While tacking hypermobile skin is often sufficient in patients with obesity, patients with more significant morbid obesity often face additional challenges to surgical repair. As patients gain weight, there is often a preferential deposition of adipose in the suprapubic area that persists even after weight loss or bariatric surgery (2). Since the phallus remains tethered to the pubis by the suspensory ligament, the redundant suprapubic fat pad eventually completely surrounds the penis. With burial of the glans and meatus, patients often have to sit to void due to dribbling. A combination of poor hygiene and persistent moisture trapped near the penis leads to chronic bacterial or fungal colonization. Chronic colonization can lead to inflammatory skin contracture and the formation of a phimotic ring of scar. This often results in invagination of the penile shaft skin and further burial of the phallus. Over time, the penile shaft skin will often break down and there will be a paucity of healthy penile tissue during time of surgical repair. Additionally, patients may have a degree of burial due to descended escutcheon or significant overlying pannus. In more severe cases of morbid obesity, surgical repair may include a formal panniculectomy, dermatolipectomy, and the tacking of the penopubic subdermis to the rectus fascia.
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If a morbidly obese patient presents with significant escutcheon that limits examination of the glans, meatus, and penile skin, we counsel the patient extensively preoperatively regarding the potential for there to be a deficiency of penile skin and possible need for local flap or graft coverage. Additionally, patients are counseled about the risk of encountering undiagnosed meatal or urethral stricture associated with chronic inflammation and LS at the time of surgery since it is difficult to discern between the voiding symptoms of a buried penis alone compared to that of a buried penis associated with a urethral stricture. Additionally, if there is significant escutcheon or overlying pannus that will need to be surgically removed, a concomitant escutcheonectomy or panniculectomy may be indicated at the time of buried penis revision. In cases that involve panniculectomy, it is our preference to include the expertise of a plastic surgeon. Many patients have concomitant comorbidities such as diabetes, hypertension, and chronic obstructive pulmonary disease (COPD) that increase their risk of perioperative complications and every attempt should be made to optimize patients medically preoperatively and insure the risk of surgery is acceptable.
In patients with voiding symptoms or the appearance of involvement of the urethral meatus, it is important to evaluate the urethra with Bougie-a-boule calibration, cystoscopy, and when there is confirmation of a stricture, urethral imaging with a retrograde urethrogram and possibly a voiding cystourethrogram. In cases of LS where there is a buried penis associated with phimosis and the meatus is not visible to permit an evaluation of the urethra, our preference is to use a technique we developed for these specific cases. The objective is to increase the circumference of the area of phimosis at the expense of skin length without removing skin which would lead to skin deficiency. This could be accomplished by a long dorsal longitudinal slit with transverse closure. However, when there is a tight constriction, considerable dorsal penile skin length loss would be required to provide adequate resolution of the phimosis. Our preference is to make four longitudinal incisions with incisions dorsally, ventrally, and bilaterally of equal length (Figure 2A) with transverse closure so that the length loss is evenly distributed along the circumference of the penis (Figure 2B). Once the glans is delivered and visible, the urethra can be evaluated. We include consent for meatotomy or extended meatotomy so that if a very short stricture is identified, it can be definitively treated at the time of surgery. In a retrospective review of 43 patients with limited involvement of LS, the aggressive use of topical steroids with minor procedures to relieve high pressure voiding may prevent disease progression (8).
The treatment generally involved the removal of the subcutaneous tissue masses and any hard scar tissue adherent to the tunica albuginea via a circumcising and/or peno-scrotal incision. If this skin appears viable, primary closure with either native skin or with advancement of local skin flaps is possible. However, there is a risk that the involved genital skin can then contract or become swollen, requiring subsequent surgery to excise the involved skin and use STSG for coverage. Alternatively, if it is apparent that the remaining penile skin is not viable, skin grafting can be performed at the time of the treatment of the buried penis.
Buried penis repair after penile and scrotal enlargement surgery. (A) There is significant buried penis after injection of silicone into the penile and scrotal skin due to scarring and tissue masses; (B) relatively normal appearance of the penis immediately postoperatively after excision of scar tissue and abnormal penile and scrotal skin; (C) normal postoperative appearance of the scrotum associated with abnormal appearing penile skin tissue; (D) subsequent operation with excision of contracture penile skin with STSG; (E) appearance of the penis and scrotum several months postop. STSG, split thickness skin grafting.
Staged surgical repair of MLL of the scrotum. (A) Preoperative appearance of MLL of the scrotum; (B) T-incision marked out on the scrotum; (C) the spermatic cord and testicles are first isolated prior to removal of any lymphedematous tissue to prevent injury; (D) after the patient has healed from scrotectomy with primary closure, he is brought back into the operating room in a staged fashion to resect residual affected tissue; (E) after all remaining affected tissue is resected, STSG are placed on the penis and scrotum; (F) final cosmetic appearance after skin grafting. MLL, massive localized lymphedema; STSG, split thickness skin grafting.
The clinical examination was similar for all five patients, a giant inguinoscrotal hernia that descended below the knees in the standing position with an anteroposterior diameter of at least 30 cm and a laterolateral diameter of about 50 cm. The penis was not visible, having been buried by the expanded scrotal sac, with only the urethral meatus apparent on examination. Peristaltic movement was clearly seen through the enlarged scrotal sac. The testes were impalpable (Figs. 1, 2).
A detailed analysis of blood tissue can be found in Additional file 4. Human blood cells have different life spans: while CD14+ monocytes (myeloid lineage) only live several weeks, CD4+ T cells (lymphoid lineage) represent a variety of cell types that can live from months to years. An interesting question is whether blood cell types have different DNAm ages. DNAm age does not vary significantly across sorted blood cells from healthy male subjects (Additional file 4T). These results combined with the fact that the age predictor works well in individual cell types (Figure 2C; Additional file 4) strongly suggest that DNAm age does not reflect changes in cell type composition but rather intrinsic changes in the methylome. While I expect significant correlations between DNAm age and abundance measures of some blood cell types (that are known to change with age), these correlations do not reflect a direct causal effect of cell type abundance on DNAm age but rather a confounding effect due to chronological age. This conclusion is also corroborated by the finding that DNAm age is highly related to chronological age in other types of cells - for example, glial cells and neurons (Figure 1H) and various brain regions (Additional file 5).
Factors affecting the relation between age and DNAm age. (A-C) Factors influencing prediction accuracy in the training and test sets. (A) The standard deviation of age (x-axis) has a strong relationship (cor = 0.49, P = 4E-5) with age correlation (y-axis). To arrive at an unbiased measure of prediction accuracy, I estimated the age correlation using a leave-one-data-set-out cross validation (LOOCV) analysis. Each point is labeled and colored according to the underlying data set (Additional file 1). (B) Sample size (x-axis) is not significantly correlated with the age correlation (y-axis). (C) Mean DNAm age per tissue (x-axis) versus mean chronological age (y-axis). Points correspond to the human tissue data mentioned in Additional file 1. Breast tissue shows signs of accelerated aging. (D,E) The effect of tissue type on the age prediction in test data set 71 even for tissues that were not part of the training data (for example, esophagus, jejunum, penis). (E) The horizontal bars report the DNAm age (x-axis) of a single tissue from a single donor (H12817). Only one sample per tissue (grey axis numbers) was available. DNAm age has a low coefficient of variation (0.12). The red vertical line corresponds to the true chronological age. (F-H) DNAm age for various tissues from data set 77 but chronological age was not available. (F,G) A multi-tissue analysis of somatic adult tissue data from an adult male and an adult female, respectively. (H) Neonatal tissues tend to have low DNAm age. (I,J) The DNAm age of sperm is significantly lower than the chronological age of the respective sperm donors in data sets 74 and 75, respectively. Error bars represent one standard error.
A more interesting analysis is to compare the DNAm ages of tissues collected from the same subjects. DNAm age does not change significantly across different brain regions (temporal cortex, pons, frontal cortex, cerebellum) from the same subjects (Additional file 5K,L). I could only find three human subjects from whom many tissues had been profiled (Figure 3E-G). Although the limited sample sizes per tissue (mostly one sample per tissue per subject) did not allow for rigorous testing, these data can be used to estimate the coefficient of variation of DNAm age (that is, the standard deviation divided by the mean). Note that the coefficient of variations for the first and second adult male are relatively low (0.12 and 0.15 in Figure 3E,F) even though the analysis involved several tissues that were not part of the training data - for example, jejunum, penis, pancreas, esophagus, spleen, pancreas, lymph node, diaphragm. The coefficient of variation in the adult female (Figure 3G) is relatively high (0.21), which reflects the fact that her breast tissue shows signs of substantial age acceleration (congruent with the previous results from Figure 3C). 2ff7e9595c
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