[Quality of life of ostomates in Germany]. / Lebensqualität von Menschen mit einem künstlichen Darmausgang in Deutschland.

BACKGROUND: The presence of an ostomy may have a serious impact on the quality of life (QoL). The aim of this study was to evaluate the QoL of ostomates in Germany. METHOD: An online survey was performed using the validated Gastrointestinal Quality of Life Index (GIQLI) by Eypasch et al. Ostomates ≥ 18 yrs. with an ostomy duration ≥ 3 months were eligible to participate. RESULTS: Completed questionnaires from 519 participants (79.3 % female) with a median age of 50 yrs. (range 19-83 yrs.) and a median ostomy duration of 3 yrs. (range 3 months-58 yrs.) were analyzed. The most common indications for an ostomy were Crohn's disease (36.5 %), colorectal cancer (19.8 %) and ulcerative colitis (18.2 %). The mean GIQLI-Score in the study population was 94.8 ± 24.6, with higher scores corresponding with better QoL and healthy individuals reach 125.8. Limitations were recorded with regard to sleep, tiredness, energy level, endurance, fitness and sexuality. Individuals with a stoma due to Colitis (103,0 ± 24,5), colorectal cancer (99,2 ± 21,7) and Crohn's (95,0 ± 22,8) had the highest mean GIQLI-scores amongst all ostomates. DISCUSSION: The findings of this study confirm that ostomates have a reduced QoL compared to the healthy population. Amongst all ostomates, those with colitis, colorectal cancer and Crohn's have a better QoL compared to ostomy carriers with other diagnoses.

Candida albicans Osteochondromyelitis after Gastroesophageal Surgery: Two Case Reports.

Candida osteochondromyelitis is a rare complication after thoracoabdominal surgery. We herein report two such cases after uncomplicated thoracoabdominal surgery, who presented with chronic postsurgical site infection and fistula. CT scans showed fistulas reaching the costochondral areas of the fifth rib. Inflammatory parameters were not elevated. Both patients were treated successfully after the initiation of systemic antimycotic treatment and surgical debridement. We conclude that C. albicans infections should always be considered in cases of chronic postoperative surgical site infections after thoracoabdominal surgery. Additional risk factors do not need to be present. Appropriate therapy consists of the application of systemic antimycotics and surgical debridement.

Correlation of perioperative biochemical variables with single adenoma weight in patients with primary hyperparathyroidism.

BACKGROUND: Single parathyroid adenoma is the main cause of primary hyperparathyroidism (PHPT), with surgery remaining the gold standard for its treatment. The ability to preoperatively predict the parathyroid adenoma size and could facilitate the decision about the extent of surgical exploration. It is reasonable to hypothesize that the perioperative levels of PHPT-related variables (i.e. calcium, parathormone, phosphate) may predict the adenoma weight or/and demonstrate whether the adenoma is successfully removed or not. Aim of this study is to explore the relationship between perioperative biochemical values and adenoma weight. Secondarily, we investigated the relationship between adenoma weight and uni-/bilateral neck exploration. METHODS: Retrospective study of all patients undergone surgery for primary hyperparathyroidism due to single adenoma in a tertiary university hospital in Germany during a 6-year period. Following variables were analyzed: preoperative serum calcium, phosphorus and parathormone, intraoperative parathormone before and after adenoma excision, intraoperative PTH decrease, postoperative serum calcium and parathormone (PTHpostop-pg/ml), calcium and PTH decrease. Bivariate correlations were calculated by the Spearman's correlation test at the 95% significance level. RESULTS: A total of 339 patients were included in the study. The median age of the patients was 60 years (range 21-90) and 77% were females. The median adenoma weight was 1 g (range 0.1-11). Adenoma weight correlated strong with maximum adenoma diameter (r = 0.72, p < 0.05), moderate with preoperative parathormone (r = 0.44) and parathormone decrease (r = 0.27), whereas there was no correlation with the intraoperative PTH decrease (r = 0.02). There was also a borderline (moderate to weak) correlation with pre- and postoperative calcium levels (r = 0.21 and r = 0.23 respectively) and a negative borderline correlation with phosphorus (r = - 0.21). Patients who required bilateral neck exploration, had significantly lighter adenomas (median weight 0.8 g vs 1.1 g, p = 0.005). CONCLUSIONS: We conclude that preoperative PTH levels may only serve as an approximate guide to adenoma weight, as direct preoperative prediction is not possible. Serum calcium levels, PTH and calcium decrease correlate only weak with adenoma weight. Patients who require bilateral neck exploration, have significantly (20-25%) lighter adenomas.

Routine preoperative mechanical bowel preparation with additive oral antibiotics is associated with a reduced risk of anastomotic leakage in patients undergoing elective oncologic resection for colorectal cancer.

BACKGROUND: Anastomotic leakage (AL) following colorectal resection is a serious issue. AL in oncologic patients might negatively affect the overall survival. Recently, mechanical bowel preparation with additive oral antibiotics (MBP + AB) prior to surgery has been suggested as a means of reducing AL. However, it is unclear whether this positive effect is secondary to MBP alone or secondary to the additive oral antibiotic (MBP + AB). The aim of this study was to investigate the effect of mechanical bowel preparation with additive oral antibiotics (MBP + AB) and without additive oral antibiotics (MBP - AB) on the rate of AL following colorectal resection for cancer. MATERIALS AND METHODS: Patients undergoing surgical management for colorectal cancer with anastomosis from January 2014 till September 2017 were included for analysis. Cases undergoing MBP + AB were included in the study group. Patients undergoing MBP - AB were included in the control group. Both groups were compared with regard to the rate of AL. RESULTS: Four hundred and ninety-six patients: 125 undergoing MBP + AB and 371 undergoing MBP - AB were included for analysis. Significantly, more male patients were included in the MBP - AB group compared to the MBP + AB group: 60.1% vs. 45.6% respectively (p = 0.03). Both groups were similar with regard to age distribution and clinicopathological findings (p > 0.05). The rate of AL was significantly higher in the control group (MBP - AB) compared to study group (MBP + AB) (9.1% vs. 4.0%, p = 0.03). CONCLUSION: Mechanical bowel preparation with additive oral antibiotics prior to elective colorectal resection with anastomosis significantly reduces the risk of AL. Therefore, mechanical bowel preparation with additive non-absorbable oral antibiotics should be recommended in all cases prior to elective colorectal surgery.

Extra nodular metastasis is a poor prognostic factor for overall survival in node-positive patients with colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is the second leading cause for cancer-related death in industrialized nations. Nodal involvement has been identified as a relevant prognostic feature in CRC. Extra nodal metastasis (ENM) describes the spread of malignant cells beyond the nodal capsule. ENM is thought to be an independent risk factor for poor survival. This study examined ENM as an independent risk factor for poor overall survival in patients with node-positive CRC. MATERIALS AND METHODS: Data from a prospectively maintained CRC database was retrospectively analyzed. Blinded slides of patients with stage III and IV CRC following radical surgical resection were re-examined for the presence of ENM. The effect of ENM on overall survival was examined using Kaplan-Meier curves. RESULTS: One hundred forty-seven cases with node-positive CRC (UICC stages III and IV) including 78 cases with ENM were included for analysis. ENM was seen in 60 patients with colon cancer (58.8%) and in 18 patients with rectal cancer (40%), p = 0.033. ENM-positive patients had a significantly higher odd for cancer-related death compared to ENM-negative patients ratio of [OR 0.44: 0.22-0.88, CI 95%, p = 0.021], p = 0.02. The median overall survival was significantly longer in patients without ENM, 51.0 ± 33 vs. 30.5 ± 42 months, p = 0.02. CONCLUSION: Extra nodal metastasis is an independent prognostic factor in patients with node-positive colorectal cancer. Extra nodal metastasis is associated with high odds of tumor-related mortality and poor overall survival.

Routine Virtual Ileostomy Following Restorative Proctocolectomy for Familial Adenomatous Polyposis.

BACKGROUND: Anastomotic leakage (AL) is the most feared complication in colorectal surgery. A diverting ileostomy is routinely used to prevent or reduce morbidity and mortality following AL. However, a diverting ileostomy cannot prevent AL. Besides, diverting ileostomy might be associated with relevant complications. Herein, we introduce the virtual ileostomy as an alternative to diverting ileostomy in patients undergoing restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) for familial adenomatous polyposis (FAP). MATERIALS AND METHODS: The results of eight patients, five females and three males with a median age of 19.5 ± 6.0 years (range 16.0-31.0 years), undergoing restorative proctocolectomy with IPAA and virtual ileostomy for FAP are presented. RESULTS: All cases were laparoscopically managed. The virtual ileostomy was released between postoperative day 7 and 9. No AL was registered. Postoperative recovery was uneventful in all cases. CONCLUSION: A diverting ileostomy was prevented via the use of virtual ileostomy in all cases. Thus, virtual ileostomy is a good alternative to diverting ileostomy in patients undergoing restorative proctocolectomy with IPAA for FAP.

Modeling human orthostatic responses on the Moon and on Mars.

PURPOSE: Since manned missions to the Moon and Mars are planned, we conducted active standing tests with lunar, Martian, terrestrial, and 1.8 loads of inertial resistance (+Gz) modeled through defined parabolic flight maneuvers. We hypothesized that the cardiovascular response to active standing is proportional to the +Gz load. METHODS: During partial-+Gz parabolic flights, 14 healthy test subjects performed active stand-up maneuvers under 1 +Gz, lunar (0.16 +Gz), Martian (0.38 +Gz), and hyper inertial resistance (1.8 +Gz) while heart rate and finger blood pressure were continuously monitored. We quantified amplitudes and timing of orthostatic response immediately following standing up. RESULTS: The maximum early heart rate increase was 21 (SD ± 10) bpm with lunar, 23 (± 11) bpm with Martian, 34 (± 17) bpm with terrestrial +Gz, and 40 (± 11) bpm hyper +Gz. The time to maximum heart rate increased gradually with increasing loads of inertial resistance. The transient blood pressure reduction was most pronounced with hyper +Gz but did not differ significantly between lunar and Martian +Gz. The mean arterial pressure nadir was reached significantly later with Martian and lunar compared to 1 +Gz. Paradoxically, the time for blood pressure to recover was shortest with terrestrial +Gz. CONCLUSION: While load of inertial resistance directly affects the magnitude of the transient blood pressure reduction and heart rate response to active standing, blood pressure stabilization is most rapidly attained during terrestrial +Gz. The observation might suggest that the human cardiovascular system is tuned to cope with orthostatic stress on earth.

Tissue sublimation follow transarterial embolization of a follicular nodular hyperplasia of the liver-report of a case.

BACKGROUND: Follicular nodular hyperplasia (FNH) is a common benign liver tumor for which conservative management is indicated. Surgical or interventional management is indicated in symptomatic cases. Transarterial embolization (TAE) has been extensively used to manage unresectable liver tumors. Sublimation describes a change of physical state from solid to gas. Hepatic tissue sublimation following TAE has so far not been reported in medical literature. CASE PRESENTATION: A 30 year - old male patient presenting with pain to the upper abdomen due to a large FNH was managed with TAE. Routine radiographic control on post-intervention day one was within normal limits. Imaging due to right upper quadrant pain with fever and elevated inflammatory markers and liver enzymes on day two after TAE revealed a marked reduction of the FNH accompanied by the presence of a large volume of gas collection without signs of abscess formation. This change of state from solid to gas without sign of abscess formation within 2 days after TAE was described as hepatic tissue sublimation. The patient was managed conservatively and discharge 12 days after TAE. CONCLUSION: Tissue sublimation has hardly been reported in medical literature. This to the best of our knowledge is the first documented case of hepatic tissue sublimation following TAE.

Outcome of acute perforated cholecystitis: a register study of over 5000 cases from a quality control database in Germany.

BACKGROUND: Acute perforated cholecystitis (APC) is probably the most severe complication of acute cholecystitis. However, data on the outcome of cholecystectomy for APC are limited to small series. This study investigated the outcomes of cholecystectomy for APC. METHODS: Data from a prospectively maintained quality control database in Germany were analyzed. Cases with APC were compared to cases without gallbladder perforation with regard to demographic characteristics, clinical findings and surgical outcomes. RESULTS: A total of 5704 patients with APC were compared to 39,661 patients without perforation. Risk factors for APC included: the male gender, advanced age (>65 years), ASA score >2, elevated white blood count (WBC), positive findings on abdominal ultrasound sonography and fever. The APC group differed significantly from the control group with regard to fever (29.8 vs. 12.2 %), elevated WBC (83.8 vs. 65.4 %) and positive findings from ultrasound sonography (84.9 vs. 78.9 %), p < 0001. Preoperative computed tomography (CT) was ordered significantly more often in the APC group compared to the control group (2.3 vs. 1.0 %, p = 0.001). Surgery lasted significantly longer in the APC group (92.3 ± 40.8 vs. 73.7 ± 34.1, p < 0.001). The rates of conversion (18.9 vs. 6.8 %), bile duct injury (1.4 vs. 0.5 %), re-intervention (6.9 vs. 2.9 %) and mortality (4.3 vs. 1.3 %) were significantly higher in the APC group (p < 0.001). Similarly, the length of stay (13.4 ± 11.4 vs. 9.0 ± 8.3, p < 0.001) was significantly longer in the APC group. CONCLUSION: Acute perforated cholecystitis is a severe complication of acute cholecystitis. Surgical dissection could be challenging with high risks of bile duct injury and conversion. The rates of morbidity and mortality are higher compared to those of patients without perforation.

Advancement Flap for Treatment of Complex Cryptoglandular Anal Fistula: Prediction of Therapy Success or Failure Using Anamnestic and Clinical Parameters.

BACKGROUND: Multiple new procedures for treatment of complex anal fistula have been described in the past decades, but an ideal single technique has yet not been identified. Factors that predict the outcome are required to identify the best procedure for each individual patient. The aim of this study was to find those predictors for advancement flap at midterm follow-up. METHODS: From 2012 to 2015 in a tertiary university clinic, all patients who underwent advancement flap for treatment of complex cryptoglandular fistula were prospectively enrolled. Pre- and postoperatively standardized anamnestic and clinical examinations were performed. Predictive factors for therapy failure were identified using univariate and multivariate analysis. RESULTS: Out of 65 patients, 61 (93%) completed all examinations and were included in the study. Therapy failure after a mean follow-up period of 25 months occurred in total n = 11 patients (18%). There was no significant disturbance of continence among the entire study cohort as shown by the incontinence score (preop 0.34 ± 0.91 pts., postop 0.37 ± 0.97 pts.; p = 0.59). Univariate analysis for risk factors for therapy failure revealed age (p = 0.004), history of surgical abscess drainage (p = 0.04), BMI (p = 0.002), suprasphincteric fistula (p = 0.019) and horseshoe abscess (p = 0.036) as independent parameters for therapy failure. During multivariate analysis, only history of surgical abscess drainage (OR = 8.09, p = 0.048, 95% CI 0.98-64.96), suprasphincteric fistula (OR = 6.83, p = 0.032, 95% CI 1.17-6.83) and BMI (OR = 1.23, p = 0.017, 95% CI 1.03-1.46) were independent parameters for therapy failure. CONCLUSION: Advancement flap for treatment of complex fistula is effective and has low risk of disturbed continence. BMI, suprasphincteric fistula and history of surgical abscess drainage are predictors for therapy failure.

New trend in colorectal cancer in Germany: are young patients at increased risk for advanced colorectal cancer?

BACKGROUND: The role of colonoscopy in the screening of colorectal cancer (CRC) has been unequivocally established. In Germany, screening colonoscopy with full insurance reimbursement is available for individuals aged 55 and above, and/or for persons with well-known risk factors for CRC. However, advanced CRC is not uncommon in individuals below 55 years. This study was designed to investigate the incidence of advanced CRC in patients < 55 years. METHODS: A retrospective analysis of data from a prospectively maintained CRC database of a university hospital in Germany was performed. Using the recommended age for screening colonoscopy as cutoff, the study population was divided into two groups: < 55 years (study group) and ≥ 55 years (control group). Both groups were compared with regard to the extent of CRC using the UICC stages. Only surgically managed patients were included for analysis. Advanced CRC was defined as UICC stage III or IV. RESULTS: Complete follow-up data was available for 609 patients treated between 2009 and 2013. The study group included 83 patients, 42 females and 41 males with a median age of 48.0 ± 10 years, while the control group was made up of 526 patients, 230 females and 296 males with a median age of 75.5 ± 8.3 years. Both groups were comparable with regard to gender distribution, p = 0.24. Significantly more patients from the study group were diagnosed with advanced CRC in comparison to the control group, 56.6 vs. 43.9%, p = 0.03. There was no statistically significant difference amongst both groups with respect to cancer-related mortality, 10.8 vs. 12.5%, p = 0.66. CONCLUSION: Patients below the recommended age for screening colonoscopy might be at increased risk for advanced CRC. There is need to decrease the recommended age for screening colonoscopy to prevent CRC or enable an early diagnosis in patients below 55 years.

Calprotectin could be a potential biomarker for acute appendicitis.

BACKGROUND: Acute appendicitis is a common cause for a visit to the emergency department and appendectomy represents the most common emergency procedure in surgery. The rate of negative appendectomy however has remained high despite modern diagnostic apparatus. Therefore, there is need for a better preoperative screening of patients with suspected appendicitis. Calprotectin represents a predominant protein in the cytosol of neutrophil granulocytes and has been extensively investigated with regard to bowel pathologies. This study investigates the expression of calprotectin in the lumen of the vermiform appendix of patients undergoing appendectomy for suspected appendicitis. METHODS: Appendix specimens from patients undergoing emergency appendectomy for suspected acute appendicitis were examined. Acute appendicitis was confirmed on histopathology. The qualitative expression of calprotectin in the vermiform appendix specimens was analyzed using specific calprotectin antibodies. RESULTS: Vermiform appendix specimens from 52 patients (22 female and 30 male) including 11 with uncomplicated and 41 with complicated appendicitis were analyzed. Strong immunostainings were achieved with calprotectin antibody in the lumen of all specimens irrespective of the extent of appendicitis. Immunostaining was negative in the uninflamed appendix. CONCLUSIONS: High calprotectin activity could be demonstrated within the lumen of vermiform appendix specimens following appendectomy for acute appendicitis. The high luminal accumulation of calprotectin-carrying cells could be interpreted as an invitation to study the expression of calprotectin in stool as a new diagnostic aid in patients with suspected appendicitis.

Aquaporin-1 and 8 expression in the gallbladder mucosa might not be associated with the development of gallbladder stones in humans.

BACKGROUND: Cholecystolithiasis is a highly prevalent condition in the Western world. Gallbladder stone-related conditions represent the second most common gastrointestinal pathology. Cholesterol stones represent over 80% of gallstones. Cholesterol stones develop secondary to crystallization of bile cholesterol. Water resorption from gallbladder bile via aquaporin in the gallbladder mucosa might play a role in the development of cholesterol stones. This study investigated the expression of Aquaporin-1 (AQP1) and Aquaporin-8 (AQP8) in the human gallbladder mucosa and their possible association with the formation of gallbladder stones. METHODS: The expression of AQP1 and AQP8 in the gallbladder mucosa was examined via immunohistochemical staining. The expression of both AQP1 and AQP8 in the gallbladder mucosa of stone carriers (study group) was compared to that of nonstone carriers (control group). RESULTS: Eighty-four gallbladder specimens from 44 male (52·2%) and 40 female (47·6%) patients were analysed. The study group included 47 specimens from stone carriers, while 37 specimens from stone-free gallbladders were included in the control group. Immunostaining for both AQP1 and AQP8 was positive in 80 cases. AQP1 was expressed both over the apical and intercellular membrane, while AQP8 was expressed only over the apical membrane. A similar distribution was recorded in specimens from the cystic duct. Immunostaining with AQP1 was generally stronger in comparison with AQP8. No significant (P > 0·05) relationship was found between aquaporin expression and the presence or absence of gallbladder stones. CONCLUSION: AQP1 and AQP8 are both expressed in the gallbladder and cystic duct mucosa. However, their role in the development of gallbladder stones is still to be proven.

A proposal for a preoperative clinical scoring system for acute cholecystitis.

BACKGROUND: Acute cholecystitis is a common diagnosis for which surgery is usually indicated. However, the heterogeneity of clinical presentation makes it difficult to standardize management. The variation in clinical presentation is influenced by both patient-dependent and disease-specific factors. A preoperative clinical scoring system designed to included patient-dependent and clinical factors might be a useful tool in clinical decision making. METHODS: The data of patients undergoing laparoscopic cholecystectomy for acute cholecystitis in a university hospital were retrospectively reviewed. Patient-dependent factors (age, sex, body mass index, and American Society of Anesthesiologists score) and disease-specific factors (history of biliary colics, white blood count, C-reactive protein, and gallbladder wall thickness) were used to compute a clinical score between zero and nine for each patient. Cholecystitis was classified as mild (score ≤ 3), moderate (4 ≤ score ≤ 6), or severe (score ≥ 7). RESULTS: Cholecystitis was mild in 45 cases, moderate in 105 cases, and severe in 27 cases. Among patient-dependent factors, the male gender, age >65 y, and American Society of Anesthesiologists score >2 correlated significantly with high scores, P = 0.001. Equally, high white blood count, elevated C-reactive protein, and gallbladder wall thickness >4 mm correlated significantly with high scores, P = 0.001. These findings were confirmed on multivariate analyses. High scores correlated significantly with the duration of surgery (P = 0.007), the need of intensive care unit management (P = 0.001) and the length of stay (P = 0.001). However, there was no significant association between the preoperative score and the rate of conversion (P = 0.103) or the rate of complication (P = 0.209). CONCLUSIONS: This preoperative clinical scoring system has a potential to select patients with severe cholecystitis and therefore might be a useful tool in clinical decision making.

Surgical management of empyematous cholecystitis: a register study of over 12,000 cases from a regional quality control database in Germany.

BACKGROUND: Acute cholecystitis is a common indication for surgery. Surgical outcomes depend among other factors on the extent of gallbladder inflammation. Data on the outcomes of patients undergoing cholecystectomy due to acute empyematous cholecystitis are rare. METHODS: Data from a prospectively maintained quality control database in Germany were analyzed. Cases with empyematous cholecystitis were compared to cases without gallbladder empyema with regard to baseline features, clinical parameters and surgical outcomes. RESULTS: A total of 12,069 patients with empyematous cholecystitis (EC) were compared to 33,296 patients without empyema. The male gender, advanced age, ASA score >2, elevated white blood count and fever were confirmed as risk factors for EC. The EC group differed significantly from the control group with regard to fever (28.0 vs. 9.5 %), elevated WBC (82.5 vs. 62.3 %) and positive findings from ultrasound sonography (87.4 vs. 76.9 %), p < 0001. Surgery lasted significantly longer in the EC group (86.1 ± 38.5 vs. 72.2 ± 33.6, p < 0.001). The rates of conversion (15.2 vs. 5.8 %), bile duct injury (0.8 vs. 0.4 %), re-intervention (5.5 vs. 2.6 %) and mortality (2.8 vs. 1.2 %) were significantly higher in the EC group, p < 0.001. Similarly, the length of stay (11.9 ± 10.5 vs. 8.8 ± 8.3, p < 0.001) was significantly longer in the EC group. CONCLUSION: Empyematous cholecystitis is a severe form of acute cholecystitis with high rates of morbidity and mortality. Even the experienced laparoscopic surgeon should expect dissection difficulties, therefore the threshold for conversion in order to prevent bile duct injury should be low.

Iatrogenic Femoral Pseudoaneurysm and Secondary Ipsilateral Deep Vein Thrombosis: An Indication for Early Surgical Exploration.

Pseudoaneurysm formation often complicates transfemoral interventional procedures. Nonsurgical treatment consists of femoral compression and thrombin injection under ultrasound guidance. We report a 74-year-old man who was diagnosed with a pseudoaneurysm, following coronary angiography. Duplex ultrasound revealed deep vein thrombosis of the ipsilateral common femoral vein. Ultrasound-guided thrombin injection was unsuccessfully performed, and the patient subsequently underwent surgical exploration for repair of the pseudoaneurysm and release of the venous compression. The increased local inflammation, because of the thrombosis, added in surgical difficulties. We conclude that early surgical intervention should be considered as a primary strategy in patients with femoral pseudoaneurysms and deep vein thrombosis secondary to femoral compression.

Ruptured Mycotic Aortic Aneurysm after Bacille Calmette-Guerin Therapy.

To report a case of a ruptured mycotic abdominal aortic aneurysm (MAA) after intravesical Bacille Calmette-Guerin (BCG) therapy because of bladder carcinoma. A 57-year-old male patient was admitted to our hospital for follow-up computed tomography 14 months after transurethral resection of a papillary carcinoma of the bladder and intravesical BCG therapy. The CT scan revealed a ruptured MAA aneurysm and the patient underwent an endovascular repair with an aorto-bi-iliac stent graft. A ruptured MAA is a rare but lethal complication after BCG instillation therapy. The standard therapy is the open reconstruction but according to the literature an endovascular therapy in combination with long-term antibiotics should be considered as a bridging or a definite solution.

Family history as a major prerequisite for microsatellite instability screening in colorectal cancer is a poor selection tool.

Background: Deficient mismatch repair (MMR) leading to microsatellite instability (MSI) in tumors is thought to be present in over 15% of colorectal cancer (CRC) cases. Testing CRC for MSI has traditionally been recommended following the fulfillment of clinical criteria. However, the performance of clinical criteria, especially the family history, as a selection tool for MSI screening in CRC is questionable. Methods: We retrospectively investigated the incidence of high degree MSI (MSI-H) tumors in an unselected population of CRC patients and compared its prevalence between individuals with and without family history of cancers within the spectrum of MSI-H tumors as defined in the revised Bethesda criteria. Results: The study population included 274 patients, 70 with positive and 204 without family history of MSI-H tumors with complete data including findings from MSI analysis. The overall incidence of MSI-H CRC was 18.98%. There was no statistically significant difference in the incidence of MSI-H CRC amongst both groups. The sensitivity and specificity of family history with regard to the presence of an MSI-H tumor in this collective was 36.5% and 77.5%, respectively. Conclusions: A relevant number of cases with high MSI-H CRC may be missed secondary to screening based on clinical criteria like family history alone. Thus, systematic screening independent of clinical characteristics, especially family history of cancer should be recommended in all cases with CRC.

Microsatellite instability is highly prevalent in older patients with colorectal cancer.

Background: Clinical guidelines suggest screening of colorectal cancer (CRC) for microsatellite instability (MSI). However, microsatellite instability-high (MSI-H) CRC is not rare in older patients. This study aimed to investigate the prevalence of MSI-H CRC in an unselected population in an age-based manner. Material and methods: A retrospective analysis of data from patients undergoing radical surgery for CRC was performed. Only cases with results from MSI testing using immunochemistry (IHC) were analyzed. Age-based analyses were performed using two cut-off ages: 50 years. as stated in Amsterdam II guidelines, and 60 years. as outlined in the revised Bethesda criteria. Results: The study population included 343 (146 female and 197 male) patients with a median age of 70 years (range 21-90 years). The prevalence of MSI-H tumors in the entire cohort was 18.7%. The prevalence of MSI-H CRC was 22.5% in the group ≤50 years vs. 18.2% in the group >50 years using the age limit in the Amsterdam II guidelines. MSI-H CRC was present in 12.6% of the group aged ≤60 years compared to 20.6% in the control group >60 years. Conclusion: MSI screening of CRC based on age alone is associated with negative selection of a relevant number of cases. MSI-H CRC is also common in elderly patients, who may be negatively selected secondary to an age-based screening algorithm. Following the results of this study, screening based on clinical criteria should be omitted in favor of systematic screening as is already internationally practiced.

A vector-encoded bispecific killer engager to harness virus-activated NK cells as anti-tumor effectors.

Treatment with oncolytic measles vaccines (MV) elicits activation of immune cells, including natural killer (NK) cells. However, we found that MV-activated NK cells show only modest direct cytotoxic activity against tumor cells. To specifically direct NK cells towards tumor cells, we developed oncolytic measles vaccines encoding bispecific killer engagers (MV-BiKE) targeting CD16A on NK cells and carcinoembryonic antigen (CEA) as a model tumor antigen. MV-BiKE are only slightly attenuated compared to parental MV and mediate secretion of functional BiKE from infected tumor cells. We tested MV-BiKE activity in cocultures of colorectal or pancreatic cancer cells with primary human NK cells. MV-BiKE mediate expression of effector cytokines, degranulation and specific anti-tumor cytotoxicity by NK cells. Experiments with patient-derived pancreatic cancer cultures indicate that efficacy of MV-BiKE may vary between individual tumors with differential virus permissiveness. Remarkably, we confirmed MV-BiKE activity in primaryhuman colorectal carcinoma specimens with autochthonous tumor and NK cells.This study provides proof-of-concept for MV-BiKE as a novel immunovirotherapy to harness virus-activated NK cells as anti-tumor effectors.