Aplicabilidad y resultados del trasplante hepático combinado con quimiorradioterapia neoadyuvante en el tratamiento del colangiocarcinoma perihiliar irresecable

BackgroundIn 2007, a multicenter protocol was developed in Catalonia, Spain, combining neoadjuvant chemoradiotherapy and liver transplantation (LT) for those patients with unresectable hilar cholangiocarcinoma (hCCA).AimTo analyse the effectiveness of the neoadjuvant chemoradiotherapy and LT for those patients enrolled in the protocol based on intention-to-treat.MethodsObservational multicenter study which includes patients ≤ 68 years-old diagnosed with unresectable, solitary tumors ≤ 3 cm in radial diameter, without evidence of lymph node metastases. The protocol was based on a strategy of neoadjuvant therapy with high-dose radiation (45 Gy in total) plus intravenous fluorouracil (5-FU) given as a daily bolus for the first 3 days of radiation follow by oral capecitabine until transplantation. The patient was included in waiting list for LT if no evidence of disseminated disease was found.ResultsBetween 2007 and 2018, 13 patients were enrolled in the transplant protocol. Of those, 61% (8/13) of the patients were transplanted. The average time spent on the waiting list was 122 days (range 5-192). Intent-to-treat survival was 69% and 39% at one and 5 years. Post-transplantation overall survival was 87% and 62% and 29% recurrence rate at 5 years.ConclusionThe suitability of the neoadjuvant chemoradiotherapy and LT protocol was 61% in our series with long-term overall survival and should be considered as an alternative to resection for patients with localized node-negative hCCA.     

不可切除的肝门部胆管癌的治疗进展

肝门部胆管癌（hCCA）是位于二级肝管与胆囊管开口之间的胆管上皮起源的恶性肿瘤,又称为Klatskin瘤。手术是hCCA唯一潜在的治愈性方法。切缘性质是行切除手术的患者获得长期生存最关键的因素,而作为胆管癌最常见的亚型,hCCA的病理学类型多为低-中分化腺癌,侵袭能力强,恶性程度高,早期症状不明显且无有效的检出手段,所以多数患者在诊断时已处于疾病晚期,丧失手术指征。虽然新辅助放化疗联合原位肝移植已经被证实是部分局部晚期不可切除的hCCA的有效治疗方式,但纳入标准严格,肝源短缺,部分患者在等待肝源的期间肿瘤进展,失去移植条件,因此该治疗方式无法成为大多数患者的治疗方案。传统的放化疗虽然在一定程度上延长了不可切除hCCA患者的生存时间,但其治疗效果始终有限。有研究表明新辅助放化疗能够将部分不可切除的hCCA降期为可切除,提高R₀切除率,但相关数据较少且陈旧,缺乏可信度。随着科技的进步,包括立体定向放疗、三维适行放疗、放射粒子植入等在内的新型放疗技术和光动力疗法的出现,hCCA的局部治疗进入了更加精准的时代。近年来,随着基因检测的发展和对肿瘤微环境的深入研究,在分子生物学层面抑制肿瘤进展是各种实体肿瘤研究的热门方向,针对不同靶点的靶向药物、免疫检查点抑制剂（PD1/PD-L1抗体、CTLA4抗体）层出不穷,并取得了突飞猛进的进展,为不可切除的hCCA的治疗提供了新的方向。但就目前的研究来看,靶向治疗、免疫治疗虽然在肝内胆管癌的治疗中取得了相当不错的成绩,但是在hCCA治疗中的表现仍令人不满意。不可切除的hCCA的单一治疗效果较差,多种治疗方式联合治疗是当前研究的重点。本文主要综述不可切除的hCCA的治疗进展及新辅助治疗在实现R₀切除方面的可行性,旨在为此类患者的治疗提供一定的参考。     

Mixed Hepatocellular Cholangiocarcinoma: A Review of Long-Term Outcomes Following Liver Transplantation

Introduction

Mixed hepatocellular cholangiocarcinoma (HCC-CC) represents a rare hepatic tumor, which demonstrates histological features of both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CC). HCC-CC can be an unexpected finding in patients undergoing liver transplantation (LT) for HCC. The objective of our review was to review and evaluate long-term outcomes in patients undergoing LT for mixed HCC-CC.

Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer

Background:

Following neoadjuvant chemoradiotherapy (CRT) and interval proctectomy, 15–20 per cent of patients are found to have a pathological complete response (pCR) to combined multimodal therapy, but controversy persists about whether this yields a survival benefit. This systematic review evaluated current evidence regarding long‐term oncological outcomes in patients found to have a pCR to neoadjuvant CRT.

Methods:

Three major databases (PubMed, MEDLINE and the Cochrane Library) were searched. The systematic review included all original articles reporting long‐term outcomes in patients with rectal cancer who had a pCR to neoadjuvant CRT, published in English, from January 1950 to March 2011.

Results:

A total of 724 studies were identified for screening. After applying inclusion and exclusion criteria, 16 studies involving 3363 patients (1263 with pCR and 2100 without) were included (mean age 60 years, 65·0 per cent men). Some 73·4 per cent had a sphincter‐saving procedure. Mean follow‐up was 55·5 (range 40–87) months. For patients with a pCR, the weighted mean local recurrence rate was 0·7 (range 0–2·6) per cent. Distant failure was observed in 8·7 per cent. Five‐year overall and disease‐free survival rates were 90·2 and 87·0 per cent respectively. Compared with non‐responders, a pCR was associated with fewer local recurrences (odds ratio (OR) 0·25; P = 0·002) and less frequent distant failure (OR 0·23; P < 0·001), with a greater likelihood of being alive (OR 3·28; P = 0·001) and disease‐free (OR 4·33, P < 0·001) at 5 years.

Conclusion:

A pCR following neoadjuvant CRT is associated with excellent long‐term survival, with low rates of local recurrence and distant failure. Copyright © 2012 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Pregnancy Outcomes After Liver Transplantation: A Systematic Review

Purpose

Liver transplantation (LT) constitutes a major therapeutic option for a number of patients suffering from liver pathologies. Pregnancy outcomes in patients who have undergone LT are assessed by a number of studies. The aim of our systematic review was to present the currently available evidence concerning the results of pregnancy in patients with LT.

Split-thickness skin graft donor-site morbidity: A systematic literature review

The purpose of this systematic literature review is to critically evaluate split-thickness skin graft (STSG) donor-site morbidities. The search of peer-reviewed articles in three databases from January 2009 to July 2019 identified 4271 English-language publications reporting STSG donor-site clinical outcomes, complications, or quality of life. Of these studies, 77 met inclusion criteria for analysis. Mean time to donor-site epithelialization ranged from 4.7 to 35.0 days. Mean pain scores (0–10 scale) ranged from 1.24 to 6.38 on postoperative Day 3. Mean scar scores (0–13 scale) ranged from 0 to 10.9 at Year 1. One study reported 28% of patients had donor-site scar hypertrophy at 8 years. Infection rates were generally low but ranged from 0 to 56%. Less frequently reported outcomes included pruritus, wound exudation, and esthetic dissatisfaction. Donor-site wounds underwent days of wound care and were frequently associated with pain and scarring. Widespread variations were noted in STSG donor-site outcomes likely due to inconsistencies in the definition of outcomes and utilization of various assessment tools. Understanding the true burden of donor sites may drive innovative treatments that would reduce the use of STSGs and address the associated morbidities.     

Abdominal aortic aneurysms (AAA) post heart transplantation: a systematic review of literature

Peripheral vascular disease is highly prevalent post heart transplantation (HTx). The prevalence of abdominal aortic aneurysms (AAA) post HTx ranges from 1.1-10%. We performed a Pub Med, EMBASE and Cochrane review search to identify articles on AAA post HTx. Data gathered from published data included: risk factors, progression of the aneurysm and clinical outcomes. Five studies were included in the systematic review. Baseline demographic data, clinical characteristics, data on AAA prevalence and characteristics, the treatment strategies and follow up were extracted from each of these studies. Our systematic review showed that the prevalence of AAA post HTx ranged from 2-10% in the retrospective studies and 6.5% in a single prospective study. Rupture rates during a follow up period ranged from 11-38% and during that time period the mean aneurysmal expansion rate ranged from 0.78±0.41 cm/yr to 1.2±0.4 cm/yr. Male gender, ischemic heart disease, corticosteroid use, smoking and improved hemodynamics and ejection fraction post HTx were reported as possible associated risk factors in the development of AAA. Open surgical management was the treatment of choice although endovascular treatment was used in a minority of patients. AAA is increasingly prevalent post HTx and may be associated with greater rupture and expansion rates. Meticulous follow up and further prospective clinical studies are warranted to determine risk factors, expansion rates and clinical outcomes.     

Treatment of hepatocellular carcinoma with macroscopic vascular invasion: A systematic review and network meta-analysis

BackgroundThis study aimed to evaluate the outcomes of different treatments for patients with hepatocellular carcinoma (HCC) and macroscopic vascular invasion.MethodsA systematic review and meta-analysis of comparative studies was performed to evaluate various treatment modalities for HCC with macroscopic vascular invasion, including liver resection (LR), liver transplantation (LT), transarterial chemoembolization (TACE), transarterial radioembolization (TARE), radiotherapy (RT), radiofrequency ablation (RFA), and antineoplastic systemic therapy (AnST).ResultsAfter applying the selection criteria, 31 studies were included. The surgical resection (SR) group (including LR and LT) had a similar mortality rate to the non-surgical resection (NS) group (RD = −0.01; 95% CI -0.05 to 0.03). The SR group had a higher rate of complications (RD = 0.06; 95% CI 0.00 to 0.12) but a higher 3-year overall survival (OS) rate than the NS group (RD = 0.12; 95% CI 0.05 to 0.20). The network analysis revealed that the overall survival was lower in the AnST group. LT and LR had similar survival benefits. The meta-regression suggested that SR has a greater impact on the survival of patients with impaired liver function.DiscussionMost likely, LT has a significant impact on long-term survival and consequently would be a better option for HCC with macroscopic vascular invasion in patients with impaired liver function. LT and LR offer a higher chance of long-term survival than NS alternatives, although LR and LR are associated with a higher risk of procedure-related complications.     

Neoadjuvant therapy in the treatment of hilar cholangiocarcinoma:Review of the literature

Cholangiocarcinoma(CCA) is a malignant tumor of the biliary system and includes, according to the anatomical classification, intra hepatic CCA(iCCA),hilar CCA(hCCA) and distal CCA(dCCA). Hilar CCA is the most challenging type in terms of diagnosis, treatment and prognosis. Surgery is the only treatment possibly providing long-term survival, but only few patients are considered resectable at the time of diagnosis. In fact, tumor's extension to segmentary or subsegmentary biliary ducts, along with large lymph node involvement or intrahepatic metastases, precludes the surgical approach. To achieve R0 margins is mandatory for the disease-free survival and overall survival. In case of unresectable locally advanced hCCA, radiochemotherapy(RCT) as neoadjuvant treatment demonstrated to be a therapeutic option before either hepatic resection or liver transplantation. Before liver surgery, RCT is believed to enhance the R0 margins rate. For patients meeting the Mayo Clinic criteria, RCT prior to orthotopic liver transplant(OLT) has proved to produce acceptable 5-years survivals. In this review, we analyze the current role of neoadjuvant RCT before resection as well as before OLT.     

Impact of neoadjuvant chemoradiation on the tumor burden before liver transplantation for unresectable cholangiocarcinoma

The very early experience with liver transplantation (LT) for cholangiocarcinoma (CC) was dismal because of the poor survival outcomes and the high recurrence rates. However, LT for CC in conjunction with neoadjuvant chemoradiation recently has shown encouraging results, although the data are extremely limited. At our institution between 2001 and 2008, 22 CC patients underwent protocol orthotopic LT at a median age of 45 years (range = 24-63 years). At a median follow-up of 601.5 days (range = 111-1388 days), the median survival time of the cohort was 3.3 years. The 1-, 2-, and 3-year Kaplan-Meier survival probabilities were 90%, 70%, and 63%, respectively, whereas the historical 5-year survival rates were 0% to 18% for intrahepatic CC and 23% to 26% for extrahepatic CC when patients underwent transplantation without neoadjuvant therapy. These encouraging survival rates for patients with this type of tumor, which is difficult to diagnose and treat, are no less significant when they are compared to the national 1- and 3-year survival rates (86% and 68%, respectively) of patients undergoing deceased donor LT for malignant neoplasms of the liver (as reported by the United Network for Organ Sharing). In our series, disease recurrence was significantly associated with a larger residual tumor [6.3 versus 2.0 cm (mean values), P = 0.008] and with a shorter waiting time for LT after the chemoradiation protocol [18 versus 56 days (mean values), P = 0.04]. Our LT protocol for CC was found to be promising for patients with truly extrahepatic CC and for patients within stages I to IIB of the American Joint Committee on Cancer Staging system (100% survival at a median follow-up of 2.2 years), but the results were notably poor for patients with stage III extrahepatic CC (median survival = 1.2 years). These observations highlight the need for accurate preoperative staging of CC for ideal LT recipient selection and the importance of a low tumor burden and a longer wait after neoadjuvant therapy. More effective chemoradiation regimens for reducing the tumor burden and the appropriate timing of LT after neoadjuvant chemoradiation require further research.     

Current status of liver transplantation for cholangiocarcinoma

Cholangiocarcinoma (CCA) is the second most common liver cancer with a median survival of 12-24 mo without treatment. It is further classified based on its location into intrahepatic CCA (iCCA), perihilar CCA (pCCA), and distal CCA. Surgical resection is the mainstay of treatment, but up to 70% of these tumors are inoperable at the time of diagnosis. CCA was previously an absolute contraindication for liver transplantation (LT) due to poor outcomes primary due to early recurrent disease. However, improvement in patient selection criteria and neoadjuvant treatment protocols have improved outcomes for inoperable pCCA patients with recent studies reporting LT may improve survival in iCCA. Future advances in the treatment of CCA should include refining patient selection criteria and organ allocation for all subtypes of CCA, determining effective immunotherapies and the evolving role of personalized medicine in patients ineligible for surgical resection or LT. Our article reviews the current status of LT in CCA, along with future directions in managing patients with CCA.     

Long-term outcomes of metabolic and bariatric surgery in adolescents with severe obesity with a follow-up of at least 5 years: A systematic review

The practice of metabolic and bariatric surgery for adolescents with severe obesity has been increasing, and evidence of the outcomes in the long term remains unclear. The aim of this study was to review and analyze the outcomes of this therapy in adolescents with a follow-up ≥5 years. MEDLINE, EMBASE, and Cochrane databases were systematically searched. Inclusion criteria were 10- to < 20-year-old adolescents, 5 years minimum of follow-up, and a retention rate ≥70% at 5 years of follow-up. Adiposity indicators outcomes, co-morbidity remission, and complications were analyzed. A total of 10 studies met the inclusion criteria. Surgeries performed included gastric bypass, gastric band, and sleeve gastrectomy. The age of the participants ranged from 13 to 17 years. The longest follow-up after intervention was 156 months. Mean body mass index at baseline and follow-up was 47 and 32.4 kg/m 2 , respectively. Most of the studies reported weight regain within 1 to 12 years of follow-up. Remission rate of co-morbidities was 75% for dyslipidemia, 78% for musculoskeletal problems, 85% for hypertension, and 85% for type 2 diabetes. Not all studies stated that they were looking for all complications. Iron deficiency and anemia were high, ranging from 30% to 70% and 16% to 50%, respectively. The review indicates that there is low to moderate evidence that metabolic and bariatric surgery in adolescents with severe obesity after 5 years of follow-up results in substantial reduction in body mass index, and very low to low evidence in the resolution of related co-morbidities. Although long-term complications were inadequately reported or nonreported, a high prevalence of iron deficiency and anemia was found. Because maternal anemia might be implicated in deleterious effects for offspring, monitoring female patients for anemia after metabolic and bariatric surgery is strongly recommended. Further high-quality studies with long-term follow-up are warranted to assess related co-morbidities and long-term complications.     

Long-term outcomes of Roux-en-Y gastric diversion after failed surgical fundoplication in a large cohort and a systematic review

BackgroundRoux-en-Y gastric diversion (RNYG) is an alternative approach for patients with persistent or recurrent gastroesophageal reflux disease (GERD) after surgical fundoplication, especially in patients with esophageal dysmotility or morbid obesity, because redo fundoplication could offer unfavorable outcomes.ObjectiveTo evaluate long-term outcomes of RNYG for failed fundoplication and its impact on esophageal function.SettingA retrospective cohort study and a systematic review.MethodsPatients who underwent RNYG after failed fundoplication between 1995 and 2019 were identified. Surgical-related complications, GERD, dysphagia, and endoscopic and esophageal manometric findings were reviewed. A literature search for relevant studies was performed from several databases from database inception to September 2019.ResultsA total of 101 patients (mean age, 52.1 yr; 86.1% female; mean body mass index, 35.8 kg/m²) were included. Overall complication rates within and more than 30 days after surgery were 36.3% and 53.5%. GERD symptoms were resolved in 70.1% after RNYG. However, 39.7% had a recurrence during a median follow-up of 56.2 months. In patients with no baseline dysphagia (n = 36), 16 (44%) developed new-onset dysphagia after surgery. In patients with severe baseline dysphagia (n = 9), 5 patients (56%) had persistent dysphagia after surgery. Seven studies involving 381 patients were included in our systematic review. High rates of GERD improvement have been reported across studies; however, long-term GERD, dysphagia, and objective outcomes were infrequently reported.ConclusionRNYG is an effective alternative surgery in a subset of patients with intractable symptoms who failed fundoplication. However, patients should be informed of the risks of postoperative GERD symptoms and dysphagia. Referral for a careful evaluation by a multidisciplinary foregut team is warranted.     

Reconstruction of the perineum following extralevator abdominoperineal excision for carcinoma of the lower rectum: a systematic review

Aim An improvement in oncological outcome has been reported following an extralevator approach to abdominoperineal excision (ELAPE) for low rectal carcinoma. A larger perineal defect following ELAPE and the impact of neoadjuvant radiotherapy are sources of considerable morbidity for patients. We report an evidence‐based systematic review of published data on the outcome of perineal reconstruction following ELAPE for low rectal carcinoma, comparing the use of tissue flap and biological mesh techniques. Method A literature search was performed of electronic databases including the Medline, Embase and Scopus databases (1995–2011). Studies describing outcomes relating to the perineum following ELAPE were included for review. Results Eleven small cohort studies reported the outcome relating to the perineum following ELAPE. Pooled‐analysis of 255 combined patients undergoing flap repair and 85 undergoing biological mesh repair showed no significant difference in the rates of perineal wound complications or perineal hernia formation. Conclusion There is little information on the optimal technique of perineal wound closure following ELAPE. With the limited data available, there was no significant difference in complication rates between biological mesh and flap repair. There is a need for high‐quality prospective trials to compare methods of reconstruction to determine the long‐term results, quality of life and function.     

Deferred cytoreductive nephrectomy in the management of metastatic renal cell carcinoma: A systematic review and meta-analysis

Deferred cytoreductive nephrectomy (dCN) after upfront systemic therapy has been utilized in the management of select patients with metastatic renal cell carcinoma (mRCC). Herein, we sought to review the current evidence and define oncologic and perioperative outcomes associated with deferred surgical management of newly diagnosed mRCC. Our objective was to critically evaluate the role of dCN in the targeted and immunotherapy eras, comparing oncologic and perioperative outcomes between dCN and upfront CN. Medline, OVID, and Scopus databases were searched for studies evaluating patients undergoing dCN following systemic therapy (ST). PRISMA guidelines were referenced and followed. Outcomes of interest included overall survival (OS), progression free survival (PFS), percent of patients proceeding to dCN, reduction in primary tumor size, complication rates, and perioperative mortality. Random effects meta-analysis was performed comparing overall survival between dCN vs. ST alone and dCN vs. upfront CN. Nineteen studies were included to assess the primary outcomes. The percent of patients proceeding to planned dCN after planned pre-surgical ST ranged from 60.5% to 84%. The most common reason for not undergoing dCN was disease progression on upfront ST. Of patients undergoing dCN, 76% to 96% were able to resume ST postoperatively. OS and PFS ranged from 12.4 to 46 months and 4.5 to 11 months, respectively. Pooled results demonstrated significantly improved OS favoring dCN over upfront CN (hazard ratio, HR = 0.56; 95% CI 0.45–0.69) and ST alone (HR = 0.45; 95% CI 0.38–0.53). Deferred CN represents a potential treatment option in appropriately selected patients with mRCC with a favorable response to upfront systemic therapy. Future randomized trials will be needed to clarify how much this is due to the surgery vs. patient selection.     

Response to preoperative chemoembolization correlates with outcome after liver transplantation in patients with hepatocellular carcinoma.

Patients with small hepatocellular carcinoma (HCC) can be cured by liver transplantation (LT). However, many patients drop out during the waiting time as a result of tumor progression. We prospectively investigated the effect of transarterial chemoembolization on long-term survival of 116 patients with HCC listed for LT. Intention-to-treat analysis revealed that patients with either complete or partial response to therapy (no vital tumor or devascularization of > or =30%, respectively) as assessed by computed tomographic scan before LT had far better 1-, 2-, and 5-year survival rates (100, 93.2, and 85.7%; and 93.8, 83.6, and 66.2%, respectively) compared with those with no response or with tumor progression (82.4, 50.7, and 19.3%). Posttransplant survival analysis showed a marked survival benefit according to transarterial chemoembolization response: patients with complete or partial response had 1-, 2-, and 5-year survival rates of 89.1, 85.1, and 85.1%, and 88.6, 77.4, and 63.9%, respectively, compared with 68.6, 51.4, and 51.4% for patients whose disease did not respond to therapy. Subgroup analysis, however, showed that these benefits were only seen in patients whose disease met the Milan criteria, but not in disease exceeding the Milan criteria but fitting the expanded University of California at San Francisco criteria. These patients were also more likely to drop out as a result of tumor progression while waiting for LT (dropout rate 12.1 vs. 2.9%) and to develop recurrent HCC (21.6 vs. 7.6%). Downstaged patients did even worse, with a dropout rate of 26.7% and a 5-year survival rate of only 25%. In conclusion, the response to preoperative chemoembolization may predict long-term outcome after LT.     

Review of long-term complications and functional outcomes of ileoanal pouch procedures in patients with inflammatory bowel disease

Background

In medically refractory Ulcerative Colitis (UC), proctocolectomy with ileoanal pouch procedure (IAPP) is the preferred continence-preserving surgical option. Functional outcomes post-surgery and long-term complication rates in the biologic era remain ambiguous. This review primarily aims to provide an update on these outcomes. Secondarily, risk factors associated with chronic pouchitis and pouch failure are explored.

Methods

Two online databases (MEDLINE and EMBASE) were searched on 4 October 2022 for English studies from 2011-present relating to long-term outcomes of IAPP in inflammatory bowel disease (IBD) patients. Adult patients with 12 month follow-up were included. Studies focused on 30-day post-operative outcomes, non-IBD patients or studies including less than 30 patients were excluded.

Results

Following screening and full-text review of 1094 studies, 49 were included. Median sample size was n = 282 (IQR: 116–519). Median incidences for chronic pouchitis and pouch failure were 17.1% (IQR: 12–23.6%) and 6.9% (IQR: 4.8–10.8%), respectively. Upon multivariate analysis, chronic pouchitis development was most significantly associated with pre-operative steroid use, pancolitis and extra-intestinal IBD manifestations, whilst pouch failure was most significantly associated with pre-operative diagnosis of Crohn's disease (compared to UC), peri-operative pelvic sepsis and anastomotic leak. Overall patient satisfaction was very high with four included studies reporting greater than 90% satisfaction rates.

Conclusion

Long-term complications for IAPP were common. However, despite this, patient satisfaction post-IAPP was high. Up-to-date knowledge of complication rates and their risk factors improves pre-operative counselling, management planning and patient outcomes.     

血液恶性肿瘤CAR-T〖WT〗治疗后患者报告结局的范围综述

目的 对血液恶性肿瘤嵌合抗原受体T细胞(CAR-T)治疗的急性、亚急性及长期随访期间患者报告结局研究进行范围综述,为临床早期判断和实施干预提供参考。方法 检索中英文数据库中血液恶性肿瘤CAR-T治疗后患者报告结局的相关研究,检索时限为建库至2023年3月20日。对纳入文献进行筛选及汇总分析。结果 共纳入16篇文献。现有研究共使用18种评价工具测量CAR-T治疗后患者报告结局,测量范围包括症状、功能性及心理状态评估。CAR-T治疗后急性期患者突出报告症状领域恶化;亚急性患者突出报告社会及角色功能的持续限制以及疲劳、疼痛、睡眠障碍症状;长期随访患者报告神经系统症状或焦虑、抑郁情绪。结论 不同时期CAR-T治疗患者报告结局存在差异,提示医护人员应长期监测。未来可开发CAR-T治疗血液恶性肿瘤患者特异性评价工具,利用电子化患者报告结局建立数字健康监测系统。     

Long-term Mortality After Nontraumatic Major Lower Extremity Amputation: A Systematic Review and Meta-analysis

Chronic wounds that lead to major lower extremity amputation have immense consequences on quality of life, and ultimately, mortality. However, mortality rates after lower extremity amputation for a chronic wound are broad within the literature and have escaped precise definition. This systematic review aims to quantify long-term mortality rates after major lower extremity amputation in the chronic wound population available in the existing literature. Ovid MEDLINE was searched for publications which provided mortality data after major, nontraumatic, primary lower extremity amputations. Lower extremity amputations were defined as below and above the knee amputation. Data from included studies was analyzed to obtain pooled 1-, 2-, 3-, 5- and 10-year mortality rates. Sixty-one studies satisfied inclusion criteria representing 36,037 patients who underwent nontraumatic major lower extremity amputation. Pooled mortality rates were 33.7%, 51.5%, 53%, 64.4%, and 80% at 1-, 2-, 3-, 5- and 10-year follow-up, respectively. Within the 8184 diabetic patients (types 1 and 2), 1- and 5-year mortality was 27.3% and 63.2%. Sources of mortality data were varied and included electronic medical records, national health and insurance registries, and government databases. Mortality after nontraumatic major lower extremity amputation is high, both in patients with diabetes as well as those without. Methods used to measure and report mortality are inconsistent, lack reliability, and may underestimate true mortality rates. These findings illustrate the need for a paradigm shift in wound management and improved outcomes reporting. A focus on amputation prevention and care within a multidisciplinary team is critical for recalcitrant ulcers.     

Systemic therapy for chromophobe renal cell carcinoma: A systematic review

Background: Chromophobe renal cell carcinoma (chRCC) subtype accounts for almost 5% of total RCC cases. It carries the best prognosis among the rest of RCC types. However, patients with metastatic chRCC disease have worse prognosis than patients with advanced clear cell RCC. Furthermore, available data regarding systemic therapy for chRCC patients are scarce and confusing. Aim: The aim of this systematic review is to search for and critically appraise studies that investigate the results of systemic therapies in patients diagnosed with metastatic chRCC disease. Methods: Search strategy included PUBMED, CENTRAL, clinicaltrials.gov databases, and abstracts of major conferences with a focus on urologic oncology (till March 2019). Studies investigating patients that were treated with systemic therapy for advanced chRCC disease were included. Primary outcomes were progression-free survival and objective response rate. Secondary outcome was overall survival. Screening of available studies was carried out by 2 groups of reviewers, as well as the quality assessment of the included studies. Results: The systematic search yielded 369 studies, of which 15 studies (2 randomized control trials and 13 cohort studies), involving 183 patients, met the eligibility criteria. The 2 randomized control trials that directly compared sunitinib vs. everolimus, suggested an advantage for sunitinib without being statistically significant. Furthermore, sunitinib seems to be superior than sorafenib at least in terms of objective response rate. Regarding mTOR inhibitors, they may have a role in a specific subset of chRCC patients, that needs to be further explored. Finally, as far as immunotherapy is concerned, available data suggest that chRCC seems to be resistant to recent immune check point inhibitors, since just a few tumor responses were observed with the administered immunotherapy regiments. Conclusion: The optimum therapy for metastatic chRCC is still missing, as results from ongoing trials are awaited. More studies, of high quality and adequate sample size, that will be based on the specific biology of chRCC, have to be carried out in order to identify the best treatment.