European Society of ColoProctology: guideline for haemorrhoidal disease.

AIM: The goal of this European Society of ColoProctology project was to establish a multidisciplinary, international guideline for haemorrhoidal disease (HD) and to provide guidance on the most effective (surgical) treatment for patients with HD. METHODS: The development process consisted of six phases. In phase one we defined the scope of the guideline. The patient population included patients with all stages of haemorrhoids. The target group for the guideline was all practitioners treating patients with haemorrhoids and, in addition, healthcare workers and patients who desired information regarding the treatment management of HD. The guideline needed to address both the diagnosis of and the therapeutic modalities for HD. Phase two consisted of the compilation of the guideline development group (GDG). All clinical members needed to have affinity with the diagnosis and treatment of haemorrhoids. Further, attention was paid to the geographical distribution of the clinicians. Each GDG member identified at least one patient in their country who could read English to comment on the draft guideline. In phase three review questions were formulated, using a reversed process, starting with possible recommendations based on the GDG's knowledge. In phase four a literature search was performed in MEDLINE (Ovid), PubMed, Embase (Ovid) and the Cochrane Database of Systematic Reviews. The search was focused on existing systematic reviews addressing each review question, supplemented by other studies published after the time frame covered by the systematic reviews. In phase five data of the included papers were extracted by the surgical resident (RT) and checked by the methodologist (JK) and the GDG. If needed, meta-analysis of the systematic reviews was updated by the surgical resident and the methodologist using Review Manager. During phase six the GDG members decided what recommendations could be made based on the evidence found in the literature using GRADE. RESULTS: There were six sections: (i) symptoms, diagnosis and classification; (ii) basic treatment; (iii) outpatient procedures; (iv) surgical interventions; (v) special situations; (vi) other surgical techniques. Thirty-four recommendations were formulated. CONCLUSION: This international, multidisciplinary guideline provides an up to date and evidence based summary of the current knowledge of the management of HD and may serve as a useful guide for patients and clinicians.

To be in pain (or not): a computer enables outpatients to inform their physician.

BACKGROUND: In the outpatient oncology clinic, pain management is often inadequate. Incorporating a systematic pain management program into visits is likely to improve this. We implemented an integrated program, including a structured pain assessment, pain treatment protocol and patient education module. In the present study, we investigated whether this intervention improved pain control. PATIENTS AND METHODS: At seven oncology outpatient clinics, patients were asked to register their pain intensity on a touch screen computer. These scores were made available into their electronic medical records. Additionally, a hospital-wide treatment protocol for cancer-related pain and a patient education module were developed. A data warehouse system enabled us to extract patient data from the electronic medical record anonymously and to use them for analysis. The primary outcome of the study was the percentage of patients with moderate to severe pain [current pain (CPI), NRS > 4] measured during 2 weeks at the start and 6 months after implementation. As secondary outcomes, we studied the percentage of pain registrations in specific patient groups and the percentage of patients treated with a curative and a palliative intention with (moderate-severe) pain. Differences were tested with the χ(2) test. RESULTS: During the first 6 months, 3407 of the 4345 patients (78%) registered their pain intensity on the touch screen computer. The percentage of patients with moderate to severe CPI decreased 32% (P = 0.021): from 12.5% at start to 8.5% after 6 months. More patients in the palliative phase than in the curative phase of their disease registered their pain intensity (82% versus 75%, respectively, P < 0.005), and more patients in the palliative phase experienced moderate to severe pain (23% versus 14%, respectively, P < 0.001). CONCLUSION: Pain registration by patients themselves is feasible, provides insight into patients' pain intensity and may improve pain control in outpatients with cancer-related pain. CLINICAL TRIAL NUMBER: Because this is an innovation project and not a primary research project, it has no clinical trial number. The protocol and all materials involved were approved by the Institutional Review Board of the Erasmus MC (MEC-2009-324).

Perianal streptococcal dermatitis in adults: its association with pruritic anorectal diseases is mainly caused by group B Streptococci.

AIM: Although perianal streptococcal dermatitis (PSD) is well known in children, it has only rarely been documented in adults. The incidence and necessity for treatment may be underestimated. We have retrospectively identified adult patients with perianal streptococcal dermatitis. METHOD: Patients with streptococcal anal dermatitis were identified from a prospective office database. Treatment was with oral antibiotics according to the organism sensitivity. Additional concomitant anorectal disease was treated according to standard guidelines. Patients were compared with a control group, without eczema or erythema, for the presence of ß-haemolysing Streptococci on perianal swab. Demographic and microbiological data were assessed and compared between and within treatment and control groups. RESULTS: Fifty-three (22 female) patients older than 20 (mean = 49) years of age were diagnosed with perianal streptococcal dermatitis between 2005 and 2009. In most cases group B ß-haemolytic Streptococci were found. Fifty patients received antibiotics for 14 days. In 28 of 33 patients who had a post-treatment swab, the result was negative. Five patients showed Streptococci of different groups in the post-treatment swab. Of the 50 patients, 21 (42%) had no further anorectal complaint and 29 (58%) required continuing treatment for another anorectal condition. In the control group ß-haemolysing Streptococcus was found in 34%. Men over 60 years of age more often required no further anorectal treatment compared with women (P < 0.05). CONCLUSION: Perianal streptococcal dermatitis occurs in adult patients more often than reported. It is mainly caused by group B ß-haemolysing Streptococcus. Its diagnosis is important because it can cause serious systemic infections, especially in the elderly and in newborns. Antibiotics resolve the condition in a high proportion of patients.

Strain-specific immunomodulatory effects of Lactobacillus plantarum strains on birch-pollen-allergic subjects out of season.

BACKGROUND: Allergic diseases are increasing world-wide, and according to the hygiene hypothesis may be related to a decreased exposure to environmental bacteria. Probiotic bacteria are recognized for their immunomodulating properties, and may benefit allergy patients. In vitro studies reveal immunomodulatory effects that are strain dependent. Differential immunomodulatory in vitro capacities cannot be extrapolated directly to in vivo efficacy. Thus, in vitro screening should preferably be followed by a comparative analysis of the selected immunomodulatory strains in an in vivo setting. OBJECTIVE: We selected five Lactobacillus strains on their IL-10-inducing capacity, and evaluated the immunomodulatory properties in birch-pollen-allergic subjects outside the hayfever season, with a reduction of IL-13 as the primary outcome. METHODS: A double-blind, placebo-controlled parallel study was performed in which 62 subjects with a proven birch-pollen allergy consumed one of five different probiotic yoghurts containing four Lactobacillus plantarum strains and one Lactobacillus casei strain or a placebo yoghurt. Blood samples were collected at the start and after 4 weeks. Several immune parameters were determined in serum and peripheral blood mononuclear cell cultures (PBMC) derived from these subjects. Results A decrease in birch-pollen-specific IgE was found for four probiotic strains. L. casei Shirota reduced the number of CD16(+) /CD56(+) cells in peripheral blood mononuclear cells. For strain L. plantarum CBS125632, the decrease in IgE coincided with significant decreases in IL-5 and IL-13 production by αCD3/αCD28-stimulated PBMC cultures. CONCLUSION AND CLINICAL RELEVANCE: Subjects with seasonal allergy can be used to determine immunomodulatory responses outside the pollen season within a 4-week study period. L. plantarum CBS125632 decreased several immune markers related to allergy, and may have the potential to alleviate the severity of seasonal allergy symptoms.

Agraffectomy after low rectal stapling procedures for hemorrhoids and rectocele.

BACKGROUND: Various sequelae which might lead to reintervention have been described after stapled rectal mucosectomy for hemorrhoids. One potential treatment modality for persistent complaints after stapled hemorrhoidopexy (SHP) or stapling for rectocele is the so-called agraffectomy (removal of the retained staples). This treatment option means a further procedure that can range from removal of the staples through the anoscope to removal of the entire staple line with the associated scar tissue. METHODS: In order to review the published literature, we conducted a search on Medline, Pubmed, and Embase using different terms for "agraffectomy." RESULTS: Overall, fourteen reports were found, dealing with agraffectomy for various conditions after low rectal stapling for hemorrhoids or rectocele. Agraffectomy is a rarely mentioned treatment option for conditions after SHP. In rectal stenosis with complete occlusion of the rectal lumen, the removal of the stenotic anastomosis and remaining staples seems to be reasonable. The same can be said of the removal of retained staples for rectal bleeding or in order to avoid penile injuries in anal intercourse. In contrast, the collected published reports on agraffectomy in this review only provide low-level evidence that this procedure provides relief for other problems such as incontinence or chronic pain. CONCLUSIONS: There is no clear evidence that agraffectomy is indicated if not in case of rectal stenosis and hemorrhage caused by the staples.

[Quality indicators in the treatment of hemorrhoids]. / Qualitätsindikatoren bei der Therapie des Hämorrhoidalleidens.

BACKGROUND: A quality indicator is a quantitative measure that can be used to monitor and evaluate the quality of certain operative procedures that may influence the result of a therapy. An indicator is not a direct measure of quality, it is merely a tool to evaluate the performance of procedures and can indicate potential problem areas. MATERIAL AND METHODS: A literature search was performed for parameters which could be included as indicators of quality in the treatment of hemorrhoids. RESULTS AND CONCLUSION: In the treatment of benign diseases, such as hemorrhoids objective indicators (e.g. recurrence or survival rates in oncological diseases) cannot be used as quality indicators. Other indicators or core outcome factors must be used. From the patient's point of view other indicators are important (such as pain, complications, continence, days off work, etc.) than those for the colorectal surgeon, health insurance and healthcare provider. The most important indicators or outcome factors for treatment of hemorrhoids are postprocedural pain, patient satisfaction, complications, residual and recurrent symptoms, pain, quality of life, costs and duration of inability to work. In terms of outcome quality various quality indicators could be identified which also play a role in the guidelines; however, in this respect valid questionnaires or scores that enable a uniform assessment exist only in a few cases. In contrast, some indicators (e. g. costs, length of hospital stay) are strongly influenced by factors such as the healthcare system making these indicators unfeasible.

Epstein-Barr virus infection or malignant lymphoma - what you see is not what you get.

Infectious mononucleosis may mimic lymphoma, both clinically and histopathologically. We present a patient with neurological symptoms and lymphadenopathy, initially diagnosed as Epstein-Barr virus (EBV)-positive angioimmunoblastic T-cell lymphoma (AITL) with cerebrospinal fluid (CSF) localisation based on lymph node pathology and a 30-fold higher EBV load in the CSF compared with serum. However, the patient fully recovered spontaneously and EBV became negative in both CSF and serum, suggestive of a dramatic presentation of EBV meningoencephalitis.

Neoadjuvant chemotherapy affects molecular classification of colorectal tumors.

The recent discovery of 'molecular subtypes' in human primary colorectal cancer has revealed correlations between subtype, propensity to metastasize and response to therapy. It is currently not known whether the molecular tumor subtype is maintained after distant spread. If this is the case, molecular subtyping of the primary tumor could guide subtype-targeted therapy of metastatic disease. In this study, we classified paired samples of primary colorectal carcinomas and their corresponding liver metastases (n=129) as epithelial-like or mesenchymal-like, using a recently developed immunohistochemistry-based classification tool. We observed considerable discordance (45%) in the classification of primary tumors and their liver metastases. Discordant classification was significantly associated with the use of neoadjuvant chemotherapy. Furthermore, gene expression analysis of chemotherapy-exposed versus chemotherapy naive liver metastases revealed expression of a mesenchymal program in pre-treated tumors. To explore whether chemotherapy could cause gene expression changes influencing molecular subtyping, we exposed patient-derived colonospheres to six short cycles of 5-fluorouracil. Gene expression profiling and signature enrichment analysis subsequently revealed that the expression of signatures identifying mesenchymal-like tumors was strongly increased in chemotherapy-exposed tumor cultures. Unsupervised clustering of large cohorts of human colon tumors with the chemotherapy-induced gene expression program identified a poor prognosis mesenchymal-like subgroup. We conclude that neoadjuvant chemotherapy induces a mesenchymal phenotype in residual tumor cells and that this may influence the molecular classification of colorectal tumors.

Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related peptide by PTH in primary fetal rat osteoblasts.

We studied the effects of parathyroid hormone (PTH) on PTH parathyroid hormone related peptide (PTHrP) receptor mRNA level, PTHrP binding and PTH-stimulated cyclic adenosine monophosphate (cAMP) accumulation in osteoblasts, derived from fetal rat calvariae (ROB). Cells isolated during 10-70 minutes of collagenase treatment were seeded at a density of 25,000 cells/cm2 and cultured for 4 days. These cells show a fast increase in cAMP production after stimulation for 5 minutes with 20 nM bovine parathyroid hormone(1-34) (bPTH(1-34)). When ROB are incubated with bPTH(1-34) (0.04-40nM) for 24 h, a dose-dependent decrease of the PTH/PTHrP receptor mRNA level, PTHrP binding, and PTH-stimulated cAMP accumulation can be observed. Pretreatment of ROB with a high concentration of bPTH(1-34) (40 nM) leads within 15 minutes to a decrease in PTH-stimulated cAMP accumulation. However, it takes > or = 3 h before a significant decrease in PTH/PTHrP receptor mRNA level can be observed. Also a significant decrease in PTHrP binding is observed after only 4 h of incubation with bPTH(1-34). Compared with bPTH(1-34), pretreatment of ROB with bPTH(3-34) (40 and 100 nM) for 24 h causes smaller decreases in PTH-stimulated cAMP accumulation, PTHrP binding, and in the PTH/PTHrP receptor mRNA level. We investigated the possible involvement of the protein kinase A signaling pathway in the regulation of the PTH/PTHrP receptor mRNA expression. Both forskolin and (Bu)2cAMP decreased PTHrP binding and PTH/PTHrP mRNA levels. These observations suggest that chronic activation of the PKA signaling pathway may down-regulate PTH/PTHrP receptor expression and thus hormone responsiveness in "normal" osteoblasts. In short, we found that the decrease of the PTH-stimulated cAMP accumulation after long-term pretreatment with bPTH(1-34) is correlated with both PTH/PTHrP receptor mRNA level and PTHrP binding. These data also suggest that the initial desensitization (< 30 minutes) of PTH-stimulated cAMP responsiveness by pretreatment with a high concentration of bPTH(1-34) (40 nM) is not dependent on the number of available PTH/PTHrP receptors. The protein kinase A signaling pathway is involved in the regulation of the PTH/PTHrP receptor, but, regarding the effect of bPTH(3-34), other signaling systems are also involved.

Down-regulation of the receptor for parathyroid hormone (PTH) and PTH-related peptide by transforming growth factor-beta in primary fetal rat osteoblasts.

We studied the effects of transforming growth factor-beta 2 (TGF beta 2) on the level of PTH/PTH-related peptide-(PTHrP) receptor messenger RNA (mRNA), PTHrP binding, and PTH-stimulated cAMP accumulation in cultured osteoblasts derived from fetal rat calvariae (ROB). When ROB were pretreated with TGF beta 2 at concentrations ranging from 1-100 pM for 24 h, dose-dependent decreases in the level of PTH/PTHrP receptor mRNA, PTHrP binding, and PTH-stimulated cAMP accumulation were observed. For the PTH/PTHrP receptor mRNA level and PTH-stimulated cAMP accumulation, the half-maximal effective concentration was approximately 4 pM. For the inhibition of PTHrP binding, the half-maximal effective concentration was much higher. A 50% decrease in both PTH/PTHrP receptor mRNA level and PTH-stimulated cAMP accumulation was obtained when ROB were treated with 100 pM TGF beta 2 for 4 h. A comparable decrease in PTHrP binding was only observed after 24 h of incubation with 100 pM TGF beta 2. Actinomycin D induced a rapid decrease in the PTH/PTHrP receptor mRNA level (70% after 4 h), indicating a half-life for the receptor mRNA of 2-3 h. Under the same conditions, PTHrP binding and PTH-stimulated cAMP accumulation did not change. When ROB were treated with cycloheximide for the same period, only a small decrease in PTHrP binding (20%) was observed, suggesting that PTH/PTHrP receptors do not have a rapid turnover. Cycloheximide also reduced PTH-stimulated cAMP production; after coincubation of cycloheximide with TGF beta 2, this inhibition was smaller than that in ROB cultures treated with TGF beta 2 exclusively. From these observations we conclude that TGF beta 2 induces a decrease in steady state levels of PTH/PTHrP receptor mRNA that results in decreased PTHrP receptor binding. The PTH-stimulated cAMP accumulation is at least to some extent independent of the PTH/PTHrP receptor availability. Furthermore, there is a high turnover of PTH/PTHrP receptor mRNA, whereas turnover of the receptor protein is much slower. Finally, protein synthesis is required for TGF beta 2-induced desensitization of cAMP responsiveness to PTH.

Depletion of GDNF from primary afferents in adult rat dorsal horn following peripheral axotomy.

Glial cell line-derived neurotrophic factor (GDNF) is produced in a subset of adult rat spinal ganglion neurons and anterogradely transported to the superficial dorsal horn. In this study the effect of sciatic nerve axotomy on the expression of GDNF protein in the dorsal horn was investigated, using immunocytochemistry. Image analysis showed a 44% decrease relative to the non-transected side after 5 days survival, progressing to more than 80% decrease after 10 days and remaining so for at least 100 days. This rapid and strong decrease suggests active down-regulation of GDNF protein after peripheral axotomy. The observed down-regulation of GDNF is compared with changes observed for other substances in primary afferents after peripheral axotomy and is discussed in light of its presumed trophic or transmitter role in nociception.

Immunocytochemical localization of GDNF in primary afferents of the lumbar dorsal horn.

Immunocytochemistry was used to identify glial cell line-derived neurotrophic factor (GDNF) in rat spinal cord. Strong GDNF labeling was found in fibers and terminals in laminae I and II (outer) and to a lesser extent in the remaining laminae. A few spinal ganglion cells also contained GDNF. After dorsal root transection GDNF disappeared from the dorsal horn and after dorsal root ligation there was accumulation of GDNF only on the ganglion side of the ligation. These findings demonstrate anterograde transport of GDNF within primary afferent fibers, which constitute the only source of GDNF labeling in the dorsal horn. The strong presence of GDNF in the superficial dorsal horn may indicate that GDNF has a role in pain transmission in the adult rat spinal cord.

High-dose intravenous immunoglobulin therapy for myasthenia gravis.

The objective of this open, retrospective study was to investigate whether intravenous immunoglobulin (IVIg) could induce a clinically obvious improvement in patients with generalized myasthenia gravis (MG), as judged by MG functional status. Fourteen patients with generalized MG were treated during at least one episode with 0.4 g IVIg per kilogram body weight per day for 5 consecutive days. Patients with confounding variables were excluded; this left 11 patients (16 episodes) to be further analysed. We defined improvement as at least a one-step improvement in MG functional status (according to the University of Virginia's Modification of Osserman's classification). Of the treatment episodes, 56% were classified as positive responses. If improvement occurred, onset of improvement started after 3 (1-12) days and peak effect was reached after 7 (4-30) days (median and range). All four patients who required artificial ventilation could be weaned from it 8.5 (6-11) days after the start of IVIg (median and range). Of the patients treated on two occasions, only one patient had a positive response during both. In MG functional status 5, improvement was observed during five of seven episodes. None of the patients with MG functional status 3 responded. Patients with an acute relapse of MG seemed to respond equally well to IVIg compared with patients with subacute deterioration/ chronic-static state (50% versus 60%). The MG functional status at the start of IVIg and on the day of maximal improvement was compared for all episodes together, and significant improvement was noted (P = 0.0052). We did not see any serious side-effects after IVIg treatment. This retrospective analysis suggests that high-dose IVIg is an effective therapy in some patients with deterioration of generalized MG. If improvement occurs, it starts within a few days of the onset of IVIg and the effect seems to peak within 2 weeks.

[Proctological diseases in routine urologic practice]. / Proktologische Erkrankungen im urologischen Alltag

Nearly two third of adults will suffer from proctologic complaints. The same symptoms could also indicate or mask an anorectal carcinoma. Therefore, the first priority should be to exclude the possibility of a neoplasm of the colon, rectum and the anal canal. Knowledge of the specific anatomy of the anal canal and the patient's history will lead to an exact proctologic diagnosis: perianal thrombosis, acute thrombosed prolapsed haemorrhoidal plexus, an anal fissure, abscess and fistula are located within the highly sensitive anoderma and are characterized by pain. Perianal thrombosis, chronic fissure, abscess and fistula require surgery. Conservative treatment is the choice for an acute anal fissure, haemorrhoids grade I-II. Haemorrhoids II-III require surgery, e.g. by haemorrhoidal artery ligation, open or closed resection of the haemorrhoidal plexus, reconstruction of the anal canal or stapled mucosectomy. Perianal diseases such as perianal tags, fibroma or condylomata acuminata are easily diagnosed and treated. Secondary perianal eczema requires treatment of the underlying proctologic disease. If it persists, a biopsy is required.

[Subacute combined degeneration of the spinal cord: easy diagnosis, effective treatment]. / Gecombineerde strengziekte door vitamine-B12-deficiëntie: eenvoudige diagnose, effectieve therapie.

Four patients, three women aged 49, 47 and 74 years, and a man aged 64 years, presented with progressive sensory deficit, pyramidal tract symptoms and postural instability. Tests revealed megaloblastic anaemia and low vitamin B12 levels. Two of the female patients had undergone gynaecological surgery with nitrous oxide anaesthesia, and the male patient had undergone a gastric resection. Subacute combined degeneration of the spinal cord is a neurological disease based on vitamin B12 deficiency. It involves the posterior and lateral columns of the spinal cord, and sometimes the peripheral nerves, the optic nerve or the brain. An MRI scan of the cervical cord revealed abnormalities for three of the four patients. Following parenteral supplementation of vitamin B12, the symptoms and the MRI abnormalities either disappeared or significantly improved. Vitamin B12 deficiency can cause subacute combined degeneration of the cord by interfering with myelin synthesis. As vitamin B12 deficiency is caused by malabsorption in the gastrointestinal tract, oral supplementation is insufficient. It is essential to recognise this treatable disease at an early stage, and not to reject the possible diagnosis if the MRI findings are abnormal. Simple blood tests can lead to the diagnosis and to effective treatment.