Peter Gillgren

Results of rectocele repair. A prospective study.

PURPOSE: This study was designed to evaluate the results of rectocele repair and parameters that might be useful in selecting patients for this operation. METHODS: Twentyfive patients with symptom-giving rectoceles were prospectively evaluated with a standardized questionnaire, physical examination, defecography, colon transit studies, anorectal manometry, and electrophysiology. Patients underwent posterior colporrhaphy and perineorrhaphy. They were followed postoperatively (mean, 1.0 year) with the same questionnaire, physical examination, defecography, anorectal manometry, and electrophysiology. RESULTS: Constipation had improved postoperatively in 21 of 24 constipated patients (88 percent). At postoperative follow-up 13 patients (52 percent) had no constipation symptoms, 8 (32 percent) had occasional symptoms, and 4 (16 percent) had symptoms more than once per week. Four patients with rectocele at preoperative defecography, but not at physical examination, had favorable outcomes following surgery. The majority of patients not using vaginal digitalization preoperatively had improved with respect to constipation. All patients with pathologic transit studies had various degrees of constipation postoperatively. Constipation was not improved in two of five patients with preoperative paradoxic sphincter reaction. CONCLUSIONS: Rectocele is one cause of constipation that can be treated with good results. Preoperative use of vaginal digitalization is not mandatory for a good postoperative result. Defecography is an important complement to physical examination. Patients with pathologic transit study might have a less favorable outcome of rectocele repair with respect to constipation. More studies about the significance of paradoxic sphincter reaction in these patients are indicated.

2-cm versus 4-cm surgical excision margins for primary cutaneous melanoma thicker than 2 mm: a randomised, multicentre trial

BACKGROUND Optimum surgical resection margins for patients with clinical stage IIA-C cutaneous melanoma thicker than 2 mm are controversial. The aim of the study was to test whether survival was different for a wide local excision margin of 2 cm compared with a 4-cm excision margin. METHODS We undertook a randomised controlled trial in nine European centres. Patients with cutaneous melanoma thicker than 2 mm, at clinical stage IIA-C, were allocated to have either a 2-cm or a 4-cm surgical resection margin. Patients were randomised in a 1:1 allocation to one of the two groups and stratified by geographic region. Randomisation was done by sealed envelope or by computer generated lists with permuted blocks. Our primary endpoint was overall survival. The trial was not masked at any stage. Analyses were by intention to treat. Adverse events were not systematically recorded. The study is registered with ClinicalTrials.gov, number NCT01183936. FINDINGS 936 patients were enrolled from Jan 22, 1992, to May 19, 2004; 465 were randomly allocated to treatment with a 2-cm resection margin, and 471 to receive treatment with a 4-cm resection margin. One patient in each group was lost to follow-up but included in the analysis. After a median follow-up of 6·7 years (IQR 4·3-9·5) 181 patients in the 2-cm margin group and 177 in the 4-cm group had died (hazard ratio 1·05, 95% CI 0·85-1·29; p=0.64). 5-year overall survival was 65% (95% CI 60-70) [corrected] in the 2-cm group and 65% (40-70) in the 4-cm group (p=0·69). INTERPRETATION Our findings suggest that a 2-cm resection margin is sufficient and safe for patients with cutaneous melanoma thicker than 2 mm. FUNDING Swedish Cancer Society and Stockholm Cancer Society.

The risk for cutaneous malignant melanoma, melanoma in situ and intraocular malignant melanoma in relation to tobacco use and body mass index

Background  The incidence of cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) has been increasing during the last 50 years. Malignant melanoma (MM) is also the most common intraocular malignancy (IMM). Besides ultraviolet radiation, the cause of these tumours is largely unknown.

Epidemiological Characteristics of Cutaneous Malignant Melanoma of the Head and Neck: A Population-based Study

Since cutaneous malignant melanoma (CMM) and melanoma in situ (MIS) of the head and neck have only partially been differentiated from CMM of other anatomic sites, these lesions are classified in detail in this study. Data from 756 patients derived from the population-based register of the Stockholm-Gotland area were analyzed and the findings showed that the incidence of CMM was 3.4 times higher in the face compared to the skin outside the head-neck area and that lentigo maligna melanoma was 74 times and nodular melanoma 2.3 times more common in the face. Mean age at diagnosis was significantly higher for patients with CMM of the head and neck irrespective of histogenetic type. Tumor site within the head and neck related to age at diagnosis. CMM of the head and neck differs from CMM of other locations. Epidemiological data are in agreement with the hypothesis that UV radiation (chronic or intermittent) may give rise to melanomas with various phenotypic traits.

A Prospective Population‐Based Study of Cutaneous Malignant Melanoma of the Head and Neck

Objectives/Hypothesis For cutaneous malignant melanoma (CMM) of the head and neck, neither prognostic factors in population‐based groups, nor outcome with respect to surgical resection margins is clear. Therefore, we analyzed data in a regional registry to align treatment results for CMM of the head and neck with prognosis and survival times.

Profiling of Atherosclerotic Lesions by Gene and Tissue Microarrays Reveals PCSK6 as a Novel Protease in Unstable Carotid Atherosclerosis

Objective—Carotid plaque instability is a major cause of ischemic stroke, but detailed knowledge about underlying molecular pathways is still lacking. Here, we evaluated large-scale transcriptomic and protein expression profiling in a biobank of carotid endarterectomies followed by characterization of identified candidates, as a platform for discovery of novel proteins differentially regulated in unstable carotid lesions. Approach and Results—Genes highly upregulated in symptomatic versus asymptomatic plaques were selected from Affymetrix microarray analyses (n=127 plaques), and tissue microarrays constructed from 34 lesions were assayed for 21 corresponding proteins by immunohistochemistry. Quantification of stainings demonstrated differential expression of CD36, CD137, and DOCK7 (P<0.05) in unstable versus stable lesions and the most significant upregulation of a proprotein convertase, PCSK6 (P<0.0001). Increased expression of PCSK6 in symptomatic lesions was verified by quantitative real-time polymerase chain reaction (n=233), and the protein was localized to smooth muscle &agr;-actin positive cells and extracellular matrix of the fibrous cap by immunohistochemistry. PCSK6 expression positively correlated to genes associated with inflammation, matrix degradation, and mitogens in microarrays. Stimulation of human carotid smooth muscle cells in vitro with cytokines caused rapid induction of PCSK6 mRNA. Conclusions—Using a combination of transcriptomic and tissue microarray profiling, we demonstrate a novel approach to identify proteins differentially expressed in unstable carotid atherosclerosis. The proprotein convertase PCSK6 was detected at increased levels in the fibrous cap of symptomatic carotid plaques, possibly associated with key processes in plaque rupture such as inflammation and extracellular matrix remodeling. Further studies are needed to clarify the role of PCSK6 in atherosclerosis.

Effect of primary site on prognosis in patients with cutaneous malignant melanoma. A study using a new model to analyse anatomical locations.

The prognostic impact of different anatomical sites in patients with cutaneous malignant melanoma (CMM) has been widely debated and requires further elucidation. Therefore, we developed EssDoll©, a new computerized method to address the question of site in relation to prognosis. A population-based cohort of 1891 patients, diagnosed between 1976 and 1987 with invasive CMM without evidence of metastasis, was identified. The body surface was divided into 24 areas. Hazard ratios (HRs) for CMM death were calculated and areas were compared in both the whole model and in pairs. Coxs proportional hazard regression model was used and adjustments were made for established prognostic factors. Furthermore, the overall effect of site was calculated using the likelihood ratio test. Overall, the tumour site was of prognostic importance (P=0.0036). There was a significantly increased risk of CMM-specific death in patients with a primary tumour site in the middle and lower back (HR=1.8, P=0.04) and in the supramammary and mammary area (HR=1.8, P=0.05). When all areas were analysed in pairs, the dorsal shoulder, superior back and clavicular area also showed a worse prognosis. CMM diagnosed in other anatomical regions, including the calves, Achilles, upper arms, forehead, temples, cheeks and face, seemed to be related to a better prognosis. It can be concluded that the tumour site is of prognostic importance, and that the middle and lower back and supramammary and mammary areas are independent factors related to a poor prognosis.

Nationwide Study of the Treatment of Mycotic Abdominal Aortic Aneurysms Comparing Open and Endovascular Repair

Background: No reliable comparative data exist between open repair (OR) and endovascular aneurysm repair (EVAR) for mycotic abdominal aortic aneurysms (MAAAs). This nationwide study assessed outcomes after OR and EVAR for MAAA in a population-based cohort. Methods: All patients treated for MAAAs in Sweden between 1994 and 2014 were identified in the Swedish vascular registry. The primary aim was to assess survival after MAAA with OR and EVAR. Secondary aims were analyses of the rate of recurrent infections and reoperations, and time trends in surgical treatment. Survival was analyzed using Kaplan-Meier and log-rank tests. A propensity score–weighted correction for risk factor differences in the 2 groups was performed, including the operation year to account for differences in treatment and outcomes over time. Results: We identified 132 patients (0.6% of all operated abdominal aortic aneurysms in Sweden). Mean age was 70 years (standard deviation, 9.2), and 50 presented with rupture. Survival at 3 months was 86% (95% confidence interval, 80%–92%), at 1 year 79% (72%–86%), and at 5 years 59% (50%–68%). The preferred operative technique shifted from OR to EVAR after 2001 (proportion EVAR 1994–2000 0%, 2001–2007 58%, 2008–2014 60%). Open repair was performed in 62 patients (47%): aortic resection and extra-anatomic bypass (n=7), in situ reconstruction (n=50), and patch plasty (n=3); 2 patients died intraoperatively. EVAR was performed in 70 patients (53%): standard EVAR (n=55), fenestrated/branched EVAR (n=8), and visceral deviation with stent grafting (n=7); no deaths occurred intraoperatively. Survival at 3 months was lower for OR than for EVAR (74% versus 96%, P<0.001), with a similar trend present at 1 year (73% versus 84%, P=0.054). A propensity score–weighted risk-adjusted analysis confirmed the early better survival associated with EVAR. During median follow-up of 36 and 41 months for OR and EVAR, respectively, there was no difference in long-term survival (5 years 60% versus 58%, P=0.771), infection-related complications (18% versus 24%, P=0.439), or reoperation (21% versus 24%, P=0.650). Conclusion: This study demonstrates a paradigm shift in treatment of MAAA in Sweden, with EVAR being the preferred treatment modality. EVAR was associated with improved short-term survival in comparison with OR, without higher associated incidence of serious infection-related complications or reoperations.

A new computerized methodology to analyse tumour site in relation to phenotypic traits and epidemiological characteristics of cutaneous malignant melanoma

Summary Background While sunlight is important in the aetiology of cutaneous malignant melanoma (CMM), the relationship between skin areas receiving intermittent or chronic sun exposure and the development of CMM has not been fully explored. There is a requirement for an improved method for more detailed site mapping and for analysis of tumour density in different areas of the skin in relation to the type of sun exposure, phenotypic traits and prognosis of patients with CMM.

The Impact of Stent Graft Material on the Inflammatory Response After EVAR

Background: Patients undergoing endovascular aneurysm repair (EVAR) due to abdominal aortic aneurysm often develop an inflammatory response, postimplantation syndrome (PIS) where fever and leukocytosis are common. Previous studies suggest that type of stent graft material (polyester or polytetrafluoroethylene [PTFE]) plays a role. Objectives: To investigate the effect of stent graft material on the inflammatory response and length of hospital stay in patients undergoing standard elective EVAR. Methods: Sixty-nine elective EVAR patients were included in this observational study. To avoid comparing patients with a different graft location and stent graft burden, 12 cases were excluded as well as cases with complication or simultaneous open surgical procedures, leaving 45 patients (32 with polyester and 13 with PTFE graft) for final analysis. Tympanic temperature, C-reactive protein (CRP), white blood cell (WBC), and procalcitonin (PCT) were measured on days −1 and +1 and +3. Duration of in-hospital stay and frequency of PIS were recorded. Results: The PIS was diagnosed in 9 (28.1%) of the 32 polyester cases and in 1 (7.7%) of the 13 cases in the PTFE group (P = .24). Median (interquartile range) in-hospital stay was 5 (5-6) days in the polyester group and 4 (4-5) days in the PTFE group (P = .009). On day +3, in the polyester group, mean CRP was 154 (95% confidence interval: 127-182) mg/L, WBC 9.5 (8.4-10.5) ×109/L, and PCT 0.17 (0.12-0.21) ng/mL. In the PTFE group, mean CRP was 70 (32-109) mg/L (P = .001), WBC 8.8 (6.4-11.1) ×109/L (P = .37), and PCT 0.09 (0.06-0.13) ng/mL (P = .009) on day +3. Conclusion: Standard EVAR with polyester stent grafts appears to result in a trend toward a more pronounced inflammatory reaction than similar EVAR using PTFE and is associated with a longer in-hospital stay.