Sacral neuromodulation in endometriosis - A promising treatment option for chronic pelvic pain.

INTRODUCTION: Chronic pelvic pain (CPP) affects over one fifth of women worldwide, and endometriosis is one of the most common causes. In the present study, we examined whether sacral neuromodulation (SNM) is effective in the treatment of refractory chronic pelvic pain in women with endometriosis. MATERIAL AND METHODS: This multicenter prospective pilot study was started in 2017 and includes patients with chronic pelvic pain with no other obvious pathology than endometriosis. Other treatment options have been tried or they are unsuitable. Patients underwent SNM implantation. The main outcome was postoperative pain reduction and secondary outcome was quality of life. The following questionnaires were used to assess the outcomes: Brief pain inventory (BPI), clinical global impression - improvement (CGI-I), 15D-measure of health-related quality of life, and Biberoglu and Behrman (B&B) score. RESULTS: A total of 35 patients underwent the SNM procedure and, at the time of analysis, 15 patients had returned one-year questionnaires. The patients had a history of endometriosis for a median of 5.5 (interquartile range 2-9) years, with no correlation between the severity of symptoms and the duration of the disease (p = 0.158). A total of 31 patients (89%) were implanted with the internal pulse generator. There were statistically significant changes in BPI pain-related items. Worst experienced daily pain decreased among those who returned 12-month questionnaires from median 9 to 5 (p = 0.006), average daily pain from 6 to 3.5 (p = 0.004), and least daily pain from 3 to 1 (p = 0.004). Based on the CGI questionnaire (n = 14), at 12 months nine patients (60%) experienced great improvement in their symptoms, three patients (20%) much improvement and two patients (13%) minimal improvement. None of the patients experienced worsening of their symptoms. There was a statistically significant change in overall 15D score at 1 month (p < 0.001), 6 months (p = 0.001) and 12 months (p = 0.018), when the results were compared to baseline values. Median B&B score also improved significantly and decreased from a baseline value of 8 (4-12) to 4.5 (0-6), p = 0.002. CONCLUSIONS: Based on the preliminary findings of our study, SNM might be a promising treatment of CPP in endometriosis patients.

Mobile-CEA - A Novel Surveillance Method for Patients with Colorectal Cancer.

OBJECTIVE: The follow-up of the increasing number of cancer survivors threatens to overload the health care system. While short message system (SMS)-based communication is widely used in other areas of the health care system, there are no studies of its appliance in cancer surveillance. The aim of the current study was to analyze the acceptability, convenience and impact of a novel mobile phone messaging -based system (Mobile-CEA) on health personnel contacts in patients with colorectal cancer (CRC) during 2 years of follow-up. METHODS: The follow-up data of 52 curatively treated patients with CRC (22 Mobile-CEA-, 30 standard surveillance) was collected retrospectively from the electronic archives. Mobile-CEA patient satisfaction was measured by a tailored non-validated questionnaire. Health personnel satisfaction was assessed by personal interviews. RESULTS: Mobile-CEA surveillance group had less health personnel contacts than the standard surveillance group: median 3 (min 0-max 7) vs 5 (min 4-max 7) and 77.2% of the Mobile-CEA group had less than 4 contacts (minimum with the standard surveillance) to health personnel. There were no recurrences in either group. Mobile-CEA patients were satisfied with this novel follow-up method. Health personnel considered it as a practical and safe tool in CRC surveillance. CONCLUSION: Mobile-CEA surveillance seems to be a promising and effective follow-up method for curatively treated patients with CRC. Further studies and experiences are needed.

Validation of the low anterior resection syndrome score in finnish patients: preliminary results on quality of life in different lars severity groups.

BACKGROUND AND AIMS: Low anterior resection syndrome is common after anterior resection for rectal cancer. Its severity can be tested with the low anterior resection syndrome score. We have translated the low anterior resection syndrome score to Finnish, and the aim of this study is to validate the translation. MATERIALS AND METHODS: The translated Finnish low anterior resection syndrome score and European Organisation for Research and Treatment of Cancer quality-of-life questionnaire-C30 and QLQ-CR29 questionnaires were sent to 159 surviving patients operated with anterior resection for rectal adenocarcinoma between 2007 and 2014 in a tertiary referral center. Psychometric properties of the translation were evaluated in comparison to quality-of-life scales and in different risk factor groups. RESULTS: In the study, 104 (65%) patients returned the questionnaires. Of these, 56 (54%) had major low anterior resection syndrome, 26 (25%) had minor low anterior resection syndrome, and 22 (21%) had no low anterior resection syndrome. Patients with major low anterior resection syndrome had a significantly lower quality of life and more defecatory symptoms as assessed with the European Organisation for Research and Treatment of Cancer questionnaires compared with those with no low anterior resection syndrome. Patients operated with total mesorectal excision had significantly higher low anterior resection syndrome scores compared with those operated with partial mesorectal excision (median/interquartile range 32/15 and 29/11, respectively, p = 0.037). The test-retest validity of the translation was good with an intraclass correlation coefficient of 0.77 (95% confidence interval 0.51-0.90). CONCLUSIONS: The Finnish low anterior resection syndrome score is a valid test in the assessment of postoperative bowel function and its impact on the quality of life. It can be implemented to use during regular follow-up visits of Finnish-speaking rectal cancer patients.

Comparison of 3D endoanal ultrasound and external phased array magnetic resonance imaging in the diagnosis of obstetric anal sphincter injuries.

OBJECTIVES: The gold standard of postpartum anal sphincter imaging has been the 3D endoanal ultrasound (EAUS). Development of magnetic resonance imaging (MRI) has allowed anal sphincter evaluation without the use of endoanal coils. The aim of this study is to compare these two modalities in diagnosing residual sphincter lesions post obstetric anal sphincter injury (OASI). METHODS: Forty women were followed up after primary repair of OASI with both 3D EAUS and external phased array MRI. Details of the anal sphincter injury and sphincter musculature were gathered and analysed. RESULTS: There was a moderate interrater reliability (κ = 0.510) between the two imaging modalities in detecting sphincter lesions, with more lesions detected by MRI. There was a moderate intraclass correlation (ICC) between the circumference of the tear (κ = 0.506) and a fair ICC between the external anal sphincter thickness measurements at locations 3 and 9 on the proctologic clock face (κ = 0.320) and (κ = 0.336). CONCLUSIONS: The results of our study indicate that the use of external phased array MRI is feasible for detecting obstetric anal sphincter lesions postpartum. This allows for imaging of the sphincter defects in centres where EAUS imaging is not available. KEY POINTS: • A two centre prospective study that showed external phased array MRI to be a valid imaging modality for diagnosing obstetric anal sphincter injuries.

Trends in presentation, treatment and survival of 1777 patients with colorectal cancer over a decade: a Biobank study.

BACKGROUND: Most survival data in colorectal cancer (CRC) is derived from clinical trials or register-based studies. Hospital Biobanks, linked with hospital electronic records, could serve as a data-gathering method based on consecutively collected tumor samples. The aim of this Biobank study was to analyze survival of colorectal patients diagnosed and treated in a single-center university hospital over a period of 12 years, and to evaluate factors contributing to outcome. MATERIAL AND METHODS: A total of 1777 patients with CRC treated during 2001-2012 were identified from the Auria Biobank, Turku, Finland. Longitudinal clinical information was collected from various hospital electronic records and date and cause of death obtained from Statistics Finland. RESULTS: Cancer-specific, overall and disease-free survival was higher in patients diagnosed during 2004-2008 as compared with patients diagnosed in 2001-2003. Further improvement was not seen during years 2009-2012. Potential factors contributing to the improvement were introduction of multidisciplinary meetings, centralization of rectal cancer surgery, use of adjuvant chemotherapy and systematic preoperative radiotherapy of rectal cancer. The proportion of patients with stage I-IV CRC remained similar over the study period, but a marked decrease in non-metastatic rectal cancer with biopsy only (locally advanced disease) was observed. In stage I-III rectal cancer, Cox multivariate analysis suggested age, comorbidity, R1 resection, T staging and tumor grade as prognostic factors. In colon cancer, prognostic factors were age, comorbidity, gender and presence of lymph node metastases. CONCLUSIONS: Organizational changes in the treatment of CRC patients made since 2004 coincide with improved survival in CRC and a marked reduction in locally advanced rectal cancers. The clinical presentation of CRC has remained similar between 2001 and 2012.

Sacral Neuromodulation: Foray into Chronic Pelvic Pain in End Stage Endometriosis.

Excision of all endometriotic lesions is the method of choice in the treatment of severe endometriosis resistant to medical therapy. The infiltrating nature of the disease as well as extensive surgery may, however, cause chronic pain that cannot be relieved by either surgery or hormonal treatment. As a pilot treatment, we tested the effect of sacral neuromodulation (SNM) for four endometriosis patients suffering chronic pelvic pain and pelvic organ dysfunction after radical surgical treatment. Three out of four patients reported improvement in their symptoms during the neuromodulation testing period and a permanent pulse generator was installed. After 2.5 years, all three patients report better quality of life and want to continue with SNM.

Akkermansia muciniphila Adheres to Enterocytes and Strengthens the Integrity of the Epithelial Cell Layer.

Akkermansia muciniphila is a Gram-negative mucin-degrading bacterium that resides in the gastrointestinal tracts of humans and animals. A. muciniphila has been linked with intestinal health and improved metabolic status in obese and type 2 diabetic subjects. Specifically, A. muciniphila has been shown to reduce high-fat-diet-induced endotoxemia, which develops as a result of an impaired gut barrier. Despite the accumulating evidence of the health-promoting effects of A. muciniphila, the mechanisms of interaction of the bacterium with the host have received little attention. In this study, we used several in vitro models to investigate the adhesion of A. muciniphila to the intestinal epithelium and its interaction with the host mucosa. We found that A. muciniphila adheres strongly to the Caco-2 and HT-29 human colonic cell lines but not to human colonic mucus. In addition, A. muciniphila showed binding to the extracellular matrix protein laminin but not to collagen I or IV, fibronectin, or fetuin. Importantly, A. muciniphila improved enterocyte monolayer integrity, as shown by a significant increase in the transepithelial electrical resistance (TER) of cocultures of Caco-2 cells with the bacterium. Further, A. muciniphila induced interleukin 8 (IL-8) production by enterocytes at cell concentrations 100-fold higher than those for Escherichia coli, suggesting a very low level of proinflammatory activity in the epithelium. In conclusion, our results demonstrate that A. muciniphila adheres to the intestinal epithelium and strengthens enterocyte monolayer integrity in vitro, suggesting an ability to fortify an impaired gut barrier. These results support earlier associative in vivo studies and provide insights into the interaction of A. muciniphila with the host.

Late complications related to palliative stenting in patients with obstructing colorectal cancer.

INTRODUCTION: Self-expanding metal stents (SEMSs) are increasingly used for the palliative treatment of incurable obstructing colorectal cancer. The aim of the current study was to evaluate clinical outcome, including technical and clinical success of stenting, and to identify factors associated with late complications of SEMS in palliation of incurable obstructing colorectal cancer. MATERIAL AND METHODS: Between 2003 and 2010 details of 56 patients who underwent an attempt of SEMS insertion for obstructive incurable colorectal cancer at Turku University Hospital were recorded to our database prospectively and analyzed retrospectively. RESULTS: Technical success was achieved in 42 patients (75%) and clinical success in 39 patients (70%). Late complications related to SEMS occurred in 13 patients (31%). Ten patients (24%) needed re-intervention because of a complication: Eight ostomies, one Hartmann´s procedure due to late perforation and one re-stenting because of stent migration. Three patients with stent-related complications were treated conservatively. Chemotherapy and prolonged survival were risk factors for SEMS-related late complications and re-intervention. CONCLUSION: SEMS insertion is a feasible procedure for the palliative treatment of obstructing colorectal cancer in patients with severe comorbidities and short life expectancy. However, for patients who are candidates for chemotherapy and have a longer life expectancy, other treatment options such as palliative tumor resection should also be considered.

[Palliative surgery of the gastrointestinal tract]. / Ruoansulatuskanavan palliatiivinen kirurgia.

Palliative surgery refers to surgical procedures that alleviate the symptoms of a patient having incurable cancer and in many cases also improve the quality of life. Regrettably often gastrointestinal cancers have progressed beyond curative surgical therapy at the time of diagnosis. Palliative surgery aims to provide a patient having an incurable cancer good-quality days of life by using treatment methods that are putting as little strain as possible on the patient. In addition to clinical expertise, communication skills are an essential part of palliative surgery know-how.

Type and location of tumor-infiltrating macrophages and lymphatic vessels predict survival of colorectal cancer patients.

The type of tumor-infiltrating macrophages may be decisive in tumor immunity, lymphangiogenesis and in the clinical outcome of cancer. Here, we elucidated the prognostic significance of lymphatic vessels, different types of macrophages and the balance between different macrophage types in colorectal cancer. We analyzed the impact of density, type and location of macrophages on the clinical behavior of 159 primary colorectal carcinomas using CD68 as a pan-macrophage marker and CLEVER-1/Stabilin-1 as a marker for regulatory/suppressive macrophages. Podoplanin was used as a pan-lymphatic vessel marker. A high number of CLEVER-1/Stabilin-1(+) peritumoral macrophages positively correlated with survival (p = 0.04). However, in more advanced disease (Stage IV), the patients with a high number of peritumoral or intratumoral CLEVER-1/Stabilin-1(+) macrophages had a shorter disease-specific survival (p = 0.05, and p = 0.008, respectively). Moreover, a low number of suppressive intratumoral CLEVER-1/Stabilin-1(+) macrophages among high numbers of CD68(+) macrophages correlated with a low number of distant recurrences (p = 0.01) and to fewer disease relapses exclusively in the liver as well (p = 0.006). A high number of intratumoral lymphatics correlated with poor survival (p = 0.03). The results of this work suggest that the type of macrophages, number of lymphatic vessels and their location contribute to the clinical behavior of colorectal cancer in a disease stage-specific manner.

Patient's age should not play a key role in clinical decisions on surgical treatment of rectal cancer.

BACKGROUND AND AIMS: Recent advances in surgical techniques and adjuvant treatments have decreased morbidity and mortality in patients with rectal cancer. The aim of this study was to clarify the effects of aging on the choice, feasibility and safety of various treatment modalities in patients with rectal cancer. PATIENTS AND METHODS: During 2003-2006, a total of 274 rectal cancers were diagnosed at Turku University Central Hospital. Patient and tumor characteristics, treatment modalities chosen, and complications were recorded, and patients were followed up prospectively for 1-3 years after treatment. Patients were then divided into two groups: under 75 (n=181) and 75 years or older (n=93) at the moment of diagnosis. Patient data in the two age groups were analysed and compared with each other. RESULTS: Of the total of 274 patients with rectal cancer, 243 (89%) underwent surgery. The percentage of patients operated was higher (p=0.03) in the younger (92%) than in the older group (83%). The main reasons for non-operative or palliative treatment were severe concomitant diseases and metastasized cancer. Preoperative radiation therapy was given more often (p<0.01) to young (72%) than old (27%) patients. With these selections, there was no difference in 30-day postoperative mortality (1% vs 1%, ns) or postoperative complications (22% vs 34%, ns) between two groups. CONCLUSION: With preoperative selection, patients over 75 with rectal cancer are suitable for major surgery, as morbidity and mortality rates are comparable to those in younger patients.

Mucosal adhesion properties of the probiotic Lactobacillus rhamnosus GG SpaCBA and SpaFED pilin subunits.

Lactobacillus rhamnosus GG is a well-established Gram-positive probiotic strain, whose health-benefiting properties are dependent in part on prolonged residence in the gastrointestinal tract and are likely dictated by adherence to the intestinal mucosa. Previously, we identified two pilus gene clusters (spaCBA and spaFED) in the genome of this probiotic bacterium, each of which contained the predicted genes for three pilin subunits and a single sortase. We also confirmed the presence of SpaCBA pili on the cell surface and attributed an intestinal mucus-binding capacity to one of the pilin subunits (SpaC). Here, we report cloning of the remaining pilin genes (spaA, spaB, spaD, spaE, and spaF) in Escherichia coli, production and purification of the recombinant proteins, and assessment of the adherence of these proteins to human intestinal mucus. Our findings indicate that the SpaB and SpaF pilin subunits also exhibit substantial binding to mucus, which can be inhibited competitively in a dose-related manner. Moreover, the binding between the SpaB pilin subunit and the mucosal substrate appears to operate through electrostatic contacts and is not related to a recognized mucus-binding domain. We conclude from these results that it is conceivable that two pilin subunits (SpaB and SpaC) in the SpaCBA pilus fiber play a role in binding to intestinal mucus, but for the uncharacterized and putative SpaFED pilus fiber only a single pilin subunit (SpaF) is potentially responsible for adhesion to mucus.

Adoption of self-expanding metallic stents in the palliative treatment of obstructive colorectal cancer-look out for perforations!

Self-expanding metallic stents (SEMSs) are increasingly used for the palliative treatment of inoperable colorectal cancer. The aim of the current study was to analyze the safety and efficacy of SEMS in the palliative treatment of obstructive colorectal cancer. Between 2003 and 2006, SEMS placement was attempted in 26 patients suffering from inoperable obstructive colorectal cancer. The recovery of the patients and the outcome of this treatment modality were analyzed prospectively. SEMS was successfully inserted in 19 (73%) of 26 patients. In 16 (84%) of these 19 cases, the placement of SEMS was the definitive treatment of colorectal obstruction and no additional surgical palliation was needed. There were 3 (16%) colonic perforations related to stent application. SEMS insertion seems to be an effective alternative in the palliative treatment of patients with malignant colorectal obstruction. However, perforation is a dangerous complication of the procedure.

Qualitative and quantitative analyses of the bifidobacterial microbiota in the colonic mucosa of patients with colorectal cancer, diverticulitis and inflammatory bowel disease.

AIM: To characterize the bifidobacterial microbiota of the colonic mucosa in patients with colon cancer, inflammatory bowel disease or diverticuitis. METHODS: A sample of the distal colonic mucosa was taken during surgery from a total of 34 patients, twenty-one with diagnosed colorectal cancer, nine with diverticulitis and four with inflammatory bowel disease, requiring surgery for their condition. Bacterial DNA was extracted from the resected mucosal samples and bifidobacterial mucosa-associated microbiota was qualitatively and quantitatively determined by means of qualitative and quantitative PCR. RESULTS: Bifidobacteria were found in 100% of the samples from patients with diverticulitis or IBD and a 76% of those suffering colon cancer. The species B. longum and B. bifidum were the most widely found, followed by B. animalis, B. catenulatum and B. adolescentis. B. breve, B. dentium and B. angulatum were not detected in any sample. A significantly higher occurrence of B. longum was observed in patients with diverticulitis than in those with colon cancer or IBD (100%, 62% and 75%, respectively, P < 0.05). Similar results were obtained for B. animalis (56%, 0% and 25%, P < 0.05), while B. adolescentis was only found in the mucosa from patients with colon cancer (5 out of 21, 24%). At the quantitative level, patients with colon cancer or IBD showed lower counts of total Bifidobacterium (4.94 and 5.91 vs 6.96 log cells/sample, respectively, P < 0.05) and of the species B. longum (4.05 and 4.79 vs 6.76, P < 0.05) than those with diverticulitis. CONCLUSION: Aberrancies in mucosa associated microbiota are present in different intestinal diseases. This may indicate a role of the microbiota in the pathogenesis of these diseases.

Antibacterial effects of human group IIA and group XIIA phospholipase A2 against Helicobacter pylori in vitro.

Group IIA phospholipase A2 (PLA2-IIA) is an enzyme which has important roles in inflammation and infection. Recently, a novel human secretory PLA2 called group XIIA PLA2 (PLA2-XIIA) has been identified. Both PLA2-IIA and PLA2-XIIA are bactericidal against Gram-positive bacteria like many other secretory PLA2s. However, PLA2-XIIA is the only known PLA2 displaying significant bactericidal activity against the Gram-negative bacterium Escherichia coli. We examined the antibacterial properties of recombinant human PLA2-IIA and PLA2-XIIA against Helicobacter pylori, a Gram-negative bacterium, in vitro. PLA2-IIA was not bactericidal against H. pylori, whereas PLA2-XIIA effectively killed H. pylori at a concentration of 50 microg/ml but was not bactericidal at concentrations of 0.5 microg/ml and 5 microg/ml.

Biochemical and clinical approaches in evaluating the prognosis of colon cancer.

BACKGROUND: Colorectal adenocarcinoma is a common malignant neoplasm in the Western world. To achieve optimal treatment results, the risk estimation of recurrence should be as accurate as possible. MATERIALS AND METHODS: Tissue material from tumour and normal mucosa was taken from six patients and was analysed to screen aberrantly expressed genes using cDNA microarray. Selected up-regulated genes were chosen for further analysis by immunohistochemistry. For this purpose a tissue array material of 114 colorectal cancer patients was obtained. In addition to the routinely used proliferation marker Ki-67, the analysed proteins included securin and CDC25B. RESULTS: Processes such as cellular defense, cell structure, motility and cell division were found to be notably represented among the most deregulated genes. A significant portion of the overexpressed genes included those functioning in the cell cycle. Immunohistochemical stainings of securin and CDC25B showed a consistent expression pattern with that of cDNA microarray analysis. There was no statistical association between the studied proliferation markers and survival. Instead, there was a significant association between the Dukes' class and the histological grade (p=0.04), but not between histological grade and survival. The survival of Dukes' B patients was significantly poorer if no regional lymph nodes were studied compared with the Dukes' B patients with even a single lymph node was studied (p=0.04, hazard ratio 2.7). CONCLUSION: Tumour stage is superior in estimating the prognosis of patients with colonic cancer compared with the grading of cell cycle regulators or histological grade of the cancer. The study of regional lymph nodes is essential to identify the patients who would benefit from adjuvant chemotherapy.

Experimental Helicobacter felis infection in transgenic mice expressing human group IIA phospholipase A2.

BACKGROUND: Both various virulence factors of Helicobacter pylori and host factors influence the clinical outcome of H. pylori infection. In animal experiments with Helicobacter felis, large variations in the severity of disease have been observed between different mouse strains infected with a single isolate of H. felis. C57BL/6 J mouse strain that lacks the expression of group IIA phospholipase A2 has been shown to develop more severe gastric inflammation than other mouse strains. Thus, group IIA phospholipase A2 has been suggested to play a role in regulating inflammation in gastric mucosa. The aim of this study was to examine the possible role of group IIA phospholipase A2 in experimental Helicobacter infection. MATERIALS AND METHODS: Transgenic mice expressing human group IIA phospholipase A2 and their group IIA phospholipase A2 deficient nontransgenic C57BL/6 J littermates were infected with H. felis. The mice were killed 3, 8, and 19 weeks after inoculation of bacteria to determine the histopathological changes in gastric mucosa. RESULTS: The infected mice developed chronic inflammation in gastric mucosa. We found no differences in the colonization of bacteria between transgenic and nontransgenic mice. At 3 and 8 weeks, no difference was found in the severity of inflammation between the two groups. Nineteen weeks after the administration of bacteria the inflammation was more marked in nontransgenic than transgenic mice. Group IIA phospholipase A2 was expressed by in situ hybridization in the neck cells of the glandular stomach in transgenic mice. CONCLUSIONS: The results of the present study suggest that the endogenous expression of group IIA phospholipase A2 diminishes chronic inflammation in gastric mucosa in experimental H. felis infection in mice.