2- Materials and Methods

3- Results

4- Discussion

5- Conclusions

References

Introduction

Hepatocellular carcinoma (HCC) is the most common primary cancer of the liver [1]. According to the NCCN guidelines, there are numerous strategies for treating HCC, including resection, transplantation, radiofrequency ablation, transarterial chemoembolization (TACE), radiotherapy (RT), and systemic therapy using sorafenib or lenvatinib [2]. All patients with HCC should be evaluated for potential curative therapies, including resection and transplantation [2]. Locoregional therapy, including ablation, TACE, and RT, is indicated for patients who are not candidates for curative therapy or indicated as a bridge therapy for patients who are candidates for transplantation [2]. Recent reports have described favorable clinical outcomes afer proton beam therapy (PBT) for HCC, based on a 5- year overall survival rate of 24–48% [3, 4] and a 5-year local control rate of approximately 80% [3, 5]. Among the external beam RT modalities, PBT may be superior to X-ray therapy based on excellent dose localization to the therapeutic target [1]. Furthermore, given the good outcomes afer PBT for HCC, some patients may be eligible for TACE treatment of intrahepatic HCC metastasis, while repeated PBT, TACE, or systemic therapy may be feasible in cases of local recurrence afer PBT. Moreover, PBT is efective for patients with HCC who also have portal vein tumor thrombus (PVTT) [6], and the efcacy of combined therapy of TACE and RT for HCC with PVTT has been reported [7, 8]. Terefore, given the growing interest in using PBT for HCC, it is possible that TACE could be used for selected patients who have previously undergone PBT. Te purpose of our study is to evaluate the angiographic fndings from patients with HCC previously treated using PBT.

Lower gastrointestinal (GI) bleeding is a frequent cause for hospital admissions with an annual incidence of approximately 20 to 27 cases per 100,000 persons in the United States.1 Morbidity and mortality vary according to the underlying cause of the GI bleed, with reported mortality rates of 2% to 20% for lower GI bleeding and as high as 40% for hemodynamically unstable patients.2 Lower GI bleeding is defined as bleeding that occurs distal to the ligament of Treitz, with upper GI bleeding occurring proximally. Clinical presentations vary based on the source of the bleed and cause; however, acute lower GI bleeds typically present with hematochezia, noting that secondary to the cathartic effects of blood, a brisk upper GI bleed may present in a similar manner.3 Causes of lower GI bleeding may be anatomic, such as diverticulosis (33.5%); vascular, such as hemorrhoids (22.5%), angioectasia, or ischemia; neoplastic (12.7%); inflammatory as with inflammatory bowel disease; or infectious.4 If the workup of the large bowel is negative, then patients are suspected of having a small bowel bleed. There are several classification schemes used to describe lower GI bleeding related to the duration and severity of the bleed as well as the results of upper and lower endoscopy/imaging. When correlating with the amount of bleeding, lower GI bleeds can be categorized as massive, moderate, or occult. Massive bleeding is defined by the passage of profuse hematochezia with hemodynamic instability. Moderate bleeding reflects hematochezia in hemodynamically stable patients. Occult bleeding refers to the presence of a positive fecal-occult blood test or iron deficiency anemia without another identifiable source and without frank hematochezia.5 Obscure bleeding refers to patients who have recurrent bleeding after negative endoscopic evaluation and advanced radiologic assessment of the small bowel and can be either acute or occult.

WORKUP RECOMMENDATIONS FOR ACUTE LOWER GASTROINTESTINAL BLEEDING

The workup of patients presenting with acute lower GI bleeding involves resuscitation, localizing the site of bleeding, and intervention to stop the source of the bleeding, as appropriate. The main tools of the workup include direct visualization with proctoscopy/colonoscopy and imaging with computed tomography angiography (CTA), nuclear scintigraphy, or angiography. Although surgery was once a necessity for patients with ongoing lower GI bleed, advanced techniques in endoscopy and angiography have improved detection and treatment, with surgery now reserved for cases in which more conservative management has failed.6 The clinical presentation of patients during the triaging process as well as the services available at a hospital dictate the order and priority in which tests are used in the workup of an active lower GI bleed.1 Any patient with hemodynamic instability must first be resuscitated. If endoscopy is available, it is generally the first test preformed; however, there are significant limitations. The colon must first be prepped in order to clear enteric contents and blood, which could obscure the source of bleeding. Even rapid bowel preparations take at least several hours, which may not be possible in patients with ongoing bleeding. Additionally, in some series, colonoscopy detects the source of bleeding in only 13% to 40%.2 In cases whereby emergent endoscopy is not indicated, patients will typically be sent for an imaging study, such as CTA, nuclear scintigraphy, or catheter angiography, depending on the local availability and clinical expertise. In patients who are clinically stable at presentation, more conservative management is generally indicated, with many patients being worked up with elective endoscopy.

The fluorescent dye indocyanine green (ICG) has been used clinically to evaluate cardiac output1 and hepatic function and in ophthalmic angiography for more than 3 decades. It shows peak spectral absorption at approximately 830 nm with an excitation wavelength of 800 nm. ICG binds tightly to plasma proteins and lipids and emits fluorescence signals in vascular structures, making it possible to observe blood flow conditions in both arterial and venous structures during vascular neurosurgery under a microscope. ICG has a half-life of 150e180 seconds and is removed from the circulation exclusively by the liver. This brief half-life permits repeat ICG injections and comparisons of blood flow status before and after neurosurgical procedures. The first clinical application of ICG, termed ICG video angiography (ICG-VAG), was described in 2003 by Raabe et al.2 ICG-VAG reveals gray-scale intensity changes in florescence signals over time and is used to confirm complete clipping of aneurysms, apart from patency of branch arteries and bypass grafts. Although currently ICG-VAG provides only qualitative or semiquantitative evaluation, we strongly believe that it is essential to establish quantitative evaluation by analyzing changes in ICG intensity over time. Previously published reports, including those from our laboratory, have suggested possible correlations between some of the parameters related to ICG-VAG analysis and actual blood flow measured with a transit-time flowmeter.3,4 Based on the foregoing factors, we believe that quantitative ICGVAG measurement will have a significant clinical impact in vascular brain surgery. Thus, we designed a 2-step study that consisted of basic experiments and clinical investigations of ICG-VAG to determine optimal parameters for quantitative measurement of blood flow.

Diabetes mellitus affects approximately 422 million individuals worldwide and the global prevalence has nearly doubled since 1980.1 Diabetic retinopathy (DR) is the leading cause of blindness among working-aged adults and affects about 92 million people globally.2 Owing to the systemic nature of the disease, DR affects eyes bilaterally and usually develops in a relatively symmetric pattern over time, although few studies have looked at this directly. Laron et al. investigated the spatial correspondence of abnormal multifocal electroretinogram responses in adolescents with type 1 diabetes and no retinopathy. Their results showed high agreement (68—94%) of inter-ocular correspondence of locations of abnormal multifocal electroretinogram implicit times, suggesting a symmetrical disease process even before the presence of clinically visible DR.3 Iino et al. prospectively followed a cohort of diabetic patients with and without symmetrical DR for the development of brain infarction. While not the main outcome of their study, they reported that only 12 of 142 (8.4%) patients had asymmetric retinopathy.4 Other studies have reported asymmetric DR in 5—10% of patients with proliferative disease.5 There has been increasing interest in peripheral retinal involvement in DR. Predominantly peripheral lesions have been associated with an increased risk of progression of both non-proliferative diabetic retinopathy and of conversion to proliferative disease. Predominantly peripheral lesions are identified by more than 50% of the lesion being located outside the seven standard fields of the Early Treatment Diabetic Retinopathy Study (ETDRS).6 These peripheral lesions are hypothesized to come from underlying capillary non-perfusion.7 Recent technological advances have greatly improved the evaluation of capillary function in the peripheral retina. Compared to standard fluorescein angiography which covers 15% of the retinal surface with the 45 degree images, ultra-widefield fluorescein angiography (UWFA) provides extended peripheral retinal views and covers 82% of the retina with the 200 degree field of view, captured in a single frame.8 The purpose of this study was to evaluate the symmetry of the amount of peripheral retinal nonperfusion in patients with diabetic retinopathy. In this article, we define symmetry as the likeness of the total value of peripheral non-perfusion as measured by ischemic index (ISI) in the right eye compared to the left eye. To our knowledge, no prior studies have reported on this.