[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.

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.

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.

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.

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.

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.

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.

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.

Mechanical Thrombectomy of Primary Distal Anterior Cerebral Artery Occlusion: A Case Report.

OBJECTIVE: Primary anterior cerebral artery (ACA) occlusion is a rare condition and sometimes leads to significant neurological deficits. We herein report on the efficacy of mechanical thrombectomy (MT) in treating the distal ACA occlusion in a clinical setting. CASE PRESENTATION: A 76-year-old woman presented with a sudden onset of right hemiparesis. Computed tomographic angiography and perfusion imaging and subsequent analysis with RAPID software revealed acute left ACA occlusion with salvageable penumbra. The patient obtained a score of 11 on the National Institutes of Health Stroke Scale. MT was performed for occlusion of the left ACA (A4), and successful reperfusion (Thrombolysis in Cerebral Infarction score of 3) was achieved on the first attempt using a stent retriever. The patient's recovery progressed well, and she was discharged 13 days after admission with a modified Rankin Scale score of 1. CONCLUSION: This case report demonstrates the clinical efficacy, safety, and favorable clinical outcome of treating a primary distal ACA occlusion with MT.

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.

Laparoscopic treatment of intestinal obstruction due to a vitelline vascular remnant and simultaneous appendicitis: a case report.

BACKGROUND: The presence of a vitelline vascular remnant is rare, and definitive preoperative diagnosis is difficult. We herein describe a case of intestinal obstruction caused by a vitelline vascular remnant with mild chronic appendicitis successfully diagnosed and treated with laparoscopic surgery. CASE PRESENTATION: A 14-year-old male was admitted to our hospital with sudden-onset right lower abdominal pain and vomiting. A blood test on admission revealed slight leukocytosis. Computed tomography scan showed that the appendiceal wall was enhanced and thickened. Although the ileum was slightly dilated and ascites was present at the recto-vesical pouch, these were thought to be inflammatory changes secondary to appendicitis. Laparoscopic surgery was performed using three trocars. Strangulated small bowel obstruction caused by a band connecting the right medial umbilical fold to the ileal mesentery was found intraoperatively. After reduction, neither ischemic change of the small intestine nor Meckel's diverticulum was detected. The appendix was slightly inflamed, and serous ascites was present at the recto-vesical pouch; therefore, appendectomy was also performed. The patient was discharged on postoperative day 4 without complications. Pathological examination revealed that the band consisted of blood vessels, and it was diagnosed as a vitelline vascular remnant. The appendix included fecal stones and showed chronic inflammatory change histologically; the patient was thus diagnosed with chronic appendicitis. CONCLUSIONS: Definitive preoperative diagnosis of a vitelline vascular remnant, especially with coexisting appendicitis, might be difficult. Laparoscopic surgery might be useful for patients who demonstrate unusual symptoms because it allows for simultaneous diagnosis and treatment.

Ruptured Aneurysm of an Aberrant Internal Carotid Artery Successfully Treated with Simultaneous Intervention and Surgery in a Hybrid Operating Room.

BACKGROUND: Aberrant internal carotid artery (aICA) is an anatomic anomaly whereby the internal carotid artery courses through the tympanic cavity without separation by bone. Because aICA is rare, there are no definite treatment strategies for aICA and its complications. CASE DESCRIPTION: We report a case of aICA accompanied by pseudoaneurysm formation and massive bleeding. The patient was a 31-year-old woman with a 2-year history of hearing loss, ear fullness, and pulsatile tinnitus in her left ear. After a diagnosis of otitis media with effusion, she underwent a myringotomy and massive arterial bleeding occurred. After the bleeding was temporarily stopped, aICA and pseudoaneurysm formation on the aICA were shown. To prevent rebleeding, we performed endovascular internal trapping around the pseudoaneurysm after performing common carotid artery to radial artery to middle cerebral artery bypass grafting. After surgery, the aneurysm disappeared. In addition, no new neurologic complications were observed, and the patient's hearing improved and the tinnitus diminished. CONCLUSIONS: This is the first case report of an aICA complicated by pseudoaneurysm formation successfully treated with simultaneous endovascular trapping and high-flow bypass in a hybrid operating room.

[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.

Optimal perioperative management of antithrombotic agents in patients with chronic subdural hematoma.

OBJECTIVE: The use of antithrombotic agents such as anticoagulants and antiplatelet agents is widespread, and the opportunities to treat patients with chronic subdural hematoma (CSDH) under antithrombotic therapy are growing. However, whether antithrombotic therapy contributes to postoperative complications and recurrences of CSDH and how these agents should be managed in the surgical treatment of CSDH remains unclear. METHODS: We retrospectively analyzed 150 consecutive patients with CSDH who underwent neurosurgical interventions at Kyushu Rosai Hospital from 2011 to 2015 and followed them for more than 3 months. RESULTS: Of the 150 study patients, 44 received antithrombotic therapy. All anticoagulants and 76% of the antiplatelet agents were discontinued before surgical treatment of CSDH and resumed within 1 week except in 4 patients whose treatment was terminated and 7 patients who developed postoperative complications or underwent reoperations before resumption of these agents. Postoperative hemorrhagic complications associated with surgical treatment of CSDH occurred in 8 patients (5.3%), and there was no significant difference in the incidence of these complications between patients with and without antithrombotic therapy (6.8% vs. 4.7%, respectively; p=0.90). Postoperative thromboembolic complications occurred in 5 patients (5.4%), including 4 patients with antithrombotic therapy; these complications developed before resumption of antithrombotic agents in 2 patients. There was a significant difference in the incidence of postoperative thromboembolic complications between patients with and without antithrombotic therapy (9.1% vs. 0.9%, respectively; p=0.04). There were no significant differences in the incidence of radiographic deterioration or reoperation of ipsilateral or contralateral hematomas between patients with and without antithrombotic therapy after surgical treatment of unilateral CSDH. CONCLUSION: A history of antithrombotic therapy was significantly correlated with the incidence of postoperative thromboembolic complications in patients with CSDH. Antithrombotic agents should be resumed as soon as possible when no hemorrhagic complication is confirmed after neurosurgical intervention for CSDH.

Laparoscopic anterior pelvic exenteration for locoregionally advanced rectal cancer directly invading the urinary bladder: A case report of low anterior resection with en bloc cystectomy for sphincter preservation.

Laparoscopic multi-visceral resection in patients with T4 colorectal cancer remains controversial. A 73-year-old man was admitted to the hospital for rectosigmoid cancer directly invading the urinary bladder trigone without distant metastasis. We successfully performed complete resection by laparoscopic anterior pelvic exenteration while preserving the anus. After laparoscopic mobilization of the rectum, urinary bladder, and prostate, the urethra and urethral catheter were dissected to reveal the lower rectum. By pulling the urethral catheter toward the head, the prostate was excised retrogradely from the lower rectum anterior wall. The lower rectum was resected and anastomosed by the double stapling technique with a safe distal margin from the tumor. Pathological findings of the resected specimen indicated no residual tumor in the surgical margin. There was no evidence of recurrence 34 months after surgery. En bloc, R0, laparoscopic anterior pelvic exenteration for T4 rectal cancer is feasible. However, further studies with long-term follow-up are required to resolve oncological outcomes.

Smad4 loss synergizes with TGFα overexpression in promoting pancreatic metaplasia, PanIN development, and fibrosis.

AIMS: While overexpression of TGFα has been reported in human pancreatic ductal adenocarcinoma (PDAC), mice with overexpressed TGFα develop premalignant pancreatic acinar-to-ductal metaplasia (ADM) but not PDAC. TGF-ß signaling pathway is pivotal to the development of PDAC and tissue fibrosis. Here we sought to investigate the interplay between TGFα and TGF-ß signaling in pancreatic tumorigenesis and fibrosis, namely via Smad4 inactivation. METHODS: The MT-TGFα mouse was crossed with a new Smad4 conditional knock-out mouse (Smad4flox/flox;p48-Cre or S4) to generate Smad4flox/flox;MT-TGFα;p48-Cre (STP). After TGFα overexpression was induced with zinc sulfate water for eight months, the pancreata of the STP, MT-TGFα, and S4 mice were examined for tumor development and fibrotic responses. PanIN lesions and number of ducts were counted, and proliferation was measured by Ki67 immunohistochemistry (IHC). Qualitative analysis of fibrosis was analyzed by Trichrome Masson and Sirius Red staining, while vimentin was used for quantification. Expression analyses of fibrosis, pancreatitis, or desmoplasia associated markers (α-SMA, Shh, COX-2, Muc6, Col1a1, and Ctgf) were performed by IHC and/or qRT-PCR. RESULTS: Our STP mice exhibited advanced ADM, increased fibrosis, increased numbers of PanIN lesions, overexpression of chronic pancreatitis-related marker Muc6, and elevated expression of desmoplasia-associated marker Col1A1, compared to the MT-TGFα mice. The inactivation of Smad4 in the exocrine compartment was responsible for both the enhanced PanIN formation and fibrosis in the pancreas. The phenotype of the STP mice represents a transient state from ADMs to PanINs, closely mimicking the interface area seen in human chronic pancreatitis associated with PDAC. CONCLUSION: We have documented a novel mouse model, the STP mice, which displayed histologic presentations reminiscent to those of human chronic pancreatitis with signs of early tumorigenesis. The STP mice could be a suitable animal model for interrogating the transition of chronic pancreatitis to pancreatic cancer.

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.