[A Case of BRAF Mutant Cecal Cancer Treated with Encorafenib, Binimetinib, and Cetuximab Triple Therapy].

A Japanese woman in her early 70's presented to our hospital with abdominal pain and nausea. Abdominal computed tomography showed irregular wall thickening of the ileocecal region and small intestine dilatation. Colonoscopy revealed a tumor lesion at the ileocecal valve and adenocarcinoma was detected in the biopsy specimen. Accordingly, the diagnosis was cecal cancer and bowel obstruction. Right hemicolectomy was performed as palliative surgery, and laparotomy findings revealed peritoneal dissemination. The final staging was pT4a, pN2b, pM1c, pStage Ⅳc, harboring a BRAFV600E mutation. Rapid postoperative tumor progression occurred, leading to multiple liver metastases and ascites. Encorafenib, binimetinib, and cetuximab triple therapy was started as a second line regimen. The therapy was extremely effective. CA19-9 level decreased to within normal range, and the liver tumor size was visibly diminished. After receiving treatment for 2 months in outpatient care, she had to discontinue the treatment due to carcinomatous peritonitis. Unfortunately, she died 6 months after initial diagnosis. BRAF-mutated colon cancer is associated with poor prognosis. In Japan, encorafenib, binimetinib, and cetuximab triple therapy is a new BRAF targeting regimen approved in 2020. We report this clinical course in hopes of eventually achieving better outcomes for patients with this aggressive disease.

[Rapid Progression in Early-Stage Primary Glioblastoma Multiforme:A Case Report].

The signs and features of early-stage primary glioblastoma multiforme(GBM)are not well-characterized. Here, we report a case of GBM that was presented at an early stage and showed extremely rapid progression within a short period. A 63-year-old woman was incidentally revealed to have a tiny lesion in her right parietal lobe. Magnetic resonance imaging(MRI)showed a hyperintense signal on T2WI, with a ring-enhancement on gadolinium(Gd)-enhanced T1WI. Two weeks later, she was admitted to our hospital for neurosurgical intervention;the MRI at that time showed rapid tumor growth, immediately followed by progressive neurological deterioration. The tumor was urgently removed;its histopathological diagnosis was GBM. This case indicates that primary GBM, even at an early stage, can rapidly progress within an extremely short period. Scheduling prompt neuroradiological assessments and neurosurgical interventions in possible cases of early-stage GBM are important, especially if a Gd-enhancement is seen on MRI.

Clinicopathological features, postoperative survival and prognostic variables for cancer-related survival in patients with mucinous colorectal carcinoma.

PURPOSE: To investigate the clinicopathological features and postoperative survival of patients with mucinous colorectal carcinoma (MC) and to identify the factors related to long-term survival. METHODS: Twenty-three patients who had undergone resection for MC at Miyazaki University Hospital from 1991 to 2006 were followed up for at least 5 years or until death. The effects of the clinicopathological variables on the 5-year cancer-specific survival were assessed by the univariate analyses. These patients' clinicopathological data were compared with those of 403 non-mucinous carcinoma (NMC) patients (102 well-differentiated adenocarcinomas, 301 moderately differentiated adenocarcinomas). RESULTS: The 5-year cancer-specific survival rate was significantly worse in MC (56.2 %) than in NMC (73.8 %; p = 0.008) cases. Univariate analyses showed the T factor, lymph node metastases, liver metastases, metastases to the distant peritoneum, remote metastases and curative resection to be significant factors predicting the survival. However, there were no significant differences in the postoperative survival in patients with stage II-IV disease. The rates of metastases to the distant peritoneum, M1, T4, a tumor size ≥5 cm and non-curative resection were higher in MC than in NMC patients. CONCLUSIONS: Patients with MC had advanced stage cancer, especially with metastases to the distant peritoneum, more frequently than did the patients with NMC. To improve the survival of these patients, it is therefore important to detect MC at an early stage and to perform curative resection.

The genotype of the transporter associated with antigen processing gene affects susceptibility to colorectal cancer in Japanese.

OBJECTIVE: Although colorectal cancer (CRC) is one of the most frequent malignancies in Japan, the associated genetic factors remain to be elucidated. Functional loss of the transporter associated with antigen processing (TAP) 1 gene induces carcinogenesis. We investigated whether single nucleotide polymorphisms (SNPs) in the TAP1 gene (rs735883) are associated with susceptibility to CRC in a Japanese population. METHODS: The study participants were 143 cases and 243 clinical controls. After extracting DNA from their peripheral blood cells, genotyping was conducted by the polymerase chain reaction-restriction fragment length polymorphism method. RESULTS: Participants with a mutated allele had an increased risk for CRC. The adjusted odds ratios for the C/T, T/T, and the mutation type (C/T + T/T) compared to that of wild type (C/C) were 2.27 [95 % confidence interval (CI), 1.43-3.67], 1.95 (95 % CI, 0.88-4.30), and 2.22 (95 % CI, 1.42-3.55), respectively. Furthermore, a significant trend in the rate of cases was observed with an increasing number of mutated alleles (P for trend = 0.0068). CONCLUSIONS: The genotype of the TAP1 gene is associated with susceptibility to CRC.

[A case report of gastrointestinal stromal tumor of the small intestine presenting with liver abscesses caused by Streptococcus constellatus].

A 49-year-old woman visited a local hospital in October 2007 with complaint of fever and melena. Abdominal ultrasonography and abdominal computed tomography revealed an irregular mass in the lower abdomen, together with multiple masses in the liver. She was admitted because of anemia, and the high fever was determined to be an inflammatory response. Blood tests revealed elevated biliary enzyme levels. Percutaneous biopsy of the liver mass was performed, which revealed liver abscesses caused by Streptococcus constellatus. On abdominal angiography, the mass was suspected to be a tumor of the small intestine. In late November 2007, laparoscopy-assisted partial small bowel resection was performed, and pathological examination of the surgical specimen confirmed gastrointestinal stromal tumor (GIST) of the small bowel. Because reports of small intestinal GIST with liver abscesses caused by Streptococcus constellatus are rare, this case description could provide valuable information.

Antiproliferative effect of 1α,25-dihydroxyvitamin D3 involves upregulation of cyclin-dependent kinase inhibitor p21 in human pancreatic cancer cells.

BACKGROUND/AIMS: The aim of this study was to investigate the effect of 1α,25-dihydroxyvitamin D3 on proliferation of human pancreatic cancer cell lines and to identify related cell cycle regulatory proteins with antiproliferative effects. METHODOLOGY: Human pancreatic cancer cell lines SUIT-2 and its four sublines, and Panc-1, AsPC-1, and MiaPaCa-2 were treated with1α,25-dihydroxyvitamin D3. The number of cells was measured by the MTT method, and the cell cycle regulatory proteins were then analyzed by Western blotting. RESULTS: Eight human pancreatic cancer cell lines expressed vitamin D receptor (VDR) mRNA. 1α,25-dihydroxyvitamin D3 inhibited proliferation of SUIT-2 and its sublines. We found p21 to be upregulated after 24 hours in S2-028, the cell line in which proliferation was most inhibited by 1α,25-dihydroxyvitamin D3. CONCLUSIONS: 1α,25-dihydroxyvitamin D3 inhibited proliferation of pancreatic cancer cells and is involved in the upregulation of cyclin-dependent kinase inhibitor p21.

Memory, Executive, and Intellectual Functions in Adults with Moyamoya Disease.

OBJECTIVE: Cognitive function can decline in adults with moyamoya disease (MMD). Memory, which is an essential but complex and multifaceted function, underpins executive and intellectual functions. However, the relationship between memory and executive or intellectual functions in adults with MMD has not been well studied. The relationship between memory and cerebral blood flow has also not been elucidated. This study investigated correlations between memory, executive function, and intellectual function, and associations between cerebral blood flow and memory in adults with MMD. METHODS: Memory, executive function, and intellectual function were assessed using the Wechsler Memory Scale-Revised (WMS-R), Frontal Assessment Battery (FAB), and Wechsler Adult Intelligence Scale (WAIS) third or fourth edition, respectively, in 31 adults with MMD. Cerebral blood flow was measured with iodine 123I-iodoamphetamine single-photon emission computed tomography. RESULTS: WMS-R scores correlated significantly with total FAB and WAIS scores before and after revascularization. Cerebral blood flow in the left posterior cerebral artery territory correlated positively with WMS-R and WAIS scores pre- and postoperatively. Postoperative cerebrovascular reserves of the right cerebellum, pons, and vermis were positively associated with visual memory, and postoperative cerebrovascular reserve of the pons was also associated with general memory. CONCLUSIONS: Memory function correlates with executive and intellectual functions in adults with MMD. The FAB, which requires about 10 min to administer, might be useful to screen for memory dysfunction. Memory might be vulnerable to hypoperfusion in the posterior cerebral artery territory among adults with MMD. Postoperative cerebrovascular reserve might help predict memory dysfunction in adults with MMD.

Angiogenic and inflammatory responses in human induced microglia-like (iMG) cells from patients with Moyamoya disease.

Angiogenic factors associated with Moyamoya disease (MMD) are overexpressed in M2 polarized microglia in ischemic stroke, suggesting that microglia may be involved in the pathophysiology of MMD; however, existing approaches are not applicable to explore this hypothesis. Herein we applied blood induced microglial-like (iMG) cells. We recruited 25 adult patients with MMD and 24 healthy volunteers. Patients with MMD were subdivided into progressive (N = 7) or stable (N = 18) group whether novel symptoms or radiographic advancement of Suzuki stage within 1 year was observed or not. We produced 3 types of iMG cells; resting, M1-, and M2-induced cells from monocytes, then RNA sequencing followed by GO and KEGG pathway enrichment analysis and qPCR assay were performed. RNA sequencing of M2-induced iMG cells revealed that 600 genes were significantly upregulated (338) or downregulated (262) in patients with MMD. Inflammation and immune-related factors and angiogenesis-related factors were specifically associated with MMD in GO analysis. qPCR for MMP9, VEGFA, and TGFB1 expression validated these findings. This study is the first to demonstrate that M2 microglia may be involved in the angiogenic process of MMD. The iMG technique provides a promising approach to explore the bioactivity of microglia in cerebrovascular diseases.

Thrombin stimulates integrin ß1-dependent adhesion of human pancreatic cancer cells to vitronectin through protease-activated receptor (PAR)-1.

BACKGROUND/AIMS: The aim of this study was to investigate the effect of thrombin and the thrombin receptor protease-activated receptor (PAR)-1 on adhesion of human pancreatic cancer cell lines to extracellular matrices (ECMs) and to identify related integrins with these effects. METHODOLOGY: Human pancreatic cancer cell lines SUIT-2 and its four sublines, and Panc- 1, AsPC-1 and MiaPaCa-2 were treated with thrombin, PAR-1 agonist TRAP-6, PAR-1 antagonist SCH79797, or anti-integrin ±vß3, ±vß5 and ß1 monoclonal antibodies. Cells were incubated for 45 minutes on micro titer plates that were pre-coated with ECMs (fibronectin, laminin, vitronectin, type IV collagen). The number of adherent cells was measured by the MTT method. RESULTS: Eight human pancreatic cancer cell lines expressed PAR-1. Thrombin significantly enhanced adhesion of SUIT-2 and its sublines and MiaPaCa-2 to vitronectin, especially in the SUIT-2 subline S2-007. We obtained similar results on S2-007 cells through treatment with TRAP-6. However, SCH79797 inhibited the effect of thrombin. Furthermore, anti-integrin ß1 antibody conspicuously inhibited 1U/mL thrombin-induced enhancement of adhesion to vitronectin. CONCLUSIONS: Thrombin significantly enhanced adhesion of pancreatic cancer cells to vitronectin through PAR- 1 depending on the presence of integrin ß1. Suppression of thrombin action by anti-integrin ß1 antibody will become a useful therapy against pancreatic cancer.

Indications for computed tomography use and frequency of traumatic abnormalities based on real-world data of 2405 pediatric patients with minor head trauma.

BACKGROUND: In pediatric patients with minor head trauma, computed tomography (CT) is often performed beyond the scope of recommendations that are based on existing algorithms. Herein, we evaluated pediatric patients with minor head trauma who underwent CT examinations, quantified its frequency, and determined how often traumatic findings were observed in the intracranial region or skull. METHODS: We retrospectively reviewed the medical records and neuroimages of pediatric patients (0-5 years) who presented at our hospital with minor head trauma within 24 h after injury. RESULTS: Of 2405 eligible patients, 1592 (66.2%) underwent CT examinations and 45 (1.9%) had traumatic intracranial hemorrhage or skull fracture on CT. No patient underwent surgery or intensive treatment. Multivariate analyses revealed that an age of 1-5 years (vs. <1 year; P < 0.001), Glasgow Coma Scale (GCS) score of 14 (vs. a score of 15; P = 0.008), sustaining a high-altitude fall (P < 0.001), using an ambulance (P < 0.001), and vomiting (P < 0.001) were significantly associated with the performance of CT examination. In addition, traumatic abnormalities on CT were significantly associated with the combination of an age of under 1 year (P = 0.042), GCS score of 14 (P < 0.001), and sustaining a high-altitude fall (P = 0.004). CONCLUSION: Although slightly broader indications for CT use, compared to the previous algorithms, could detect and evaluate minor traumatic changes in pediatric patients with minor head trauma, over-indications for CT examinations to detect only approximately 2% of abnormalities should be avoided and the indications should be determined based on the patient's age, condition, and cause of injury.

Intraoperative Tissue Expansion Using a Foley Catheter for a Scalp Defect: Technical Note.

BACKGROUND: Primary closure of the surgical wound during neurosurgical procedures is sometimes difficult because of limited ability to expand the scalp, or because the skin defect is large. Hence, our institution recently adopted the technique of intraoperative tissue expansion using a Foley catheter for these cases. We describe this easily accomplished, readily available, effective, economical technique and describe our experience performing the technique. METHODS: With this procedure, the subcutaneous tissue (usually the subperiosteal layer) surrounding the skin defect is dissected to make a subcutaneous pocket in which to place a 20-French Foley catheter. The standard expander is a 30-mL balloon. The catheter is inserted into the subcutaneous pocket, and the balloon is inflated with 10-30 mL of saline for 5 minutes, after which the balloon is deflated for 3 minutes in a cyclic loading manner. After sufficient expansion, the primary closure of the surgical wound is achieved with minimal tension on the surrounding skin. RESULTS: Between November 2018 and February 2020, we performed this technique in 5 patients, each with a large surgical defect in the scalp. Primary closure was achieved, and postoperative wound healing was excellent in all 5 patients. CONCLUSIONS: Intraoperative skin expansion using a Foley catheter-which is easily performed, readily available, and economical-can be used to achieve surgical wound closure during various neurosurgical procedures.

Massive Ossification with Hematopoietic Marrow on Both Surfaces of the Expanded Polytetrafluoroethylene Artificial Dura Mater.

BACKGROUND: Artificial dural substitute made from an expanded polytetrafluoroethylene (ePTFE) sheet has been widely used in surgical application. CASE DESCRIPTION: We describe a 19-year-old woman in whom massive ossification with hematopoietic marrow was noted on both surfaces of an ePTFE sheet during epilepsy surgery. At age 8, she underwent decompressive craniectomy for a ruptured arteriovenous malformation in the right frontal lobe, followed by duraplasty with an ePTFE sheet and autologous cranioplasty fixed with titanium miniplates. CONCLUSIONS: Since the ossification was prominent in the wrinkle dents of the ePTFE sheet and fibrotic membrane with repetitive hemorrhagic events was noted under the ePTFE sheet, the most plausible mechanism of ossification development is the organization of epiartificial and subartificial dural hematoma. Surgeons should be aware of the possibility of ossification development when working with ePTFE sheets for duraplasty.

Multidisciplinary Treatments of True Posterior Inferior Cerebellar Artery Aneurysms: Single-Center Retrospective Study and Treatment Algorithm.

BACKGROUND: True posterior inferior cerebellar artery (PICA) aneurysms outside the vertebral artery-PICA region are rare, with approximately 30 cases reported in just a few papers; no treatment paradigm has been advocated. The objective of this study was to present detailed clinical features and outcomes for several treatments for true PICA aneurysms and suggest an algorithm for treatment strategies. METHODS: We retrospectively analyzed outcomes of patients treated for PICA aneurysms with microsurgical and endovascular treatments. We also investigated the influence of several factors on the modified Rankin Scale score. RESULTS: Cases with PICA aneurysms (n = 36) outside the vertebral artery-PICA region were identified angiographically. Aneurysm locations included anterior medullary (n = 7), lateral medullary (n = 10), tonsillomedullary (n = 4), telovelotonsillar (n = 12), and cortical (n = 3) segments of the PICA. Aneurysm morphology was as follows: dissecting: 22; fusiform: 6; and saccular: 8. On multivariate analysis, age (P = 0.028) and lack of vermian infarction (P =0.037) were associated with a significantly better prognosis. Prognosis was not significantly different for the 5 aneurysm locations and among the 4 treatment groups: clipping/coiling, trapping/parent artery occlusion, trapping/parent artery occlusion + bypass, and observation including external ventricular drainage. CONCLUSIONS: This study suggests that factors associated with significantly better prognosis include age, clip/coil treatments, and no vermian infarction complication. A treatment algorithm for true PICA aneurysms was supported according to pretreatment H and K grade, PICA segments, aneurysm morphology, and 3 types of ischemia linked to the brainstem, cerebellar hemisphere, or vermis.

Pyogenic liver abscesses concomitant with advanced gastric cancer: a case report.

It has been reported that gastric cancer rarely causes pyogenic liver abscesses because of its mucosal acid barrier. Herein, we describe a rare case of pyogenic liver abscesses concomitant with advanced gastric cancer. A 61-year-old man was transferred to our hospital with persistent nausea and fever. Computed tomography showed a lobulated lesion in the caudate lobe of the liver, slightly rim-enhanced lesions in the right lobe, enhanced mass on the lesser curvature of the upper gastric body, and enlarged regional lymph nodes. Subsequent upper gastrointestinal endoscopy revealed a type 3 tumor on the lesser curvature of the upper gastric body; pathological examination of a biopsy showed adenocarcinoma. After treatment with antibiotics, the lesion in the caudate lobe decreased in size and the enhanced lesions in the right lobe resolved. The patient underwent curative gastrectomy; the pathological diagnosis was gastric cancer, T4aN3aM0 stage IIIB, according to the Japanese classification of gastric carcinoma (Third English edition). The patient was discharged without complications and underwent adjuvant chemotherapy. Gastric cancer can cause pyogenic liver abscesses. Although differentiating between liver abscesses and hepatic metastases can be difficult, multidisciplinary and appropriate treatment strategies are needed.

Recurrent intraductal papillary mucinous neoplasms of the pancreas mimicking ampullary cancer.

Although several studies have reported that some patients developed metachronous/recurrent intraductal papillary mucinous neoplasms (IPMNs) after partial pancreatectomy, recurrence of IPMN mimicking ampullary cancer is extremely rare. We report the case of a 62-year-old man who developed recurrent IPMN mimicking ampullary cancer. Every 3-6 months, the patient had received surveillance with computed tomography after distal pancreatectomy for IPMN, high-grade, pancreatobiliary type. However, a villous tumor at the major duodenal papilla was found incidentally by upper gastrointestinal endoscopy 2 years and 3 months after initial surgery, and the biopsy result was adenocarcinoma. Endoscopic ultrasonography showed a tumor at the periampullary lesion; however, the origin of the tumor could not be determined definitively. Remnant total pancreatectomy was performed, and the histological diagnosis revealed IPMN, high-grade, pancreatobiliary type. Some patients develop recurrent IPMN mimicking ampullary cancer; thus, careful surveillance for periampullary lesions as well as remnant pancreas should be performed.

Coiling for a saccular aneurysm on the caudal channel in double origin of the posterior inferior cerebellar artery.

BACKGROUND: Double origin of the posterior inferior cerebellar artery (DOPICA) is a rare cranial imaging finding with an incidence of 0.36-6% reported in various retrospective studies. Aneurysms on a DOPICA are even rarer. CASE DESCRIPTION: A 34-year-old women hospitalised for subarachnoid haemorrhage showed a ruptured aneurysm arising from the caudal channel of the DOPICA. Endovascular treatment was selected, and the aneurysm was successfully and completely embolised using two coils. CONCLUSIONS: To date, a total of three previous saccular aneurysms of the DOPICA itself have been reported, all of which were treated using endovascular methods. Our case is the first report of a ruptured saccular aneurysm arising from the non-branching segment of the caudal channel of the DOPICA.

Coiling for an unruptured saccular aneurysm at the non-branching segment of the distal anterior cerebral artery: Case report and literature review.

BACKGROUND: Saccular aneurysms in the non-branching segment of the distal anterior cerebral artery (DACA) are extremely rare. Here, we describe the first case of coil embolization using a simple, non-adjunctive technique for an aneurysm at this rare location. CASE DESCRIPTION: A 74-year-old man with an asymptomatic, unruptured aneurysm of the right DACA was followed up annually for 3 years by medical checkup. Endovascular treatment was proposed because of a slight angiographic change in the shape of the aneurysm in the past year. The aneurysm at the non-branching site of the right calloso-marginal artery was 2 mm distal to the origin, and measured 3 mm in height and 3.3 mm in width, with a neck measuring 1.7 mm wide; the calloso-marginal artery diameter was 1.6 mm. The aneurysm was successfully embolized with a simple technique using a Pre-Shaped S Microcatheter and two coils. CONCLUSIONS: The simple, non-adjunctive technique for coil embolization of saccular side-wall type aneurysm in the non-branching segment of the DACA could be performed using the appropriate catheter and a softer coil.

An unusual variant of a left paraduodenal hernia diagnosed and treated by laparoscopic surgery: report of a case.

An 80-year-old woman who had undergone both a cholecystectomy and an appendectomy presented with intermittent abdominal pain. Computed tomography (CT) revealed an encapsulated circumscribed cluster of jejunal loops in the left upper quadrant. The hernia orifice was adjacent to the left side of the superior mesenteric artery and vein. An upper gastrointestinal series also revealed a cluster of jejunal loops, suggesting the possibility of an internal hernia. Laparoscopic surgery was performed. The hernia orifice was found to be caused by abnormal adhesion between the transverse mesocolon and the jejunum mesentery. An adhesiotomy reduced the jejunum entrapped in the hernia. The hernia space was a large mesocolic fossa composed of transverse mesocolon and mesentery, continuing to the splenic flexure. The hernia was classified as a variant of paraduodenal hernia.

[Prognostic factors and usefulness of chemotherapy with S-1 in patients received gastrectomy for stage IV gastric cancer].

Clinicopathological factors influencing the survival and the effect of chemotherapy with special reference to S-1 were retrospectively analyzed in 41 patients who underwent gastrectomy for stage IV gastric cancer. Significantly better outcomes were observed in patients with H0, P0 or M0 than those with H1, P1 or M1, respectively. Curability B surgery showed a significantly better result than curability C. A significantly better result was demonstrated in patients treated with S-1 alone than those treated with chemotherapy other than S-1 or in patients without chemotherapy. Multivariate analysis revealed that H0, M0 and chemotherapy with S-1 were significant and independent prognostic factors. Moreover, the patients treated with S-1 for more than 12 months showed a significantly better outcome than those treated with S-1 for less than 12 months. It is concluded that curative resection (curability B) and the longer period of postoperative chemotherapy with S-1 is the treatment of choice to improve the outcome of patients with stage IV gastric cancer.

Asymptomatic malignant melanoma of the gallbladder with multiple brain metastases diagnosed with endoscopic ultrasound-guided fine-needle aspiration cytology.

Malignant melanoma of the gallbladder (MMG) is extremely rare and its early stage diagnosis is difficult. Most reports of MMG describe metastatic tumors. We herein report a rare case of presumed primary MMG diagnosed by endoscopic ultrasonography-guided fine-needle aspiration (EUS-FNA) cytology without surgical resection. A 72-year-old Japanese male was diagnosed with multiple brain metastases. Fluorodeoxyglucose (FDG) positron emission tomography showed an abnormal uptake of FDG at the gallbladder; enhanced CT and MRI also showed an enhanced gallbladder lesion, which indicated a malignancy. We performed endoscopic naso-gallbladder drainage. However, cytological examination of the drained bile showed no evidence of malignancy. Finally, EUS-FNA was performed to confirm the histological diagnosis; cytopathological assessment, including immunohistochemical analysis, showed a cluster of small to large-sized cells with nuclear pleomorphism and melanin pigment, which was compatible with malignant melanoma. The patient subsequently underwent chemotherapy; however, he died 2 months after diagnosis. In patients with gallbladder tumors, MMG should be suspected even in patients with no history of malignant melanoma or any cutaneous lesions. EUS-FNA is safe and useful to confirm histological diagnoses and to determine optimal treatment strategies.