The Effect of Renin-Angiotensin System Inhibitors in Patients Undergoing Pancreatic Cancer Resection.

OBJECTIVES: The local renin-angiotensin system promotes angiogenesis and proliferation via vascular endothelial growth factor or epidermal growth factor receptor expression. In this study, we aimed to evaluate the impact of angiotensin system inhibitors (ASIs) on long-term outcomes in patients undergoing surgical resection of pancreatic ductal adenocarcinoma (PDAC). METHODS: A single institutional retrospective analysis was performed using the medical records of patients who underwent pancreatic resection with curative intent for PDAC between January 2005 and December 2018. Patient characteristics and surgical outcomes were compared between patients taking ASIs and those who are not. RESULTS: A total of 272 patients were included in the study and classified into the ASI group (n = 121) and the non-ASI group (n = 151). The median overall survival times in the ASI group and non-ASI group were 38.0 and 34.0 months ( P = 0.250), and the median recurrence-free survival times were 24.0 and 15.0 months ( P = 0.025), respectively. Multivariate analysis for recurrence-free survival identified the use of ASIs ( P = 0.020), CA19-9 level >500 IU/L ( P = 0.010), positive lymph node metastasis ( P < 0.001), and no adjuvant chemotherapy ( P < 0.001) as independent prognostic factors. CONCLUSIONS: The use of ASI may improve long-term outcomes after surgery for PDAC.

Right lateral approach to the superior mesenteric artery in robotic pancreaticoduodenectomy.

Ninomiya and colleagues introduced a novel approach to the superior mesenteric artery in robotic pancreaticoduodenectomy. The right lateral approach allows repositioning of the superior mesenteric artery to the right-most surface, facilitating safer artery division and simplifying detachment around the superior mesenteric vein, potentially reducing operative time and minimizing blood loss.

Probe-based confocal laser endomicroscopy for real-time evaluation of colorectal liver metastasis in resected surgical specimens.

Probe-based confocal laser endomicroscopy (pCLE) enables real-time examination of tissue structure. This study investigated pCLE with or without fluorescein sodium for the intraoperative diagnosis of colorectal liver metastasis (CLM) and detection of surgical margins. Thirty-four specimens of CLM and adjacent noncancerous tissue were obtained from 21 patients and examined by pCLE between May 2017 and March 2018. Images were obtained both without and with fluorescein sodium applied to the cut surface and compared with hematoxylin and eosin-stained tissue. Fluorescence intensity (FI) was measured by luminance-analysis software. Without external fluorophores, pCLE visualized 91.2% of CLM tissues as an irregular structure with low autofluorescence and 90.5% of noncancerous liver tissues as a regular structure with high autofluorescence. The median FI was significantly lower in cancer than in benign tissue in patients without chemotherapy [70.4 (51.6-110) vs. 48.3 (39.0-59.4), p = 0.002] and with chemotherapy [67.9 (54.6-89.2) vs. 48.6 (28.8-82.1), p < 0.001]. The border was clearly visible; pCLE with fluorescein sodium clearly showed their morphologies. In summary, our study demonstrated real-time pCLE distinguished CLM and noncancerous tissue by differences in structure and FI regardless of prehepatectomy chemotherapy. Fluorescein spray facilitated clear visualization of differences in the morphology.

Predicting conversion surgery in patients with locally advanced pancreatic cancer after modified FOLFIRINOX treatment.

BACKGROUND: /Objective: FOLFIRINOX therapy (FFX) for locally advanced pancreatic cancer (LAPC) is increasingly recognized as a potent neoadjuvant therapy that enables transition to conversion surgery (CS). However, predictors of CS achievement after chemotherapy are controversial. This study aimed to demonstrate the efficacy of CS after modified FFX (mFFX) in patients with LAPC and to identify and score predictors of CS. METHODS: From January 2014 to December 2018, patients with LAPC who received mFFX as a first-line treatment were screened. Patients' overall survival was compared with and without CS. Moreover, the predictors for CS were analyzed to create scores for the CS factors. RESULTS: Forty-three patients received mFFX, including 20 patients who underwent CS (CS group, 46.5%). R0 resection was achieved in 16 patients (80%). The median survival time was 39.2 months (95% confidence interval [CI] 17.3-53.8) for the CS group and 16 months (95% CI 10.5-22.6) for the non-CS group (P < 0.001; hazard ratio 0.25, 95% CI 0.12-0.54). Since an average relative dose intensity of ≥90%, tumor reduction of ≥35%, and carbohydrate antigen 19-9 reduction of ≥70% or normalization were associated with successful transition to CS in the multivariate analysis, these factors were scored (CS score, range 0-3). All of the patients in the CS group fell into the 2-3 category, compared with 2 of 23 patients in the non-CS group (P < 0.001). CONCLUSION: CS after FFX contributes to the long-term survival of patients with LAPC. The CS score could be an indicator for transition to CS.

Safety and usefulness of fluorescence imaging using methylene blue as a fluorophore in a Japanese population with hepatobiliary and pancreatic diseases: A phase I study.

BACKGROUND: Methylene blue (MB) has been used to treat methemoglobinemia. Recently, a fluorescence imaging technique using MB as a fluorophore was used in several region but still not in hepatobiliary and pancreatic surgery; thus, information on the safety of intraoperative fluorescence imaging using MB in a healthy Japanese population is lacking. We aimed to evaluate the usefulness of MB fluorescence imaging in patients undergoing hepatobiliary and pancreatic surgery and the safety of intraoperative administration of MB in patients without methemoglobinemia. METHODS: Eighteen patients undergoing hepatobiliary and pancreatic surgery were enrolled. We developed and used a fluorescence imaging system to visualize MB as fluorescence. The fluorescence intensity of the blood vessels, tumors, liver, and intestine were measured. The primary endpoint was the ability of the MB fluorescence imaging to visualize vessels and tumors with fluorescence. The secondary endpoint was the safety of fluorescence imaging using MB in patients without methemoglobinemia. RESULTS: For the 18 patients undergoing MB fluorescence imaging, no intraoperative and postoperative complications related to MB administration occurred. Seventeen patients (94%) successfully visualized the target object as fluorescence by MB fluorescence imaging, including 100% of neuroendocrine tumors (four tumors) and peripancreatic vessels (n = 13). CONCLUSION: The administration of MB and application of fluorescence imaging using MB can visualize blood vessels and pancreatic neuroendocrine neoplasms. And it also showed the safety of using MB as a fluorophore in Japanese patients without methemoglobinemia.

Quantitative Assessment of the Accuracy of Real-Time Virtual Sonography for Liver Surgery.

Background. Real-time virtual sonography (RVS) is a navigation system for liver surgery. In this study, the degree of misalignment of intraoperative RVS images with computed tomographic (CT) images was measured. Methods. Between December 2014 and July 2015, intraoperative RVS was performed in a total of 33 patients undergoing liver surgery. Reconstructed CT images, rendered like intraoperative ultrasonographic (IOUS) images, were adjusted with the IOUS images and visualized side by side. The degree of misalignment between the reconstructed CT images and IOUS images was measured at anterior section, posterior section, and left liver in each patient. Furthermore, the time required for the adjustment was measured as the "adjustment time." Results. The degree of misalignment between the images could potentially be measured for a total of 96 points in the 33 patients. Of these, the actual measurement could not be conducted for 35 points due to poor visualization of the intrahepatic vasculature (n = 20) or to a large misalignment that hampered continuation of further adjustment (n = 15). The median degree of misalignment was 9.8 mm (range = 2.4-37.6 mm) in the right anterior section, 9.8 mm (range = 2.7-71.5 mm) in the right posterior section, and 9.5 mm (range = 0.9-37.6 mm) in the left liver. The median adjustment time was 105 seconds (range = 51-245 seconds). Conclusions. Although some misalignment occurred, it might be acceptable for selected situations. Further investigation is needed to reduce the frequency of adjustment failure.

Ectopic Jejunal Variceal Rupture in a Liver Transplant Recipient Successfully Treated With Percutaneous Transhepatic Coil Embolization: A Case Report.

Here we present the rupture of ectopic jejunal varices developing in a liver transplant recipient without portal hypertension, which was successfully treated with percutaneous transhepatic coil embolization.A 48-year-old man with massive melena was admitted to our department. He had undergone liver transplantation for hepatitis B virus-related liver cirrhosis 8 months before, and his postoperative course was satisfactory except for an acute cellular rejection. No evidence of bleeding was detected by upper endoscopy or colonoscopy, but dynamic multidetector computed tomography of the whole abdomen revealed an intestinal varix protruding into the lumen of the jejunum with suspected extravasation. There was no evidence of portal venous stenosis or thrombosis. Immediately upon diagnosis of the ruptured ectopic jejunal varix, percutaneous transhepatic coil embolization was performed, achieving complete hemostasis. The portal venous pressure measured during the procedure was within normal limits. He was discharged from the hospital 11 days after embolization and remained in stable condition without re-bleeding 6 months after discharge.This is the first report of an ectopic intestinal variceal rupture in an uneventful liver transplant recipient that was successfully treated with interventional percutaneous transhepatic coil embolization. Clinicians encountering liver transplant recipients with melena should be aware of the possibility of late-onset rupture of ectopic varices, even in those having an uneventful post-transplant course without portal hypertension.

[Can cerebral blood flow measurement predict clinical outcome in the acute phase in patients with artherosclerotic occlusive carotid artery disease?].

It has been thought that the clinical course of patients with acute carotid occlusive disease depends on their collateral cerebral blood flow (CBF) and duration of ischemia. However, there have been few clinical reports to prove this hypothesis. Therefore, we performed CBF study in patients with artherosclerotic carotid occlusive disease in the very acute phase, and precisely assessed the prognosis of those patients under intensive medical therapy. This prospective study included a total of 44 patients (72+/-13 years) who were admitted to our hospital between April, 2007 and December, 2008. To evaluate their initial CBF, single photon emission computed tomography (SPECT) studies were performed within 6 hours after the onset. All patients included in this study were medically treated and were periodically followed up by neurological and radiological examination. Moreover, in patients with reduced CBF (ipsilateral CBF/contralateral CBF x 100: %CBF< 80%), dobutamine-induce hyperdynamic therapy was performed. Multivariate analysis was performed to detect significant predictors for the occurrence of further cerebral infarction. Multivariate analysis showed that the occurrence of further infarction was associated with older age and smaller %CBF. Of 44 patients, 21 experienced further cerebral infarction within 10 days after onset. Fourteen out of 15 patients with %CBF< 60% developed cerebral infarction. This study showed that the prognosis of the patients with artherosclerotic carotid occlusive disease in the acute phase is associated with their initial residual CBFs. It may be difficult to stop the developed cerebral infarction in those patients with %CBF< 60% despite intensive medical therapy.

Ruptured aneurysms of the choroidal branches of the posterior inferior cerebellar artery: a review of the literature and a case report.

Aneurysms of the choroidal branches of the posterior inferior cerebellar artery (PICA) are quite rare; only seven such cases have been reported thus far. In this study, we present a very rare case of a ruptured aneurysm of a choroidal branch of the PICA; the aneurysm was exposed by splitting the vermis and resected after proximal arterial ligation. We have also undertaken a thorough review of the literature on aneurysms in choroidal branches of the PICA, focusing on the clinical presentation, etiology, radiological findings, and surgical strategies. We found that the aneurysms in our patient and the aneurysms in seven published case reports were small, and frequently associated with vascular anomalies. Intraventricular hemorrhage (IVH) in the fourth ventricle was detected in all eight cases. The outcomes of surgical treatment were generally favorable, notwithstanding the high incidence of rebleeding after rupture of distal PICA aneurysms. The recognition of predominant fourth ventricular hemorrhage should raise the suspicion of the presence of an underlying aneurysm, and digital subtraction angiograms (DSAs) should be immediately obtained in order to detect small aneurysms of the choroidal branches of the PICA.

[A case of brainstem variant of reversible posterior leukoencephalopathy syndrome].

A rare case of a brainstem variant of reversible posterior leukoencephalopathy syndrome (RPLS) is reported. A 34-year-old man with a past history of untreated chronic renal failure and hypertension was admitted to our hospital complaining of severe nuchal headache lasting for about four days. His neurological examination was normal, however physical examination revealed his blood pressure was 216/120 mmHg. Computed tomography imaging (CT) showed his brain stem with a low attenuation. Magnetic resonance imaging (MRI) revealed extensive hyperintensity and enlargement of the midbrain and pons on T2 weighted and fluid attenuated inversion-recovery (FLAIR) image. However, there was no abnormal lesion seen in either bilateral occipital lobe. Diffusion-weighted image (DWI) was normal at the brainstem, but apparent diffusion coefficient (ADC) values were slightly elevated at the left midbrain. There was no contrast enhancement. His symptom and radiological finding improved soon after his blood pressure was controlled. A repeated MRI taken two weeks later showed complete resolution of the lesion. RPLS associated with predominant involvement of the brainstem and sparing of the supratentorial region is rare, but it should be differentiated from brain stem infarction, pontine glioma, central pontine myelinolysis and infective encephalitis, since the neulological consequences are potentially fully reversible after adequate and prompt treatment.

Expression of immunological molecules by cardiomyocytes and inflammatory and interstitial cells in rat autoimmune myocarditis.

BACKGROUND: In a heart with myocarditis, there are cardiomyocytes, inflammatory cells, and non-inflammatory interstitial cells. Immunological molecules are thought to influence not only inflammatory cells but also cardiac function and remodeling. Whatever their origin, the cells they target and the intercellular crosstalk they mediate remain unclear. Here, we examined native gene expression of immunological molecules in normal and rat experimental autoimmune myocarditis (EAM) 18 and 90 days after immunization, using real time RT-PCR in cardiomyocytes, CD11b(+) cells, alphabetaT cells and non-cardiomyocytic non-inflammatory (NCNI) cells. METHODS AND RESULTS: Cells were isolated by collagenase perfusion on a Langendorff apparatus and purified by passing through a stainless-steel sieve followed by magnetic bead column separation using appropriate monoclonal antibodies. Most immunological molecules were expressed in inflammatory cells. However, some were expressed in NCNI cells or cardiomyocytes. Interestingly, most of interleukin (IL)-10, monocyte chemoattractant protein (MCP)-1, or tumor necrosis factor (TNF)-alpha receptor were found in NCNI cells and most of fractalkine were found in NCNI cells and cardiomyocytes. Moreover, TNF-alpha significantly upregulated fractalkine and MCP-1 mRNA in cultivated cells from EAM hearts. CONCLUSION: In the rat experimental myocarditis heart, inflammatory cells express many immunological molecules. Some of them are thought to influence NCNI cells or cardiomyocytes directly via receptors on these cell types. It is further suggested that fractalkine, IL-10, and MCP-1 expressed in NCNI cells or cardiomyocytes regulate inflammatory cells.

Plasma concentrations of cytokines and neurohumoral factors in a case of fulminant myocarditis successfully treated with intravenous immunoglobulin and percutaneous cardiopulmonary support.

A 53-year-old Japanese man with fulminant myocarditis was referred. Percutaneous cardiopulmonary support (PCPS) was introduced immediately and intravenous immunoglobulin (IVIG) therapy followed for 2 days. Cardiac function showed signs of recovery on the 4th hospital day and the patient was weaned from PCPS on the 7th hospital day. Creatine kinase-MB peaked at 12 h after admission and was 176 ng/ml. Endomyocardial biopsy showed active myocarditis. A marked increase of the neutralizing antibody titer suggested coxsackievirus B3 infection. Plasma concentrations of cytokines and neurohumoral factors were analyzed. Proinflammatory cytokines, such as interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF-alpha), and anti-inflammatory cytokines, such as IL-1 receptor antagonist, soluble TNF receptor-1 and IL-10, were elevated on admission and all had decreased on the 7th hospital day. Brain natriuretic peptide and noradrenaline were already elevated upon admission (1,940 pg/ml and 4.6 ng/ml, respectively) and decreased thereafter. Although IVIG therapy under PCPS is a common treatment for fulminant myocarditis, the immunological response in vivo remains unclear. This case demonstrated suppression of serum cytokines after IVIG and PCPS treatment. Immunological parameters in those who have been treated with IVIG and PCPS and survived without complications are of great value for evaluation of the therapy. Further analysis with more cases in a multicenter study is necessary.