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Objective: This study aimed to evaluate all mesh-related problems during reoperations after mesh-reinforcement 15 years after the start of the PRIMA trial. SUMMARY BACKGROUND DATA Prophylactic mesh reinforcement during closure of a midline laparotomy has proven to reduce the incidence of incisional hernia, especially in high-risk patients, but long-term mesh-related morbidity is largely unknown., Methods: Patients receiving a prophylactic onlay or retro-rectus mesh in the PRIMA trial between 2009 and 2012 were included on an as-treated basis from participating centers that made reoperation notes available. Main outcomes were the incidences of complications requiring mesh explantation, mesh-related ileus, and mesh-related problems during laparotomy for other diagnoses., Methods: Out of 373 patients randomized to prophylactic mesh reinforcement, 242 were included: 127 with onlay and 115 patients with retrorectus mesh. Median follow-up is 27 months (IQR 12-78). Thirty-four patients underwent reoperation for any reason during entire follow-up, 22 after onlay (17.3%) and 12 after retrorectus mesh (10.4%). Reoperation rate for complications that required mesh explantation was 4/127 (3.1%) after onlay and 0/115 (0%) after retrorectus mesh. Mesh-related ileus occurred in none of the onlay group, and 3/115 (2.6%) in the retrorectus group. During subsequent laparotomies for other primary diagnoses, adhesions to the mesh were noted in 3/10 patients in the onlay group and 1/5 patients in the retro-rectus group. Overall, the mesh was removed in 10/127 (7.9%) in the onlay group and 7/115 (6.1%) patients in the retro-rectus group., Conclusions: In high-risk patients receiving a prophylactic mesh during midline laparotomy closure, low incidences of mesh-related complications requiring reoperation and mesh-related problems during unrelated subsequent laparotomies were found, for both the onlay and retrorectus techniques., Competing Interests: Funding statement: The authors report no conflicts of interest. Furthermore, no funding was received from any (non) profit organisation. The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The goal of this study was to assess the long-term effectiveness of combination therapy for intermittent claudication, compared with supervised exercise only., Background: Supervised exercise therapy is recommended as first-line treatment for intermittent claudication by recent guidelines. Combining endovascular revascularization plus supervised exercise shows promising results; however, there is a lack of long-term follow-up., Methods: The ERASE study is a multicenter randomized clinical trial, including patients between May 2010 and February 2013 with intermittent claudication. Interventions were combination of endovascular revascularization plus supervised exercise (n = 106) or supervised exercise only (n = 106). Primary endpoint was the difference in maximum walking distance at long-term follow-up. Secondary endpoints included differences in pain-free walking distance, ankle-brachial index, quality of life, progression to critical limb ischemia, and revascularization procedures during follow-up. This randomized trial report is based on a post hoc analysis of extended follow-up beyond that of the initial trial. Patients were followed up until 31 July 2017. Data were analyzed according to the intention-to-treat principle., Results: Median long-term follow-up was 5.4 years (IQR 4.9-5.7). Treadmill test was completed for 128/212 (60%) patients. Whereas the difference in maximum walking distance significantly favored combination therapy at 1-year follow-up, the difference at 5-year follow-up was no longer significant (53 m; 99% CI-225 to 331; P = 0.62). No difference in pain-free walking distance, ankle-brachial index, and quality of life was found during long-term follow-up. We found that supervised exercise was associated with an increased hazard of a revascularization procedure during follow-up (HR 2.50; 99% CI 1.27-4.90; P < 0.001). The total number of revascularization procedures (including randomized treatment) was lower in the exercise only group compared to that in the combination therapy group (65 vs 149)., Conclusions: Long-term follow up after combination therapy versus supervised exercise only, demonstrated no significant difference in walking distance or quality of life between the treatment groups. Combination therapy resulted in a lower number of revascularization procedures during follow-up but a higher total number of revascularizations including the randomized treatment., Trial Registration: Netherlands Trial Registry Identifier: NTR2249., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

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Objective: The new 2019 guideline of the European Society for Vascular Surgery (ESVS) recommends consideration for elective iliac artery aneurysm (eIAA) repair when the iliac diameter exceeds 3.5 cm, as opposed to 3.0 cm previously. The current study assessed diameters at time of eIAA repair and ruptured IAA (rIAA) repair and compared clinical outcomes after open surgical repair (OSR) and endovascular aneurysm repair (EVAR)., Methods: This retrospective observational study used the nationwide Dutch Surgical Aneurysm Audit (DSAA) registry that includes all patients who undergo aorto-iliac aneurysm repair in the Netherlands. All patients who underwent primary IAA repair between 1 January 2014 and 1 January 2018 were included. Diameters at time of eIAA and rIAA repair were compared in a descriptive fashion. The anatomical location of the IAA was not registered in the registry. Patient characteristics and outcomes of OSR and EVAR were compared with appropriate statistical tests., Results: The DSAA registry comprised 974 patients who underwent IAA repair. A total of 851 patients were included after exclusion of patients undergoing revision surgery and patients with missing essential variables. eIAA repair was carried out in 713 patients, rIAA repair in 102, and symptomatic IAA repair in 36. OSR was performed in 205, EVAR in 618, and hybrid repairs and conversions in 28. The median maximum IAA diameter at the time of eIAA and rIAA repair was 43 (IQR 38-50) mm and 68 (IQR 58-85) mm, respectively. Mortality was 1.3% (95% CI 0.7-2.4) after eIAA repair and 25.5% (95% CI 18.0-34.7) after rIAA repair. Mortality was not significantly different between the OSR and EVAR subgroups. Elective OSR was associated with significantly more complications than EVAR (intra-operative: 9.8% vs. 3.6%, post-operative: 34.0% vs. 13.8%, respectively)., Conclusion: In the Netherlands, most eIAA repairs are performed at diameters larger than recommended by the ESVS guideline. These findings appear to support the recent increase in the threshold diameter for eIAA repair., (Copyright © 2020 European Society for Vascular Surgery. Published by Elsevier B.V. All rights reserved.)

Aortocaval fistulas are a rare and potentially life-threatening complication of aortic aneurysms. They pose a significant diagnostic challenge due to their aspecific presentation. We describe two cases of patients who were admitted to the emergency room with an unusual presentation. The first patient was a 69-year-old male, with a history of hypertension and hyperlipidemia, who was admitted to our hospital with a painful and swollen left leg. The second patient was a 75-year-old male with a history of coronary artery bypass graft and cholecystectomy who was admitted due to a swollen left leg and dyspnea. We also give a review of the literature regarding the clinical presentation, diagnosis and management of aortocaval fistulas.

Intravesical administration of bacille Calmette-Guérin (BCG) is considered to be the therapy of choice for treating superficial bladder carcinoma. Created from a live attenuated strain of Mycobacterium bovis, BCG is theoretically unable to cause infections. However, both local and systemic complications due to infection are known to arise, including vascular complications. We describe the case of a patient with a history of BCG instillations presenting with an arterial rupture of his left iliac artery due to an abscess in the iliopsoas muscle., (Copyright © 2017 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Importance: Supervised exercise is recommended as a first-line treatment for intermittent claudication. Combination therapy of endovascular revascularization plus supervised exercise may be more promising but few data comparing the 2 therapies are available., Objective: To assess the effectiveness of endovascular revascularization plus supervised exercise for intermittent claudication compared with supervised exercise only., Design, Setting, and Participants: Randomized clinical trial of 212 patients allocated to either endovascular revascularization plus supervised exercise or supervised exercise only. Data were collected between May 17, 2010, and February 16, 2013, in the Netherlands at 10 sites. Patients were followed up for 12 months and the data were analyzed according to the intention-to-treat principle., Interventions: A combination of endovascular revascularization (selective stenting) plus supervised exercise (n = 106) or supervised exercise only (n = 106)., Main Outcomes and Measures: The primary end point was the difference in maximum treadmill walking distance at 12 months between the groups. Secondary end points included treadmill pain-free walking distance, vascular quality of life (VascuQol) score (1 [worst outcome] to 7 [best outcome]), and 36-item Short-Form Health Survey (SF-36) domain scores for physical functioning, physical role functioning, bodily pain, and general health perceptions (0 [severe limitation] to 100 [no limitation])., Results: Endovascular revascularization plus supervised exercise (combination therapy) was associated with significantly greater improvement in maximum walking distance (from 264 m to 1501 m for an improvement of 1237 m) compared with the supervised exercise only group (from 285 m to 1240 m for improvement of 955 m) (mean difference between groups, 282 m; 99% CI, 60-505 m) and in pain-free walking distance (from 117 m to 1237 m for an improvement of 1120 m vs from 135 m to 847 m for improvement of 712 m, respectively) (mean difference, 408 m; 99% CI, 195-622 m). Similarly, the combination therapy group demonstrated significantly greater improvement in the disease-specific VascuQol score (1.34 [99% CI, 1.04-1.64] in the combination therapy group vs 0.73 [99% CI, 0.43-1.03] in the exercise group; mean difference, 0.62 [99% CI, 0.20-1.03]) and in the score for the SF-36 physical functioning (22.4 [99% CI, 16.3-28.5] vs 12.6 [99% CI, 6.3-18.9], respectively; mean difference, 9.8 [99% CI, 1.4-18.2]). No significant differences were found for the SF-36 domains of physical role functioning, bodily pain, and general health perceptions., Conclusions and Relevance: Among patients with intermittent claudication after 1 year of follow-up, a combination therapy of endovascular revascularization followed by supervised exercise resulted in significantly greater improvement in walking distances and health-related quality-of-life scores compared with supervised exercise only., Trial Registration: Netherlands Trial Registry Identifier: NTR2249.

Introduction: In this multicenter, randomized controlled trial, endovenous laser ablation (EVLA) is compared with conventional surgery for the treatment of varicose veins based on incompetence of the small saphenous vein and the saphenopopliteal junction (SPJ)., Methods: In two Dutch hospitals, 189 patients were enrolled and randomized to receive EVLA (810-nm laser) or ligation of the SPJ. End points were success rate measured with duplex ultrasound (6 weeks post-treatment), perioperative pain, quality of life, duration of surgery, difficulty of surgery, complications, cosmetic results, and number of days to resume work and normal activities. Pain was measured on a visual analog scale (VAS). Quality of life was assessed using the Aberdeen Varicose Vein Questionnaire (AVVQ) and Euro Qol-5D. The follow-up duration in this article is 6 weeks., Results: One hundred seventy-five patients have been treated and analyzed. One hundred eighteen patients (67%) underwent EVLA, and 57 patients (33%) underwent ligation of the SPJ. The patient characteristics were similar in both groups. In the surgery group, 21% residual incompetence of the SPJ was seen after 6 weeks, compared with 0.9% in the laser group. Both treatment modalities reduced pain after 6 weeks. One week post-treatment, patients in the EVLA group temporarily experienced more pain compared with the surgery group (31 vs 18 on a VAS from 0 to 100). There were no significant differences between the two groups with respect to quality of life. Both treatments did show improvement in quality of life. Also with regard to the cosmetics, there were no differences, aside from the fact that patients rated their scar as more beautiful after EVLA. After EVLA, patients could return to work more quickly. The operation time was longer in the surgery group. After 2 weeks, there were significantly more neurological complications in the surgery group: 18 (31%) vs 16 (17%) patients in the EVLA group. Ten percent of patients in the surgery group developed a surgical site infection vs 0% in the EVLA group., Conclusions: EVLA provides an excellent alternative to conventional surgery in the treatment of symptomatic varicose veins due to an incompetent small saphenous vein with SPJ. EVLA has a superior immediate success rate, is easier and faster, and has fewer complications., (Copyright © 2013 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)

Objective: To assess the involvement of the multidrug resistance-associated protein 1 (MRP1) and the glutathione pathway in the multidrug resistant (MDR) phenotype of prostate cancer in vitro., Materials and Methods: Chemoselection of human prostate cancer cell lines PC3 and DU145 with etoposide resulted in the resistant cell lines PC3-R and DU-R. Resistance against etoposide, doxorubicin and vincristine, and its reversal with leukotriene D4 antagonists MK-571 and zafirlukast, and buthionine sulfoximine (BSO), was assessed using tetrazolium-dye viability assays. Western blot analysis of MRP1 expression and glutathione content were measured, and MRP1 function assessed in fluorescence assays., Results: MRP1 was increased in the MDR models; the glutathione content was significantly higher in PC3-R but there was no increase in glutathione in DU-R. Adding non-toxic doses of MK-571, zafirlukast or BSO significantly increased the sensitivity of the MDR models to cytotoxic drugs. MRP1 function was inhibited with MK-571 in the MDR models., Conclusion: MRP1 and glutathione mediate MDR in newly developed prostate cancer models.

Advanced hormone-refractory prostate cancer remains a therapeutic challenge, because all available pharmaceutical concepts have been ineffective in improving cancer-specific survival. Failure of chemotherapy may be caused by multidrug resistance (MDR) mechanisms protecting cancer cells against cytotoxic drugs, and the question arises whether prostate cancer is also using MDR principles resulting in resistance against chemotherapeutic agents. In consequence, an array of diverse pathways known to lead to MDR such as MDR1, MRPs, glutathione, and apoptosis have been examined and partially established at varying degrees in hormone-refractory prostate cancer. Thus, evidence keeps accumulating for the involvement of some MDR mechanisms in the chemoresistance of prostate cancer in vitro and in vivo. For some of them, e.g. MRP1, functional expression appears to be probable. This lends credit to the idea that reversal, circumvention, or overcoming of MDR pathways in advanced prostate cancer may be feasible and will lead to new avenues with improved treatment efficacy in otherwise intractable disease., (Copyright 2003 S. Karger GmbH, Freiburg)

Purpose: Advanced disseminated prostate cancer is highly resistant to cytotoxic chemotherapy. We identified proteins that may be involved in multidrug resistance in clinical prostate cancer. Expression of these proteins was examined in the context of tumor progression., Materials and Methods: Paraffin embedded, formalin fixed prostate cancer specimens from archival sources of 3 distinct patient groups were examined. These groups were clearly distinct with regard to pathological stage and responsiveness to antihormonal therapy. Group 1 consisted of patients with organ confined prostate cancer treated with radical prostatectomy (early pathological stage T2N0M0). Group 2 patients had disseminated, early advanced prostate cancer and were treated with transurethral prostatic resection for urinary obstruction before receiving antihormonal therapy. Group 3 patients had disseminated prostate cancer with relapse despite antihormonal treatment (late advanced prostate cancer) and they underwent transurethral prostatic resection to relieve the symptoms of urinary obstruction. Immunohistochemical study was done to detect P-glycoprotein, multidrug resistance associated protein, lung resistance protein, glutathione-S-transferase pi, p53, Bcl-2, Bax, topoisomerase I, IIalpha and IIbeta, and Ki-67., Results: Advanced tumors were distinguished from locally confined tumors because they exhibited significantly higher histological grade and proliferative activity. The expression of multidrug resistance associated protein, p53, topoisomerase IIalpha, Ki-67 and topoisomerase IIbeta was significantly related to a higher Gleason sum score. The number of cases expressing multidrug resistance associated protein, lung resistance protein, glutathione-S-transferase pi, p53, Bcl-2, topoisomerase IIalpha and Ki-67 was significantly increased in the group with advanced disseminated prostate cancer. Topoisomerase I and IIbeta were homogeneously and highly expressed at all stages of prostate cancer progression, while P-glycoprotein was not expressed in any tumors regardless of the patient group., Conclusions: Up-regulation of the expression of the drug transporters multidrug resistance associated protein and lung resistance protein, detoxifying enzyme glutathione-S-transferase pi, and apoptosis inhibiting proteins Bcl-2 and p53 may be an explanation of the resistance of disseminated progressive prostate cancer to chemotherapy. As shown by the up-regulation of Ki-67 and topoisomerase IIalpha, increased proliferation reflects the aggressiveness of metastatic prostate cancer. Research on agents that counteract multidrug resistance mechanisms and may sensitize prostate carcinoma to cytotoxic chemotherapy may possibly lead to more effective treatment of progressive disseminated prostate cancer.

A 56-year old woman was admitted to the emergency ward after suffering a blunt thoraco-abdominal high-velocity trauma as she hit the wheel when her car drove into a tree. A laparotomy was performed because of haemodynamic instability and radiographic suspicion of a diaphragmatic rupture. Besides haemorrhage from liver and spleen injuries, an abdominal herniation of the heart through a ruptured pericardium and diaphragm was found. Haemostasis of liver, splenectomy and suturing of defects in pericardium and diaphragm resulted in a haemodynamically stable situation. A high index of suspicion of rupture of pericardium and diaphragm with luxation of the heart in the trauma patient is important to reduce morbidity and mortality due to delay of surgical intervention.

Introduction: Hormone-refractory disseminated prostate cancer is a major oncological problem. Preclinical studies with temozolomide, an oral alkylating agent, in prostate cancer have shown encouraging results. In phase I studies the safety of temozolomide in non-prostate cancer patients has been demonstrated. Based on these results, a phase II study of temozolomide in patients with metastatic disease who had developed progressive symptomatic disease while on antiandrogen therapy, was initiated., Methods: A group of 18 patients started a 5-day temozolomide regimen, with a 28-day treatment cycle. Response parameters (prostate-specific antigen, bone scan, quality of life questionnaire) and toxicity (common toxicity criteria for international studies) were recorded at regular intervals., Results: Of the 18 patients, 16 were evaluable by completing two or three cycles. All patients developed progressive disease within two cycles, except one who had progressive disease at the end of cycle 3. Of the 16 evaluable patients, 11 developed new bone metastases (bone scan), 1 developed lung metastases, 4 had progressive disease as reflected by a 25% increase in serum PSA together with subjective progression, and 7 and 5 had progressive disease as reflected by decreased quality of life and increased pain score, respectively. Toxicity was limited to nausea and vomiting, which was effectively treated with antiemetic medication, and anemia and thrombocytopenia, which returned to normal values within 1 week., Discussion: Treatment with temozolomide was generally well tolerated, with occasionally moderate toxicity. As all patients developed progressive disease the results are rather discouraging. Temozolomide is ineffective for the treatment of patients with symptomatic progressive hormone-refractory prostate cancer.

The aim of this study was to obtain insight into the role of the multidrug resistance (MDR) phenomenon in hormone-independent progressive prostate cancer. Using immunocytochemistry and Western blotting we determined the expression of P-glycoprotein (Pgp), multidrug resistance-associated protein (MRP), glutathione-S-transferase-pi (GST-pi), Bcl-2, Bax, topoisomerase (Topo) I, II alpha and II beta in the human prostate cancer cell lines PC3, TSU-Pr1, DU145 and LNCaP derivatives LNCaP-R, LNCaP-LNO and LNCaP-FGC. Proliferative activity was assessed by immunocytochemistry. MTT assays were used to determine the sensitivity to etoposide, doxorubicin and vinblastin. Pgp was not expressed in any of the cell lines. MRP was variably expressed. GST-pi was expressed in TSU-Pr1, PC3 and DU145. The expression of Bcl-2 was restricted to TSU-Pr1, whereas Bax was found in all cell lines. Topo II alpha was expressed at the highest level in the rapidly proliferating cell lines TSU-Pr1 and DU145. Topo I and II beta were equally expressed. Resistance profiles varied among the cell lines, with TSU-Pr1 being the most sensitive and LNCaP-LNO relatively resistant. Multiple MDR proteins were expressed in prostate cancer cell lines and may well influence response to chemotherapy. Future functional studies, using chemo-selected MDR models, may further help to determine the mechanism or combination of mechanisms underlying the resistance of prostate cancer to chemotherapy.

Chemotherapy is the principal strategy to systemically challenge metastasized cancers of genitourinary origin. Unfortunately, the efficacy of chemotherapy is often hampered by multidrug resistance, the resistance to a variety of structurally and functionally distinct cytotoxic agents. Multidrug resistance can be either intrinsic or acquired, and can be caused by several mechanisms. The so-called classical multidrug resistance, mediated by the MDR1 gene product P-glycoprotein, has been held mainly responsible for inferring the multidrug resistance phenotype on urologic malignancies. However, several other multidrug resistance pathways have been identified. Multidrug resistance can be caused by the membrane-bound multidrug-resistance-associated protein, the detoxifying glutathione metabolism, the antiapoptotic protein BCL2, and changes in levels or activity of the topoisomerase enzymes. Strategies to overcome multidrug resistance of genitourinary tumors have arisen from the better understanding of the biologic and molecular mechanisms of multidrug resistance, and have been studied in experimental and clinical settings. However, attempts to modulate multidrug resistance in clinical renal cell, bladder, prostate, and testicular cancer have not been very rewarding so far, despite the optimism that had arisen from experimental data. Nevertheless, application of novel therapies to reverse multidrug resistance and to increase efficacy of chemotherapy for urologic cancers should be further pursued, within the setting of controlled clinical trials, to improve on current strategies.

Wilkie's syndrome is a rare disease that should be considered in the differential diagnosis of upper abdominal discomfort and weight loss. Compression of the inferior part of the horizontal duodenum by the superior mesenteric artery may result in high intestinal obstruction with postprandial or positional discomfort, vomiting and weight loss. The diagnosis is based on clinical presentation and confirmed by radiographic studies during a symptomatic period. Therapy of first choice is conservative. Nevertheless, surgical intervention with duodenojejunostomy is often required.