Adynamic response to cold pain reflects dysautonomia in type 1 diabetes and polyneuropathy.

Cardiac autonomic neuropathy (CAN), widely assessed by heart rate variability (HRV), is a common complication of long-term diabetes. We hypothesized that HRV dynamics during tonic cold pain in individuals with type 1 diabetes mellitus (T1DM) could potentially demask CAN. Forty-eight individuals with long-term T1DM and distal symmetrical polyneuropathy and 21 healthy controls were included. HRV measures were retrieved from 24-h electrocardiograms. Moreover, ultra-short-term HRV recordings were used to assess the dynamic response to the immersion of the hand into 2 °C cold water for 120 s. Compared to healthy, the T1DM group had expectedly lower 24-h HRV measures for most components (p < 0.01), indicating dysautonomia. In the T1DM group, exposure to cold pain caused diminished sympathetic (p < 0.001) and adynamic parasympathetic (p < 0.01) HRV responses. Furthermore, compared to healthy, cold pain exposure caused lower parasympathetic (RMSSD: 4% vs. 20%; p = 0.002) and sympathetic responses (LF: 11% vs. 73%; p = 0.044) in the T1MD group. QRISK3-scores are negatively correlated with HRV measures in 24-h and ultra-short-term recordings. In T1DM, an attenuated sympathovagal response was shown as convincingly adynamic parasympathetic responses and diminished sympathetic adaptability, causing chronometric heart rhythm and rigid neurocardiac regulation threatening homeostasis. The findings associate with an increased risk of cardiovascular disease, emphasizing clinical relevance.

Altered functional connectivity between brain structures in adults with type 1 diabetes and polyneuropathy.

OBJECTIVE: Alterations of the central nervous system are increasingly being recognized as a part of diabetes, especially in the thalamus and the default mode network (DMN). However, the functional involvement in diabetic peripheral neuropathy (DPN) is poorly understood. This study aimed to investigate functional connectivity of thalamus and DMN in individuals with DPN and the associations to clinical characteristics. METHODS: Forty-seven type 1 diabetes mellitus (T1DM) individuals with DPN and 28 healthy controls underwent resting-state functional magnetic resonance imaging. Seed-to-voxel and ROI-to-ROI analyses were performed for thalamus and DMN. The connectivity for both thalamus and DMN were correlated to clinical parameters. RESULTS: Alterations in the functional connectivity of the thalamus and DMN were observed in individuals with T1DM and DPN. Thalamus showed decreased connectivity to the middle frontal, superior frontal, and precentral cortex (all pFWE-corrected<0.05). DMN ROIs showed increased connectivity to the superior frontal cortex (all puncorrected<0.05). A trend towards increased overall connectivity within DMN was observed in the T1DM compared to healthy controls (p=0.051). The subgroup with painful DPN had significantly increased overall connectivity compared to healthy controls (p=0.038). No associations were found to clinical parameters. CONCLUSION: Individuals with DPN had disrupted connectivity between thalamus/DMN and other brain structures and disrupted overall mean connectivity within DMN. Our findings support the existing knowledge of central nervous system involvement in diabetes and provide support for the involvement of thalamus and DMN in people with T1DM and DPN.

The antroduodenal transition time is prolonged in adults with type 1 diabetes.

BACKGROUND: The gastroparetic syndrome encompasses antral hypomotility, gastric dysrhythmia, impaired antroduodenal coordination, pyloric dysfunction, and abnormal duodenal motility; the last three collectively referred to as pylorospasms. We hypothesized that antroduodenal motility is diminished and transition time is prolonged in adults with type 1 diabetes (T1D) and polyneuropathy. METHODS: This cross-sectional study included 124 participants, of which 21 were healthy, 53 had T1D and 50 had T1D with distal symmetrical polyneuropathy (T1D + DSPN). We used the wireless motility capsule to assess antroduodenal transition time, gastric emptying time, gastric and small bowel motility indices (MI), and numbers of alkalic/acidic exposures. RESULTS: In comparison with controls, patients with T1D had prolonged antroduodenal transition time (1.85±1.5 vs. 6.6±4.8 minutes; p=0.02), which was even more pronounced in patients with T1D+DSPN (1.85±1.5 vs. 17.8±28.5 minutes; p<0.008. T1D+DSPN tended to have diminished gastric MI (11.9±2.4 vs. 12.7±1.0, p=0.07) and small bowel MI (13.1±1.4 vs. 13.6±0.6, p=0.05) and experienced more antral/pyloric alkalic episodes (1.2±1.3 vs. 2.0±2.1, p=0.02) compared with controls. CONCLUSION: The current method may assess a proxy for severity of pylorospasms in patients with diabetes and other diseases associated with upper gastrointestinal motility disorders, which ultimately may optimize future management.

Long-term gastrointestinal sequelae in colon cancer survivors: prospective pilot study on identification, the need for clinical evaluation and effects of treatment.

AIM: The aim of the present pilot study was to describe the type and frequency of long-term gastrointestinal symptoms within a well-defined cohort of colon cancer survivors, their wish for clinical evaluation and treatment outcomes. METHOD: A screening survey was sent to colon cancer survivors 12, 24 and 36 months after surgery. Based on their main symptoms, patients who wished to have a consultation were referred to the gastroenterological or surgical unit of our late cancer sequelae clinic. Treatment effect was monitored by questionnaires on bowel symptoms and the EuroQol five-dimensional (EQ-5D) quality-of-life score. RESULTS: Overall, 953 patients who had survived colon cancer received the screening survey and 767 replied (response rate 80.5%). Of these, 76 (9.9%; 95% CI 7.9%-12.2%) were referred for algorithm-based clinical evaluation and treatment of bowel dysfunction. The majority were women (69.7%) who had undergone a right-sided colonic resection (65.8%). Patients reported various symptoms, mainly including urgency, fragmented defaecation, loose stools and incontinence for liquid stools. Patients with emptying difficulties and low anterior resection syndrome-like symptoms were referred to the surgical unit and patients with diarrhoea were referred to the gastroenterological unit for clinical work-up. Our main endpoint, mean EQ-5D index after treatment, was improved compared with baseline (baseline 0.809, after treatment 0.846; p = 0.049). After treatment, self-rated bowel function and several bowel symptoms were improved as well. CONCLUSION: This study highlights the importance of identifying colon cancer survivors in need of treatment of late gastrointestinal sequelae and clinical management in a multidisciplinary team setting.

Abnormal Neuronal Response to Rectal and Anal Stimuli in Patients Treated for Distal Rectal Cancer With High-Dose Chemoradiotherapy Followed By Watchful Waiting.

BACKGROUND: Watchful waiting in patients with rectal cancer with complete clinical response after chemoradiation therapy has gained increased popularity to avoid morbidity and mortality associated with surgery. Irradiation of the pelvis causes bowel dysfunction, but the effect on anorectal sensory function remains obscure in this patient category. OBJECTIVE: The aim of this study was to characterize the sensory pathways of the gut-brain axis in patients with rectal cancer treated solely with chemoradiation therapy (nonconventional regime/dose) compared with healthy volunteers. DESIGN: This is an explorative study. SETTINGS: Sensory evaluation by rectal distension was performed and cortical evoked potentials were recorded during rapid balloon distensions of the rectum and anal canal. Latencies and amplitudes of cortical evoked potentials were compared, and the relative amplitude of 5 spectral bands from recorded cortical evoked potentials was used as an additional proxy of neuronal processing. PATIENTS: Patients with rectal cancer solely with chemoradiation therapy (n = 13) a median of 3.2 years ago (range, 2.3-5.6 y) and healthy volunteers (n = 13) were included. MAIN OUTCOME MEASURES: Cortical evoked potentials were measured. RESULTS: Patients had 35% lower rectal capacity at a maximum tolerable volume (p = 0.007). We found no differences in rectal cortical evoked potential latencies (p = 0.09) and amplitudes (p = 0.38) between groups. However, spectral analysis of rectal cortical evoked potentials showed a decrease in θ (4-8 Hz) and an increase in ß (12-32 Hz) band activity in patients (all p < 0.001). Anal cortical potentials showed an increase in α (8-12 Hz) and ß and a decrease in γ (32-70 Hz) band activity (all p < 0.001) in patients compared with healthy volunteers. LIMITATIONS: This is an explorative study of limited size. CONCLUSIONS: Chemoradiation therapy for distal rectal cancer causes abnormal cortical processing of both anal and rectal sensory input. Such central changes may play a role in symptomatic patients, especially when refractory to local treatments. See Video Abstract at http://links.lww.com/DCR/B270. RESPUESTA NEURONAL ANORMAL A ESTÍMULOS RECTALES Y ANALES, EN PACIENTES TRATADOS POR CÁNCER RECTAL DISTAL, CON QUIMIORRADIOTERAPIA DE DOSIS ALTA, SEGUIDA DE ESPERA VIGILANTE: La espera vigilante en pacientes de cáncer rectal, con respuesta clínica completa después de la quimiorradiación, ha ganado una mayor popularidad en evitar la morbilidad y mortalidad asociadas con la cirugía. La irradiación de la pelvis causa disfunción intestinal, pero el efecto sobre la función sensorial ano-rectal sigue siendo no claro, en esta categoría de pacientes.El objetivo de este estudio, fue caracterizar las vías sensoriales del eje intestino-cerebro en pacientes con cáncer rectal, tratados únicamente con quimiorradiación (régimen / dosis no convencional), en comparación con voluntarios sanos.Es un estudio exploratorio.Se realizó una evaluación sensorial por distensión rectal y se registraron los potenciales evocados corticales, durante las distensiones rápidas con balón en recto y canal anal. Se compararon las latencias y amplitudes de los potenciales evocados corticales, y la amplitud relativa de cinco bandas espectrales registradas, de potenciales evocados corticales, se usaron como proxy adicional del procesamiento neuronal.Pacientes de cáncer rectal, únicamente con terapia de quimiorradiación (n = 13) mediana de 3.2 años (rango 2.3-5.6) y voluntarios sanos (n = 13).Potenciales evocados corticales.Pacientes tuvieron una capacidad rectal menor del 35%, al volumen máximo tolerable (p = 0.007). No encontramos diferencias en las latencias potenciales evocadas corticales rectales (p = 0.09) y amplitudes (p = 0.38) entre los grupos. Sin embargo, el análisis espectral de los potenciales evocados corticales rectales, mostró una disminución en theta (4-8 Hz) aumento en beta (12-32 Hz), y actividad en banda en pacientes (todos p <0.001). Los potenciales evocados corticales anales mostraron un aumento en alfa (8-12 Hz) y beta, disminución en gamma (32-70 Hz), y actividad en banda (todos p <0.001), en pacientes comparados a voluntarios sanos.Este es un estudio exploratorio de tamaño limitado.La quimiorradiación para el cáncer rectal distal, ocasiona procesos corticales sensoriales anormales anales y rectales. Tales cambios centrales pueden desempeñar un papel en pacientes sintomáticos, especialmente cuando son refractarios a tratamientos locales. Consulte Video Resumen en http://links.lww.com/DCR/B270.

Clinical evaluation and treatment of chronic bowel symptoms following cancer in the colon and pelvic organs.

Background: Chronic gastrointestinal symptoms are common among patients surviving surgery and/or radio-/chemotherapy for cancer in the pelvic organs. However, little is known about the pathophysiology behind symptoms or the effect of treatment. The aim of the present study was to present the results of clinical evaluation and treatment of patients with chronic bowel symptoms after treatment for cancer in the colon or pelvic organs. Material and methods: All patients referred to our department of gastroenterology between May 2016 and June 2018 with chronic bowel symptoms after treatment for cancer in the colon or pelvic organs were prospectively evaluated. Results: In total, 60 patients had been referred. The patients were treated for cancer in the right colon (n = 31), sigmoid colon (n = 1), rectum (n = 14), anal canal (n = 4), cervix uteri (n = 5), corpus uteri (n = 2), ovary (n = 2), and prostate (n = 1). The median time from cancer treatment to referral was 5.5 (range 1-36) years. Symptoms mainly included frequent bowel movements (65%), loose stools (87%), urgency for defecation (57%), and fecal incontinence (50%). A specific cause of bowel dysfunction was found in 48 (80%) of the patients and 21 (35%) had more than one cause of bowel symptoms. Bile acid malabsorption was present in 35 patients and small intestinal bacterial overgrowth was detected in 32. Treatment included bile acid sequestrants (n = 36), antibiotics (n = 33), loperamide (n = 21), and dietary intervention (n = 20). Major improvement in bowel symptoms was reported by 23 (38%) patients, while another 27 (45%) reported some improvement. Conclusion: Most patients with chronic bowel symptoms following cancer in the colon or pelvic organs will benefit from expert clinical evaluation and targeted treatment.

MRI assessed pancreatic morphology and exocrine function are associated with disease burden in chronic pancreatitis.

BACKGROUND AND AIM: The aim of this study was to explore the association between morphological and functional secretin-stimulated MRI parameters with hospitalization, quality of life (QOL), and pain in patients with chronic pancreatitis (CP). PATIENTS AND METHODS: This prospective cohort study included 82 patients with CP. Data were obtained from clinical information, QOL, and pain as assessed by questionnaires (The European Organization for Research and Treatment of Cancer Quality of Life Questionnaire and modified Brief Pain Inventory short form). Secretin-stimulated MRI morphological parameters included pancreatic gland volume, main pancreatic duct diameter, the modified Cambridge Classification of Duct Abnormality, apparent diffusion coefficient, fat signal fraction, and the pancreatic secretion volume as a functional parameter. The primary outcomes were time to first hospitalization related to the CP, as well as annual hospitalization frequency and duration. The secondary outcomes were pain severity, QOL, and pain interference scores. RESULTS: A main pancreatic duct diameter below 5 mm was associated with reduced time to first hospitalization (hazard ratio=2.06; 95% confidence interval: 1.02-4.17; P=0.043). Pancreatic secretion volume was correlated with QOL (r=0.31; P=0.0072) and pain interference score (r=-0.27; P=0.032), and fecal elastase was also correlated with QOL (r=0.28; P=0.017). However, functional and morphological findings were not related to pain intensity. CONCLUSION: Advanced pancreatic imaging techniques may be a highly sensitive tool for prognostication and monitoring of disease activity and its consequences.

Diagnosis of autoimmune pancreatitis by core needle biopsy: application of six microscopic criteria.

Autoimmune pancreatitis (AIP) has been established as a special entity of chronic pancreatitis (CP). However, its clinical distinction from pancreatic cancer and other types of CP is still difficult. The aim of this study was to evaluate the efficacy of pancreatic core needle biopsy for the diagnosis of AIP. In 44 core needle biopsy specimens, we assessed the following microscopic features: granulocytic epithelial lesions (GELs), more than ten IgG4-positive plasma cells/HPF, more than ten eosinophilic granulocytes/HPF, cellular fibrosis with inflammation, lymphoplasmacytic infiltration, and venulitis. All biopsies that showed four or more of the six features (22 of 44) were obtained from 21 of 26 patients whose clinical diagnosis and follow-up were consistent with AIP. All non-AIP CP patients (n = 14) showed three or less than three of the features in their biopsies. GELs were only observed in biopsy specimens from AIP patients. In conclusion, our data indicate that the six criteria we applied were able to recognize AIP in 76% of biopsy specimens using a cut-off level of four. When the specimens that revealed only three features but showed GELs were added, the sensitivity rose to 86%. Pancreatic core needle biopsy can therefore make a significant contribution to the diagnosis of AIP.