Increased prevalence of human papillomavirus in fresh tissue from penile cancers compared to non-malignant penile samples: a case-control study.

BACKGROUND: HPV has been detected in approximately 50% of invasive penile cancers but with a large span between 24 and 89%, most likely due to different types of tumors and various methods for HPV analysis. Most studies of HPV in penile cancer have been performed using paraffin-embedded tissue, argued to be at risk for contaminated HPV analysis. Viral activity of HPV, by the use of HPV mRNA expression is well studied in cervical cancer, but seldom studied in penile cancer. The aim was to determine prevalence of HPV types in fresh tissue of penile cancers compared to non-malignant age-matched penile controls. Additional aims were to analyze the viral expression and copy numbers of HPV16-positive tumors and 10 mm adjacent to the tumor. METHODS: Fresh tissue from penile cancer cases was biopsied inside the tumor and 10 mm outside the tumor. Controls were males circumcised for non-malignant reasons, biopsied at surgery. PCR and Luminex assays were used for identification of HPV types. HPV16-positive samples were investigated for copy numbers and expression of HPV16-mRNA. RESULTS: Among tumors (n = 135) and age-matched controls (n = 105), HPV was detected in 38.5% (52/135) and 11.4% (12/105), respectively (p < 0.001), adjusted odds ratio 12.8 (95% confidence interval 4.9-33.6). High-risk HPV types were found in 35.6% (48/135) of tumors and 4.8% (5/105) of controls (p < 0.001). Among tumors and controls, HPV16 was present in 27.4% (37/135) and 1% (1/105), respectively (p < 0.001). Among HPV16-positive penile cancers, mean HPV16 viral copy/cell was 74.4 (range 0.00003-725.4) in the tumor and 1.6 (range 0.001-14.4) 10 mm adjacent from the tumor. HPV16-mRNA analysis of the tumors and 10 mm adjacent from the tumors demonstrated viral activity in 86.5% (32/37) and 21.7% (5/23), respectively. CONCLUSIONS: The prevalence of HPV was significantly higher in penile cancer (38.5%) than among age-matched non-malignant penile samples (11.4%). HPV16 predominates (27.4%) in penile tumors. HPV16 expression was more common in penile cancer than in adjacent healthy tissue, strongly suggesting an etiological role for HPV16 in the development of penile cancer.

Incidence of penile intraepithelial neoplasia and treatment strategies in Sweden 2000-2019.

OBJECTIVES: To analyse the incidence, treatment strategies and complications associated with penile intraepithelial neoplasia (PeIN) in Sweden over a period of 20 years. MATERIALS AND METHODS: Data on PeIN from the Swedish National Penile Cancer Register were analysed regarding treatment in relation to age, size of the PeIN lesion, localization of the PeIN lesion and complications using chi-squared tests and logistic regression. The incidence of PeIN was calculated and age-standardized according to the European Standard population. RESULTS: Between 2000 and 2019 a total of 1113 PeIN cases were reported. The age-standardized incidence of PeIN was 1.40 per 100 000 men (95% confidence interval [CI] 1.32-1.49). An increase in incidence over time was seen, with a standardized incidence rate of 2.37 (95% CI 1.56-3.70) in 2019 compared to the baseline year, 2000. Surgical or topical treatments were given in 75.0% and 14.6% of cases, respectively. The complication rate was higher in laser surgery (12.1%, 7/58) compared to local surgery (4.6%, 16/348; P = 0.03) with an age-adjusted odds ratio (OR) of 2.82 (95% CI 1.10-7.19; P = 0.03). Local surgery was more common than laser surgery in the last 5 years compared to the first 5 years of the study period: OR 5.75 (95% CI 2.94-11.27). Treatments with imiquimod and topical 5-fluorouracil (5-FU) were more common than destructive methods such as photodynamic therapy, cryotherapy, curettage and electrocautery in the last 5 years compared to the first 5 years: OR 9.48 (95% CI 2.29-39.24). CONCLUSIONS: A twofold increase in the age-standardized incidence of PeIN was seen in Sweden over 20 years. Complications were three times more common in laser surgery compared to local surgery. Changes in treatment showed an increase of treatment strategies such as local surgery and treatment with imiquimod and topical 5-FU over time.

Penile intraepithelial neoplasia, penile cancer precursors and human papillomavirus prevalence in symptomatic preputium: a cross-sectional study of 351 circumcised men in Sweden.

OBJECTIVES: To investigate the prevalence of pathological disease and spectrum of human papillomavirus (HPV) types among symptomatic foreskin tissue. PATIENTS AND METHODS: Consecutively excised symptomatic foreskins from 351 men were sent for histopathological evaluation. During the surgical procedure, a fresh biopsy was taken for HPV analysis by modified general primer polymerase chain reaction. A medical questionnaire regarding medication, smoking habits, number of lifetime sexual partners, former diseases and surgery performed on penis was completed by all participants. RESULTS: The most common clinical diagnosis and cause for circumcision was phimosis, seen in 85.2%. Histopathologically inflammatory dermatological conditions were present in 87% of the men. The most common histopathological diagnosis was lichen sclerosus (LS) observed among 58.7%. Notably, penile intraepithelial neoplasia (PeIN) was present in 2% without former clinical suspicion. Overall, HPV was detected in 17.1% of the men and 28 different HPV types were found. High-risk (HR) HPV types were identified in 9.1% and HPV16 was present in 2.3%. Current smoking increased the risk of HPV (crude odds ratio [OR] 2.8, confidence interval [CI] 1.4-5.6; P = 0.005). Having >15 lifetime sexual partners increased the risk of HPV (crude OR 2.6, 95% CI 1.4-5.1; P = 0.003) and when adjusted for current smoking the OR was substantially increased (OR 6.0, 95% CI CI 2.2-16.8; P < 0001). CONCLUSIONS: Histopathological evaluation of circumcised symptomatic foreskin revealed PeIN in 2% of the men without any clinical suspicion of malignancy and that treatable dermatological conditions were present in 87%, LS being the most common. HR-HPV types were present in 9%. Due to risk of malignant development both in PeIN and in inflammatory skin diseases we recommend sending all excised foreskins from patients with symptoms for histopathological evaluation as guidance for further clinical management.

Risk Factors for Penile Intraepithelial Neoplasia: A Population-based Register Study in Sweden, 2000-2012.

Studies on risk factors for penile intraepithelial neo-plasia have been small in size, have not distinguished penile intraepithelial neoplasia from invasive cancer, and have relied on self-reported information. This study investigated risk factors for penile intraepithelial neoplasia in a cohort of 580 penile intraepithelial neoplasia cases and 3,436 controls using information from 7 Swedish registers. Cases with penile intraepithelial neoplasia had increased odds ratios (ORs) for inflammatory skin diseases (14.7, 95% CI 6.5-33.4) including lichen planus (12.0, 95% CI 3.0-48.0), indicating lichen planus to be an important risk factor. Increased ORs were also observed for diseases of the prepuce (4.0, 95% CI 2.2-7.4), immunosuppressive drugs (5.0, 95% CI 2.5-9.8), penile surgical procedures (4.8, 95% CI 2.2-10.8), balanitis (9.2, 95% CI 5.0-16.8), genital warts (9.9, 95% CI 4.3-22.7) and organ transplantation (7.0, 95% CI 2.4-20.8). This study demonstrates important risk factors for penile intraepithelial neoplasia, providing knowledge that can help prevent the development of penile cancer.

Cardiophrenic lymph node resection in advanced ovarian cancer: surgical outcomes, pre- and postoperative imaging.

OBJECTIVE: To evaluate the accuracy of preoperative imaging in the diagnosis of cardiophrenic lymph node (CPLN) metastases and to report perioperative outcomes after resection of CPLN at the time of cytoreductive surgery for advanced epithelial ovarian cancer (EOC). Furthermore, to assess clearance of CPLN by postoperative imaging. METHODS: All women with stage IIIC/IV EOC subjected to surgery at our institution from January 2014 to October 2016 were retrospectively identified from a database. Among these, women subjected to CPLN resection during surgery were identified. Pre- and postoperative computed tomography (CT) scans, pathology reports, surgical approach and outcomes were reviewed. RESULTS: One hundred and eighty women with stage IIIC/IV EOC subjected to surgery with curative intent were identified. Twenty-four (13%) of these women underwent CPLN resection. All had CT imaging suggestive of CPLN metastases. 20/24 (83%) had confirmed metastases upon final pathology. CPLN resection was associated with longer operation time, more often advanced upper abdominal surgery and more postoperative complications but there was no difference in days from surgery to initiation of chemotherapy. Postoperative CT was still indicative of CPLN metastases in 13/22 (59%) women despite resection with confirmative pathology. CONCLUSIONS: Resection of CPLN metastases is highly feasible without considerable added morbidity. Concern regarding surgical clearance is raised since postoperative imaging was indicative of metastases in the majority of women. The prognostic significance of stage IV disease based exclusively on CPLN metastases is unclear and any survival benefit from the procedure is yet to be determined.

Mechanical effects of negative pressure wound therapy on abdominal wounds - effects of different pressures and wound fillers.

The mechanical deformation of the wound edge resulting from negative pressure wound therapy (NPWT) at the standard setting of around -120 mmHg has positive effects in promoting wound healing. However, it may cause pain to the patient during treatment. It is therefore important to study the mechanical effects of the wound edges using lower pressure and different wound fillers. Abdominal wounds were created on eight pigs. The wounds were sealed for NPWT using foam or gauze. Negative pressures between -20 and -160 mmHg were applied, and the decrease in wound diameter and the force with which the edges of the wound were drawn together (wound edge force) were measured. Increasing levels of negative pressure resulted in a gradual decrease in wound diameter and increase in wound edge force and reached a maximum at -120 mmHg, which is the pressure commonly used in clinical practice. Both the decrease in wound diameter and the increase in wound edge force was greater with foam than with gauze. A pressure of -80 mmHg has only 15% less effect than -120 mmHg, while a lower pressure (-40 mmHg) diminished the effects on diameter and force markedly. The NPWT-induced decrease in wound diameter and increase in wound edge force are greater at higher levels of negative pressure and when using foam than when using gauze as a wound filler. It may be possible to tailor the type of wound filler and level of negative pressure to obtain the best balance between wound healing and patient comfort.

Socioeconomic factors and penile cancer risk and mortality; a population-based study.

OBJECTIVE: To investigate possible associations between socioeconomic status (SES) and penile cancer risk, stage at diagnosis, and mortality. PATIENTS/SUBJECTS AND METHODS: A population-based register study including men in Sweden diagnosed with penile cancer between 2000 and 2012 (1676 men) and randomly chosen controls (9872 men). Data were retrieved from the National Penile Cancer Register (NPECR) and several other population-based healthcare and sociodemographic registers. Educational level, disposable income, marital status, and number of individuals in the household, were assessed as indicators of SES. The risk of penile cancer and penile cancer death in relation to SES were estimated using logistic regression and proportional hazards models, respectively. Cumulative cause-specific mortality (CSM) estimates by SES were calculated using the Kaplan-Meier method. RESULTS: A low educational level and low disposable income were associated with an increased risk of invasive penile cancer. Furthermore, low educational level was associated with more advanced primary tumour stage. Divorced and never married men had a generally increased risk of penile cancer and were diagnosed with more advanced primary tumour stages. However, neither educational level nor marital status was associated with lymph node or distant metastases. Also, men in single-person households had an increased risk of both non-invasive and invasive disease. In men with invasive penile cancer, there were no significant associations of indicators of SES and CSM. CONCLUSIONS: Low educational level, low disposable income, being divorced or never married, and living in a single-person household, all increase the risk of advanced stage penile cancer, but not lymph node or distant metastases. The assessed indicators of SES did not influence penile CSM. In conclusion, our findings indicates that SES influences the risk and stage of penile cancer, but not survival.

A rigid disc for protection of exposed blood vessels during negative pressure wound therapy.

BACKGROUND: There are increasing reports of serious complications and deaths associated with negative pressure wound therapy (NPWT). Bleeding may occur when NPWT is applied to a wound with exposed blood vessels. Inserting a rigid disc in the wound may protect these structures. The authors examined the effects of rigid discs on wound bed tissue pressure and blood flow through a large blood vessel in the wound bed during NPWT. METHODS: Wounds were created over the femoral artery in the groin of 8 pigs. Rigid discs were inserted. Wound bed pressures and arterial blood flow were measured during NPWT. RESULTS: Pressure transduction to the wound bed was similar for control wounds and wounds with discs. Blood flow through the femoral artery decreased in control wounds. When a disc was inserted, the blood flow was restored. CONCLUSIONS: NPWT causes hypoperfusion in the wound bed tissue, presumably as a result of mechanical deformation. The insertion of a rigid barrier alleviates this effect and restores blood flow.

The use of a rigid disc to protect exposed structures in wounds treated with negative pressure wound therapy: effects on wound bed pressure and microvascular blood flow.

There are increasing reports of deaths and serious complications associated with the use of negative pressure wound therapy (NPWT). Bleeding may occur in patients when NPWT is applied to a wound with exposed blood vessels or vascular grafts, possibly due to mechanical deformation and hypoperfusion of the vessel walls. Recent evidence suggests that using a rigid barrier disc to protect underlying tissue can prevent this mechanical deformation. The aim of this study was to examine the effect of rigid discs on the tissue exposed to negative pressure with regard to tissue pressure and microvascular blood flow. Peripheral wounds were created on the backs of eight pigs. The pressure and microvascular blood flow in the wound bed were measured when NPWT was applied. The wound was filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. The discs were created with or without channels (to accommodate exposed sensitive structures such as blood vessels and nerves), perforations, or a porous dressing that covered the underside of the discs (to facilitate pressure transduction and fluid evacuation). When comparing the results for pressure transduction to the wound bed, no significant differences were found using different discs covered with dressing, whereas pressure transduction was lower with bare discs. Microvascular blood flow in the wound bed decreased by 49 ± 7% when NPWT was applied to control wounds. The reduction in blood flow was less in the presence of a protective disc (e.g., -6 ± 5% for a dressing-covered, perforated disc, p = 0.006). In conclusion, NPWT causes hypoperfusion of superficial tissue in the wound bed. The insertion of a rigid barrier counteracts this effect. The placement of a rigid disc over exposed blood vessels or nerves may protect these structures from rupture and damage.

Sentinel Node Identification with Hybrid Tracer-guided and Conventional Dynamic Sentinel Node Biopsy in Penile Cancer: A Prospective Study in 130 Patients from the Two National Referral Centres in Sweden.

BACKGROUND: Studies suggest that a hybrid indocyanine green (ICG)-99mTc-nanocolloid tracer improves sentinel node (SN) identification compared to conventional dynamic sentinel node biopsy (DSNB). OBJECTIVE: To investigate hybrid tracer-guided SN identification in a multicentre setting and determine false-negative (FN) and complication rates. DESIGN, SETTING, AND PARTICIPANTS: A total of 130 patients with penile cancer scheduled for DSNB were prospectively included between February 2016 and December 2017 at two national Swedish referral centres. ICG-99mTc-nanocolloid hybrid tracer was used in the standard DSNB protocol. INTERVENTION: SNs were identified intraoperatively using radioguidance, fluorescence imaging, and blue dye. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The number of SNs identified by each tracer and the rates of complications and nodal recurrence during median follow-up of 34 mo were recorded. Differences in proportions between groups were compared using χ2 and McNemar's tests. RESULTS AND LIMITATIONS: Overall, 453 SNs were identified preoperatively via single-photon emission computed tomography/computed tomography. Among the 425 SNs excised, radioguidance, fluorescence, and blue dye identified 414 (97%), 363 (85%), and 349 (82%), respectively. Fluorescence imaging helped to detect six SNs that were negative using the other tracers, two of which were from the same patient and contained metastases. Histopathological examination detected 33 metastatic SNs in 20/130 patients (15%). The FN rate was 12% per groin (95% confidence interval 8-16%). CONCLUSIONS: Identification of SNs in patients with penile cancer relies mainly on radioguidance, while fluorescence (ICG) and blue dye methods for optical SN identification are comparable. However, the value of fluorescence imaging should be further evaluated in studies with long-term follow-up. PATIENT SUMMARY: In this study, we investigated addition of a dye called indocyanine green (ICG) for assessment of lymph nodes in patients with cancer of the penis. ICG did not improve the rate of detection of nodes most likely to harbour cancer because of their location in the drainage pathway for lymphatic fluid, but did help in identifying additional metastases.

The influence on wound contraction and fluid evacuation of a rigid disc inserted to protect exposed organs during negative pressure wound therapy.

The use of a rigid disc as a barrier between the wound bed and the wound filler during negative pressure wound therapy (NPWT) has been suggested to prevent damage to exposed organs. However, it is important to determine that the effects of NPWT, such as wound contraction and fluid removal, are maintained during treatment despite the use of a barrier. This study was performed to examine the effect of NPWT on wound contraction and fluid evacuation in the presence of a rigid disc. Peripheral wounds were created on the backs of eight pigs. The wounds were filled with foam, and rigid discs of different designs were inserted between the wound bed and the foam. Wound contraction and fluid evacuation were measured after application of continuous NPWT at -80 mmHg. Wound contraction was similar in the presence and the absence of a rigid disc (84 ± 4% and 83 ± 3%, respectively, compared with baseline). Furthermore, the rigid disc did not affect wound fluid removal compared with ordinary NPWT (e.g. after 120 seconds, 71 ± 4 ml was removed in the presence and 73 ± 3 ml was removed in the absence of a disc). This study shows that a rigid barrier may be placed under the wound filler to protect exposed structures during NPWT without affecting wound contraction and fluid removal, which are two crucial features of NPWT.

Changes in cardiac pumping efficiency and intra-thoracic organ volume during negative pressure wound therapy of sternotomy wounds, assessment using magnetic resonance imaging.

Knowledge on the effects of negative pressure wound therapy (NPWT) on the intra-thoracic organs is limited. The present study was performed to investigate the effects of NPWT on the volume of the intra-thoracic organs, using magnetic resonance imaging (MRI), in a porcine sternotomy wound model. Six pigs underwent median sternotomy followed by NPWT at -75, -125 and -175 mmHg. Six pigs were not sternotomised. MR images covering the thorax and heart were acquired. The volumes of the thoracic cavity, lungs, wound fluid and heart were then determined. The volumes of the thoracic cavity and intra-thoracic organs increased after sternotomy and decreased upon NPWT application. The total heart volume variation, which is a measure of cardiac pumping efficiency, was higher after sternotomy and decreased during NPWT. NPWT did not result in the evacuation of wound fluid from the bottom of the wound. NPWT largely closes and restores the thoracic cavity. Cardiac pumping efficiency returns to pre-sternotomy levels during NPWT. This may contribute to the clinical benefits of NPWT over open-chest care, including the stabilizing effects and the reduced need for mechanical ventilation.

Changes in cardiac pumping efficiency and intra-thoracic organ volume during negative pressure wound therapy of sternotomy wounds, assessment using magnetic resonance imaging.

Knowledge on the effects of negative pressure wound therapy (NPWT) on the intra-thoracic organs is limited. The present study was performed to investigate the effects of NPWT on the volume of the intra-thoracic organs, using magnetic resonance imaging (MRI), in a porcine sternotomy wound model. Six pigs underwent median sternotomy followed by NPWT at -75, -125 and -175 mmHg. Six pigs were not sternotomised. MR images covering the thorax and heart were acquired. The volumes of the thoracic cavity, lungs, wound fluid and heart were then determined. The volumes of the thoracic cavity and intra-thoracic organs increased after sternotomy and decreased upon NPWT application. The total heart volume variation, which is inversely related to cardiac pumping efficiency, was higher after sternotomy and decreased during NPWT. NPWT did not result in the evacuation of wound fluid from the bottom of the wound. NPWT largely closes and restores the thoracic cavity. Cardiac pumping efficiency returns to pre-sternotomy levels during NPWT. This may contribute to the clinical benefits of NPWT over open-chest care, including the stabilizing effects and the reduced need for mechanical ventilation.

Long-term Outcomes of Follow-up for Initially Localised Clear Cell Renal Cell Carcinoma: RECUR Database Analysis.

BACKGROUND: Optimal follow-up (FU) strategy to detect potentially curable (PC) recurrences after treatment of localised clear cell renal cell carcinoma (ccRCC) is unclear. This study retrospectively analysed a large international database to determine recurrence patterns and overall survival (OS), as part of a wider project to issue recommendations on FU protocols. OBJECTIVE: To analyse associations between RCC recurrences in patients with ccRCC, their risk group stratifications, treatments, and subsequent outcomes. DESIGN, SETTING, AND PARTICIPANTS: Nonmetastatic ccRCC patients treated with curative intent between 1 January 2006 and 31 December 2011, with at least 4 yr of FU, were included. Patient, tumour and recurrence characteristics, Leibovich score, and management and survival data were recorded. Isolated local, solitary, and oligometastatic (three or fewer lesions at a single site) recurrences were considered PC, while all others were probably incurable (PI). INTERVENTION: Primarily curative surgical treatment of ccRCC while at recurrence detection metastasectomy, systemic therapy, best supportive care, or observation. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Incidence, time to recurrence (TTR), and OS were measured. Competing risk analysis, Kaplan-Meier, and Cox regression models were used. RESULTS AND LIMITATION: Of 1265 patients with ccRCC, 286 had a recurrence, with 131 being PC and 155 PI. Five-year cumulative risks of recurrence for low- (n=53), intermediate- (n=105), and high-risk (n=128) patients were, respectively, 7.2%, 23.2%, and 61.6%, of whom 52.8%, 37.1%, and 30.5% were PC, respectively. Median TTR was 25.0 for PC patients versus 17.3 mo for PI patients (p=0.004). Median OS was longer in PC compared with that in PI patients (p<0.001). Competing risk analysis showed highest risk of ccRCC-related death in younger and high-risk patients. Limitations were no data on comorbidities, retrospective cohort, and insufficient data excluding 12% of cohort. CONCLUSIONS: Low-risk group recurrences are rare and develop later. Treatment of recurrences with curative intent is disappointing, especially in high-risk patients. An age- and risk score-dependent FU approach is suggested. PATIENT SUMMARY: We analysed data from eight European countries, and found that the incidence of the kidney cancer recurrence and patient survival correlated with clinical factors known to predict cancer recurrence reliably and age. We conclude that these factors should be used to design follow-up strategies.

Intensive Imaging-based Follow-up of Surgically Treated Localised Renal Cell Carcinoma Does Not Improve Post-recurrence Survival: Results from a European Multicentre Database (RECUR).

The optimal follow-up (FU) strategy for patients treated for localised renal cell carcinoma (RCC) remains unclear. Using the RECUR database, we studied imaging intensity utilised in contemporary FU to evaluate its association with outcome after detection of disease recurrence. Consecutive patients with nonmetastatic RCC (n=1612) treated with curative intent at 12 institutes across eight European countries between 2006 and 2011 were included. Recurrence occurred in 336 patients. Cross-sectional (computed tomography, magnetic resonance imaging) and conventional (chest X-ray, ultrasound) methods were used in 47% and 53%, respectively. More intensive FU imaging (more than twofold) than recommended by the European Association of Urology (EAU) was not associated with improved overall survival (OS) after recurrence. Overall, per patient treated for recurrence remaining alive with no evidence of disease, the number of FU images needed was 542, and 697 for high-risk patients. The study results suggest that use of more imaging during FU than that recommended in the 2017 EAU guidelines is unlikely to improve OS after recurrence. Prospective studies are needed to design optimal FU strategies for the future. PATIENT SUMMARY: After curative treatment for localised kidney cancer, follow-up is necessary to detect any recurrence. This study illustrates that increasing the imaging frequency during follow-up, even to double the number of follow-up imaging procedures recommended by the European Association of Urology guidelines, does not translate into improved survival for those with recurrence.

Pressure transduction to the thoracic cavity during topical negative pressure therapy of a sternotomy wound.

The present study was performed to examine pressure transduction to the thoracic cavity during topical negative pressure (TNP) therapy of a sternotomy wound. Seven pigs underwent median sternotomy. Pressure transduction catheters were placed on the anterior surface of the heart (under the foam), in the pericardium (under the heart), in the left pleura and in the oesophagus at the level of the heart. The wound was sealed as for TNP therapy. The vacuum source was set to deliver negative pressures between -50 and -200 mmHg. The pressure on the anterior surface of the heart changed in a linear relationship with the applied negative pressure and was slightly lower than the applied negative pressure (-102 +/- 9 mmHg at delivered -125 mmHg). Further down in the thoracic cavity, in the pericardium (under the heart), in the left pleura and in the oesophagus, the wound pressure was only slightly affected by TNP therapy. In conclusion during TNP therapy, negative pressure is effectively transmitted to anterior portions of the heart. This may explain our recent findings that TNP increases microvascular blood flow in the myocardium. The pressure difference between the anterior and the posterior portions of the heart causes the right ventricle to be sucked up towards the posterior parts of the sternum, where it might be exposed to the sharp edges of the sternal bone, which may result in heart injury.

Blood Perfusion in a Full-Thickness Eyelid Flap, Investigated by Laser Doppler Velocimetry, Laser Speckle Contrast Imaging, and Thermography.

Purpose: The eyelid is commonly dissected and divided in the process of, for example, blepharotomy, entropion repair, or when preparing a full-thickness eyelid flap to reconstruct a tumor defect. No study has yet been conducted to examine how perfusion in an eyelid is affected by dissection, using modern imaging techniques. Methods: The eyelid was divided with a 10-mm vertical incision, 5 mm from the medial canthus, and the incision was extended horizontally by 30 mm to provide a full-thickness eyelid. Blood perfusion was measured along the length of the free dissected eyelid using both laser Doppler velocimetry and laser speckle contrast imaging. Tissue temperature was visualized using a high-resolution infrared camera (thermography). Results: Measurements using laser speckle contrast imaging showed that blood flow decreased gradually from the pedicel base to the tip of the free dissected eyelid: 83% at 10 mm, stabilizing at 80% at 20 mm from the pedicel base. These results were supported by laser Doppler velocimetry, showing a reduction in perfusion to 67%, 15 mm from the pedicel base. Thermographic imaging showed a corresponding decrease in temperature from the tip to the pedicel base compared with nondissected eyelids. Conclusions: Dissection of an eyelid, to provide a full-thickness eyelid flap, results in only a slight decrease in blood flow. The results support the view that plastic surgery of the eyelids is permissive, and the rich vascularization of the eyelid due to the anastomotic network of vessels in the tarsal plate may increase the likelihood of flap survival and surgical success.

Hypoperfusion in response to epinephrine in local anaesthetics: Investigation of dependence on epinephrine concentration, spread of hypoperfusion and time to maximal cutaneous vasoconstriction.

OBJECTIVES: The present study aimed to examine hypoperfusion in response to epinephrine following the administration of a local anaesthetic. The concentration of epinephrine that causes maximal hypoperfusion, the spread of hypoperfusion in the tissue and the time to the stabilization of hypoperfusion were investigated. METHODS: Blood perfusion was monitored using laser Doppler velocimetry and laser speckle contrast imaging of random-pattern advancement flaps (1 × 4 cm) or intact skin on the pig flank. Epinephrine was either injected cumulatively (0.1, 1.0, 10 or 100 µg/ml) after injecting 20 mg/ml lidocaine, to determine the concentration response, or given as a single dose (12.5 µg/ml epinephrine+20 mg/ml lidocaine). Control experiments were performed with saline or lidocaine (without epinephrine). RESULTS: Increasing concentrations of epinephrine resulted in a gradual decrease in skin perfusion, approaching a minimum after injecting 10 µg/ml. The area of hypoperfusion was 12 mm in radius, and the time from the injection to the stabilization of hypoperfusion was approximately 120 s. After the administration of 10 µg/ml epinephrine in flaps with small pedicle, 25% blood perfusion still remained. CONCLUSIONS: Local anaesthetic with an epinephrine concentration of approximately 10 µg/ml appears to be adequate for vasoconstriction before surgery. Incisions were required to be delayed only for 2 min following local anaesthetic with epinephrine in pigs. The remaining 25% blood perfusion observed after the administration of epinephrine supports the use of epinephrine in flaps with a small pedicle. Obviously, these experimental findings must be clinically assessed before being considered for infiltration anaesthesia during plastic surgery procedures.

Perfusion and Oxygenation of Random Advancement Skin Flaps Depend More on the Length and Thickness of the Flap Than on the Width to Length Ratio.

OBJECTIVE: The aim was to investigate the relationship between the dimensions (length, width, and thickness) of random advancement skin flaps and retained tissue perfusion and oxygenation. METHODS: Flaps were raised on the flanks of pigs. The flaps were either 0.5 or 1.0 cm wide, thin (dissected halfway through the subcutaneous tissue) or thick (dissected down to the muscle fascia). Tissue perfusion was measured by laser Doppler velocimetry, and tissue oxygenation (pO2) was measured using a Licox system, every 0.5 cm along the flaps' length. Tissue temperature was visualized by high-resolution infrared camera. RESULTS: Perfusion and oxygenation decreased gradually from the base to the tip of the flap, reaching approximately 40% of presurgical values (2.0 cm) and approximately 20% (2.5 cm) from the base of the flap. There was virtually no blood flow, nor oxygen tension, 3.0 cm from the base of the flap. The width to length ratio of the flap did not determine blood flow or oxygenation, being approximately 30% in a 0.5 cm wide and 2 cm long flap, and 0% in a 1.0 cm wide and 4 cm long flap, both with a width to length ratio of 1:4. Blood flow and oxygenation were preserved to a greater extent in the thick flaps (∼40%) than in the thin flaps (∼20%), in a 0.5 cm wide and 2 cm long flap. CONCLUSIONS: The dissection of a random advancement flap results in hypoperfusion and oxygenation that cannot be predicted by the width to length ratio but depend on the length and thickness of the flap.

Organ-sparing reconstructive surgery in penile cancer: initial experiences at two Swedish referral centres.

OBJECTIVE: The aim of this study was to present early outcome data for patients treated for penile cancer with organ-sparing reconstructive surgery at two referral centres in Sweden. MATERIAL AND METHODS: Oncological, cosmetic and functional outcome and complications were analysed retrospectively during the period 2011-2013. Twelve patients with non-invasive penile cancer were treated with glans resurfacing (GR), while 15 patients with invasive penile cancer underwent total glansectomy with neoglans reconstruction (TGN). RESULTS: The 12 patients treated with GR had a median age of 66 years (range 35-83 years) and a median follow-up time of 16 months (range 4-40 months). All patients showed carcinoma in situ and negative surgical margins in the final pathology report. The 15 patients treated with TGN had a median age of 71 years (range 37-78 years) and the median follow-up time was 10 months (range 1-25 months). All patients had invasive penile cancer and the surgical margins were negative in all cases except one. Complications occurred in five of the 27 patients (18%), and in most cases these were minor and infection related. No recurrences were seen in either group during follow-up, and all patients except one, who had undergone GR, were satisfied with the functional and cosmetic results. CONCLUSIONS: GR and TGN seem to be oncologically safe procedures for treating carefully selected patients with penile cancer, and the functional and cosmetic results are promising. Based on these findings, the authors recommend that penile amputation should only be carried out in patients who are not suitable for organ-sparing reconstructive surgery.