Predictive factors for transition to conversion therapy in hepatocellular carcinoma using atezolizumab plus bevacizumab.

BACKGROUND: To identify predictive factors associated with successful transition to conversion therapy following combination therapy with atezolizumab and bevacizumab in the treatment of unresectable hepatocellular carcinoma (HCC). METHODS: In total, 188 patients with HCC, who received atezolizumab plus bevacizumab combination therapy as the first-line chemotherapy, were studied. Patients who achieved complete response (CR) with systemic chemotherapy alone were excluded. Clinical factors possibly linked to successful transition to conversion therapy and the achievement of cancer-free status were identified. RESULTS: Fifteen (8.0%) patients underwent conversion therapy. In the conversion group, there was a significantly higher proportion of patients with Barcelona Clinic Liver Cancer (BCLC) stage A or B (73.3% versus [vs.] 45.1%; p = .03) and tended to have lower Child-Pugh scores and alpha-fetoprotein levels. Multivariate analysis revealed that BCLC stage was a predictive factor for the implementation of conversion therapy (A or B; odds ratio 3.7 [95% CI: 1.1-13]; p = .04). Furthermore, 10 (66.7%) patients achieved cancer-free status and exhibited a smaller number of intrahepatic lesions at the start of treatment (3.5 vs. 7; p < .01), and a shorter interval between systemic chemotherapy induction and conversion therapy (131 vs. 404 days; p < .01). In addition, the rate of achieving cancer-free status by undergoing surgical resection or ablation therapy was significantly higher (p = .03). CONCLUSION: BCLC stage was the sole predictive factor for successful transition to conversion therapy when using combination therapy with atezolizumab and bevacizumab to treat HCC. Furthermore, a small number of intrahepatic lesions and early transition to conversion therapy were associated with the achievement of cancer-free status.

Association of depression and smoking cessation: outcomes of an 18-year retrospective cohort study.

BACKGROUND: Depression is frequently associated with unsuccessful smoking cessation. OBJECTIVE: In this study, we investigated the impact of depression history on smoking cessation success in a clinical setting. METHODS: This retrospective study included 726 patients who visited our smoking cessation clinic between January 1, 2001, and December 31, 2018. Kaplan-Meier analyses and Cox proportional hazards regression models were used to perform univariate and multivariate analyses of smoking cessation success factors. RESULTS: Among the 726 patients, 76 had a history of depression and demonstrated significantly lower 12-week quit rate compared to those without (33.6% vs. 69.6%, p < .001). Multivariate Cox analysis revealed a significant association between abstinence rate and history of depression (hazard ratio 2.251, 95% CI 1.505-3.315, p < .001), history of schizophrenia (hazard ratio 2.716, 95% CI 1.427-4.840, p = .003), and Fagerström Nicotine Dependence Test scores (hazard ratio 1.519, 95% CI 1.053-2.197, p = .025). CONCLUSIONS: Our findings suggested that a history of depression is a significant prognostic factor for smoking cessation, underscoring the need for targeted interventions for patients with a history of depression. The findings of this study are subject to potential selection bias due to recruitment from a single hospital, which may limit the generalizability of our results. This study highlights the necessity for novel, specialized smoking cessation therapies to support patients with a history of depression in their cessation journey.

Surgical Management of Giant Unruptured Left Sinus of Valsalva Aneurysm With Severe Aortic Regurgitation.

Left sinus of Valsalva aneurysms are extremely rare. Concomitant aortic valve regurgitation is a comorbidity in this pathology. This case report summarizes successful surgical treatment with aortic root replacement with a modified Bentall procedure in a 49-year-old female patient who had an unruptured huge left sinus of Valsalva aneurysm with severe aortic valve regurgitation. The intraoperative assessment showed severe adhesion between the left main trunk of the coronary artery and the left sinus of Valsalva aneurysm, and meticulous adhesion detachment was required.

Successful Medical Treatment for Aortoesophageal Fistula after Thoracic Endovascular Aortic Repair.

Aortoesophageal fistula is a fatal disease that requires surgical treatment. Due to the patient's wishes, we chose medical treatment for aortoesophageal fistula after thoracic endovascular aortic repair for a pseudoaneurysm in the distal anastomotic site after total aortic arch replacement. Satisfactory early and long-term outcomes were obtained with complete fasting and appropriate antibiotics.

Posterior mitral leaflet augmentation with autologous pericardial patch for the surgical treatment of severe atrial functional mitral regurgitation.

Atrial functional mitral regurgitation (MR) in patients with chronic atrial fibrillation has not been thoroughly discussed. Although there is insufficient evidence to surgically treat atrial functional MR, it is considered to be reasonable for those patients with severe atrial functional MR who have symptoms of heart failure despite adequate medical therapy. Herein, we report a useful technique for mitral valve repair using posterior mitral leaflet (PML) augmentation with autologous pericardium to obtain good mitral valve coaptation and eliminate atrial functional MR, including tethered PML, in a nonelderly patient.

Acute Limb Ischemia Caused by Embolus of Primary Lung Cancer Complicating Trousseau's Syndrome.

Limb ischemia caused by tumor embolus is rare. In this study, we report the case of a 77-year-old woman who suffered from acute ischemic limb. Computed tomography showed a tumor in the right bronchus invading the left atrium. The tumor fragments scattered resulting in the occlusion of the right iliac artery. The excluded embolus was revealed as a squamous cell carcinoma. Regarding the popliteal venous thrombus, Trousseau's syndrome was complicated. The patient was discharged without any complications. We believe that advanced lung cancer is a differential diagnosis of acute ischemic limbs and that successful limb rescue contributed to a patient's quality of life.

Reconstruction for rupture of profunda femoris artery aneurysm in a patient with sarcopenia.

Profunda femoris artery aneurysm (PFAA) is rare and has a high incidence of rupture. Herein, we report the case of an 80-year-old man who developed sarcopenia after gastric surgery. The patient presented to our hospital with a reddish thigh and was diagnosed with PFAA rupture. We performed aneurysmectomy and graft interposition in emergency. Postoperative enhanced computed tomography revealed an interposed graft, and the patient was discharged on postoperative Day 7. We considered that the PFAA patients with sarcopenia has a high risk of rupture because the muscles surrounding the profunda femoris artery became weak, and should be followed-up closely.

Nutritional supplement drink reduces inflammation and postoperative depression in patients after off-pump coronary artery bypass surgery.

BACKGROUND: Coronary artery bypass grafting is a surgical treatment for ischemic heart disease. Although development in surgical technique and improvement of perioperative management reduced the postoperative complications, some patients still delayed in progress of postoperative rehabilitation. In this study, we aimed to investigate the effect of daily intake of an herbal medicine-containing drink for rehabilitation after surgery in patients with ischemic heart disease. AIM: To investigate the effect of taking an herbal medicine-containing, commercially available drink for postoperative rehabilitation in those patients. METHODS: Patients who underwent isolated off-pump coronary artery bypass (OPCAB) surgery were divided into two groups depend on the timing of the admission to the hospital: the Yunker (YKR) group, that consumed one bottle of a caffeine-free nutritional supplement drink on a daily basis and the control group (CTL) that underwent regular rehabilitation. RESULTS: A total of 229 patients (CTL = 130, YKR = 99) were enrolled. No significant differences were observed in the baseline characteristics between the two groups. The YKR group had a significantly increased number of daily steps postoperatively (P < 0.05) and had significantly lower postoperative serum tumor necrosis factor-alpha levels (P < 0.01), while no significant differences were observed in the levels of other inflammatory or stress-related cytokines (interleukin-6, adiponectin, superoxide dismutase, and urine 8-hydroxy-2'-deoxyguanosine) between the two groups. Also, the YKR group showed a significant improvement in the Hospital Anxiety and Depression Score (P < 0.05). Moreover, there were no differences in postoperative complications and the duration of postoperative hospital stay between the two groups. CONCLUSION: Our results demonstrated that the daily intake of an herbal medicine-containing drink after OPCAB surgery may have beneficial effects on cardiac rehabilitation by reducing inflammation markers and depression.

Randomized controlled study to examine the efficacy of hepatic arterial infusion chemotherapy with cisplatin before radiofrequency ablation for hepatocellular carcinoma.

AIM: Hepatic arterial infusion chemotherapy (HAIC) with cisplatin is beneficial to patients with advanced hepatocellular carcinoma (HCC) treated with sorafenib. This study aimed to examine the effect of HAIC with cisplatin before radiofrequency ablation (RFA) in patients with HCC. METHODS: This was a multicenter, single-blinded, randomized controlled study (UMIN000007267). Early-stage HCC patients were randomly assigned (1:1) to receive HAIC with cisplatin before RFA therapy (HAIC group) or RFA monotherapy (non-HAIC group). The primary end-point was recurrence-free survival. Efficacy analysis and safety analysis followed the intention-to-treat principle. RESULTS: Between August 2012 and July 2016, 74 patients were recruited. A total of 70 eligible patients were randomly assigned to the HAIC group (n = 35) and non-HAIC group (n = 35). Recurrence-free survival rates at 1 (3) year in the HAIC group and non-HAIC group were 82.9% (54.3%) and 74.3% (34.3%), respectively (hazard ratio [HR], 0.597; 95% confidence interval [CI], 0.320-1.091; p = 0.094]. Subgroup analysis showed that the beneficial effect of HAIC was observed in patients with a single nodule and Child-Pugh score 5. Intrahepatic distant recurrence-free survival rate in the HAIC group was significantly better than that in the non-HAIC group (HR, 0.468; 95% CI, 0.235-0.896; p = 0.022). Adverse events were observed in just two patients in the HAIC group (6%) - grade 2 cholecystitis and grade 2 hyperkalemia. CONCLUSIONS: HAIC with cisplatin before RFA did not significantly decrease recurrence in patients with early-stage HCC. However, it might be effective in preventing intrahepatic distant recurrence.

Changes in polysomnographic findings following transcatheter aortic valve implantation in a patient with aortic stenosis.

Patients with aortic stenosis (AS) are likely to have sleep-disordered breathing (SDB) and improvements in AS by transcatheter or surgical aortic valve replacement alter the type and severity of SDB. However, limited data are available whether polysomnographic findings changed following transcatheter aortic valve implantation (TAVI). In this report, we describe the case of a patient with severe AS and SDB whose polysomnographic findings showed that after TAVI, sleep disturbances occurred in association with worsened periodic leg movements despite improvement in the SDB. .

The Efficacy and Safety of Steroids for Preventing Postembolization Syndrome after Transcatheter Arterial Chemoembolization of Hepatocellular Carcinoma.

Steroids are often administered at the time of transcatheter arterial chemoembolization (TACE), a standard treatment of hepatocellular carcinoma (HCC), with the expectation of preventing postembolization syndrome. Here we investigated the precise effects of steroids on TACE. We prospectively enrolled 144 HCC patients from 10 hospitals who underwent TACE. Three hospitals used steroids (steroid group, n=77) and the rest did not routinely use steroids (control group, n=67). The occurrence of adverse events and the algetic degree at 1-5 days post-treatment were compared between the groups. Fever (grades 0-2) after TACE was significantly less in the steroid group (56/21/0) compared to the control group (35/29/3, p=0.005, Cochran-Armitage test for trend). The suppressive effect of steroids against fever was prominent in females (p=0.001). Vomiting (G0/G1/ G2-) was also less frequent in the steroid group (70/5/2) versus the control group (53/10/3), but not significantly (p=0.106). The algetic degree and the grade of hematological adverse events, including hyperglycemia, did not differ between the groups. We conclude that the administration of steroids was useful for the prevention of adverse events after TACE in patients with HCC.

Time-dose response of oxygen delivery during cardiopulmonary bypass predicts acute kidney injury.

OBJECTIVE: Previous studies have reported that nadir oxygen delivery during cardiopulmonary bypass is associated with the occurrence of postoperative acute kidney injury (AKI). However, these measurements only considered the bottom point of the oxygen delivery (DO2) but did not consider the duration of DO2. We aimed to examine whether the time-dose response of DO2 during cardiopulmonary bypass can be used to estimate the risk for postoperative AKI. METHODS: We evaluated 112 patients who underwent cardiac surgeries with cardiopulmonary bypass. We analyzed the perfusion parameters recorded every 20 seconds. To obtain time-dose response of DO2 index (DO2i), the area under the curve was calculated as below the 300 mL/min/m2 threshold, which accounts for depth and duration of cumulative oxygen debt. In addition, the cumulative time below DO2i 300 mL/min/m2 was also calculated. Receiver operating characteristic analysis, univariate regression analysis, and multivariate regression analysis were used to evaluate associations between perioperative variables and postoperative AKI. RESULTS: Patients who developed AKI had larger area under the curve below the 300 mL/min/m2 threshold (1581 vs 632; P < .01) and cumulative time below DO2i 300 mL/min/m2 (34.7 vs 15.3 minutes; P < .01). Nadir DO2i was not significantly different between the non-AKI and AKI groups (263.4 vs 247.0 mL/min/m2; P = .291). CONCLUSIONS: The time-dose response of DO2i during cardiopulmonary bypass is a better indicator than nadir DO2i in evaluating AKI risk. Maintaining DO2i levels >300 mL/min/m2 may result in decreased risk for postoperative AKI.

Villous atrophy in the terminal ileum is a specific endoscopic finding correlated with histological evidence and poor prognosis in acute graft-versus-host disease after allo-hematopoietic stem cell transplantation.

BACKGROUND: Graft-versus-host disease (GVHD) is a common complication of allo-hematopoietic stem cell transplantation (allo-HSCT). Endoscopic biopsy can provide a definitive diagnosis, but the optimal endoscopic approach for diagnosis remains uncertain. This study evaluated whether ileocolonoscopic imaging can predict acute GVHD severity after allo-HSCT. METHODS: Consecutive patients who underwent allo-HSCT were referred to our institution, and those diagnosed with acute GVHD by pathology were included in this retrospective study. RESULTS: Fifty-one of 261 patients who underwent ileocolonoscopy were suspected to have acute intestinal GVHD. We performed univariate and multivariate conditional logistic regression with stepwise variable selection; villous atrophy in the terminal ileum remained a statistically significant predictor of GVHD severity (odds ratio, 4.69; 95% confidence interval, 1.07-20.60, P = 0.04). Patients were classified into three groups based on ileal endoscopic findings in the terminal ileum: group S, GVHD with severe villous atrophy; group M, mild atrophy; and group N, no atrophy. Compared with patients in groups M and N, those in group S had significant clinical GVHD at diagnosis (P = 0.03). In group S, three of four, compared with five of 13 patients in groups M and N, required the addition of second-line agents (P = 0.02). CONCLUSIONS: This study showed that severe atrophy of the terminal ileum predicts severe clinical GVHD that is likely to be refractory to steroid treatment. Thus, the severity of terminal ileum atrophy may serve as a tool in predicting clinically severe GVHD. TRIAL REGISTRATION: Trial Registration Number UMIN 000022805 , Registration date July 1, 2016.

Independent Effect of Low Flow on Outcomes in Patients Undergoing Aortic Valve Replacement for Severe Aortic Stenosis.

BACKGROUND: Low flow (LF; i.e., reduced left ventricular stroke volume index <35 mL/m2) can occur with severe aortic stenosis (AS). However, few studies have investigated the effects of LF on early and late outcomes after aortic valve replacement (AVR) for severe AS.Methods and Results:In all, 285 severe AS patients undergoing isolated AVR at Juntendo University Hospital between August 2002 and August 2015 were enrolled in the study. In this cohort, 52 patients (18%) had LF. Compared with patients with normal flow (NF) severe AS, early postoperative mortality (9.6% vs. 1.2%; P=0.006), gastrointestinal complications (5.7% vs. 0.8%; P=0.04), and the duration of the intensive care unit (ICU) stay (81.7 vs. 35.3 h; P=0.02) were increased in LF patients with severe AS. LF was an independent predictor of early mortality (Model A, odds ratio [OR] 6.81, P=0.01; Model B, OR 6.69, P=0.01) and composite complications (Model A, OR 2.44, P=0.02). In propensity score-matched comparisons, early mortality (12.8% vs. 0%; P=0.02), composite complications (28.2% vs. 10.2%; P=0.04), and duration of ICU stay (97.4 vs. 22.1 h; P=0.006) were significantly increased in LF than NF patients. CONCLUSIONS: LF, as an important independent risk factor for postoperative mortality and morbidity, should be included in risk stratification and assessment in severe AS patients.

Bleeding in patients who underwent scheduled second-look endoscopy 5 days after endoscopic submucosal dissection for gastric lesions.

BACKGROUND: Bleeding after endoscopic submucosal dissection (ESD) in antithrombotic drug users is still one of the important issues to be solved. We performed scheduled second-look endoscopy (SLE) 5 days after ESD, when the resumption of antithrombotic agents is assumed to have achieved a steady state, rather than on the day after ESD. We investigated bleeding incidence and the status of ulcers. METHODS: A total of 299 lesions in 299 patients subjected to ESD for gastric neoplasms were enrolled. A double dose of proton pump inhibitors was administered after ESD. SLE was planned 5 days after ESD. Post-ESD bleeding occurring before SLE was defined as early phase post-ESD bleeding, whereas bleeding after SLE was defined as later phase post-ESD bleeding. Forrest IIa and IIb ulcers are defined as high-risk ulcers requiring prophylactic hemostasis. We investigated risk factors for post-ESD bleeding, particularly focusing on the use of antithrombotic agents and the presence of high-risk ulcers requiring prophylactic hemostasis during SLE. RESULTS: Under a double dose of proton pump inhibitors, early phase post-ESD bleeding occurred in 2.3% of non-users (5/218) and 6.2% of users of antithrombotic agents (5/81). High-risk ulcers were found in 19.0% of the cases during scheduled SLE (55/289). Later phase bleeding occurred in 5.5% of cases [2.8% of non-users (6/213) and 13.2% of users of antithrombotic agents (10/76)]. Cox regression analysis revealed that the risk factor for post-ESD bleeding was antithrombotic treatment (HR: 3.56; 95% CI: 1.63-8.02, p = 0.002) alone. Among patients with high-risk ulcers, a statistically significant increase in bleeding was observed in the later phase in patients under antithrombotic therapy, compared to those not receiving any antithrombotic agents (p = 0.001). CONCLUSIONS: Antithrombotic treatment is a risk factor for post-ESD bleeding despite SLE being scheduled 5 days after ESD. Later phase post-ESD bleeding was observed in 13.2% of the patients under antithrombotic treatment even after prophylactic hemostasis for high-risk ulcers. TRIAL REGISTRATION: This study was registered in the UMIN Clinical Trials Registry System ( 000023306 ). Retrospectively registered on 23rd July 2016.

Transcatheter Arterial Chemoembolization to Reduce Size of Hepatocellular Carcinoma before Radiofrequency Ablation.

Transcatheter arterial chemoembolization (TACE) is often performed before radiofrequency ablation (RFA) for the treatment of early-stage hepatocellular carcinoma (HCC). TACE prior to RFA can expand the ablated area and reduce the tumor size, facilitating complete ablation. However, the factors correlated with size reduction remain uncertain. The aim of this study was to identify the factors associated with size reduction by TACE and develop a formula to predict the reduction rate. A total of 100 HCC patients treated with TACE followed by RFA at least 20 days later were enrolled. The tumor size was measured at the time of TACE and RFA, and correlations between the reduction rate and 13 clinical factors were examined. A formula to predict the reduction rate was built using the factors obtained by the analysis. Reduction in the tumor size was observed in 69 nodules, and the median reduction rate was 16.2%. A multivariate regression analysis revealed that a large tumor size (p< 0.01) and a long interval between the therapies (p= 0.01) were factors for a high tumor reduction rate, with tumor size more strongly related to the degree of reduction. A size reduction of more than 10% can be expected by waiting 20 days after TACE when the size of the tumor at TACE is over 25 mm in diameter. The tumor size.

[Aortic Root Replacement for Patients with Aortic Root Aneurysms;Clinical Outcomes Compared Among Different Types of Abnormality and Operative Procedures].

Aortic root operations are established procedures for patients with aortic root aneurysms, however there is a little insight for comparative long-term outcomes among different types of anatomical abnormalities and procedures. In this study, we sought to compare the results of patients with aortic abnormalities undergoing different procedures. From January 2008 to March 2017, a total of 105 patients without aortic dissection were performed the elective aortic root surgery. Patients with bicuspid aortic valve had enlarged annulus, and those with Marfan syndrome had enlarged Valsalva without enlarged annulus. Bentall operation with mechanical valve or bioprothetic valve was performed for patients with enlarged annulus and/or abnormal aortic cusp, and David operations for patients with normal cusps. This comparative study showed that these different procedures according to our policy were associated with reduced cardiac mortality and valve-related complications. The results suggest David procedure is the treatment of choice for young patients with aortic root aneurysm and normal aortic cusps, however, careful patient selection is paramount.

Factors for C-Kit Expression in Cardiac Outgrowth Cells and Human Heart Tissue.

We determined the factors associated with the expression of c-kit in the heart and the proliferation of c-kit-positive (c-kitpos) cardiac stem cells among the outgrowth cells cultured from human cardiac explants.Samples of the right atrium (RA), left atrium (LA), and left ventricle obtained from patients during open-heart surgery were processed for cell culture of outgrowth cells and tissue analysis. The total number of growing cells and the population of c-kitpos cells were measured and compared with c-kit expression in native tissues and characteristics of the patients according to the region of the heart.We analyzed 452 samples from 334 patients. Atrial fibrillation (AF) in the patients reduced the number of outgrowth cells from the RA and LA, and aging was a co-factor for the LA. The c-kitpos population from the RA was associated with serum brain natriuretic peptide (BNP). C-kit expression in native tissue was also associated with BNP expression. However, we observed no relationship in expression between outgrowth cells and native tissue. In addition, the RA tissue provided the highest number of c-kitpos cells, and the left ventricle provided the lowest.C-kit was weakly expressed in response to damage. In addition, no correlation between outgrowth cells and native tissue was found for c-kit expression.