumor volume was 255.8 cm3 (Fig. 3). We performed CT angiography before the surgery to confirm the blood supply of tumor. In surgery, we cut off the main blood vessels of the tumor and successfully removed the entire tumor with minimal blood loss. With continuous efforts and improvement of surgical skills, we achieved GTR in 87.5% (28/32) of patients in this series.
Surgical treatment for infants under 3 years old is the most difficult part in GPITs. Owing to their weak physical function and immature immune system, the surgery itself was a challenge for them, the probability of postoperative infection is also significantly higher than that of older children. Besides, radiation therapy is the contraindication for infants. Our strategy is that complete resect the tumor as far as possible and combine it with postoperative chemotherapy. In this series, 18 infants received the surgery, 72.2% (13/18) got improvement in 6 months. Unfortunately, the case of immature teratoma, which is also the biggest tumor in this study, died of excessive bleeding in the surgery. 4 cases recurred and 2 cases including CPC and AT/RT therein died in one year. The prognosis of the high-grade malignant tumors is poor, but to some extent, surgical treatment can extend survival time and strive time for the following treatment. Some surgeons remove some GPITs in twice with different craniotomy approaches[17], yet we assumed that a staged operation may increase the risk of operation-related complication and it might be meaningless in highly malignant tumors. New experimental treatment including molecular targeted therapy, gene therapy, autologous stem cell transplantation combined with chemotherapy and so on have shown certain benefit on highly malignant tumors in recent research[18–20], which forebode a bright future.