Visceral Medicine最新文献

Background: Oesophageal adenocarcinoma (OAC) is a lethal cancer with an overall 5-year survival of <20%. Given the presence of a pre-invasive disease stage, also known as Barrett's oesophagus (BO), and the availability of minimally invasive treatments for BO-related neoplasia, it is thought that early detection is the best strategy to improve patient outcomes. Clinical guidelines recommend endoscopic screening in patients with symptoms of acid reflux and additional risk factors. This strategy is flawed by the cost and invasiveness of endoscopy as well as by the fact that a significant proportion of OAC patients deny a history of reflux symptoms.

Summary: New research on the use of epidemiologic and clinical data has allowed the creation of risk-prediction algorithms to identify the population at risk. In addition, newer less-invasive devices such as transnasal endoscopy, Cytosponge, volumetric laser endomicroscopy, and volatile organic compounds are emerging as promising options to allow screening in the primary care setting. Finally, there is an opportunity to intervene at the pre-invasive stage with pharmacological strategies to reduce the risk burden.

Key messages: In this review, we provide a critical appraisal of the different screening approaches and chemopreventive strategies and a guide to readers on how to implement research evidence in clinical practice.

Background: Endoscopic therapy has replaced esophagectomy for the management of early Barrett's neoplasia, allowing for the curative treatment of intramucosal adenocarcinoma, dysplastic Barrett's esophagus (BE), and the prevention of metachronous recurrences.

Summary: Endoscopic therapy relies on the resection of any visible lesion, suspicious of harboring cancer, followed by the eradication of the residual BE, potentially harboring dysplastic foci. Currently, endoscopic mucosal resection (EMR) using the multiband mucosectomy technique is the gold standard for the resection of visible lesions. Endoscopic submucosal dissection (ESD) is feasible with comparable complication rates to EMR, but longer procedural times. It is still limited to EMR failures or suspected submucosal adenocarcinoma. Eradication of residual BE mainly relies on radiofrequency ablation, with over 90% efficacy in expert centers. Despite initial complete eradication of BE, intestinal metaplasia and dysplasia recur in time, justifying prolonged endoscopic surveillance.

Key messages: The first step of the therapeutic endoscopy for BE is a careful diagnostic evaluation, searching for visible(s) lesion(s). EMR is the recommended resection technique for visible lesions. ESD has not demonstrated its superiority on EMR in routine practice. Endoscopic follow-up after Barrett's eradication therapy is mandatory.

Introduction: Clinically significant drug-induced liver injury (DILI) is defined by elevations of alanine aminotransferase (ALT) ≥5 times the upper limit of normal (ULN), alkaline phosphatase (ALP) ≥2 × ULN, or ALT ≥3 × ULN and total bilirubin TBIL >2 × ULN. However, DILI might also occur in patients who do not reach those thresholds and still may benefit from discontinuation of medication.

Methods: Fifteen patients recruited for our prospective study on potentially hepatotoxic drugs were included. DILI diagnosis was based on RUCAM (Roussel Uclaf Causality Assessment Method) score and expert opinion and was supported by an in vitro test using monocyte-derived hepatocyte-like (MH) cells.

Results: Median RUCAM score was 6 (range 4-8), indicating that DILI was possible or probable in all cases. The predominant types of liver injury were mixed (60%) and cholestatic (40%). While no elevation above 2 × ULN of ALP and TBIL was observed, gamma-glutamyltransferase (GGT) above 2 × ULN was identified in 8 of the patients. Six of the 15 patients did not achieve full remission and showed persistent elevation of GGT, which was significantly associated with peak GGT elevation above 2 × ULN (p = 0.005).

Conclusion: Here we present a case series of patients with liver enzyme elevation below the conventional thresholds who developed DILI with a predominant GGT elevation leading to drug withdrawal and/or chronic elevation of liver parameters, in particular of GGT. Thus, we propose that DILI should be considered in particular in cases with marked increase of GGT even if conventional DILI threshold levels are not reached, resulting in discontinuation of the causative drug and/or close monitoring of the patients.

Background: Given the limitation that endoscopic resection only enables local intraluminal treatment without lymphadenectomy, the standard treatment of esophageal adenocarcinoma (EAC) with invasion of the submucosa (T1b) has long been surgical esophageal resection. However, in recent literature, the risk of lymph node metastases (LNM) associated with T1b EAC appears to be lower than previously assumed, and endoscopic management is increasingly being considered a valid and less invasive alternative to surgery.

Summary: Surgical esophageal resection performed after radical endoscopic resection of T1b EAC often does not show any residual tumor or LNM in the resected specimen. Given the morbidity and mortality associated with surgical esophageal resection, endoscopic management with strict surveillance protocols has been more widely applied provided that the initial tumor was radically removed by endoscopic resection, reserving surgery for those cases where the additional risk of surgical esophageal resection is justified. These are the cases where intraluminal recurrent neoplasia is found that cannot be retreated endoscopically or cases with locoregional LNM detected during follow-up. In the future, selection of patients who can safely be managed endoscopically and those who may benefit from additional surgery after endoscopic resection of T1b EAC may become more tailored, using risk prediction calculators or sentinel node navigated surgery.

Key messages: Management of patients with T1b EAC is shifting from surgical treatment to less invasive endoscopic treatment strategies, including watchful waiting approaches. The risk of LNM of T1b EAC appears to be lower than long assumed. In the future, management of T1b EAC may become more individualized based on tools to predict LNM risk per patient case.

Introduction: Compared to abdominoperineal resection (APR), sphincter preservation using low anterior resection (AR) for rectal cancer (RC) implies the risk of impaired functional outcome and postoperative complications associated with a persistent or additionally required ostomy. The aim of our study was to compare quality of life (QoL) after AR and APR with a special separate analysis of AR patients with a stoma.

Methods: QoL of 84 APR, 356 AR, and 29 AR patients with complications and an additional stoma, termed converted therapy (COT) patients, was compared with regard to groups and effect of radiotherapy (RT). All patients received rectal resection between 1998 and 2013, and 47% of the patients had RT. QoL was assessed using extended EORTC QLQ-C30 and -CR38 questionnaires.

Results: Questionnaires from 57 APR, 165 AR, and 25 COT patients alive were evaluated after a median time of 4 years after surgery. Global health status was equally high in AR and APR patients (score: 67), whereas COT patients turned out with a significantly lower score of 50 (p = 0.007). Compared to APR and COT, AR patients revealed less symptoms and higher functionality, especially for physical, role, and social functioning (p < 0.001). The reduction of QoL instances was significant in the COT group and in all patients treated by RT.

Conclusion: QoL after RC resection may be further improved by avoiding additionally required ostomy after AR but also RT by a better individual selection of qualified patients. Qualification parameters urgently need to be defined by prospective studies.

Background: Advanced epithelial ovarian cancer (EOC) is an incurable disease with over 75% of the patients developing recurrence in the peritoneum. Hyperthermic intraperitoneal chemotherapy (HIPEC) is a promising treatment option for both first-line therapy and treatment of recurrence. In this article, we review the rationale and current evidence for performing HIPEC and the role of HIPEC in the light of targeted systemic therapies.

Summary: There are few randomized trials and several retrospective studies on the role of HIPEC in the management of EOC. A 12-month-overall survival (OS) benefit of the addition of HIPEC to interval cytoreductive surgery (CRS) was demonstrated in 1 randomized trial following which HIPEC has been included as a treatment option for this indication in several national/international guidelines. One retrospective propensity score-matched analysis showed a 16-month OS benefit of adding HIPEC to primary CRS. One randomized trial showed no benefit of the addition of carboplatin HIPEC to secondary CRS over secondary CRS alone. For patients undergoing primary CRS and secondary CRS for recurrence, the results of ongoing randomized trials are needed to define the role of HIPEC in these situations. All clinical trials have shown that the morbidity of HIPEC performed after CRS is acceptable. Along with the emergence of HIPEC as a promising surgical therapy, targeted therapies like bevacizumab and poly adenosine diphosphate-ribose polymerase inhibitors have been developed that have shown a survival benefit in selected patients. In principle, HIPEC and targeted therapies work in different ways and it is plausible to assume that their benefit could be additive, and their combination should be evaluated in clinical trials. The impact of prognostic factors like the disease extent, pathological response to systemic chemotherapy (SC), the histological subtype and molecular profile on the benefit of HIPEC, and targeted therapies has not been evaluated in clinical trials.

Key messages: HIPEC is an important therapeutic strategy in the treatment of EOC. While its role in patients undergoing interval CRS has been established, the results of ongoing randomized trials are needed to define its benefit at other time points. The morbidity of HIPEC in addition to CRS is acceptable. More research is needed to define subgroups that benefit most from HIPEC based on the extent of disease, response to SC, histology, and molecular profile. The combination of HIPEC and maintenance therapies should be evaluated in well-designed randomized clinical trials that evaluate not just the survival benefit and morbidity but also the cost-effectiveness of each therapy.

Background: The surgical management of peritoneal metastases from colorectal cancer has been a topic of controversial discussion for many decades. Peritonectomy and perioperative intraperitoneal chemotherapy added options for surgical treatment of this condition beyond palliative surgery. The most favorable outcomes are recorded when peritoneal metastases from colorectal cancer can be resected to no visible evidence of disease.

Methods: To determine if any benefit from surgical treatment of patients with colorectal peritoneal metastases can occur from incomplete resection of peritoneal metastases, we studied patients by the completeness of cytoreduction (CC) score. The CC-3 indicated a palliative resection, CC-2 gross residual disease, and CC-1 almost complete cytoreduction but visible residual disease. The impact of clinical-, pathologic-, and treatment-related variables on the survival of the three groups was compared.

Results: Eighty-five patients with long-term follow-up were available for study. The median age was 53 years (range 18-82). There were 60 males (70.6%). Symptomatic patients, those with bowel obstruction, and patients with positive retroperitoneal lymph nodes had significantly reduced survival. The median survival of the CC-3, CC-2, and CC-1 groups were significantly different (p = 0.0027). The 2-year or greater survivals of the three groups were 4.8%, 15.1%, and 38.7%, respectively.

Conclusions: If a near complete cytoreduction combined with hyperthermic intraperitoneal chemotherapy can be performed, short-term survival benefit could be observed.