Renal and Vascular Effects of Combined SGLT2 and Angiotensin-Converting Enzyme Inhibition.

BACKGROUND: The cardiorenal effects of sodium-glucose cotransporter 2 inhibition (empagliflozin 25 mg QD) combined with angiotensin-converting enzyme inhibition (ramipril 10 mg QD) were assessed in this mechanistic study in patients with type 1 diabetes with potential renal hyperfiltration. METHODS: Thirty patients (out of 31 randomized) completed this double-blind, placebo-controlled, crossover trial. Recruitment was stopped early because of an unexpectedly low proportion of patients with hyperfiltration. Measurements were obtained after each of the 6 treatment phases over 19 weeks: (1) baseline without treatment, (2) 4-week run-in with ramipril treatment alone, (3) 4-week combined empagliflozin-ramipril treatment, (4) a 4-week washout, (5) 4-week combined placebo-ramipril treatment, and (6) 1-week follow-up. The primary end point was glomerular filtration rate (GFR) after combination treatment with empagliflozin-ramipril compared with placebo-ramipril. GFR was corrected for ramipril treatment alone before randomization. At the end of study phase, the following outcomes were measured under clamped euglycemia (4 to 6 mmol/L): inulin (GFR) and para-aminohippurate (effective renal plasma flow) clearances, tubular sodium handling, ambulatory blood pressure, arterial stiffness, heart rate variability, noninvasive cardiac output monitoring, plasma and urine biochemistry, markers of the renin-angiotensin-aldosterone system, and oxidative stress. RESULTS: Combination treatment with empagliflozin-ramipril resulted in an 8 mL/min/1.73 m2 lower GFR compared with placebo-ramipril treatment (P=0.0061) without significant changes to effective renal plasma flow. GFR decrease was accompanied by a 21.3 mL/min lower absolute proximal fluid reabsorption rate (P=0.0092), a 3.1 mmol/min lower absolute proximal sodium reabsorption rate (P=0.0056), and a 194 ng/mmol creatinine lower urinary 8-isoprostane level (P=0.0084) relative to placebo-ramipril combination treatment. Sodium-glucose cotransporter 2 inhibitor/angiotensin-converting enzyme inhibitor combination treatment resulted in additive blood pressure-lowering effects (clinic systolic blood pressure lower by 4 mm Hg [P=0.0112]; diastolic blood pressure lower by 3 mm Hg [P=0.0032]) in conjunction with a 94.5 dynes × sex/cm5 lower total peripheral resistance (P=0.0368). There were no significant changes observed to ambulatory blood pressure, arterial stiffness, heart rate variability, or cardiac output with the addition of empagliflozin. CONCLUSIONS: Adding sodium-glucose cotransporter 2 inhibitor treatment to angiotensin-converting enzyme inhibitor resulted in an expected GFR dip, suppression of oxidative stress markers, additive declines in blood pressure and total peripheral resistance. These changes are consistent with a protective physiologic profile characterized by the lowering of intraglomerular pressure and related cardiorenal risk when adding a sodium-glucose cotransporter 2 inhibitor to conservative therapy. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT02632747.

Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure.

BACKGROUND: Sodium-glucose cotransporter 2 (SGLT2) inhibitors reduce the risk of hospitalization for heart failure in patients regardless of the presence or absence of diabetes. More evidence is needed regarding the effects of these drugs in patients across the broad spectrum of heart failure, including those with a markedly reduced ejection fraction. METHODS: In this double-blind trial, we randomly assigned 3730 patients with class II, III, or IV heart failure and an ejection fraction of 40% or less to receive empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. The primary outcome was a composite of cardiovascular death or hospitalization for worsening heart failure. RESULTS: During a median of 16 months, a primary outcome event occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio for cardiovascular death or hospitalization for heart failure, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P<0.001). The effect of empagliflozin on the primary outcome was consistent in patients regardless of the presence or absence of diabetes. The total number of hospitalizations for heart failure was lower in the empagliflozin group than in the placebo group (hazard ratio, 0.70; 95% CI, 0.58 to 0.85; P<0.001). The annual rate of decline in the estimated glomerular filtration rate was slower in the empagliflozin group than in the placebo group (-0.55 vs. -2.28 ml per minute per 1.73 m2 of body-surface area per year, P<0.001), and empagliflozin-treated patients had a lower risk of serious renal outcomes. Uncomplicated genital tract infection was reported more frequently with empagliflozin. CONCLUSIONS: Among patients receiving recommended therapy for heart failure, those in the empagliflozin group had a lower risk of cardiovascular death or hospitalization for heart failure than those in the placebo group, regardless of the presence or absence of diabetes. (Funded by Boehringer Ingelheim and Eli Lilly; EMPEROR-Reduced ClinicalTrials.gov number, NCT03057977.).

Direct oral anticoagulants increase bleeding risk after endoscopic sphincterotomy: a retrospective study.

BACKGROUND: Bleeding can be a serious adverse event of endoscopic sphincterotomy (EST). However, the risk of EST bleeding between direct oral anticoagulant (DOAC) users and those who received no antithrombotic agents has not been clarified. This study analyzed the risk factors for bleeding after EST in patients on DOAC and evaluated the Japan Gastroenterological Endoscopy Society (JGES) guidelines for gastroenterological endoscopy in patients undergoing antithrombotic treatment. METHODS: We retrospectively analyzed 524 patients treated with EST who received DOAC or no antithrombotic drug from May 2016 to August 2019. We investigated the risk factors for bleeding. DOAC was typically discontinued for ≤ 1-day based on the JGES guideline. Although DOAC therapy recommenced the next morning after EST in principle, the duration of DOAC cessation and heparin replacement were determined by the attending physician based on each patient's status. RESULTS: The number of patients on DOAC (DOAC group) and those not on antithrombotic drug (no-drug group) was 42 (8.0%) and 482 (92.0%), respectively. DOAC was discontinued for ≤ 1-day in 17 (40.0%) patients and for > 1-day in 25 (60.0%). Of the 524 patients, 21 (4.0%) had EST bleeding. The bleeding rate was higher in the DOAC group (14.0%) (p = 0.004). Multivariate analysis showed that bleeding occurred more frequently in patients on DOAC (odds ratio [OR] 3.95, 95% confidence interval [CI] 1.37-11.4, p = 0.011), patients with low platelet counts (< 100,000/µl) (OR 6.74, 95% CI 2.1-21.6, p = 0.001), and elderly patients (> 80 years old) (OR 3.36, 95%CI 1.17-9.65, p = 0.024). CONCLUSIONS: DOAC treatment, low platelet count, and old age (> 80 years old) are risk factors for EST bleeding. Although the bleeding incidence increased in patients on DOAC who received antithrombotic therapy according to the JGES guidelines, successful hemostasis was achieved with endoscopy in all cases, and no thrombotic events occurred after cessation of DOAC. Thus, the JGES guidelines are acceptable.

Clinical and endoscopic features of aorto-duodenal fistula resulting in its definitive diagnosis: an observational study.

BACKGROUND: Upper gastrointestinal (GI) bleeding is the most important presentation of an aorto-duodenal fistula (ADF). Early diagnosis is difficult, and the disease is associated with high mortality. The present study aimed to examine the clinical and the endoscopic characteristics of ADF in eight patients who presented to our hospital. We also sought to clarify the diagnostic approach towards the disease. METHODS: The present study examined the clinical and the endoscopic/computed tomography (CT) characteristics of ADF in eight patients who were definitively diagnosed with this condition in a 12-year period at our hospital. RESULTS: The patients comprised of five men and three women, with a mean age of 69.8 years. Upper gastrointestinal bleeding was the chief complaint for all the patients. Out of these, two patients presented with shock. The patients' mean haemoglobin at presentation was 7.09 g/dL, and the mean number of blood transfusions was 7.5. All patients had undergone intervention to manage an aortic pathology in the past. As the first investigation, an upper GI endoscopy in 5 and a CT scan in 3 patients were performed. In cases where CT scan was performed first, no definitive diagnosis was obtained, and the diagnosis was confirmed by performing an upper GI endoscopy. In cases where endoscopy was performed first, definitive diagnosis was made in only one case, and the other cases were confirmed by the CT scan. In some cases, tip attachments, converting to long endoscopes, and marking clips were found useful. CONCLUSIONS: In patients who have undergone intervention to manage an aortic pathology and have episodes of upper gastrointestinal bleeding, ADF cannot be definitively diagnosed with only one investigation. In addition, when performing upper GI endoscopy in cases where an ADF is suspected, tip attachment, converting to a long endoscope, and using marking clips can be helpful.

A suspected case of serum IgG4-negative type 1 autoimmune pancreatitis detected due to localized pancreatic duct narrowing: a case report.

A 50-year-old woman was referred to our hospital with elevated serum amylase levels. Physical examination revealed no jaundice or abdominal tenderness. Serum IgG4 was negative. Computed tomography revealed a localized pancreatic duct narrowing in the pancreatic head, with caudal pancreatic duct dilation and an intraductal papillary mucinous neoplasm. Pancreatic enlargement was not observed. Endoscopic ultrasonography (EUS) showed a small hypoechoic mass. Although EUS-guided, fine-needle aspiration was performed, no diagnosis was established. Endoscopic retrograde pancreatography showed a localized narrowing in the main pancreatic duct of the pancreatic head. A biopsy of the narrowing was performed through the minor papilla because of difficult access from the major papilla. The specimen showed the infiltration of numerous IgG4-positive plasma cells, suggesting type 1 autoimmune pancreatitis (AIP). Six months later, magnetic resonance cholangiopancreatography revealed improvement in the narrowing without specific treatment. The patient presented with localized narrowing of the pancreatic duct and caudal duct dilation, which was distinct from pancreatic cancer. Diagnostic difficulties arose from negative serum IgG4 results, the lack of typical imaging characteristics of AIP, and failure to meet the AIP criteria according to the relevant Japanese and international guidelines. However, AIP was suspected and surgery was successfully avoided through a biopsy.

Difficulty in the diagnosis of pancreatic cancer based on the initial CT report: A retrospective study.

The role of computed tomography (CT) in the initial diagnosis of pancreatic cancer (PC) is well-known. CT reports made by radiologists are important as not all patients with PC are examined by specialists; however, some cases are not identified based on CT reports. Diagnosis via imaging of PC is sometimes difficult, and the diagnostic rate of PC and other pancreatic diseases can vary across radiologists. This study aimed to examine the diagnostic rate of PC in initial CT reports and the details of cases with diagnostic difficulties. This single-centered, retrospective study collected clinical data of 198 patients with histologically diagnosed PC between January 2018 and April 2022. Out of these contrast-enhanced CT was performed in 192 cases. PC was not reported as the main diagnosis in 18 patients (9.4%; 11 men and 7 women). Among these 18 cases, intrapancreatic mass lesions were detected in 3 (1.6%), indirect findings such as bile/pancreatic duct stenosis or dilation were detected in 5 (2.6%), and no PC-related findings were found in 10 (5.2%). The specialists suspected PC in 15 of these 18 cases based on initial CT reports. 17 cases were confirmed by endoscopic ultrasound-fine needle aspiration and one by biopsy after upper gastrointestinal endoscopy. To improve accuracy of its diagnosis, it is important that specialists provide feedback to diagnostic radiologists regarding the findings they did not report. Endoscopic ultrasound-fine needle aspiration should be performed by specialists when there is clinical information which indicates pancreatic disease of any kind.

Phlegmonous Colitis after Cold Snare Polypectomy in an Immunosuppressed Patient: A Case Report.

Introduction: Cold snare polypectomy (CSP) is a procedure with a low risk of complications. Here, we present our experience of a rare case of submucosal abscess following CSP in an immunosuppressed patient. Case Presentation: Seventy-eight-year-old man underwent CSP, developing a fever, chills, and right lower abdominal pain 8 days later. Ultrasound and computed tomography revealed wall thickening of the ascending colon, presenting as whitening and thickening of the same region, and excretion of pus was observed after biopsy. The diagnosis was made as phlegmonous colitis, for which antibiotic therapy was commenced. The patient was diagnosed with chronic myelomonocytic leukemia (CMML) during admission. We considered the following reasons as possible causes of infectious complications after CSP: (1) the patient had a highly immunosuppressed state with comorbidities such as CMML as well as diabetes mellitus and (2) disruption of the mucosal barrier occurred during endoscopic resection. Conclusion: Although CSP is generally considered safe, our case highlights the potential for serious complications in immunosuppressed patients. Therefore, the decision to perform CSP in such patients should be made with caution to avoid unnecessary interventions. In instances where treatment is essential, thorough bowel preparation and prophylactic antibiotic use may be necessary to mitigate the risks.

Efficacy of Short-Course Antibiotic Therapy for Acute Cholangitis With Positive Blood Cultures: A Retrospective Study.

BACKGROUND: Short-term treatment of acute cholangitis is sufficient for cure compared with the standard treatment duration. Whether this short-course antimicrobial therapy is effective in patients with acute cholangitis with positive blood cultures has not been fully investigated. This study assessed whether patients with acute cholangitis could achieve successful outcomes with a three-day or shorter antimicrobial treatment period, even with a positive blood culture. METHODS: This single-center retrospective study involved patients with acute cholangitis, defined according to the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a seven-day or shorter antimicrobial treatment. Patients were categorized into six groups based on the duration of antibiotic use (short or standard) after endoscopic retrograde cholangiopancreatography and blood culture findings (positive, negative, or no collection). The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 after biliary drainage and no recurrence or death by day 30. Secondary outcomes included a three-month recurrence rate and length of hospital stay. RESULTS: In total, 389 cases were selected, and 27 patients (6.9%) undergoing short-course therapy tested positive for blood culture. The clinical cure rate (n=25, 92.6%) in this group was comparable to that in the other groups. For the three-month recurrence rate (n=1, 3.7%) and median hospital stay (six days), this group's outcomes were either better or similar to those of the other groups. CONCLUSIONS: For cases of successful drainage in acute cholangitis, even with positive blood cultures, short-term antibiotic therapy may be appropriate.

Antimicrobial therapy outcomes in acute cholangitis: Hilar multiple obstructions versus single hilar and common bile duct obstructions.

Background and Aim: The appropriate duration of antimicrobial therapy for acute cholangitis (AC) arising from multiple hilar biliary obstructions as opposed to simple obstruction in the extrahepatic bile duct has not been established. This study assessed the efficacy of the duration of antimicrobial treatments in the Tokyo Guidelines 2018 for AC based on the cause and site of obstruction. Methods: This single-center retrospective study involved patients with AC who underwent successful biliary drainage and completed a 7-day or shorter antimicrobial treatment. Patients were categorized into three groups: Group 1, bile duct stone or benign obstruction; Group 2, simple biliary obstruction due to malignancy; and Group 3, multiple hilar biliary obstruction due to malignancy. The primary outcome was clinical cure rate, and the secondary outcomes were 3-month recurrence rate and length of hospital stay. Results: A total of 373 patients were selected. Patients in Group 3 were younger or had Charlson Comorbidity Index ≥4, and had fewer positive blood cultures. In Group 3, the clinical cure rate (87.1%) and 3-month recurrence rate (32.3%) were less favorable than those in the other groups. In Group 1, the clinical cure rate was significantly higher (98.1%, P = 0.02) with a much lower 3-month recurrence rate of only 3.4% (P < 0.001) than that in the other groups. The median hospital stay for all groups was 7 days. Conclusion: This study suggests that the outcomes in Group 3 may be worse than those in Groups 1 or 2, regardless of the duration of the antibiotic treatment.

Association of short-course antimicrobial therapy and bacterial resistance in acute cholangitis: Retrospective cohort study.

Background and study aims Although the number of resistant bacteria tends to increase with prolonged antimicrobial therapy, no studies have examined the relationship between the duration of antimicrobial therapy and increase in the number of resistant bacteria in acute cholangitis. We hypothesized that the short-term administration of antimicrobial agents in acute cholangitis would suppress bacterial resistance. Patients and methods This was a single-center, retrospective, observational study of patients with acute cholangitis admitted between January 2018 and June 2020 who met the following criteria: successful biliary drainage, positive blood or bile cultures, bacteria identified from cultures sensitive to antimicrobials, and subsequent cholangitis recurrence by January 2022. The patients were divided into two groups: those whose causative organisms at the time of recurrence became resistant to the antimicrobial agents used at the time of initial admission (resistant group) and those who remained susceptible (susceptible group). Multivariate analysis was used to examine risk factors associated with the development of resistant pathogens. Multivariate analysis investigated antibiotics used with the length of 3 days or shorter after endoscopic retrograde cholangiopancreatography (ERCP) and previously reported risk factors for the development of bacterial resistance. Results In total, 89 eligible patients were included in this study. There were no significant differences in patient background or ERCP findings between the groups. The use of antibiotics, completed within 3 days after ERCP, was associated with a lower risk of developing bacterial resistance (odds ratio, 0.17; 95% confidence interval, 0.04-0.65; P =0.01). Conclusions In acute cholangitis, the administration of antimicrobials within 3 days of ERCP may suppress the development of resistant bacteria.

Comparison of antimicrobial therapy termination in febrile and afebrile patients with acute cholangitis after drainage.

The standard treatment duration for acute cholangitis (AC) involves a 4-7-day antimicrobial treatment post-biliary drainage; however, recent studies have suggested that a ≤ 2-3 days is sufficient. However, clinical practice frequently depends on body temperature as a criterion for discontinuing antimicrobial treatment. Therefore, in this study, we assessed whether patients with AC can achieve successful outcomes with a ≤ 7-day antimicrobial treatment, even with a fever, assuming the infection source is effectively controlled. We conducted a single-center retrospective study involving patients with AC, defined following the Tokyo Guidelines 2018 for any cause, who underwent successful biliary drainage and completed a ≤ 7-day antimicrobial treatment. Patients were categorized into the febrile and afebrile groups based on their body temperature within 24 h before completing antimicrobial treatment. The primary outcome was the clinical cure rate, defined as no initial presenting symptoms by day 14 post-biliary drainage without recurrence or death by day 30. The secondary outcome was a 3-month recurrence rate. Logistic regression with inverse probability of treatment weighting was used. Overall, 408 patients were selected, among whom 40 (9.8%) were febrile. The two groups showed no significant differences in the clinical cure and 3-month recurrence rates. Notably, the subgroups limited to patients with a ≤ 3-day antibiotic treatment duration also showed no differences in these outcomes. Therefore, our results suggest that discontinuing antibiotics within the initially planned treatment period was sufficient for successful drainage cases of AC, regardless of the patient's fever status during the 24 h leading up to termination.

White gastric mucosa during endoscopy as a new endoscopic feature of chronic ischemic gastritis: A case report.

Chronic ischemic gastritis (CIG) requires early diagnosis and treatment as complications of thromboembolism can be fatal. Although computed tomography (CT) is useful in the diagnosis of CIG, it is difficult to diagnose from a patient's history, endoscopic findings, and tissue biopsy. Identification of the key findings that motivate computed tomography is an important issue. We report a case of CIG diagnosed by endoscopic findings of white patches of mucosa over time. A 63-year-old man presented with epigastric pain. He had a history of repeated gastric ulcers of an undetermined cause. We performed upper endoscopy and observed the appearance of multiple white patches on the gastric mucosa. Central vessel stenosis was considered, and aortic computed tomography revealed complete occlusion of the superior mesenteric artery and stenosis of the celiac artery. We carried out a surgical bypass and found no postoperative endoscopic mucosal changes or abdominal pain. White patch changes in the gastric mucosa over time during endoscopy may indicate CIG. This finding may help in the future diagnosis of CIG.

A case of unsuccessful obliteration of percutaneous transhepatic gastric varices using the IMPEDE embolization plug.

Key Clinical Message: Embolization with IMPEDE embolization plug cannot be confirmed on site. Therefore, we propose that the diameter of the device selected be up to 50% larger than the vein diameter to prevent embolization failure and recanalization. Abstract: Balloon-occluded retrograde transvenous obliteration and percutaneous transhepatic obliteration (PTO) are performed for treating sporadic gastric varices. IMPEDE embolization plug has been recently developed for these procedures; however, no studies have reported its use. This is the first report on its use in PTO of gastric varices.

Comprehensive review on endoscopic ultrasound-guided tissue acquisition techniques for solid pancreatic tumor.

Pancreatic ductal adenocarcinoma is speculated to become the second leading cause of cancer-related mortality by 2030, a high mortality rate considering the number of cases. Surgery and chemotherapy are the main treatment options, but they are burdensome for patients. A clear histological diagnosis is needed to determine a treatment plan, and endoscopic ultrasound (EUS)-guided tissue acquisition (TA) is a suitable technique that does not worsen the cancer-specific prognosis even for lesions at risk of needle tract seeding. With the development of personalized medicine and precision treatment, there has been an increasing demand to increase cell counts and collect specimens while preserving tissue structure, leading to the development of the fine-needle biopsy (FNB) needle. EUS-FNB is rapidly replacing EUS-guided fine-needle aspiration (FNA) as the procedure of choice for EUS-TA of pancreatic cancer. However, EUS-FNA is sometimes necessary where the FNB needle cannot penetrate small hard lesions, so it is important clinicians are familiar with both. Given these recent dev-elopments, we present an up-to-date review of the role of EUS-TA in pancreatic cancer. Particularly, technical aspects, such as needle caliber, negative pressure, and puncture methods, for obtaining an adequate specimen in EUS-TA are discussed.

Endoscopic Papillary Balloon Dilation Can Be Safely Performed in Patients on Dual Antiplatelet Therapy: A Pilot Study.

BACKGROUND AND AIMS: Endoscopic papillary balloon dilation (EPBD), a low-risk procedure for bleeding, has been suggested as an alternative to endoscopic sphincterotomy for papillary dilatation in patients undergoing endoscopic stone removal who are at a higher risk of bleeding. Several guidelines recommend that combination of two antiplatelet agents should be reduced to single antiplatelet therapy when endoscopic sphincterotomy is performed. However, there is no evidence that EPBD affects the risk of bleeding in patients receiving a combination of two antiplatelet agents; thus, we aimed to explore this problem. METHODS: We included 31 patients who underwent EPBD for common bile duct stones at our hospital from May 2014 to August 2022 and received either a combination of two antiplatelet agents or single antiplatelet therapy prior to the procedure. The group receiving a combination of two antiplatelet agents included patients who underwent EPBT without antiplatelet therapy withdrawal or with a shorter withdrawal period than those recommended by the guidelines. RESULTS: In the group that received a combination of two antiplatelet agents, one of the two antiplatelet agents used was thienopyridine. No bleeding was observed after EPBD in this study. We did not find any significant between-group differences in hemoglobin levels and rate of post-endoscopic retrograde cholangiopancreatography pancreatitis. CONCLUSIONS: In patients treated with a combination of two antiplatelet agents, EPBD could be safely performed without bleeding. Therefore, future prospective studies are warranted.

Exploration of predictors associated with bleeding in computed tomography-guided core needle splenic biopsy: A retrospective study.

Splenic diseases may be caused by infections and can be either malignant, such as lymphoma and lung cancer, or benign, such as hemangioma. In some cases, diagnostic uncertainty of imaging persists, and image-guided splenic needle biopsy is a useful diagnostic tool to avoid the disadvantages of incorrect diagnosis, including performing unnecessary splenectomy or not giving the necessary treatment. Splenic biopsies can be divided into ultrasound-guided, computed tomography (CT)-guided fine-needle aspiration, or core needle biopsy (CNB). However, few studies have focused exclusively on complications associated with CT-guided CNB of the spleen. Therefore, we assessed bleeding, the most common complication of CT-guided CNB of the spleen, and evaluated factors associated with the bleeding. Using the biopsy database maintained at the institution, all patients who underwent CT-guided CNB of the spleen between May 2012 and September 2022 were identified retrospectively. The 18 identified patients were divided into post-biopsy bleeding and non-bleeding groups for analysis. In total, 17 patients (94.4%) could be diagnosed accurately with CT-guided CNB. Bleeding complications occurred in 7 cases of CT-guided CNB; of these, 2 patients with Common Terminology Criteria for Adverse Events grade 4 disease required transcatheter arterial embolization. The bleeding group was characterized by diffuse spleen tumors in all cases, with significantly more diffuse spleen tumors than the non-bleeding group. CT-guided CNB is a useful option for neoplastic lesions of the spleen that are difficult to diagnose using imaging alone. However, consideration should be given to post-biopsy bleeding in patients with diffuse splenic tumors.