Promising Results of a Cooperative Group Phase II Trial of Preoperative Chemoradiation for Locally Advanced Rectal Cancer (TROG 9801)

PURPOSE This article reports the overall survival, failure-free survival, local failure, and late radiation toxicity of a phase II trial of preoperative radiotherapy with continuous infusion 5-fluorouracil for rectal cancer after a minimum 3.5 years of follow-up.METHODS Eligible patients were those with newly diagnosed localized adenocarcinoma of the rectum, within 12 cm of the anal verge, staged T3–T4 and deemed suitable for curative resection. Radiotherapy (50.4 Gy in 28 fractions in five weeks and three days) was given with continuous infusion 5-fluorouracil throughout the course of radiotherapy.RESULTS A total of 82 patients were accrued in 13 months. The median follow-up time was 4.1 (range, 2.3–4.5) years. There were 55 males (67 percent) and the median age was 59 (range, 27–87) years. Patients were staged pretreatment as T3 (89 percent) and resectable T4 (11 percent). Endorectal ultrasound was performed in 70 percent and magnetic resonance imaging in another 5 percent. The four-year overall and failure-free survival rates were 82 percent (95 percent CI: 72–89) and 69 percent (95 percent CI: 58–78), respectively. The cumulative incidence of local failure at four years was 3.9 percent (95 percent CI: 1.3–11). Risk of failures, local and distant, has not reached a plateau phase.CONCLUSION This regimen can be delivered safely and without leading to a significant increase in late toxicity. It provides excellent local control and favorable overall survival. There is a need for longer follow-up than has commonly been used for the proper evaluation of failures after an effective regimen of preoperative chemoradiation.Reprints are not available.     

Clinical and Technical Guideline for Endoscopic Ultrasound (EUS)-Guided Tissue Acquisition of Pancreatic Solid Tumor: Korean Society of Gastrointestinal Endoscopy (KSGE)

Endoscopic ultrasound (EUS)-guided tissue acquisition of pancreatic solid tumor requires a strict recommendation for its proper use in clinical practice because of its technical difficulty and invasiveness. The Korean Society of Gastrointestinal Endoscopy (KSGE) appointed a task force to draft clinical practice guidelines for EUS-guided tissue acquisition of pancreatic solid tumor. The strength of recommendation and the level of evidence for each statement were graded according to the Minds Handbook for Clinical Practice Guideline Development 2014. The committee, comprising a development panel of 16 endosonographers and an expert on guideline development methodology, developed 12 evidence-based recommendations in eight categories intended to help physicians make evidence-based clinical judgments with regard to the diagnosis of pancreatic solid tumor. This clinical practice guideline discusses EUS-guided sampling in pancreatic solid tumor and makes recommendations on circumstances that warrant its use, technical issues related to maximizing the diagnostic yield (e.g., needle type, needle diameter, adequate number of needle passes, sample obtaining techniques, and methods of specimen processing), adverse events of EUS-guided tissue acquisition, and learning-related issues. This guideline was reviewed by external experts and suggests best practices recommended based on the evidence available at the time of preparation. This guideline may not be applicable for all clinical situations and should be interpreted in light of specific situations and the availability of resources. It will be revised as necessary to cover progress and changes in technology and evidence from clinical practice. (Gut Liver 2021;15:-374)     

Combined Versus Separate Sessions of Endoscopic Ultrasound and Endoscopic Retrograde Cholangiopancreatography for the Diagnosis and Management of Pancreatic Ductal Adenocarcinoma with Biliary Obstruction

Digestive Diseases and Sciences - A single-procedure session combining EUS and ERCP (EUS/ERCP) for tissue diagnosis and biliary decompression for pancreatic duct adenocarcinoma (PDAC) is...     

Utility of Rectoscopy in the Assessment of Response to Neoadjuvant Treatment for Locally Advanced Rectal Cancer

Background/Aims:

The management of locally advanced rectal cancer has changed substantially over the last few decades with neoadjuvant chemoradiotherapy. The aim of the present study is to compare the results between neoadjuvant post-treatment rectoscopy and the anatomopathological findings of the surgical specimen.

Patients and Methods:

We conducted a prospective study of 67 patients with locally advanced adenocarcinoma of the rectum (stages II and III). Two groups were established: One with complete clinical response (cCR) and one without (non-cCR), based on the findings at rectoscopy. Assessment of tumor regression grade in the surgical specimen was determined using Mandard''s tumor regression scale.

Results:

Seventeen patients showed a cCR. Thirty-five biopsies were negative and 32 were positive for mailgnancy. All the cCR patients had a negative biopsy (P < 0.0001). All 32 positive biopsies revealed the presence of adenocarcinoma, and of the 35 negative biopsies, 18 had no malignancy and 17 were diagnosed with adenocarcinoma (P < 0.0001). Sixteen of the 17 cCR patients showed a complete pathological response and one patient showed the presence of adenocarcinoma. Of the 50 non-cCR patients 48 revealed the presence of adenocarcinoma and two had absence of malignancy. According to the Mandard classification, 16 of the 17 cCR patients were grade I and 1 grade II; 2 non-cCR patients were grade I, 7 grade II, 13 grade III, 19 grade IV, and 9 grade V.

Conclusions:

Endoscopic and histological findings could be determinants in the assessment of response to neoadjuvant treatment.     

重组人血管内皮抑制素联合FOLFOX4方案治疗晚期结直肠癌的临床对照研究

背景：临床前和临床研究结果显示重组人血管内皮抑制素能抑制血管内皮细胞增殖、血管生成和肿瘤生长．且耐受性良好。目的：评价重组人血管内皮抑制素联合FOLFOX4方案治疗晚期结直肠癌（ACRC）的反应率（RR）、临床获益率（CBR）、中位疾病进展时间（TTP）和肿瘤进展率,观察患者生活质量（QOL）改善情况和药物不良反应。方法：收集50例病理学诊断为Ⅳ期、初治或复治、Karnofsky评分（KPS）≥60分的ACRC患者,随机分为试验组和对照组。试验组25例,联合应用FOLFOX4方案和重组人血管内皮抑制素（7．5mg／m^2,d1-14）。对照组25例,应用FOLFOX4方案＋安慰剂（0．9％NaCl溶液,用法同重组人血管内皮抑制素）。结果：50例患者均可评价疗效。试验组总RR（44．0％对16．0％,P-0．062）、总CBR（76．0％对48．0％,P=0．041）、总中位TTP（7．8个月对5．0个月,P=0．040）和QOL改善率（64．0％对36．0％,P=0．048）均高于对照组,肿瘤进展率低于对照组（P〈0．05）。初治患者中,试验组RR、CBR和中位TTP均显著高于对照组（P〈0．05）;复治患者中,试验组和对照组上述指标无明显差异。两组间不良反应发生率差异无统计学意义。结论：重组人血管内皮抑制素联合FOLFOX4方案能明显提高ACRC患者,尤其是初治患者的RR．延长中位TTP,在一定程度上改善患者的QOL,且安全性较好。     

Preoperative Chemoradiotherapy with Concomitant Small Field Boost Irradiation for Locally Advanced Rectal Cancer: A Multi-Institutional Phase II Study (KROG 04-01)

Purpose This study was designed to determine the effect of concomitant small field boost irradiation given during preoperative chemoradiotherapy for patients with locally advanced rectal cancer. Methods The study prospectively enrolled 38 patients scheduled for preoperative chemoradiotherapy. Pelvic radiotherapy of 43.2 Gy/24 fractions was delivered and boost radiotherapy of 7.2 Gy/12 fractions was concomitantly administered during the latter half of the pelvic radiotherapy treatment period. Two cycles of a bolus 5-fluorouracil and leucovorin injection in the first and fifth weeks of radiotherapy were administered. The median time to surgery after completion of chemoradiotherapy was six weeks. Tumor responses to chemoradiotherapy were assessed by using magnetic resonance volumetry and postchemoradiotherapy pathology tests to determine tumor downstaging and tumor regression rate. Results Thirty-six of 38 patients (94.7 percent) underwent the scheduled surgery. The mean tumor volume reduction rate was 70.3 percent, and the clinical response rate was 66.7 percent. The downstaging rates were 41.7 percent for T classification, 85.2 percent for N classification, and 72.2 percent for stage. Tumor regression grades after preoperative chemoradiotherapy were Grade 1 in 5 patients (13.9 percent), Grade 2 in 24 patients (66.7 percent), Grade 3 in 3 patients (8.3 percent), and Grade 4 in 4 patients (11.1 percent). Ten patients (26.3 percent) experienced ≥ Grade 3 acute toxicity. Conclusions Our data suggest that concomitant boost irradiation does not improve clinical outcomes compared with other published preoperative chemoradiotherapy regimens. In addition, the clinicians choosing to use concomitant small field boost irradiation should be cautious to minimize the risk of unplanned sphincter ablation. Supported by a grant from the National R&D Program for Cancer Control, Ministry of Health & Welfare, Republic of Korea (0320320-2).     

Combined Neuromuscular Electrical Stimulation (NMES) with Fiberoptic Endoscopic Evaluation of Swallowing (FEES) and Traditional Swallowing Rehabilitation in the Treatment of Stroke-Related Dysphagia

Dysphagia is common after stroke. Neuromuscular electrical stimulation (NMES) and fiberoptic endoscopic evaluation of swallowing (FEES) for the treatment of dysphagia have gained in popularity, but the combined application of these promising modalities has rarely been studied. We aimed to evaluate whether combined NMES, FEES, and traditional swallowing rehabilitation can improve swallowing functions in stroke patients with moderate to severe dysphagia. Thirty-two patients with moderate to severe dysphagia poststroke (≥3 weeks) were recruited. Patients received 12 sessions of NMES for 1 h/day, 5 days/week within a period of 2–3 weeks. FEES was done before and after NMES for evaluation and to guide dysphagic therapy. All patients subsequently received 12 sessions of traditional swallowing rehabilitation (50 min/day, 3 days/week) for 4 weeks. Primary outcome measure was the Functional Oral Intake Scale (FOIS). Secondary outcome measures included clinical degree of dysphagia, the patient’s self-perception of swallowing ability, and the patient’s global satisfaction with therapy. Patients were assessed at baseline, after NMES, at 6-month follow-up, and at 2-year follow-up. Twenty-nine patients completed the study. FOIS, degree of dysphagia, and patient’s self-perception of swallowing improved significantly after NMES, at the 6-month follow-up, and at the 2-year follow-up (p < 0.001, each compared with baseline). Most patients reported considerable satisfaction with no serious adverse events. Twenty-three of the 29 (79.3 %) patients maintained oral diet with no pulmonary complications at 2-year follow-up. This preliminary case series demonstrated that combined NMES, FEES, and traditional swallowing rehabilitation showed promise for improving swallowing functions in stroke patients with moderate-to-severe dysphagia. The benefits were maintained for up to 2 years. The results are promising enough to justify further studies.     

L-Alpha-Methyldopa Hydrazine (Carbidopa) Combined with L-Dopa in the Treatment of Parkinson's Disease

Summary: Clinical experience with the use of L-alpha-methyldopa hydrazine (Carbidopa), an inhibitor of peripheral decarboxylation of L-dopa, in the treatment of idiopathic Parkinson's disease in twenty-six patients is described. Malaise, nausea and vomiting associated with L-dopa therapy were relieved in most patients. Improved motor function was marked in 25%, moderate in 50% of the patients, while the necessary dosage of L-dopa was reduced by a mean of 65%. It is concluded that the use of this decarboxylase inhibitor with L-dopa significantly improves the symptomatic treatment of Parkinson's disease, particularly in those patients in whom L-dopa dosage is limited by nausea and vomiting     

胰岛素联合中医汤剂治疗1.5型糖尿病(LADA)的疗效分析

目的 研究胰岛素联合中医汤剂治疗1.5型糖尿病(LADA)的疗效.方法 2014年3月—2020年5月选择该院收治的78例LADA成年患者.按照随机原则分为对照组及观察组,各39例.对照组采用胰岛素治疗;观察组采用胰岛素及中药汤剂联合治疗.连续治疗3个月后进行指标评价,包括血糖水平(FPG、2 hPG)、空腹血浆C肽水...     

Beneficial effects of 1-year optimal medical treatment with and without additional PTA on inflammatory markers of atherosclerosis in patients with PAD. Results from the Oslo Balloon Angioplasty versus Conservative Treatment (OBACT) study

The influence of optimal medical treatment (OMT) with or without additional percutaneous transluminal angioplasty (PTA) on vascular inflammation in peripheral arterial occlusive disease (PAD) patients was investigated. Patients with intermittent claudication (IC) and angiographically verified PAD were randomized to OMT (n = 28) or OMT + PTA (n = 28) and followed for 12 months. Ankle-brachial index (ABI), treadmill walking distances (WD), visual analogue scale (VAS), and blood sampling for the determination of selected soluble biomarkers were undertaken at baseline and after 3 and 12 months. After both 3 and 12 months, ABI, WD and VAS were highly significantly improved in favour of OMT + PTA (p < 0.05 for all). Significant improvements were recorded in both groups in serum lipids (p < 0.01 for all), except for triglycerides, and in the inflammatory markers P-selectin, interleukin-6, interleukin-10, monocyte chemoattractant protein-1 and fibrinogen (p < 0.05 for all). There were, however, no differences in the changes from baseline between the groups in any variable. Intervention with OMT alone or in combination with PTA did not differ with regard to the effects on serum lipids and markers of inflammation in our population of PAD patients. The combined treatment was, however, better for the treadmill walking distance.     

A joined analysis of two European Organization for the Research and Treatment of Cancer (EORTC) studies to evaluate the role of pegylated liposomal doxorubicin (Caelyx) in the treatment of elderly patients with metastatic breast cancer

We have performed a retrospective analysis to evaluate the impact of age, using a 70 year cutoff, on the safety and efficacy of pegylated liposomal doxorubicin (Caelyx) given at 60 mg/m(2) every 6 weeks (treatment A) or 50 mg/m(2) every 4 weeks (treatment B) to 136 metastatic breast cancer patients in two EORTC trials, of whom 65 were 70 years of age or older. No difference in terms of toxicity was observed between younger and older patients treated with the 4-week schedule, while a higher incidence of hematological toxicity, anorexia, asthenia, and stomatitis was observed in older patients when the 6-week schedule was used. Antitumor activity was not affected by age. In the older cohort of patients, no dependence was found between the incidence of grade 3-4 toxicity or antitumor activity and patients' baseline performance status, number and severity of comorbidities, or number of concomitant medications. The higher therapeutic index of Caelyx 50 mg/m(2) every 4 weeks makes it, of the two dose schedules investigated, the preferred regimen in the elderly.