Locally recurrent rectal cancer: oncological outcomes with different treatment strategies in two tertiary referral units.

BACKGROUND: The optimal treatment for patients with locally recurrent rectal cancer (LRRC) is controversial. The aim of this study was to investigate different treatment strategies in two leading tertiary referral hospitals in Europe. METHODS: All patients who underwent curative surgery for LRRC between January 2003 and December 2017 in Catharina Hospital, Eindhoven, the Netherlands (CHE), or Karolinska University Hospital, Stockholm, Sweden (KAR), were studied retrospectively. Available MRIs were reviewed to obtain a uniform staging for optimal comparison of both cohorts. The main outcomes studied were overall survival (OS), local re-recurrence-free survival (LRFS), and metastasis-free survival (MFS). RESULTS: In total, 377 patients were included, of whom 126 and 251 patients came from KAR and CHE respectively. At 5 years, the LRFS rate was 62.3 per cent in KAR versus 42.3 per cent in CHE (P = 0.017), whereas OS and MFS were similar. A clear surgical resection margin (R0) was the strongest prognostic factor for survival, with a hazard ratio of 2.23 (95 per cent c.i. 1.74 to 2.86; P < 0.001), 3.96 (2.87 to 5.47; P < 0.001), and 2.00 (1.48 to 2.69; P < 0.001) for OS, LRFS, and MFS respectively. KAR performed more extensive operations, resulting in more R0 resections than in CHE (76.2 versus 61.4 per cent; P = 0.004), whereas CHE relied more on neoadjuvant treatment and intraoperative radiotherapy, to reduce the morbidity of multivisceral resections (P < 0.001). CONCLUSION: In radiotherapy-naive patients, neoadjuvant full-course chemoradiation confers the best oncological outcome. However, neoadjuvant therapy does not diminish the need for extended radical surgery to increase R0 resection rates.

Pretreatment MRI in Primary Rectal Cancer as a Predictor for Oncological Outcomes After Surgery for Local Recurrence.

BACKGROUND/AIM: For patients with locally recurrent rectal cancer (LRRC) extensive surgery is often the only curative option and patient selection is crucial. This study aimed to investigate whether magnetic resonance imaging (MRI) characteristics of the primary tumour can predict oncological outcome after surgery for locally recurrent rectal cancer (LRRC). PATIENTS AND METHODS: All patients undergoing surgery for LRRC with a curative intent at the Karolinska University Hospital 2003-2013 were included. MRI examinations of the primary tumour were re-evaluated. RESULTS: In total, 54 patients were included. A tumour volume decrease of <70% after preoperative radiotherapy or chemoradiotherapy (C)RT for the primary tumour was correlated with a lower proportion of R0 resection of the LRRC (OR=0.07, 95% CI=0.01-0.84). No association between MRI characteristics of the primary tumour and prognosis after LRRC surgery was found. CONCLUSION: Long-term outcomes after surgery for LRRC were not significantly associated with MRI characteristics of the index tumour. However, factors associated with increased risk of R1 resection of LRRC were identified.

Magnetic resonance imaging as a predictor of surgical outcome in patients with local pelvic recurrence of colorectal cancer.

INTRODUCTION: Pelvic local recurrence of colorectal cancer (PRCRC) may be cured if radical surgery is performed. Preoperative assessment normally includes magnetic resonance imaging (MRI). The aim of this study was to evaluate the influence of specific MRI-related findings on outcome of surgery of PRCRC. MATERIALS AND METHODS: Clinical data from 95 consecutive patients, operated with a curative intent for PRCRC at Karolinska University Hospital during 2003-2013, were collected from medical records. Preoperative MRI examinations of the PRCRC were re-evaluated. The potential influence of clinical factors and specific MRI-findings (location, solid/mucinous, size, volume and border) on surgical resection margins (R0-R1) and survival were calculated with logistic and cox regression. RESULTS: Eighty-seven patients had available MRI scans and were included in the study. Sixty-five patients (75%) had a R0 resection and 22 patients (25%) had a R1 resection of their PRCRC. In all, 47 patients (54%) had an involved lateral compartment. Lateral location was the only MRI finding associated with both an increased risk of R1 resection (OR 3.97, 95%CI: 1.31-12.04) and death (HR 1.94, 95%CI: 1.07-3.51). Lateral location entailed an increased risk of death also after R0 resection (HR2.09, 95%CI: 1.07-4.10). Five-year survival was 35% for all patients, 44% after R0 resection and 7% after R1 resection. CONCLUSION: Tumour involvement of the lateral and posterior compartments on MRI was a predictor for R1 resection, but only lateral involvement was associated with an increased risk of death. An increased risk of death associated with lateral involvement was still present after R0 resection.

Lateral Nodal Features on Restaging Magnetic Resonance Imaging Associated With Lateral Local Recurrence in Low Rectal Cancer After Neoadjuvant Chemoradiotherapy or Radiotherapy.

Importance: Previously, it was shown in patients with low rectal cancer that a short-axis (SA) lateral node size of 7 mm or greater on primary magnetic resonance imaging (MRI) resulted in a high lateral local recurrence (LLR) rate after chemoradiotherapy or radiotherapy ([C]RT) with total mesorectal excision (TME) and that this risk was lowered by a lateral lymph node dissection (LLND). The role of restaging MRI after (C)RT with regard to LLR risk and which specific patients might benefit from an LLND is not fully understood. Objective: To determine the factors on primary and restaging MRI that are associated with LLR in low rectal cancer after (C)RT and to formulate specific guidelines on which patients might benefit from an LLND. Design, Setting, and Participants: In this retrospective, multicenter, pooled cohort study, patients who underwent surgery for cT3 or cT4 low rectal cancer with a curative intent from 12 centers in 7 countries from January 2009 to December 2013 were included. All patients' MRIs were rereviewed according to a standardized protocol, with specific attention to lateral nodal features. The original cohort included 1216 patients. For this study, patients who underwent (C)RT and had a restaging MRI were selected, leaving 741 for analyses across 10 institutions, including 651 who underwent (C)RT with TME and 90 who underwent (C)RT with TME and LLND. Main Outcomes and Measures: The main purpose was to identify the factors on primary and restaging MRI associated with LLR after (C)RT with TME. Whether high-risk patients might benefit in terms of LLR reduction from an LLND was also studied. Results: Of the 741 included patients, 480 (64.8%) were male, and the mean (SD) age was 60.4 (12.0) years. An SA lateral node size of 7 mm or greater on primary MRI resulted in a 5-year LLR rate of 17.9% after (C)RT with TME. At 3 years, there were no LLRs in 28 patients (29.2%) with lateral nodes that were 4 mm or less on restaging MRI. Nodes that were 7 mm or greater on primary MRI and greater than 4 mm on restaging MRI in the internal iliac compartment resulted in a 5-year LLR rate of 52.3%, significantly higher compared with nodes in the obturator compartment of that size (9.5%; hazard ratio, 5.8; 95% CI, 1.6-21.3; P = .003). Compared with (C)RT with TME alone, treatment with (C)RT with TME and LLND in these unresponsive internal nodes resulted in a significantly lower LLR rate of 8.7% (hazard ratio, 6.2; 95% CI, 1.4-28.5; P = .007). Conclusions and Relevance: Restaging MRI is important in clinical decision making in lateral nodal disease. In patients with shrinkage of lateral nodes from an SA node size of 7 mm or greater on primary MRI to an SA node size of 4 mm or less on restaging MRI, which occurs in about 30% of cases, LLND can be avoided. However, persistently enlarged nodes in the internal iliac compartment indicate an extremely high risk of LLR, and an LLND lowered LLR in these cases.

Neoadjuvant (Chemo)radiotherapy With Total Mesorectal Excision Only Is Not Sufficient to Prevent Lateral Local Recurrence in Enlarged Nodes: Results of the Multicenter Lateral Node Study of Patients With Low cT3/4 Rectal Cancer.

PURPOSE: Improvements in magnetic resonance imaging (MRI), total mesorectal excision (TME) surgery, and the use of (chemo)radiotherapy ([C]RT) have improved local control of rectal cancer; however, we have been unable to eradicate local recurrence (LR). Even in the face of TME and negative resection margins (R0), a significant proportion of patients with enlarged lateral lymph nodes (LLNs) suffer from lateral LR (LLR). Japanese studies suggest that the addition of an LLN dissection (LLND) could reduce LLR. This multicenter pooled analysis aims to ascertain whether LLNs actually pose a problem and whether LLND results in fewer LLRs. PATIENTS AND METHODS: Data from 1,216 consecutive patients with cT3/T4 rectal cancers up to 8 cm from the anal verge who underwent surgery in a 5-year period were collected. LLND was performed in 142 patients (12%). MRIs were re-evaluated with a standardized protocol to assess LLN features. RESULTS: On pretreatment MRI, 703 patients (58%) had visible LLN, and 192 (16%) had a short axis of at least 7 mm. One hundred eight patients developed LR (5-year LR rate, 10.0%), of which 59 (54%) were LLRs (5-year LLR rate, 5.5%). After multivariable analyses, LLNs with a short axis of at least 7 mm resulted in a significantly higher risk of LLR (hazard ratio, 2.060; P = .045) compared with LLNs of less than 7 mm. In patients with LLNs at least 7 mm, (C)RT plus TME plus LLND resulted in a 5-year LLR of 5.7%, which was significantly lower than that in patients who underwent (C)RT plus TME (5-year LLR, 19.5%; P = .042). CONCLUSION: LLR is still a significant problem after (C)RT plus TME in LLNs with a short axis at least 7 mm on pretreatment MRI. The addition of LLND results in a significantly lower LLR rate.

Changes in Clinical Practice Reduce the Rate of Anastomotic Leakage After Colorectal Resections.

BACKGROUND: Anastomotic leakage is a serious clinical problem after colorectal resections and is associated with a significantly increased length of stay, morbidity and mortality. The aim of the present study was to evaluate the effect of changes in clinical practice on anastomotic leakage rate after colorectal resections. METHODS: Retrospective cohort study based on prospectively collected data. All 894 patients with primary anastomosis after colorectal resection at a tertiary referral center between 2006 and 2013 were analyzed. Changes in clinical practice aiming at reducing the rate of anastomotic leakages were introduced in January 2010 and were characterized by exclusion of perioperative nonsteroidal anti-inflammatory drugs, introduction of intra-operative goal-directed fluid therapy and avoidance of primary anastomoses in emergency resections. The study population was divided into two groups, one treated before and one after the introduction of changes in clinical practice. Groups were compared regarding patient characteristics and incidence of anastomotic leakage. RESULTS: The cumulative incidence of anastomotic leakage after colorectal resections decreased from 10.0% (41 of 409) to 4.5% (22 of 485) after changing clinical practice, relative risk 0.45 (95% CI 0.27-0.75, p = 0.002). The adjusted odds ratio was 0.45 (0.26-0.78, p = 0.004). A separate analysis showed a decrease after colon resections from 9.1% (23 of 252) to 4.5% (14 of 310), relative risk 0.49 (0.26-0.94, p = 0.039), and from 11.5% (18 of 157) to 4.6% (8 of 175) after rectal resections, relative risk 0.40 (0.18-0.89, p = 0.024). CONCLUSION: Implementing a structured change of clinical practice can significantly reduce the anastomotic leakage rate after colorectal resections. TRIAL REGISTRATION: Clinical trial registration number: ACTRN12617001497392.

Transcranial direct current stimulation as a memory enhancer in patients with Alzheimer's disease: a randomized, placebo-controlled trial.

BACKGROUND: The purpose of this study was to assess the efficacy of transcranial direct current stimulation (tDCS) on verbal memory function in patients with Alzheimer's disease. METHODS: We conducted a randomized, placebo-controlled clinical trial in which tDCS was applied in six 30-minute sessions for 10 days. tDCS was delivered to the left temporal cortex with 2-mA intensity. A total of 25 patients with Alzheimer's disease were enrolled in the study. All of the patients were diagnosed according to National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer's Disease and Related Disorders Association criteria. Twelve patients received active stimulation, and thirteen patients received placebo stimulation. The primary outcome measure was the change in two parallel versions of the California Verbal Learning Test-Second Edition, a standardized neuropsychological memory test normalized by age and gender. The secondary outcome measures were the Mini Mental State Examination, clock-drawing test, and Trail Making Test A and B. RESULTS: Changes in the California Verbal Learning Test-Second Edition scores were not significantly different between the active and placebo stimulation groups for immediate recall (p = 0.270), delayed recall (p = 0.052), or recognition (p = 0.089). There were nonsignificant differences in score changes on the Mini Mental State Examination (p = 0.799), clock-drawing test (p = 0.378), and Trail Making Test A (p = 0.288) and B (p = 0.093). Adverse effects were not observed. CONCLUSIONS: Compared with placebo stimulation, active tDCS stimulation in this clinical trial did not significantly improve verbal memory function in Alzheimer's disease. This study differs from previous studies in terms of the stimulation protocol, trial design, and application of standardized neuropsychological memory assessment. TRIAL REGISTRATION: ClinicalTrials.gov identifier NCT02518412 . Registered on 10 August 2015.

Fabry disease simulating Crohn's ileitis.

Fabry disease is an inherited (X-linked) lysosomal storage disorder caused by deficiency of α-galactosidase A, leading to accumulation of globotriaosylceramide in various tissues. A 57-year-old male with a family history and laboratory findings of Fabry disease, was consulted for severe abdominal pain, undulating pyrexia, weight loss and diarrhea. The tentative clinical diagnosis of Crohn's ileitis was supported at computed tomographic examination, at laparotomy and at inspection of the resected ileal segment. Histology revealed chronic and acute inflammation, thick-walled occluded vessels, fibrosis and characteristic bi-refringent lamellar deposits of globotriaosylceramide and calcifications. Multi-nucleated giant cells contained phagocytized bi-refringent material. Transmission electron microscopy showed cells with irregular cytoplasmic bodies displaying distinctive zebra-like lamellar structures. It is submitted that the gastrointestinal phenotype of Fabry disease may concur with symptoms resembling abdominal Crohn's disease.