Risk factors associated with the progression and metastases of hindgut neuroendocrine tumors: a retrospective study.

BACKGROUND: The worldwide incidence of neuroendocrine tumors (NETs) has increased remarkably, with the hindgut being the second most common site for such tumors. However, the mechanisms underlying progression and metastasis of hindgut NETs are unclear. A retrospective study was conducted to elucidate these mechanisms. METHODS: Clinicopathological data of cases of hindgut NET between April 1996 and September 2015 were analyzed, retrospectively. Patients with neuroendocrine carcinoma were excluded. Formalin-fixed paraffin-embedded tissues of hindgut NET cases were subjected to detailed morphometric and immunohistochemical analyses. Statistical analyses were performed using the non-parametric Mann-Whitney U test, Spearman's correlation coefficient, and chi-squared test. Multivariate logistic regression analysis was conducted as appropriate for the data set. RESULTS: Fifty-six hindgut NET cases were considered. Microvessel density and lymphatic microvessel density were identified as significant risk factors for venous and lymphatic invasion. There was a positive correlation between microvessel density and the maximum tumor diameter. Multivariate logistic regression analysis revealed that the maximum tumor diameter alone was an independent predictor of lymph node metastasis, whereas lymphovascular invasion and MVD was not the predictor of lymph node metastasis. There were no significant correlations between the Ki-67 labeling index and any of the parameters evaluated including age, sex, the maximum tumor diameter, venous invasion, lymphatic invasion, microvessel density, lymphatic microvessel density, and lymph node metastasis. CONCLUSIONS: Angiogenic mechanisms may play important roles in the progression of hindgut NET. Otherwise, the maximum tumor diameter alone was an independent predictor of lymph node metastasis in hindgut NETs. Moreover, our study raises the question of whether the presence of lymphovascular invasion, in endoscopically obtained hindgut NET tissues, is an absolute indication for additional surgery or not.

Evaluation of an e-learning system for diagnosis of gastric lesions using magnifying narrow-band imaging: a multicenter randomized controlled study.

Background and study aim Magnifying narrow-band imaging (M-NBI) is useful for the accurate diagnosis of early gastric cancer (EGC). However, acquiring skill at M-NBI diagnosis takes substantial effort. An Internet-based e-learning system to teach endoscopic diagnosis of EGC using M-NBI has been developed. This study evaluated its effectiveness. Participants and methods This study was designed as a multicenter randomized controlled trial. We recruited endoscopists as participants from all over Japan. After completing Test 1, which consisted of M-NBI images of 40 gastric lesions, participants were randomly assigned to the e-learning or non-e-learning groups. Only the e-learning group was allowed to access the e-learning system. After the e-learning period, both groups received Test 2. The analysis set was participants who scored < 80 % accuracy on Test 1. The primary end point was the difference in accuracy between Test 1 and Test 2 for the two groups. Results A total of 395 participants from 77 institutions completed Test 1 (198 in the e-learning group and 197 in the non-e-learning group). After the e-learning period, all 395 completed Test 2. The analysis sets were e-learning group: n = 184; and non-e-learning group: n = 184. The mean Test 1 score was 59.9 % for the e-learning group and 61.7 % for the non-e-learning group. The change in accuracy in Test 2 was significantly higher in the e-learning group than in the non-e-learning group (7.4 points vs. 0.14 points, respectively; P < 0.001). Conclusion This study clearly demonstrated the efficacy of the e-learning system in improving practitioners' capabilities to diagnose EGC using M-NBI.Trial registered at University Hospital Medical Information Network Clinical Trials Registry (UMIN000008569).

The clinicopathological significance of angiogenesis in hindgut neuroendocrine tumors obtained via an endoscopic procedure.

BACKGROUND: As the World Health Organization grading system for gastroenteropancreatic-neuroendocrine tumors (GEP-NETs) may not always correlate with tumor progression, it is imperative that other independent predictors of tumor progression be established. To identify such predictors, we conducted a retrospective histopathological study of hindgut NETs, obtained from endoscopic procedures, and used statistical analyses to evaluate predictive factors. METHODS: We first obtained clinicopathological data of cases of hindgut NETs. Tissue sections from tumor samples were prepared and subjected to pathological examination. In particular, we calculated the microvessel density (MVD) and lymphatic microvessel density (LMVD) values, and performed appropriate statistical analyses. RESULTS: A total of 42 cases of hindgut NETs were selected for the study, 41 from the rectum and 1 from the sigmoid colon. Based on the Ki-67 labeling index, 34 cases were classified as NET G1 tumors and 8 as NET G2 tumors. MVD values ranged from 1.4/mm2 to 73.9/mm2 and LMVD values from 0/mm2 to 22.9/mm2. MVD and LMVD were identified as risk factors for venous and lymphatic invasion of hindgut NETs. Moreover, MVD positively correlated with the maximum diameter of the tumor. CONCLUSIONS: Tumor progression of NETs may cause angiogenesis and lymphangiogenesis, via an unknown mechanism, as well as lymphovascular invasion. Angiogenesis likely plays an important role in occurrence and progression in the initial phase of hindgut NETs.

Duodenal Rare Neuroendocrine Tumor: Clinicopathological Characteristics of Patients with Gangliocytic Paraganglioma.

Gangliocytic paraganglioma (GP) has been regarded as a rare benign tumor that commonly arises from the second part of the duodenum. As GP does not exhibit either prominent mitotic activity or Ki-67 immunoreactivity, it is often misdiagnosed as neuroendocrine tumor (NET) G1. However, the prognosis might be better in patients with GP than in those with NET G1. Therefore, it is important to differentiate GP from NET G1. Moreover, our previous study indicated that GP accounts for a substantial, constant percentage of duodenal NETs. In the present article, we describe up-to-date data on the clinicopathological characteristics of GP and on the immunohistochemical findings that can help differentiate GP from NET G1, as largely revealed in our new and larger literature survey and recent multi-institutional retrospective study. Furthermore, we would like to refer to differential diagnosis and clinical management of this tumor and provide intriguing information about the risk factors for lymph node metastasis on GP.

Outcomes and precautions of endoscopic submucosal dissection for undifferentiated-type early gastric cancer.

OBJECTIVES: Since the development of techniques for endoscopic submucosal dissection (ESD), the indication range of endoscopic resection (ER) has been extended in early gastric cancer (EGC) treatment. For undifferentiated-type EGC, tumors with an intramucosal depth of invasion, no ulceration and a diameter of 20 mm or less were included in the expanded indications for ER in the Japanese Gastric Cancer Treatment Guidelines 2010. Nonetheless, because of difficulty in detecting lesions that meet the criteria for ER, the number of endoscopically resected cases of undifferentiated-type EGC is less than that of differentiated-type EGC. METHODS: We retrospectively investigated the outcomes of ESD in 38 patients with 40 lesions of EGC in which the dominant pathological type was confirmed to be undifferentiated (signet ring cell carcinoma, poorly differentiated adenocarcinoma, mucinous adenocarcinoma) on histological examination of resected specimens. RESULTS: Margin involvement and submucosal infiltration were common noncurative factors. Precise evaluation of the area and depth of lesions is a problem to be solved. Among a total of five patients with involved or uncertain horizontal margins, one of two patients who underwent additional surgery had residual cancer, and one of three patients who were observed had recurrence. CONCLUSIONS: Undifferentiated-type EGC with a positive horizontal margin may relapse after ESD. It is therefore essential to precisely evaluate the area of the lesion and to perform resection with an adequate safety margin to decrease the risk of recurrence.

Two-point fixed endoscopic submucosal dissection in rectal tumor (with video).

BACKGROUND: Polypectomy, EMR, transanal endoscopic microsurgery, and surgery have been performed as treatments of rectal tumors. Endoscopic procedures are the least-invasive treatments for patients. Complete resection of the lesion is required to prevent its recurrence, and endoscopic submucosal dissection (ESD) has begun to be performed. With increasing requirements for safety, reliability, and simplicity in ESD, we decided to use a 2-point fixed ESD with a transparent hood fitted with a mucosal forceps channel in a case of a rectal tumor and report its usefulness. OBJECTIVE: To evaluate the safety, simplicity, and usefulness of 2-point fixed ESD performed on a rectal tumor. DESIGN: Case series. SETTING: Kanagawa Cancer Center Hospital. MAIN OUTCOME MEASUREMENTS: Safety, simplicity, and usefulness of 2-point fixed ESD performed on a rectal tumor. RESULTS: The mean duration of the procedure was 45 minutes (range 30-110 minutes). Hemostasis and manipulation of the vessels were easy in all patients who did not have postoperative bleeding, perforation, or retroperitoneal emphysema as complications. LIMITATIONS: Uncontrolled study. CONCLUSION: This study of 2-point ESD performed in 12 patients with rectal lesions revealed that the 2-point ESD with a transparent hood fitted with a mucosal forceps channel is a useful auxiliary device, enabling safe and reliable ESD on a rectal lesion.

[Three cases of radiotherapy combined with S-1 and mitomycin C for anal canal squamous cell carcinomas].

We report three cases of anal canal squamous cell carcinoma treated with radiotherapy combined with S-1 and mitomycin C(MMC). During radiotherapy, MMC was administered as intravenous bolus injection at a dose of 10mg/m2 on day 1 and 29. S-1 was administered orally at a dose of 80mg/m2 on days 1-14 and 29-43. Total radiation doses ranged 55. 8-60 Gy to pelvic lesions. The rates of grade 3 toxicity were: neutropenia, 100%; leucopenia, 100%; anemia, 33. 3%; anorexia, 66. 7%. These adverse events were tolerated. All of the three cases showed complete response without recurrences. These results suggested that this treatment schedule was safe and effective for anal canal carcinomas.

Endoscopic submucosal dissection (two-point fixed ESD) for early esophageal cancer.

BACKGROUND: We have been attempting to improve the safety, reliability and simplicity of endoscopic submucosal dissection for the treatment of early esophageal cancer and to shorten the time needed for this operation. METHODS: The present study involved nine patients with well-differentiated intramucosal early esophageal cancer over 20 mm in diameter. Two-point fixed endoscopic submucosal dissection was carried out. RESULTS: In all nine cases, the mucosal area to be dissected was successfully identified and kept under direct vision, allowing two-point fixation of the mucosa with forceps and the hood during adequate counter-traction. In this way, the respiration-caused movement of submucosal tissue between the two fixing points was suppressed almost completely. Hemostasis and manipulation on blood vessels were easy with this procedure and dissection could be completed safely, without causing perforation. CONCLUSION: Endoscopic submucosal dissection with a transparent hood fitted with a mucosa-holding forceps channel is highly useful, safe and simple when applied to the esophagus.

[A case of infant epidural hematoma treated by continuous drainage of cephalohematoma].

A female infant was born at 36 weeks with vacuum extraction. Her weight was 2.216 g and Apgar score was 9. She had a cephalohematoma at right parietal region. The cephalohematoma grew during 6 days after birth, then she came to our hospital. On arrival, her consciousness was alert and there were no neurological deficits. Her head circumference was 22.5 cm, and she had a pulsatile soft cephalohematoma, 7 cm in diameter, at right parietal region. Ultrasound examination showed a midline shift of the brain and CT scan revealed an epidural hematoma with bone fracture and cephalohematoma. We chose the puncture and continuous drainage of cephalohematoma as a primary therapy, because cephalohematoma was considered to be liquified and to be continuous to the epidural hematoma. The reason was that the pulsatile cephalohematoma became harder when she cried. The epidural hematoma was completely reduced on the next day's CT and then drainage was removed. She discharged on 15th post-operative day. We conclude that the puncture and continuous drainage of cephalohematoma may be one of the good therapeutic methods for the mild symptomatic neonate who has epidural hematoma with the cephalohematoma and bone fracture.

Thrombosed vertebral artery aneurysm presenting with hemorrhage and bulbar compression: report of two cases.

Bulbar compression by vertebral artery (VA) aneurysm is extremely rare and only reported in a few cases. We report two cases with thrombosed VA aneurysm compressing medulla oblongata; one presented with bulbar apoplexy hemorrhage and the other with subarachnoid hemorrhage (SAH). A 61-year-old male (case 1) presented with consciousness disturbances, left hemiplegia, and subsequent respiratory arrest. He was subjected to controlled ventilation, and computed tomography (CT) scan showed bulbar hemorrhage. Magnetic resonance imaging (MRI) and digital subtraction angiogram (DSA) revealed fusiform right VA aneurysm with partial thrombosis and bulbar compression. Intra-aneurysmal embolization with Guglielmi detachable coils (GDCs) relieved his clinical symptom including respiratory disturbance. Three months after the onset, he remained moderately disabled. A 76-year-old male (case 2) presented with severe headache and subsequent respiratory disturbance. CT scan on admission showed subarachnoid hemorrhage with acute hydrocephalus. Ventricular drainage rapidly improved consciousness while respiratory disturbance persisted over several days. MRI and DSA suggested spontaneous thrombosis of the right VA dissection with bulbar compression. He showed gradual recovery of his respiration over a week. After ventriculo-peritoneal shunting, he was transferred with moderate disability. These results suggest that the elimination of the pulsatile effect of VA aneurysm adjacent to medulla oblongata can improve symptoms caused by aneurysm-related compression. Early diagnosis and appropriate treatment such as intra-aneurysmal embolization for ameliorating the blood flow inside the aneurysm can relieve mass effect and clinical symptoms.

Cerebral infarction in the caudate nucleus associated with acute epidural hematoma and diffuse brain injury in a child after severe head injury.

CASE REPORT: A 6-year-old boy was admitted to our hospital 20 min after receiving a direct impact to his head in an automobile accident. He was semi-comatose on admission and computed tomography showed acute epidural hematoma in the right supratentorial region. Three hours later, his consciousness deteriorated due to the enlargement of the hematoma. Surgical removal of hematoma relieved his consciousness disturbance. Post-operative magnetic resonance imaging revealed spotty high-intensity lesions in the corpus callosum on T2-weighted images, and a solitary high-intensity lesion in the left caudate nucleus extending to the medial globus pallidum on T2-weighted and diffusion-weighted images. Magnetic resonance angiography showed no abnormality in the main arteries. These results suggested cerebral infarction in the vascular territory supplied by the recurrent artery of Heubner in association with diffuse brain injury. Post-operative course was uneventful and he was discharged without neurological deficit. CONCLUSIONS: Post-traumatic cerebral infarction in the caudate nucleus is extremely rare, and its association with diffuse brain injury and epidural hematoma is apparently unique.

Hydrocephalus due to cerebrospinal fluid overproduction by bilateral choroid plexus papillomas.

CASE REPORT: A 10-month-old boy, with congenital deafness and blindness associated with chromosomal deletion [46XY, del(13)(q32)], presented with intractable ascites 9 months after ventriculo-peritoneal shunting for congenital hydrocephalus. Revision of the ventriculo-atrial shunt resulted in shunt failure 1 month later. External ventricular drainage revealed cerebrospinal fluid (CSF) overproduction (2,000 ml/day). Magnetic resonance imaging showed marked lobular enlargement of the bilateral choroid plexuses extending from the trigone to the body and inferior horn of the lateral ventricle. Multi-staged resection was performed via bilateral temporo-occipital transcortical approaches, and CSF production significantly decreased to 100 ml/day postoperatively. Histological assessment of the villous surface suggested villous hyperplasia of the choroid plexus and thorough evaluation including the proximal portion of the lobular lesion near the attachment revealed choroid plexus papilloma. He was discharged after ventriculo-peritoneal shunting without additional neurological deficits except for hyperreflexia of the left extremities. CONCLUSION: CSF overproduction caused by bilateral choroid plexus papillomas can result in hydrocephalus. Radical resection of the bilateral ventricular lesions should be considered for this entity. Thorough evaluation of the surgical specimen is recommended because histological examination of only the lobular surface of the choroid plexus lesion may fail to identify choroid plexus neoplasm.

Lipomatous meningioma of the brain harboring metastatic renal-cell carcinoma: a case report.

A 70-year-old woman presented with mild left hemiparesis and intermittent global headache. Magnetic resonance imaging showed a 6 x 6 x 6-cm tumor in the right frontal lobe, and abdominal computed tomography revealed a 8 x 8 x 7-cm mass lesion in the left kidney. Magnetic resonance imaging showed that the brain tumor consisted of a central hyperintense cystic component and an outer hypointense component. The patient underwent total surgical excision of the intracranial mass. Histological and immunohistochemical examination showed that the lesion was a lipomatous meningioma harboring metastatic renal-cell carcinoma. Both of these tumors are rare. The magnetic resonance imaging findings are indicative of but not specific to meningioma harboring metastatic tumor.

A distal anterior cerebral artery aneurysm in infant: disappearance and reappearance of the aneurysm.

The incidence of intracranial aneurysms in childhood is rare, especially in infancy. Spontaneous thrombosis of a cerebral aneurysm in a child is very rare, particularly in a non-giant aneurysm. We report a case of a 1-month-old girl with a distal anterior cerebral artery aneurysm which disappeared spontaneously after subarachnoid hemorrhage and reappeared 6 months later. Surgical resection of the aneurysm was performed and she discharged uneventfully 10 days later. Histological examination revealed an aneurysm with a fibrous muscular layer, absence of the internal elastic lamina and partial hypertrophy of the intimal layer. Though the pathogenesis of this aneurysm is uncertain, two hypotheses are discussed.

[Two cases of impending herniation due to multiple traumatic acute subdural hematomas: combination of burr hole evacuation and craniotomy].

A contralateral extra-axial hematoma sometimes occurs during an operation on an acute subdural hematoma and may become fatal. Using a combined procedure of burr hole evacuation and craniotomy, we treated 2 cases of multiple traumatic acute subdural hematomas. Our policy for such cases is first to perform a burr hole evacuation for the acute subdural hematoma in the emergency room, while simultaneously preparing the operation room for a possible further operation. Next, we perform computed tomography (CT) of the brain. If the evacuation does not provide enough decompression, we either carry out a craniotomy at the same site, or, we observe the patient without resorting to craniotomy. However, if the patient's condition deteriorates, burr hole evacuation is repeated and/or craniotomy is carried out as soon as possible on the lesion at the already prepared operation room. Both of our patients received craniotomy for another subdural hematoma after the burr hole evacuation. Though his intracranial pressure was well managed during the acute stage, one of the patients died 21 days after the trauma due to an extensive brain infarction caused by vasospasm. The other regained consciousness and was able to walk 5 months after the trauma in spite of cerebral infarction from vasospasm. The possible mechanism of vasospasm in severe head injury is also discussed.

[A case of vertebral artery occlusion following heading play in soccer].

A 13-year-old boy suffered from cerebeller infarction due to right vertebral artery occlusion after heading a ball during a rainy soccer game. Dissection of the vertebral artery after trivial head trauma is well known, but heading as the cause has not been reported. We speculated in this present case that excessive impact force to the young boy's neck due to the heavy rain-soaked ball might have caused right vertebral artery dissection and occlusion. High quality balls are recommended for young amateur players on rainy days.

Unruptured carotid-duplicated middle cerebral artery aneurysm: case report.

We demonstrate the first case with unruptured carotid-duplicated middle cerebral artery (IC-Dup MCA) aneurysm combined with ruptured opposite carotid aneurysm. Eleven IC-Dup MCA aneurysm reported until now had all ruptured. It is noteworthy that 8 patients of the 11 were Japanese.

Growth of small unruptured intracranial aneurysm: case report.

Magnetic resonance angiography (MRA) revealed silent but rapid growth of a small unruptured intracranial aneurysm until it was surgically treated to prevent rupture. Modern neuroimaging methods such as MRA and 3-dimensional computed tomography have increased opportunity to detect small unruptured cerebral aneurysms. Strict follow up is an option for the incidentally discovered small intact aneurysms using these methods.

Single burr hole evacuation for traumatic acute subdural hematoma of the posterior fossa in the emergency room.

A 57-year-old man and a 55-year-old man presented with acute subdural hematoma of the posterior cranial fossa due to trauma. Both were comatose preoperatively. Emergent single burr hole evacuation in the posterior cranial fossa was performed in the emergency room immediately after computed tomography. Neurological symptoms improved dramatically just after initiating the burr hole evacuation in both patients. A 57-year-old man became alert and could walk unassisted 1 month after surgery. The other could walk with assistance 4 months after surgery, although psychic disturbance resulting from cerebral contusion remained. Single burr hole evacuation in the emergency room is a useful treatment for acute subdural hematoma of the posterior cranial fossa because the procedure can be performed easily and rapidly, thus achieving reduction of intracranial pressure. Progressing neurological deterioration, reversibility of brainstem function by mannitol administration and the sign of brainstem compression and noncommunicating hydrocephalus are good indicators for this treatment.