Efficacy and Safety of Salvage-line Nivolumab Monotherapy for Advanced Esophageal Squamous Cell Carcinoma: Comparison of 240 mg Versus 480 mg Doses.

BACKGROUND: Nivolumab monotherapy is the standard second-line treatment for advanced esophageal squamous cell carcinoma (ESCC) after failure of platinum-based chemotherapy without anti-PD-1 antibody. Fixed dosing with 240 mg every 2 weeks was approved initially, followed by fixed dosing with 480 mg every 4 weeks based on pharmacokinetics data. However, information on the comparative efficacy and safety of the two doses remains limited. METHODS: We compared progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and the incidence of adverse events (AEs) between the two doses in 117 patients who received second-line (n = 85) or later-line (n = 32) nivolumab monotherapy at our institution between January 2016 and December 2021. RESULTS: In the second-line group, patient characteristics for the 240 mg and 480 mg groups were as follows (240 mg vs. 480 mg): performance status (PS) 0/1/2 was 34/61/5% vs. 54/42/4%, and prior fluoropyrimidine plus platinum therapy (FP) was 81.3% vs. 42.3%. In the later-line group, the characteristics were: PS 0/1/2 was 28/60/12% vs. 14/86/0%, and prior FP was 60.0% vs. 42.8%. ORR was 11.9 vs. 24.0% in the second-line group (p = 0.19) and 0 vs. 14.3% in the later-line group (p = 0.22). Median PFS was 1.7 vs. 4.1 months on second-line (hazard ratio [HR] 0.60, 95% confidence interval [CI] 0.35-1.01, p = 0.056) and 1.4 vs. 1.8 months on later-line (HR 0.58, 95% CI 0.23-1.46, p = 0.25); AEs of any grade were observed in 58.3 vs. 69.7%, respectively. CONCLUSIONS: The efficacy and safety of the two doses of nivolumab monotherapy were comparable in patients with advanced ESCC.

Nivolumab in unresectable advanced, recurrent or metastatic esophageal squamous cell carcinoma.

Esophageal cancer (EC) is the eighth most common cancer worldwide. In view of biology and anatomical restrictions, multimodality treatment strategies have been developed for EC. However, the prognosis of patients with advanced EC remains especially poor. Immunotherapy, such as PD-1/PD-L1 and CTLA-4/B7 blockade, has emerged as a potent treatment for many types of cancer and has been approved in many countries. Based on the results of the ATTRACTION-3 trial, nivolumab, an anti-PD-1 monoclonal antibody, was approved by the US FDA for patients with platinum-resistant, unresectable, recurrent or metastatic esophageal squamous cell carcinoma. The CheckMate 648 trial demonstrated that the combination of nivolumab with platinum-based fluoropyrimidine chemotherapy and combination immunotherapy with nivolumab and ipilimumab, an anti-CTLA-4 monoclonal antibody, showed a survival benefit in patients with advanced esophageal squamous cell carcinoma compared with doublet chemotherapy. This review focuses on nivolumab-containing treatments for patients with advanced esophageal squamous cell carcinoma.

Diagnostic Ability of Endoscopic Ultrasound-Guided Tissue Acquisition Using 19-Gauge Fine-Needle Biopsy Needle for Abdominal Lesions.

Attempts at performing endoscopic ultrasound-guided tissue acquisition (EUS-TA) with a 19G needle are increasing because histological diagnosis and comprehensive genomic profiling are a necessity. However, the diagnostic ability of the 19G fine-needle biopsy (FNB) needle, especially the third-generation FNB needle, is unclear and has been retrospectively reviewed. The 19G TopGain needle was used in 147 patients and 160 lesions between September 2020 and December 2021. The technical success rate of the biopsies was 99.4% (159/160). The early adverse event rate was 4.1% (6/147), and moderate or severe adverse event rate occurrence was 2.0% (3/147). The sensitivity, specificity, and accuracy of the 19G TopGain needle for 157 lesions with a confirmed diagnosis were 96.7%, 100%, and 96.8%, respectively. Rescue EUS-TA using the 19G TopGain needle was performed for nine lesions, and a successful diagnosis was made in six of these lesions (66.7%). The diagnostic ability of EUS-TA using the third-generation 19G TopGain needle was favorable. However, the use of 19G FNB needles may increase adverse events. Therefore, EUS-TA with a 19G FNB needle is mainly indicated in lesions where comprehensive genomic profiling may be necessary or the diagnosis could not be determined via EUS-TA using the 22G needle.

[Comparison of Current Perspectives of Perioperative Treatments for Esophageal Cancer between Japan and the Western Countries-Toward International Collaborative Studies].

There are 2 main histologic types of esophageal cancer: squamous cell carcinoma and adenocarcinoma. Squamous cell carcinoma is the most common histology type in the world, but in Europe and the United States, adenocarcinoma is the most common type. The standard treatments differ between Japan and the Europe and the United States, especially in the perioperative treatments. Standard treatment in Japan is preoperative chemotherapy based on the results of the JCOG1109 trial. While in Europe and the United States, the standard treatment is preoperative chemoradiotherapy based on the results of the CROSS trial and postoperative nivolumab according to the results of CheckMate 577 trial. In surgical treatment, 3- region lymph node dissection is the standard in Japan, whereas in Europe and the United States, where the lower esophagus, mainly adenocarcinoma, is often treated, 2-region lymph node dissection of the middle and lower mediastinum is the standard. Due to these differences in established treatments, the results of clinical trials in other countries cannot be extrapolated to standard treatment in Japan. Therefore, it is essential to understand the differences in standard treatment in East Asia, where esophageal squamous cell carcinoma frequently occurs, and other countries, and to deepen exchanges with experts in each country, so that international clinical trials can be designed and standard treatment can be established.

Safety and short-term efficacy of preoperative FOLFOX therapy in patients with resectable esophageal squamous cell carcinoma who are ineligible for cisplatin.

BACKGROUND: The standard preoperative treatment for resectable locally advanced esophageal squamous cell carcinoma (LAESCC) in Japan is docetaxel, cisplatin (CDDP), and 5-fluorouracil. However, patients with renal or cardiac dysfunction and elderly patients are ineligible for a CDDP-containing regimen because of toxicities. Oxaliplatin, leucovorin, and 5-fluorouracil (FOLFOX) therapy has less renal toxicity than CDDP-containing regimens and does not require hydration. However, there are limited data on preoperative FOLFOX therapy in these patients. METHODS: This retrospective study analyzed patients with resectable LAESCC who were aged ≥ 75 years or had renal or cardiac dysfunction and received preoperative FOLFOX between 2019 and 2021. FOLFOX was administered every 2 weeks for 3 or 4 cycles and was followed by surgery. Adverse events associated with chemotherapy, the complete resection (R0) rate, relative dose intensity (RDI), and histopathological response were evaluated. RESULTS: Thirty-five patients were eligible. Median age was 77 (range 65-89) years; 68.6% were aged ≥ 75 years, 74.3% had renal dysfunction, and 17.1% had cardiac dysfunction. The RDI was 70.2% and 87.1% for bolus and continuous intravenous 5-fluorouracil, respectively and 85.2% for oxaliplatin. The most common grade ≥ 3 adverse events were neutropenia (60.0%) and leucopenia (28.6%). Two patients (5.7%) had febrile neutropenia and grade 3 pneumonia. Thirty-one patients underwent surgery. The R0 resection rate was 87.1%, and there was no histopathological evidence of residual tumor in 16.1%. There were no treatment-related deaths. CONCLUSIONS: Preoperative FOLFOX had a manageable safety profile and showed favorable short-term efficacy in patients with resectable LAESCC who were ineligible for CDDP-containing treatment.

Fine-needle biopsy with 19G needle is effective in combination with endoscopic ultrasound-guided tissue acquisition for genomic profiling of unresectable pancreatic cancer.

OBJECTIVES: Comprehensive genomic profiling (CGP) has been approved in Japan since June 2019, enabling mutation-specific therapy. Although tissue sampling via endoscopic ultrasound-guided tissue acquisition (EUS-TA) is standard in pancreatic cancer, reports on obtaining appropriate samples for CGP, especially for the OncoGuide NCC Oncopanel System (NOP) and FoundationOne CDx (FOne), are lacking. Therefore, we investigated the success rate and factors related to appropriate EUS-TA sampling for CGP analysis suitability in unresectable pancreatic ductal adenocarcinoma (UR-PDAC). METHODS: Participants comprised 150 UR-PDAC patients who underwent EUS-TA and tumor sample evaluation for CGP analysis suitability between June 2019 and December 2021. The proportion of patients meeting the criteria was evaluated considering tumor size, puncture lesion, presence of metastasis, type and size of puncture needle, suction method, number of punctures, and puncture route. RESULTS: In total, 39.2% (60/153) of samples met NOP analysis suitability criteria and 0% met FOne analysis suitability criteria. The suitability rate was significantly higher with 19G fine-needle biopsy (FNB) (56.0%; 42/75) than with 22G FNB (32.6%; 14/43) and 22G fine-needle aspiration (11.4%; 4/35). Nineteen-gauge needle (odds ratio [OR] 2.53; 95% confidence interval [CI] 1.15-5.57; P = 0.021) and FNB (OR 3.57; 95% CI 1.05-12.20; P = 0.041) were independent factors contributing to NOP analysis suitability. Among 30 patients who underwent actual NOP analysis, the analysis success rate was 100% (30/30). CONCLUSION: In sample collection via EUS-TA, 19G and FNB needles contribute to NOP analysis suitability.

Proportion of unresectable pancreatic cancer specimens obtained by endoscopic ultrasound-guided tissue acquisition meeting the OncoGuide™ NCC Oncopanel System analysis suitability criteria: a single-arm, phase II clinical trial.

BACKGROUND: There are limited studies on the results of comprehensive genomic profiling testing for pancreatic cancer tissue specimens by endoscopic ultrasound-guided tissue acquisition (EUS-TA). This study aimed to evaluate the proportion of specimens obtained by EUS-TA using a 19-gauge (G) fine-needle biopsy (FNB) needle for unresectable pancreatic cancer (UR-PC) that met the OncoGuide™ NCC Oncopanel System (NOP) analysis suitability criteria. METHODS: In this single-arm, prospective, phase II study, EUS-TA was performed using a 19G FNB biopsy needle in patients with suspected UR-PC based on a contrast-enhanced computed tomography scan. The primary endpoint was the proportion of patients who met the NOP analysis suitability criteria, with a threshold, expected value, α-error, and power of 40%, 70%, 0.025, and 0.9, respectively, and the planned number of enrolled patients was 33. The NOP analysis suitability criteria were defined as tumor cell content ≥ 20% and tissue size ≥ 4 mm2. RESULTS: Thirty-three patients were enrolled. The procedural success rate was 100%, and the cytodiagnosis of class V was observed in all patients. The proportion of patients meeting the NOP analysis suitability criteria was 63.6% (95% CI 47.22-80.05), which satisfied the predefined criteria to be considered valid. Adverse events occurred in 9.0% of the patients. CONCLUSIONS: The proportion of patients with UR-PC who met the NOP analysis suitability criteria for EUS-TA using a 19G FNB needle was effective for achieving the primary endpoint, making it a valid test method. Adverse events occurred at a higher rate than that previously reported.

Brainstem anesthesia during removal operation of ventriculoperitoneal shunt - A case report.

Background: Brainstem anesthesia is a transient loss of brainstem function usually associated with retrobulbar block and rarely seen by neurosurgeons. Case Description: Here, we report a case of brainstem anesthesia during shunt revision operation in a 79-year-old woman. Local anesthesia administered at the end of surgery was thought to have infiltrated the subarachnoid space through a burr hole, causing prolonged unconsciousness and cranial nerves' impairment. Spontaneous resolution occurred during systemic support. Conclusion: As brainstem anesthesia may occur by leakage of local anesthetic through small burr holes, timing injections carefully can avoid this rare complication.

Bilateral Risk Assessments of Surgery and Nonsurgery Contribute to Providing Optimal Management in Early Gastric Cancers after Noncurative Endoscopic Submucosal Dissection: A Multicenter Retrospective Study of 485 Patients.

BACKGROUND AND AIMS: Surgery is recommended in early gastric cancer (EGC) after noncurative endoscopic submucosal dissection (ESD), although observation can be an alternative. We aimed to develop a tailor-made treatment strategy for noncurative EGCs by comparing the lymph node metastasis risk (LNMR) and the surgical risk. METHODS: We retrospectively identified 485 patients with differentiated-type, noncurative EGCs removed by ESD and classified them into two groups: a surgery-preferable group and an observation-preferable group, according to the clinical courses. Subsequently, LNMR and surgery-related death risk were assessed using a published scoring system and a risk calculator for gastrectomy, respectively. Finally, we investigated the optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to efficiently allocate these cases into either of two groups, surgery-preferable or observation-preferable. RESULTS: In 485 patients (surgery in 322, observation in 163), 57 and 428 patients were classified into the surgery-preferable group and the observation-preferable group, respectively. The optimal cutoff value of the risk difference (LNMR minus surgery-related death risk) to allocate the cases to the two preferable groups was 7.85 with the highest area under the curve (0.689). When cases with >7.85 LNMR over the surgery-related death risk were allocated into the surgery-preferable group and vice versa, the discriminability was 73.2%, which was sufficiently higher than that in the clinical decision (44.5%). CONCLUSION: Personalized comparison of LNMR and surgery-related death risk is helpful to provide a favorable treatment option for each patient with EGCs after noncurative ESD.

A Proposed New Clinical Classification of Metastatic Gastric Cancer: Pyloric and Antral Gastric Cancer.

BACKGROUND: We aimed to classify metastatic pyloric/antral gastric cancer in terms of macroscopic morphology and metastatic form. METHODS: Thirty-eight patients with pyloric/antral gastric cancer were included in the study. Patients were classified according to a combination of Borrmann classification type and metastatic type, and the clinicopathological characteristics of each group were compared. RESULT: Of the 38 patients, 33 (type II: 9 and type III: 24) (87%) had ulcerative gastric cancer. Ulcerative gastric cancer was classified into four groups: lymphatic only group (L+H-P-), lymphatic + hematogenous group (L+H+P-), disseminated ± lymphatic group (L±H-P+), and lymphatic + hematogenous + disseminated group (L+H+P+). In the L+H-P- group, all patients had bulky lymph nodes and serum levels of both carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were high; the condition of patients was good, and the therapeutic response was good. In the L+H+P- group, metastases other than liver metastases were rare, and serum CEA levels were high. In the L±H-P+ group, the predominant histological type was signet ring cell carcinoma; both serum CEA and CA19-9 levels were low. Patients in the L+H+P+ group had higher serum CA19-9 levels and were more prone to hematogenous metastasis to various organs; these patients had worse patient status and lower treatment response. Gastric cancer other than ulcerative type was only detected in five patients (type V: 3, type IV: 1, type I: 1). CONCLUSION: Classification by a combination of macroscopic and metastatic form in pyloric/antral metastatic gastric cancer might be useful for diagnosis and treatment.

The safety of current treatment options for advanced esophageal cancer after first-line chemotherapy.

The prognosis of advanced esophageal cancer (EC) remains poor, and few effective agents are available. For advanced EC patients, a combination of platinum and fluoropyrimidine is recognized as the standard first-line treatment. After first-line treatment, taxane or irinotecan has been used. Based on the KEYNOTE-181 and the ATTRACTION-3 trials, immune checkpoint inhibitors (ICIs) such as pembrolizumab and nivolumab appear to prolong survival, compared with cytotoxic agents, as second-line treatments for advanced EC patients. In addition, ICIs have different safety profiles than conventional cytotoxic agents. Herein, we discuss the differences in the safety profiles of cytotoxic agents and ICIs for the treatment of advanced EC patients after first-line chemotherapy.ICIs as a second-line treatment are tolerable in advanced EC patients. Although infrequent, ICIs can cause immune-related adverse events that are sometimes fatal. Therefore, regular monitoring of physical and laboratory examinations is needed during and after the administration of ICIs. As the major toxicities of taxane are neutropenia and neuropathy, while those of irinotecan are neutropenia and diarrhea, appropriate supportive care or dose modification may be needed for individual patients. ICI-containing treatments have been developed not only as second-line treatments, but also as first-line treatments or for use in perioperative settings; thus, particular attention with regard to immune-related toxicities is needed.

Outcome of Endovascular Therapy Aiming for Single-session Obliteration of Intracranial Dural Arteriovenous Fistulas.

The goal of dural arteriovenous fistula (dAVF) treatment is obliteration of the arteriovenous shunt and/or retrograde leptomeningeal venous drainage (RLVD). Single-session obliteration could improve symptoms early and reduce risk of neurological sequelae. This study investigated the efficacy and adverse events of endovascular therapy (EVT) aiming for single-session obliteration in dAVF treatment. We retrospectively examined post-treatment arteriovenous shunt status, number of treatments per case, treatment-related complications, and long-term outcome in 92 dAVF patients who underwent initial EVT at our institution. Single-session obliteration was intended in all cases, but a second session was performed in cases of partial shunt occlusion or remaining RLVD. Complete occlusion was achieved in 85 cases (92.4%) after the single session; RLVD was obliterated in 66 of the 67 Borden type II and III cases combined (98.5%). A second session was necessary in seven cases (7.6%). Complete shunt obliteration was eventually achieved in all cases. The average number of treatments was 1.08 per case. dAVF-related stroke and mortality did not occur after the treatment. On the other hand, radiation-induced skin erythema and alopecia, although all symptoms were transient, occurred in 26 cases (28.3%). Over an average 60.2-month follow-up period, recurrence was observed in seven cases (7.6%). Single-session obliteration was successful in 92% of cases. Especially, single-session obliteration of RLVD may contribute to early prevent of future stroke events. However, reducing total radiation dose during each session is an issue of further study.

Endosonographic features in patients with non-alcoholic early chronic pancreatitis improved with treatment at one year follow up.

Since the prevention of early chronic pancreatitis (ECP) into chronic pancreatitis might be critical for the reduction of pancreatic cancer, we tried to clarify the pathophysiology of ECP patients, focusing on ECP patients without alcoholic chronic pancreatitis. 27 ECP patients without alcoholic chronic pancreatitis and 33 patients with functional dyspepsia with pancreatic enzyme abnormalities (FD-P) were enrolled in this study. Diagnosis of ECP was made when imaging findings showed the presence of more than 2 out of 7 endoscopic ultrasound features. Duodenal degranulated eosinophils and glucagon-like peptide 1 producing cells were estimated by immunostaining. There were no significant differences in characteristics and psychogenic factors between ECP and FD-P patients. Interestingly, endoscopic ultrasound score in ECP patients significantly improved, albeit clinical symptoms in ECP patients showed no improvement at one year follow up. The extent of migration of duodenal degranulated eosinophils in FD-P patients was significantly higher compared to that in ECP patients. The levels of elastase-1 and trypsin in ECP patients with improved endoscopic ultrasound features were significantly reduced by the treatment. Further studies will be needed to clarify whether clinical symptoms and endoscopic ultrasound features in ECP patients without alcoholic chronic pancreatitis were improved in longer follow up study.

High fibrin/fibrinogen degradation product value as a risk factor for progressive remote traumatic intracranial haemorrhage following neurosurgery.

INTRODUCTION: Remote traumatic intracranial haemorrhage (RTIH) may develop after neurosurgery. Recognition of the risk factors for RTIH before surgery might be of great value. The purpose of this study was to verify if the fibrin/fibrinogen degradation product (FDP) value may be a risk factor for RTIH. METHODS: This was a retrospective study of the data of 56 patients with traumatic intracranial hematomas shown on initial computed tomography (CT) who were treated with craniotomy or decompressive craniectomy and underwent a follow-up CT at a single centre over a period of approximately 10.5 years. We divided the patients into 2 groups: those who developed RTIH (Positive: P-group) and those who did not (Negative: N-group). We compared the 2 groups in terms of not only the laboratory data before surgery, but also patient age, sex, antiplatelet/antithrombotic medications received, cause of injury, and GCS score on arrival. RESULTS: RTIH was observed in 22 patients (P-group, 39.3%). The FDP value was the only significant risk factor identified in this study (p = 0.00076). The cut-off value was estimated on the basis of the area under the receiver operating characteristic (ROC) curve. The cut-off FDP value was 120 µg/mL (63.6% sensitivity and 85.3% specificity). CONCLUSIONS: FDP levels over 120 µg/mL were determined to be a risk factor for progressive RTIH after neurosurgery. We suggest the FDP level be checked before surgery for traumatic intracranial haemorrhage and follow-up CT be done as soon as possible after the surgery if the serum FDP level is over 120 µg/mL.

Readministration of Cancer Drugs in a Patient with Chemorefractory Metastatic Colorectal Cancer.

A 63-year-old woman was admitted to our institution for severe pain in her right lower abdomen caused by the perforation of cecal cancer. She underwent emergency surgery, from which she was diagnosed with cecal carcinoma with liver, lung, and lymph node metastases. As she was taking aspirin to prevent cerebral infarction, anti-vascular endothelial growth factor (receptor) antibody and regorafenib therapy were not used. Thus, we started a modified FOLFOX 6+cetuximab regimen. This first-line treatment initially achieved a partial response (PR), but she then developed progressive disease (PD) after 14 months. We changed the regimen to FOLFIRI, followed by trifluridine/tipiracil, but her progression-free survival periods were 2.7 months and 1 month, respectively. Although we cycled through the available array of standard cancer drugs, the patient showed a good performance status, and some benefit from treatment still seemed plausible. We readministered the 5-fluorouracil oral preparation S-1, which maintained stable disease (SD) for 7 months. After PD emerged, we readministered the anti-epidermal growth factor receptor (EGFR) antibody panitumumab for 7.5 months of SD. Finally, 39 months after her diagnosis, she died from rapidly progressing disease. However, her relatively long survival implies that readministering drugs similar to those used in previous regimens might benefit patients with metastatic colorectal cancer.

Acotiamide attenuates central urocortin 2-induced intestinal inflammatory responses, and urocortin 2 treatment reduces TNF-α productions in LPS-stimulated macrophage cell lines.

BACKGROUND: To determine whether central and in vitro administration of urocortin 2 (Ucn 2) affected intestinal inflammatory responses in LPS-stimulated rat models and macrophage cell lines and acotiamide modified mucosal inflammation in this model. METHODS: Rats were divided into four groups. LPS-stimulated group (n = 4); LPS- and urocortin 2-treated group (n = 4); LPS- and acotiamide-treated group (n = 4); and LPS-, urocortin 2-, and acotiamide-treated group (n = 4). CD68-, CCR2-, and corticotropin-releasing hormone receptor type 2 (CRHR2)-positive cells were assessed by immunostaining. Myeloperoxidase (MPO) activity was measured. TNF-α, IL-6, and IL-4 levels were measured by ELISA method. Gastric emptying and small intestinal transit time were determined using Evans blue. KEY RESULTS: Central administration of Ucn 2 significantly aggravated infiltrations of CD68- and CCR2-positive cells in the intestinal mucosa of LPS-stimulated rat models compared to those in LPS treatment alone. Interestingly, acotiamide treatment significantly reduced the migrations of both CD68- and CCR2-positive cells in the jejunum of central Ucn 2-treated LPS-stimulated rat models. Acotiamide significantly reduced the expression levels of IkB-α phosphorylation in LPS- and MCP-1-stimulated NR8383 cells. Central administration of Ucn 2 significantly delayed gastric emptying. In contrast, Ucn 2 stimulation significantly reduced TNF-α and IL-6 productions in LPS-stimulated NR8383 cells and astressin B reversed the inhibition of TNF-α production in stimulated NR8383 cells. Acotiamide (30 µmol/L) significantly reduced TNF-α and IL-6 productions in LPS- and MCP-1-stimulated NR8383 cells. CONCLUSIONS AND INFERENCES: Central and in vitro treatments of Ucn 2 affected intestinal inflammatory responses, respectively, and acotiamide improved them.

Effectiveness of Low-Dose Intravenous Fentanyl for Postoperative Headache Management After Neck Clipping of Ruptured Intracranial Aneurysms.

BACKGROUND: After subarachnoid hemorrhage (SAH), headache management is often difficult owing to the need to use multiple analgesic drugs. Fentanyl is an opioid we can use after surgery, and it can decrease pain post SAH. The aim of this study was to investigate the effectiveness and safety of fentanyl for management of headache after SAH. METHODS: Twenty-two patients who underwent surgical clipping for ruptured intracranial aneurysms and complained of severe headache after the surgery were enrolled. Among them, 9 patients were given fentanyl combined with other analgesic drugs. The numeric rating scale score and dietary intake were measured in the acute phase after the SAH. RESULTS: The numeric rating scale scores were significantly lower in the fentanyl (+) group. The maximum numeric rating scale decreased to <5 points within 16.5 ± 2.9 days in the fentanyl (-) group and within 12.0 ± 2.6 days in the fentanyl (+) group. The median numeric rating scale decreased to <5 points over 14.0 ± 4.2 days in the fentanyl (-) group and >7.7 ± 3.8 days in the fentanyl (+) group. At day 14, the fentanyl (+) group showed significantly better dietary intake than that of the fentanyl (-) group. CONCLUSIONS: Using fentanyl after surgical clipping for ruptured intracranial aneurysms might decrease headache and produce few adverse effects. Adequate headache control showed improved dietary intake after SAH.

Acylated ghrelin levels were associated with depressive status, physical quality of life, endoscopic findings based on Kyoto classification in Japan.

BACKGROUND AND AIMS: To determine whether serum acylated ghrelin levels were associated with anxiety, clinical symptoms, depressive status, quality of life, gastric motility and endoscopic findings based on Kyoto classification in functional dyspepsia (FD) patients. METHODS: We enrolled three groups, FD patients (n = 15) with high levels of acylated ghrelin, FD patients (n = 33) with normal levels of acylated ghrelin and FD patients (n = 35) with low levels of acylated ghrelin. There was no significant differences in the positivity of Helicobacter pylori infection among the three groups. Clinical symptoms were evaluated by Gastrointestinal Symptom Rating Scale (GSRS) and FD symptoms based on Rome III classification. Acylated ghrelin levels were measured by ELISA methods. Depressive status, anxiety, sleep disturbance were respectively asscessed by Self-rating questionnaire for depression (SRQ-D) score, STAI-state/-trait, Pittsburgh sleep quality index (PSQI) scores. Endoscopic findings were evaluated based on Kyoto classification. RESULTS: Body Mass Index (BMI) in FD patients with low levels of acylated ghrelin was significantly higher (p<0.001 and p = 0.008, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. SRQ-D scores in FD patients with low levels of acylated ghrelin was significantly lower (p = 0.008 and p<0.001, respectively) compared to those in FD patients with high and normal levels of acylated ghrelin. Scoring of gastric atrophy, intestinal metaplasia, xanthoma and mucus based on Kyoto classification in FD patients with low levels of acylated ghrelin were significantly higher (p<0.001, p = 0.0077, p = 0.036 and p = 0.0063, respectively) compared to those in FD patients with more than low levels of acylated ghrelin. CONCLUSION: Acylated ghrelin levels were associated with BMI, depressive status, and endoscopic findings based on Kyoto classification in FD patients.

Spinal Cord Infarction in the Region of the Posterior Spinal Artery After Embolization for Vertebral Artery Dissection.

BACKGROUND: Endovascular surgery for vertebral artery dissections (VADs) carries the risk of spinal cord infarction (SCI). Although SCI in the region of the anterior spinal artery (ASA) has been reported, SCI in the region of the posterior spinal artery (PSA) is rare. OBJECTIVE: To investigate PSA infarction after endovascular surgery for VAD. METHODS: Infarction in the region of the PSA after endovascular surgery for VADs carried out in consecutive 21 cases was investigated. The variables of aneurysmal location, status, intra-aneurysmal thrombosis, antithrombotic therapy, and endovascular procedure were investigated in relation to the occurrence of spinal cord or brain stem infarction. RESULTS: Thirteen cases were unruptured aneurysms, and 8, ruptured aneurysms. The endovascular surgical method was internal trapping in 10 cases, stent-assisted coil embolization in 8 cases, and proximal occlusion (PO) in 3 cases. Periprocedural symptomatic infarction was detected in 4 of the 21 cases (19%): 3 SCIs and 1 lower medulla infarction, after 1 stent-assisted coil embolization and 3 PO. All 3 symptomatic SCIs were PSA infarction. On univariate analysis, the variables of posterior inferior cerebellar artery-involved-type, PO, and intraprocedural proximal flow arrest were significantly correlated with occurrence of PSA infarction. CONCLUSION: PSA infarction after endovascular surgery for VAD seems not to be a rare potential complication. Insufficiency of collateral blood flow and artery-to-artery embolism due to intraprocedural flow stagnation of the VA seem to be the possible mechanisms of PSA infarction in addition to previously reported mechanisms such as direct obliteration by the embolic materials and extended thrombosis of the VA stump.

Early retreatment after surgical clipping of ruptured intracranial aneurysms.

BACKGROUND: Although a rerupture after surgical clipping of ruptured intracranial aneurysms is rare, it is associated with high morbidity and mortality. The causes for retreatment and rupture after surgical clipping are not clearly defined. METHODS: From a prospectively maintained database of 244 patients who had undergone surgical clipping of ruptured intracranial aneurysms, we selected patients who experienced retreatment or rerupture within 30 days after surgical clipping. Aneurysm occlusions were examined by microvascular Doppler ultrasonography and indocyanine green video-angiography. Indications for retreatment included rerupture and partial occlusion. We analyzed the characteristics and causes of early retreatment. RESULTS: Six patients (2.5%, 95% CI 0.9 to 5.3%) were retreated within 30 days after surgical clipping, including two patients (0.8%, 95% CI 0.1 to 2.9%) who experienced a rerupture. The retreated aneurysms were found in the anterior communicating artery (AcomA) (n = 5) and basilar artery (n = 1). Retreatment of the AcomA (7.5%) was performed significantly more frequently than that of other arteries (0.56%) (p < 0.01). A laterally projected AcomA aneurysm (17.4%) was more frequently retreated than were other aneurysm types (2.3%). Cases of laterally projecting AcomA aneurysms tended to result from an incomplete clip placed using a pterional approach from the opposite side of the aneurysm projection. CONCLUSIONS: Despite developments, the rates of retreatment and rerupture after surgical clipping remain similar to those reported previously. Retreatment of the AcomA was significantly more frequent than was retreatment of other arteries. Patients underwent retreatment more frequently when they were originally treated for lateral type aneurysms using a pterional approach from the opposite side of the aneurysm projection. The treatment method and evaluation modalities should be considered carefully for AcomA aneurysms in particular.