Experiences and needs of partners as informal caregivers of patients with major low anterior resection syndrome: A qualitative study.

PURPOSE: After treatment, many rectal cancer survivors are confronted with ongoing bowel problems, called low anterior resection syndrome. The cancer diagnosis and treatment poses a burden on informal caregivers and results in higher levels of psychological distress and loneliness which is persistent after treatment as well. Our study aimed to investigate the experiences and needs of partners as informal caregivers of patients with major low anterior resection syndrome. METHODS: A ground theory study was conducted. Semi-structured interviews with partners as informal caregivers of patients with major low anterior syndrome were performed in three hospitals between 2017 and 2019. In the first phase, maximum variation sampling was used and later theoretical sampling. Data analysis was done using the constant comparative method and investigators triangulation. RESULTS: Twenty partners as informal caregivers were interviewed until data saturation. Low anterior resection syndrome of their partner was overwhelming and they failed to live a normal life. They had the feeling that they stood at the side-line and partly because of that felt lonely. Partners experienced three levels of loneliness: because of their changed own life, the changed life of their partner and the changed life in the environment. CONCLUSION: Low anterior resection syndrome has a large impact on the lives of partners as informal caregivers and induces loneliness at three levels. It is key that the HCPs of the interdisciplinary team understand this impact. A clinical nurse specialist/oncology nurse navigator could help in alleviate that burden by addressing both patients' and partners' needs.

The trajectory of hope and loneliness in rectal cancer survivors with major low anterior resection syndrome: A qualitative study.

PURPOSE: Rectal cancer survivors are often confronted with long-term bowel function impairment, called low anterior resection syndrome. This has a large impact on patients' lives. The aim was to explore the experiences of patients with major low anterior resection syndrome with a specific focus on hope and loneliness. METHODS: A grounded theory approach was used. Individual semi-structured interviews (n = 28) were performed between 2017 and 2019. Patients were recruited in three hospitals and a call was distributed in two patients' organizations. During data analysis, the constant comparative method and investigators' triangulation was used. RESULTS: Hope was important at different stages in the trajectory. After treatment patients hoped to pick up their previous life. Confrontation with low anterior resection syndrome was unexpected and patients hoped to manage it through trial and error. They lost hope if further improvement was absent. At that turning point some tried to accept the new lifestyle, others pushed their boundaries and some opted for a permanent stoma. Loneliness presented itself in several layers. Patients experience loneliness due being toilet-bound, changes in their lives and activities outside their homes and the impact on their family life. CONCLUSION: Assessment of the impact on patients' lives and tailored counselling is possible if healthcare professionals gain more insight into the different layers of loneliness and where the patient is located in the trajectory of hope.

Experiences and needs of patients with rectal cancer confronted with bowel problems after stoma reversal: A systematic review and thematic-synthesis.

PURPOSE: After the reversal of the temporary stoma, rectal cancer survivors are often confronted with bowel complaints largely impacting on their quality of life. This systematic review aims to identify and synthesise the experiences and needs of patients with rectal cancer confronted with bowel problems after stoma reversal. METHODS: A systematic search was performed through Pubmed, CINAHL and Web of Science. Only studies with a qualitative design were included in this review. Quality assessment was done by the critical appraisal skill programme (CASP) Qualitative Studies Checklist. A thematic-synthesis was performed. RESULTS: Of 2713 identified papers, 10 were included in this systematic review. Two general themes were identified: 'experiences and needs about bowel function before surgery' and 'experiences and needs afterwards'. Before restoration of continuity patients had to cope with the temporary stoma, and they felt uncertain about what to expect. Patients indicated that the timing of providing information was crucial but varied. Bowel problems after surgery had a physical and emotional impact on patients' family life. They were also confronted with shame and stigma. Patients were happy to be alive and cancer free but were hopeful that the bowel problems would resolve. They used several strategies to manage and cope with these symptoms. Peers and healthcare professionals proved valuable resources of support. CONCLUSION: Rectal cancer survivors experience ongoing bowel problems after treatment. Patients describe experiences and needs before rectal cancer surgery and afterwards when confronting with bowel problems. Follow-up care should be organised proactively and focus on management strategies and emotional support.

Impact of low anterior resection syndrome (LARS) on the quality of life and treatment options of LARS - A cross sectional study.

PURPOSE: The purpose of this study was to assess the relationship between the low anterior resection syndrome (LARS) and quality of life (QOL). Furthermore, in patients with major LARS, therapeutic management options were explored. METHODS: A cohort of surviving patients, who underwent a low anterior resection for rectal cancer after long course of radiochemotherapy, were identified. These patients were treated in Ghent University Hospital between 2006 and 2016. QOL was assessed using the European Organization for Research and Treatment of Cancer Quality Of Life questionnaire-C30 and the bowel function using the LARS-score. The relationship between LARS and QOL was analysed. Patients with major LARS (≥30 points) were contacted to explore their therapeutic management of LARS. RESULTS: 69% of the participants had major LARS. QOL was closely associated with LARS. Significant differences were found between those with and without LARS in the global health status (p ≤ 0.001) and in the following functional scales: physical (p ≤ 0.001), role (p ≤ 0.001), cognitive (p = 0.04) and social (p ≤ 0.001). Patients with major LARS experienced more diarrhea (p ≤ 0.001), fatigue (p = 0.002), insomnia (p ≤ 0.001) and pain (p = 0.02), compared to patient with no/minor LARS. Most patients tried dietary regimens (71%), medication (71%) and incontinence material (63.8%) in an attempt to manage their LARS and found some of them useful. The level of the anastomosis (low) was a significant risk factor for major LARS (p=0.03). CONCLUSION: More than half of the patients in this cohort still suffered from major LARS. Patients confronted with major LARS had a lower QOL than patients with no/minor LARS. Currently, there is no gold standard for the management of LARS. Patients manage it through trial and error.

NF-kB2 induces senescence bypass in melanoma via a direct transcriptional activation of EZH2.

Enhancer of Zeste homologue 2 (EZH2) belongs to the polycomb repressive complex 2 and catalyzes the methylation of histone H3 lysine 27. These pivotal epigenetic marks are altered in many cancers, including melanoma, as a result of EZH2 overexpression. Here, we show that the non-canonical-NF-kB pathway accounts for most of the NF-kB activity in melanoma cells, in contrast to non-cancer cells. We identify the non-canonical-NF-kB pathway as a key regulator of EZH2 expression in melanoma. We show a striking correlation between NF-kB2 and EZH2 expression in human melanoma metastases. We demonstrate that inhibition of the non-canonical NF-kB pathway by targeting NF-kB2/p52 or the upstream kinase NIK restores the senescence program in melanoma cells through the decrease of EZH2. On the contrary, the overexpression of NF-kB2/p52 in normal human melanocytes prevents stress- and oncogene-induced senescence. Finally, we show in mouse models that the inhibition of the non-canonical NF-kB pathway restores senescence and induces a dramatic reduction in tumor growth compared with controls, thus providing potential drug targets for the re-induction of senescence in melanoma and other cancers where EZH2 is overexpressed.

Severe scurvy: an underestimated disease.

Scurvy is one of the oldest diseases in human history. Nowadays, although scurvy tends to become a forgotten disease in developed country, rare cases still occur, especially in people undergoing extreme diet, old people or children with poor diet and patients with malabsorption. We describe three cases of scurvy. The first case is a patient diagnosed with Crohn's disease, the second one is in a context of anorexia nervosa and drug addiction, and the third case is in a context of social isolation. Early recognition of scurvy can be difficult because symptoms may appear nonspecific and can mimic more common conditions. In any patient with spontaneous hematoma and purpura, in the context of nutritional disorder, scurvy should be systematically considered. As this disease can lead to severe complications, such as bone pain, heart failure or gastrointestinal symptoms, nothing should delay vitamin C supplementation, which is a simple and rapidly effective treatment.

Desmopressin-related myocardial infarction in a patient with Wegener's granulomatosis: a case report and review of the literature.

Desmopressin is a synthetic vasopressin analog that increases the plasma levels of coagulation factor VIII, von Willebrand factor, and tissue plasminogen activator. This hemostatic agent, which can be administered either parenterally or intranasally, has been approved for use in the prevention and treatment of hemorrhagic events during surgery in patients with hemophilia A, in cases of prolonged idiopathic bleeding, and for complications associated with platelet antiaggregant therapy. This case report describes cardiac toxicity associated with desmopressin administered according to the recommended indications: a 55-year-old woman diagnosed with Wegener's granulomatosis (WG) was treated with desmopressin to improve hemostasis and shorten bleeding time before a planned renal biopsy. She developed cardiac arrest within 60 minutes of the desmopressin injection. Cardiopulmonary resuscitation began immediately and was successful, although the patient subsequently died of WG-associated complications. Desmopressin administration thus appears, in some cases, to be associated with a high risk of thrombotic events, possibly by stimulating the rapid release of endothelial factors such as an abnormal multimeric form of von Willebrand factor, which might cause platelet aggregation. Clinicians should be aware of the possible occurrence of this little-known but potentially serious cardiac event associated with desmopressin administration and be prepared to initiate cardiopulmonary resuscitation immediately if needed.

Evolutionary history shapes the association between developmental instability and population-level genetic variation in three-spined sticklebacks.

Developmental instability (DI) is the sensitivity of a developing trait to random noise and can be measured by degrees of directionally random asymmetry [fluctuating asymmetry (FA)]. FA has been shown to increase with loss of genetic variation and inbreeding as measures of genetic stress, but associations vary among studies. Directional selection and evolutionary change of traits have been hypothesized to increase the average levels of FA of these traits and to increase the association strength between FA and population-level genetic variation. We test these two hypotheses in three-spined stickleback (Gasterosteus aculeatus L.) populations that recently colonized the freshwater habitat. Some traits, like lateral bone plates, length of the pelvic spine, frontal gill rakers and eye size, evolved in response to selection regimes during colonization. Other traits, like distal gill rakers and number of pelvic fin rays, did not show such phenotypic shifts. Contrary to a priori predictions, average FA did not systematically increase in traits that were under presumed directional selection, and the increases observed in a few traits were likely to be attributable to other factors. However, traits under directional selection did show a weak but significantly stronger negative association between FA and selectively neutral genetic variation at the population level compared with the traits that did not show an evolutionary change during colonization. These results support our second prediction, providing evidence that selection history can shape associations between DI and population-level genetic variation at neutral markers, which potentially reflect genetic stress. We argue that this might explain at least some of the observed heterogeneities in the patterns of asymmetry.

[Non-tuberculous systemic granulomatosis mimicking sarcoidosis but related to a specific etiology. Study of 67 cases]. / Granulomatoses systémiques pseudosarcoïdosiques d'étiologie déterminée et non tuberculeuse. Etude de 67 observations.

PURPOSE: Systemic granulomatosis (SG) are frequently encountered in internal medicine. Despite a large list of aetiologies, the investigations remain often negative leading to the diagnosis of atypical sarcoidosis. The spectrum of the causes, as well as evolution of these SG is not clearly delineated in the literature. METHOD: We analyzed the case reports of all but tuberculous GS submitted at the National Meetings of the National French Society of Internal Medicine from 1990 to 2006. RESULTS: Sixty-seven cases were included in the study. The average age at the beginning of the symptoms was 47.8 years and 28.4% of the patients were female. The median diagnostic delay was one year. General symptoms were present in 73.1% of the cases. The involved organs were the liver (46.3%), lungs (25.4%), lymph nodes (22.4%), digestive tract (16.4%), skin (16.4%), spleen (14.9%). The granuloma were detected mainly in the liver (38.8%), lymph nodes (17.9%), bone marrow (16.4%) and lungs (11.9%). Elevated erythrocyte sedimentation rate or increased C reactive protein serum levels were noted in 65.6% of the patients. Before diagnosis, 19.4% of the patients received a corticotherapy. The most common diagnoses were infections (65.6%) followed by drugs (19.5%), "toxic substances" or various foreign bodies (5.9%), neoplasias (5.9%) and immune deficiencies (3%). The evolution was favourable in 80% of the cases but 8.3% of the patients died. The disease course of the patients having received a corticotherapy prior to the diagnosis was more unfavourable with a death rate of 45%. CONCLUSION: In atypical sarcoidosis (fever, advanced age, increased acute phase reactants...) a specific aetiology and especially an infectious disease should be ruled out before considering the diagnosis of sarcoidosis. Corticotherapy is a factor of poor prognosis.

Diagnostic validity of somatosensory evoked potentials in subgroups of patients with sciatica.

The diagnostic utility of scalp-recorded somatosensory evoked potentials (SEP) in patients with sciatica has generally been regarded as low. The purpose of the present study was to determine the validity of sensory nerve SEP in different subgroups of sciatic patients. A total of 65 consecutive patients with sciatica showing disc pathology and/or facet joint hypertrophy on lumbar computed tomography (CT) and/or myelography were studied. Symptomatic myelographically compressed nerve roots were defined as truly compromised roots. Asymptomatic myelographically normal nerve roots were defined as truly normal roots. Bilateral sensory nerve SEP representing nerve roots L4, L5, and S1 were performed in all patients. Evaluation of SEP included the use of P1 latency inter-root comparison. The false-positive rate of SEP was low. Pathological L4, L5, and S1 SEP therefore strongly indicate true compromise of the corresponding nerve roots. The true-positive rate was higher in patients with facet joint hypertrophy with or without additional disc disease than in patients with disc pathology only, and highest if the sciatic sensory symptoms were present during the SEP registration. Diagnostic validity was not influenced by previous episodes of sciatica, the duration of the present episode, or the number of spinal levels with ipsilateral myelographically compressed nerve roots. Pathological SEP strongly indicate sensory radiculopathy in patients with sciatica. Diagnostic efficacy is higher in patients with facet joint hypertrophy than in patients with disc pathology only and highest when the sciatic symptoms are present during registration.

Sensory nerve somatosensory evoked potentials (SEP) in the evaluation of patients with sciatica: false P1 latency prolongation may be due to admixture of dermatomal SEP.

Patient-reported stimulus-related radiating sensory symptoms within the territory of the stimulated nerve have been used to verify stimulation in sensory nerve scalp recorded somatosensory evoked potentials (SEP). The main aim of the present study of false positive P1 latency prolongation in lumbosacral sensory nerve SEP was to investigate whether elicitation of such symptoms secures adequate sensory nerve stimulation. Nerve roots were studied on the asymptomatic side in 64 patients with unilateral sciatica. Saphenous (L4), superficial peroneal (L5), and sural (S1) nerve SEP were registered in all patients. Pretibial dermatomal SEP were registered in ten of them. Stimulation was equidistant from the registration electrode in all SEP registrations. The false positive rate was lower in saphenous nerve SEP with than without verified supramaximal stimulation (1/30 vs. 6/22, P = 0.03) in spite of radiating stimulus-related sensory symptoms in both groups. This difference was not caused by subclinical myelographic nerve root compression or general peripheral nerve dysfunction. The P1 latency was longer in the pretibial dermatomal SEP than in the saphenous and superficial peroneal nerve SEP with the same conduction distance (mean difference 4.7 (95% CI = 3.8 to 5.6) and 4.4 ms (95% CI = 3.4 to 5.4), respectively). It is concluded that dermatomal SEP have longer P1 latency than sensory nerve SEP. Verified supramaximal nerve simulation is recommended to avoid false results due to admixture of dermatomal to sensory nerve SEP.

Sensory nerve somatosensory evoked potentials as add-on diagnostic procedure to imaging procedures in patients with sciatica.

The aim of the present study was to evaluate the ability of sensory nerve somatosensory evoked potentials (SEP) to discriminate between lumbar spine computed tomography (CT) findings with and without relevance for the radiating sensory symptoms in patients with sciatica in whom myelography does not have such discriminatory capacity. Forty consecutive sciatic patients in whom CT without intrathecal contrast showed degenerative changes which did not cause probable compression in at least one symptomatic nerve root, or caused probable compression in at least one asymptomatic nerve root, and in whom there were corresponding discrepancies between the radiating sensory symptoms and myelographic nerve root compression, were studied. Sensory nerve SEP representing nerve roots L4, L5 and S1, were performed in all patients. The sensory nerve conduction velocity (SNCV) and the amplitude of the sensory nerve action potential (SNAP) were recorded from the stimulated nerves. The odds ratios (OR 95% CI) of the association of positive SEP to symptomatic nerve roots were 24.0 (4.8 to 54.5) in nerve roots with probable and 39.0 (5.9 to 258.9) with possible CT compression. The corresponding associations between myelography and sciatic symptoms were not statistically significant. Comparisons of SNCVs and SNAP amplitudes did not indicate that postganglionic nerve dysfunction contributed to the sensory symptoms or to the SEP results. SEP examination may be used to discriminate between CT findings with and without relevance to the radiating sensory symptoms in patients with sciatica in whom myelography does not show this discriminatory capacity.

P1-latency interroot comparison enhances the validity of scalp-recorded somatosensory-evoked potentials to diagnose nerve root dysfunction in sciatica.

STUDY DESIGN: A prospective validity study was done of scalp-recorded somatosensory-evoked potentials as a diagnostic procedure to show lumbosacral radiculopathy in 100 consecutive patients with unilateral or bilateral sciatica. OBJECTIVE: To determine the validity gained by the use of P1-latency interroot comparison to show P1-latency prolongation. SUMMARY OF THE BACKGROUND DATA: The validity of scalp-recorded somatosensory-evoked potentials in diagnosing lumbosacral radiculopathy has been debated and is uncertain. METHOD: Sensory nerves representing nerve roots L4, L5, and S1 were stimulated bilaterally. Height-corrected P1-latency, two new P1-interroot comparison-based criteria, and absence of P1 were studied. The gold standard was defined as clinically-involved nerve roots with radiologic nerve root compression. The false-positive nerve root compression rate was determined, and the gold standard was corrected accordingly. Clinically relevant cut-off values were defined by multilevel likelihood ratio analysis. RESULTS: The positive and negative likelihood ratios of P1-latency prolongation were 6.79 and 0.53, respectively, for the gold standard, and 10.57 and 0.21, respectively, for the corrected gold standard. The validity was not reduced when scalp-recorded, somatosensory-evoked potentials were blinded to the radiologic results. Absence of P1 was associated to the gold standard and the corrected gold standard. Compared with the combined use of P1-latency interside difference and height-corrected latency, the combination of P1-interroot comparison and height-corrected P1-latency increased the sensitivity by 20% for the gold standard and 32% for the corrected gold standard, and when absent P1 was added, the overall sensitivity was 53% for the gold standard and 81% for the corrected gold standard. The corresponding specificity was 92%, and in asymptomatic nerve roots it was 98%. CONCLUSION: The P1-interroot comparison permits the use of scalp-recorded somatosensory-evoked potentials as a contributory "rule in" procedure in patients with sciatica.

Endogenously labeled thyroid hormones (131I-T3/T4) in sera of patients with differentiated thyroid carcinoma.

Patients with differentiated thyroid carcinoma (DTC), who have undergone thyroidectomy and radioablation with iodine (131I), are usually monitored with ultrasonography (US) of the neck, 131I whole body scan (WBS), and determination of thyroglobulin (Tg) concentrations in serum. A chromatographic method (CHROM), designed for detection of in vivo labeled thyroid hormones (131I-T3/T4) that circulate in the body after administration of 131I for a WBS, may be used in monitoring of these patients. This study included 35 patients with DTC. Ultrasonography, WBS, Tg, and CHROM method were performed for each of them. One patient was followed-up 6 times, 11 were monitored twice, and the remaining group of 23 patients was examined only once (51 diagnostic tests). We found CHROM results to be in disagreement with the WBS and/or Tg findings in three patients out of 35 at the time of the first visit. In one of them WBS was negative, while Tg and CHROM findings were positive. In this patient the local metastases were proven by US with fine needle biopsy (FNB). In another patient (without signs of thyroid tissue remnant, determined by WBS, Tg, and US) only CHROM was positive. Finally, in the third patient, a thyroid remnant was proven positive on WBS and US (negative CHROM and Tg). We registered an additional peak (peak 4) in chromatograms of 12 out of 35 patients. This component could be tentatively characterized as 3,3'-diiodo-L-thyronine (131I-3,3'-T2). Although this preliminary study included a small number of patients, we show that the CHROM method can be useful as an additional test in monitoring of patients with DTC, especially those with discordant WBS and Tg results.