Anatomical Flow Diversion by Hybrid Strategy for Intractable Large Cerebral Aneurysms.

BACKGROUND AND IMPORTANCE: Flow diverters (FDs) provide curative endovascular treatment for wide-necked sidewall aneurysms. The efficacy of FDs for bifurcation or branching sidewall aneurysms is probably limited. We used anatomical flow diversion (AFD) for intractable large cerebral aneurysms. We report our experiences with AFD. METHODS: The concept of AFD is the transformation from the bifurcation or branching sidewall type to the nonbranching sidewall type. Linearization of the parent artery by stenting, intentional branch occlusion, and aneurysmal coil embolization were performed. Furthermore, bypass surgery is performed for patients intolerant to branch occlusions. We evaluated the clinical outcomes of intractable aneurysms treated with AFD. RESULTS: AFD was performed in seven unruptured large aneurysms. Aneurysmal locations were the top of the basilar artery (BA), BA-superior cerebellar artery (SCA), internal carotid artery (IC)-posterior communicating artery (PcomA), and IC terminal. The mean dome diameter was 17.0 ± 4.6 mm. Six patients underwent bypass surgery. The occluded branches were the PCA + SCA, PcomA, and anterior cerebral artery (ACA) A1. An FD was used in three patients and a neck bridge stent in four patients. No intraprocedural complications occurred. Two postprocedural ischemic complications occurred in one patient. Six (86%) patients demonstrated a modified Rankin Scale (mRS) 0 at the 3-month follow-up, and one with an ischemic complication showed an mRS 5. Complete occlusion of all aneurysms was maintained with a median follow-up duration of 60 months. CONCLUSION: AFD is useful for intractable large cerebral aneurysms with high curability, although safety verification is required.

Additional outlet occlusion as an important factor in avoiding retreatment after transvenous embolization for cavernous sinus dural arteriovenous fistulas.

BACKGROUND: Transvenous embolization (TVE), such as selective shunt occlusion, is the first line treatment for cavernous sinus dural arteriovenous fistula (CSDAVF). Despite the favorable outcomes of TVE, some cases necessitating retreatment due to recurrence or incomplete occlusion persist. Given the physical, psychological, and financial burden of multiple treatments, understanding the predictive factors for recurrence, spontaneous occlusion, or retreatment is important. However, few reports have addressed these factors, complicating decision making regarding the need for retreatment. This study analyzed predictive factors for retreatment and spontaneous occlusion to offer new insights into CSDAVF management. METHODS: This retrospective, observational study was conducted in two acute care hospitals. Patients aged 18-100 years undergoing endovascular treatment for CSDAVF from January 2011 to December 2022 were included. RESULTS: Of 65 patients treated with TVE, 29 experienced immediate complete occlusion. Meanwhile, 22 of 36 patients with incomplete occlusion had spontaneous occlusion, and retreatment was performed in 20% of patients. Additional outlet occlusion was negatively associated with retreatment (P=0.046), and it tended to promote spontaneous occlusion (P=0.056). Favorable functional outcomes were observed in all patients, and approximately 94% of patients showed complete occlusion at the latest follow-up. CONCLUSION: TVE is an effective treatment for CSDAVF. Outlet occlusion, when immediate complete occlusion is unattainable, is important to reduce retreatment and promote spontaneous occlusion. Substantially reducing shunt flow, carefully assessing dangerous drainage routes, and closely monitoring the residual shunt are crucial for preventing intracranial hemorrhage when outlet occlusion is performed.

Targeted Transarterial Embolization for Treatment of a Symptomatic Venous Varix in the Draining Vein of an Arteriovenous Malformation: Case Report and Literature Review.

BACKGROUND: Venous varices in the draining vein of arteriovenous malformations (AVMs) can result in compression symptoms. This condition is extremely rare, and its treatments and long-term outcomes are unresolved. Herein, we describe the treatment of a thrombosed venous varix in a draining vein and review the relevant literature. PATIENT: The patient presented with progressive right-sided hemiparalysis and aphasia. Magnetic resonance imaging revealed flow void accumulation from the corpus callosum to the left ventricle and a 30-mm mass in the left putamen. The patient underwent targeted transarterial embolization to reduce the blood flow to the venous varix and relieve the neurological symptoms. The patient had recovered completely from the right hemiparesis and aphasia 4 years after treatment, with a modified Rankin Scale score of 0. CONCLUSION: Targeted transarterial embolization for symptomatic venous varix is a palliative treatment that may improve long-term functional outcomes.

The combination of gemcitabine plus an anti-FGFR inhibitor can have a synergistic antitumor effect on FGF-activating cholangiocarcinoma.

Anti-FGFR treatment for cholangiocarcinoma (CCA) with fibroblast growth factor receptor (FGFR) alteration is a promising treatment option. Since the antitumor mechanisms of anti-FGFR inhibitors and conventional cytotoxic drugs differ, synergistic effects can be possible. This study aimed to evaluate the efficacy of the combined administration of gemcitabine (GEM) and pemigatinib in CCA cells with FGFR2 alterations. To simulate the treatment for patients with 3 kinds of CCA, chemonaïve CCA with activation of the FGF pathway, chemo-resistant CCA with activation of the FGF pathway, and CCA without FGF pathway activation (as controls), we evaluated 3 different CCA cell lines, CCLP-1 (with a FGFR2 fusion mutation), CCLP-GR (GEM-resistant cells established from CCLP-1), and HuCCT1 (without FGFR mutations). There was no significant difference between CCLP-1 and HuCCT1 in GEM suspensibility (IC50 = 19.3, 22.6 mg/dl, p = 0.1187), and the drug sensitivity to pemigatinib did not differ between CCLP-1 and CCLP-GR (IC50 = 7.18,7.60 nM, p = 0.3089). Interestingly, only CCLP-1 showed a synergistic effect with combination therapy consisting of GEM plus pemigatinib in vitro and in vivo. In a comparison of the reaction to GEM exposure, only CCLP-1 cells showed an increase in the activation of downstream proteins in the FGF pathway, especially FRS2 and ERK. In association with this reaction, cell cycle and mitosis were increased with GEM exposure in CCLP-1, but HuCCT1/CCLP-GR did not show this reaction. Our results suggested that combination therapy with GEM plus pemigatinib is a promising treatment for chemonaïve patients with CCA with activation of the FGF pathway.

Temporal Muscle Swelling after Clipping Surgery with Frontotemporal Craniotomy Is Associated with Immediate Postcraniotomy Headache.

Immediate postcraniotomy headache frequently occurs within the first 48 h after surgery. The mechanisms underlying immediate postcraniotomy headache are not yet fully understood, and effective treatments are not yet established. This study aimed to identify the factors associated with immediate postcraniotomy headache in patients who underwent clipping surgery with frontotemporal craniotomy and to examine the effects of these factors on postcraniotomy headache. A total of 51 patients were included in this study. Immediate postcraniotomy headache was defined as pain with numerical rating scale score ≥4 on postoperative day 7. Sixteen patients (31.4%) had immediate postcraniotomy headache. The headache-positive group had a higher incidence of preoperative analgesic use (50.0% vs. 5.7%, respectively, p < 0.001), increased temporal muscle swelling ratio (137.0%±30.2% vs. 112.5%±30.5%, respectively, p = 0.01), and higher postoperative analgesic use (12.9±5.8 vs. 6.7±5.2, respectively, p < 0.001) than the headache-negative group. The risk factors independently associated with immediate postcraniotomy headache were preoperative analgesic use and temporal muscle swelling by >115.15% compared with the contralateral side in the receiver operating characteristic analysis. Postcraniotomy headache was significantly more common in patients with preoperative analgesic use and temporal muscle swelling than in those without (p < 0.001 and p = 0.002, respectively). Altogether, patients with immediate postcraniotomy headache had greater preoperative analgesic use, greater temporal muscle swelling ratio, and higher postoperative analgesic use than those without. Thus, temporal muscle swelling is a key response to immediate postcraniotomy headache.

Hidden Bow Hunter's Syndrome Diagnosed Using Dynamic Cerebral Angiography and Successfully Treated with Spinal Surgery: A Case Report and Review of the Literature.

Hidden bow hunter's syndrome (HBHS) is a rare disease in which the vertebral artery (VA) occludes in a neutral position but recanalizes in a particular neck position. We herein report an HBHS case and assess its characteristics through a literature review. A 69-year-old man had repeated posterior-circulation infarcts with right VA occlusion. Cerebral angiography showed that the right VA was recanalized only with neck tilt. Decompression of the VA successfully prevented stroke recurrence. HBHS should be considered in patients with posterior circulation infarction with an occluded VA at its lower vertebral level. Diagnosing this syndrome correctly is important for preventing stroke recurrence.

Evaluation of Venous Structures that Are Involved in Transsylvian Approach Using 3D Rotational Venography.

In the transsylvian (TS) approach, as characterized by clipping surgery, the presurgical visualization of the superficial middle cerebral vein (SMCV) can help change the surgical approach to ensure safe microsurgery. Nevertheless, identifying preoperatively the venous structures that are involved in this approach is difficult. In this study, we investigated the venous structures that are involved in the TS approach using three-dimensional (3D) rotational venography (3D-RV) and evaluated the effectiveness of this method for presurgical simulation. Patients who underwent 3D-RV between August 2018 and June 2020 were involved in this retrospective study. The 3D-RV and partial maximum intensity projection images with a thickness of 5 mm were computationally reconstructed. The venous structures were subdivided into the following three portions according to the anatomic location: superficial, intermediate, and basal portions. In the superficial portion, predominant frontosylvian veins were observed on 31 (41%) sides, predominant temporosylvian veins on seven (9%) sides, and equivalent fronto- and temporosylvian veins on 28 (37%) sides. The veins in the intermediate (deep middle cerebral and uncal veins) and basal portions (frontobasal bridging veins) emptied into the SMCV on 57 (75%) and 34 (45%) sides, respectively. The 3D-RV images were highly representative of the venous structures observed during microsurgery. In this study, 3D-RV was utilized to capture the details of the venous structures from the superficial to the deep portions. Presurgical simulation of the venous structures that are involved in the TS approach using 3D-RV may increase the safety of microsurgical approaches.

Effect of Sleep Deprivation on Simulated Microsurgical Vascular Anastomosis.

BACKGROUND: The effects of sleep deprivation on surgical performance have been well documented. However, reports on the effects of sleep deprivation on microneurosurgery are limited. This study aimed to investigate the effects of sleep deprivation on microneurosurgery. METHODS: Ten neurosurgeons participated in the anastomosis of a vessel model using a microscope in sleep-deprived and normal states. We evaluated the procedure time (PT), stitch time (ST), interval time (IT), number of unachieved movements (NUM), leak rate, and practical scale for anastomosis quality assessment. Each parameter was compared between normal and sleep-deprived states. Subanalyses were performed on the two groups based on PT and NUM under the normal state (proficient and nonproficient groups). RESULTS: Although no significant differences were noted in PT, ST, NUM, leak rate, or practical scale, IT was significantly prolonged under sleep deprivation compared with the normal state (mean: 258.8 ± 94.0 vs. 199.3 ± 74.9 seconds; p = 0.02). IT was significantly prolonged under sleep deprivation in the nonproficient group based on both PT and NUM (PT: 234.2 ± 71.6 vs. 321.2 ± 44.7 seconds, p = 0.04; NUM: 173.3 ± 73.6 vs. 218.7 ± 97.7; p = 0.02), whereas no significant difference was observed in the proficient group (PT: 147.0 ± 47.0 vs. 165.3 ± 61.1 seconds, p = 0.25; NUM: 173.3 ± 73.6 vs. 218.7 ± 97.7; p = 0.25). CONCLUSIONS: Although IT was significantly prolonged under sleep deprivation in the nonproficient group, there was no decline in performance skills in either the proficient or nonproficient group. The effect of sleep deprivation may require caution in the nonproficient group, but it is possible that certain microneurosurgical outcomes can be achieved under sleep deprivation.

Induction of angiogenesis and neural progenitor cells by basic fibroblast growth factor-releasing polyglycolic acid sheet following focal cerebral infarction in mice.

Biodegradable sheets loaded with basic fibroblast growth factor (bFGF) are prepared as novel bFGF-releasing systems from polyglycolic acid nonwoven fabric by oxygen plasma treatment followed by bFGF adsorption. In the present study, we investigated the therapeutic effects of this system on a focal cerebral infarction model (CB-17 mouse). A preliminary in vitro study showed that this system released bFGF in an acellular culture medium, thereby keeping the bFGF concentration in the medium at ≥5 ng/ml for a prolonged period of 7 days. The released bFGF from this system retained its biological activity to enhance endothelial tube formation in vitro. In a mouse model of subacute focal cerebral infarction, this system increased the expression of endogenous vascular endothelial growth factor in the peri-infarct cortex and subventricular zone, promoted angiogenesis in the striatum, and increased neural progenitor cells in the peri-infarct cortex. Thus, this bFGF-releasing system has the potential to be a novel therapeutic approach for cerebral infarction.

A Ruptured Aneurysm in Aplastic or Twig-like Middle Cerebral Artery: A Case Report with Histological Investigation.

Aplastic or twig-like middle cerebral artery (Ap/T-MCA) is a rare vascular anomaly that can cause a hemorrhagic or ischemic event. We report a 38-year-old man who presented with intracerebral hemorrhage from a ruptured aneurysm associated with an Ap/T-MCA. After aneurysm trapping and resection, histopathological examination revealed an internal elastic lamina (IEL) disruption and a thin aneurysmal wall. The patient recovered well after surgery and rehabilitation. No hemorrhagic or ischemic events have occurred during 2 years of follow-up. Ap/T-MCA-associated aneurysms exhibit a disrupted IEL and thin wall, which demonstrates the fragility of the "twig-like" vessels.

[Disseminated Bone Marrow Carcinomatosis from Colon Cancer-A Case Report].

A 77‒year‒old man came to our hospital with complaints of abdominal pain and difficulty to defecate. Abdominal CT scan showed an abnormal region in the ascending colon, which was suspected to be an ascending colon cancer. D‒dimer was remarkably high, and the platelet count was 63,000/µL; these results suggested disseminated intravascular coagulation caused by tumor activation. After he was admitted, we performed a contrast enhanced CT, and found no signs of remote metastasis. We decided to resect the tumor without colonoscopy examination in order to release the DIC state. After the surgery, the platelet count did not increase, and leukopenia was observed. We conducted a bone marrow biopsy, and made a diagnosis of disseminated carcinomatosis from colon cancer. The patient's condition did not improve, and he died on day 42 after admission. Pathological autopsy was performed and several minimal remote metastases were found throughout the body.

[A Case of Transverse Colon Cancer with Metastatic Recurrence in Bilateral Inguinal Lymph Nodes].

A woman in the 60s. She was referred to our hospital because the fecal occult blood test was positive. Colonoscopy was performed. Cancer is found in the transverse colon. There were no metastases in the lungs and liver. Laparoscopic left hemicolectomy was performed. Histopathological examination was adenocarcinoma(tub1>tub2>muc), pT1b, pN2, ly2, v1, pPM0, pDM0, pRM0, budding(0, Grade 1), fStage Ⅲb. After postoperative adjuvant chemotherapy, she visited an outpatient clinic 8 months after surgery with a complaint of swelling of both inguinal lymph nodes. The swollen inguinal lymph node was relatively soft and there was no evidence of infection. A biopsy of the bilateral lymph nodes was performed. Histopathological examination revealed adenocarcinoma containing mucus components. These findings were consistent with histological findings in transverse colon cancer. Based on these results, we diagnosed metastatic recurrence from transverse colon cancer to both inguinal lymph nodes.

[Tumor Embolisms from Colon Cancer Detected on Transcatheter Examination-A Case Report].

A 58-year-old woman underwent surgery and systemic chemotherapy(FOLFIRI plus panitumumab)for ascending colon cancer with multiple lymph node and liver metastases; the preoperative Virchow lymph node aspiration cytology showed adenocarcinoma.After 4 courses of chemotherapy, contrast-enhanced CT showed an embolus in the left subclavian vein.An anticoagulation therapy was started, but the embolus tended to increase.Three months later, the patient developed dyspnea and was diagnosed with pulmonary artery thromboembolism and superior vena cava thrombosis.Transcatheter examination was performed because of the anticoagulation-resistant embolism, and the biopsy revealed tumor embolism due to colon cancer.She died of respiratory failure 10 days after the biopsy.The tumor directly infiltrating the vein because of left subclavian lymph node metastases might have resulted from increased tumor emboli.Although cases of tumor emboli infiltrating the veins and developing from lymph node metastases are rare, a transcatheter biopsy may help to detect them.

Prediction of the Cerebral Hyperperfusion Phenomenon after Carotid Endarterectomy Using a Transit Time Flowmeter.

The purpose of this study was to investigate the relationship between the cerebral hyperperfusion phenomenon (CHP) and carotid artery flow volume as measured by a transit time flowmeter during carotid endarterectomy (CEA). We retrospectively investigated 74 patients who underwent both transit time flowmetry and single photon emission computed tomography (SPECT). The flow volumes of the internal carotid artery (ICA) before and after the endarterectomy were recorded during surgery as the pre- and the post-ICA (mL/min), respectively. We defined the difference between the pre- and the post-ICA as the ΔIC (mL/min). Two independent board-certified neurosurgeons analyzed the asymmetry index (affected side/contralateral side) of regional qualitative cerebral blood flow before and after the CEA respectively. We defined the CHP as an excessive increase in this asymmetry index between preoperative and postoperative SPECT. The CHP was observed in five of the 74 patients (6.8%). The pre-ICA of the CHP cases was significantly lower than that of the non-CHP cases (in mL/min, median 29 vs. 97; P = 0.01). The ΔIC of the CHP cases was significantly higher than that of the non-CHP cases (in mL/min, median 154 vs. 50; P = 0.002). The cut-off value of the ΔIC was 81 mL/min (sensitivity 100%, specificity 78.3%, area under the curve 0.912). The findings of this study suggest that the ΔIC is associated with the CHP. The transit time flowmeter is useful to predict the CHP during surgery.

Combined Endoscopic Endonasal and Bilateral Subfrontal Approach for a Nonfunctioning Pituitary Adenoma Associated with an Internal Carotid Artery-Superior Hypophyseal Artery Aneurysm.

BACKGROUND: An aneurysm embedded in a pituitary adenoma is rare, and treatment for both the aneurysm and pituitary adenoma is complex and controversial. CASE DESCRIPTION: A 53-year-old woman presented with a visual field defect. Magnetic resonance imaging showed a pituitary adenoma and coexistence of an aneurysm located at the orifice of the superior hypophyseal artery (SHA) from the internal carotid artery (ICA). The aneurysm was embedded in the pituitary adenoma; therefore, obliteration of the aneurysm was needed prior to tumor removal to prevent intraoperative rupture of the aneurysm. Although endovascular coil embolization was tried first, it was not successful. A combined endoscopic endonasal approach and transcranial approach was performed for simultaneous tumor removal and aneurysm clipping. A bilateral subfrontal approach was selected for aneurysm clipping because, using this approach, the parent artery was safely controlled from the ipsilateral trajectory, whereas exposure and clipping of the aneurysm were easily done from the contralateral trajectory. Additionally, the supine head position without rotation is comfortable for endoscopic endonasal surgery. The tumor was totally removed, and the aneurysm was safely and completely obliterated with a clip. The patient's postoperative course was uneventful, and her visual disturbance improved. CONCLUSIONS: A combined endoscopic endonasal and bilateral subfrontal approach is effective for a pituitary adenoma associated with an ICA-SHA aneurysm.

[Resection of a Desmoid Tumor Originated from Greater Omentum with No History of Open Surgery].

Here we report a case of a 41-year-old male patient who underwent resection of a desmoid tumor originating from the greater omentum with no history of open surgery. An elastic hard mass was palpated in the left upper abdomen, but there were no abnormalities on serum chemical tests, including tumor markers. Computed tomography showed a parenchymal tumor located near the descending colon. Integrated positron-emission tomography and computed tomography revealed moderate accumulation of tracer in the tumor. An intra-abdominal malignant mesenchymoma was suspected and surgery was performed. The tumor was located in the anterior portion of the greater omentum. It partially invaded the diaphragm, and the affected regions were concurrently resected. The resected specimen measured 80 mm at longest diameter. The cut surface was grayish white and parenchymal. The histopathological findings showed the atypical spindle shaped tumor cells grown with collagen fiber progression. Immunohistochemical staining for ß-catenin showed strong staining in the nuclei and cytoplasm of tumor cells. The patient was diagnosed with desmoid tumor originating from the greater omentum. The desmoid tumor with no history of open surgery was rare. We report this rare case, along with a discussion of the literature.

[Cognitive Dysfunction in Children who Underwent Surgery after a Traumatic Brain Injury:A Single Institute Investigation].

The cognitive function of children who underwent surgical therapy after a traumatic brain injury is poorly studied. In this study, we investigated the characteristics of 27 children who received surgical therapy at our institution. The children were between 1 and 16 years of age, of which 15 had cognitive dysfunction. Their Glasgow Coma Scale score at the acute stage of dysfunction was worse than in children who did not have cognitive dysfunction. Acute subdural hematoma was more frequent in the cognitive dysfunction group. Moreover, all children in this group showed brain injury by imaging analysis. Differences in imaging characteristics and the association with cognitive dysfunction could not be readily associated with a specific injury. Memory and verbal disorder were the most common cognitive dysfunctions:these symptoms were present among children of all ages;conversely, behavior disorder, impaired attention, and infeasibility were limited to the children under 9 years of age. Since the immature brain is developing, the acquisition of new abilities may be blocked by the injury;thus, we speculate that brain injury at a younger age causes greater cognitive dysfunction.

[A Case of Stevens-Johnson Syndrome Induced by Chemotherapy for Metastatic Colon Cancer].

A 78-year-old woman had a semicircular ulcerative lesion of AV 7 cm, as detected using colonoscopy, and pathologic examination based on a biopsy showed well-differentiated adenocarcinoma. On contrast-enhanced CT of the liver, a number of nodular lesions that seemed to be liver metastases were observed. It was decided to administer chemotherapy containing mFOLFOX6 plus panitumumab. Bilateral hemorrhage of the ocular conjunctiva and eyelid edema were observed from the 4th day of chemotherapy. Edema of the lips, epidermolysis, and erythema appeared in addition to vision impairment. We diagnosed her with SJS based on these symptoms. We also administered steroid pulse therapy. Eyelid edema improved, and vision impairment improved 24 hours after the initiation of treatment. For severe cases with visual impairment, systemic administration of corticosteroids is recommended. In this case, administering steroid pulse therapy from an early stage resulted in improvement without sequelae.

Treatment Outcomes of Cerebral Aneurysms Presenting with Optic Neuropathy: A Retrospective Case Series.

BACKGROUND: Optic neuropathy due to an aneurysm is relatively rare, with only a few small case series on this topic, and no randomized trials having been published until now. As such, the functional prognosis and treatment for aneurysm-induced optic neuropathy remain controversial. OBJECTIVE: We quantified optic nerve injuries using an objective index (the visual impairment score) and evaluated prognostic factors of postoperative visual function. MATERIALS AND METHODS: Of 960 patients treated for an unruptured intracranial aneurysm, 18 (1.9%) patients had optic neuropathy. Visual acuity and visual field were assessed before surgery and 6 months' postoperatively. Cases were classified on the basis of treatment modality (coil embolization or flow alteration [FA]) and prognostic factors of the two treatment groups. RESULTS: Of the 18 patients with an intracranial aneurysm and optic neuropathy, 12 (67%) were treated using coil embolization and 6 (33%) were FA. Visual function improved after surgery in 8 patients (44%), 5 (42%) in the coil embolization group, and 3 (50%) in the FA group. The visual function remained stable after surgery in 6 (33%) patients and worsened in 4 (22%). Patients with an aneurysms <15 mm in size had a favorable outcome (P = 0.05). CONCLUSIONS: Surgical treatment improved vision in 44% of cases, with no difference in the prognosis of coil embolization and FA and no effect of the duration of symptoms on outcomes. Further, the prognosis of visual function recovery was better for aneurysms <15 mm in diameter.

[A Case of Nephrotic Syndrome Induced by FOLFIRI plus Ramucirumab for Metastatic Descending Colon Cancer].

We report a case of multiple lung metastases of RAS mutant type descending colon cancer with development of nephrotic syndrome after the introduction of FOLFIRI plus ramucirumab(RAM). A female patient in her 50s underwent adjuvant chemotherapy with capecitabine and oxaliplatin after primary tumor and partial lung resection. For recurrent multiple lung metastases, 4 years of capecitabine and bevacizumab therapy was administered. FOLFIRI plus RAM therapy was introduced because of tumor progression. After treatment, the patient showed increased urine protein content, decreased serum albumin levels, marked hypertension, and increased edema, and was diagnosed with nephrotic syndrome. The patient's condition improved with prednisolone, additional doses of antihypertensive, and diuretics. Even in cases where it is possible to control proteinuria during bevacizumab administration, it is necessary to keep in mind that RAM administration as second-line therapy may cause nephrotic syndrome.