Vice Chair, University of Minnesota Medical School
This suggests a minimum tumor dose of approximately 66 Gy in 2-Gy fractions over a period of 6 1 2 weeks (45 days) skin care ingredients to avoid discount aknesil 30mg fast delivery. Hypofractionated courses (fraction size >2 Gy) may be associated with worse toxicity anti acne buy line aknesil. An alternative approach to consider among patients with bilateral metastases is neoadjuvant chemotherapy followed by surgical resection as described by Pagliaro and colleagues (2010) skin care gadgets buy aknesil 10mg line. Bulky Adenopathy and Fixed Nodal Metastasis Survival in patients with bulky adenopathy and fixed nodal metastasis is related to complete eradication of extensive disease acne 6 dpo generic 20 mg aknesil fast delivery. This task is difficult to achieve with surgery, chemotherapy, or radiation therapy alone. The combination of surgery and chemotherapy has shown some benefit in advanced penile carcinoma (Pizzocaro et al, 1997; Corral et al, 1998; Bermejo et al, 2007; Leijte et al, 2007; Pagliaro et al, 2010). A reasonable approach in this cohort of patients is to use neoadjuvant chemotherapy followed by an aggressive surgical resection for patients demonstrating either response to therapy or stable disease. The neoadjuvant approach could improve surgical resectability and avoid long delays in the administration of chemotherapy resulting from delays in postoperative healing. The prognosis is poor in patients exhibiting progression while they are receiving chemotherapy. Palliative groin dissection is a consideration but rarely provides significant palliation (Leijte et al, 2007). Hemipelvectomy in patients without distant metastases has been reported (Block et al, 1973). Endoluminal vascular stents have also been reported to have transient success in preventing vascular erosion by tumor (Link et al, 2004). Clinical trials of novel systemic strategies and radiation therapy to affected areas provide the next level of care. With further progression, supportive care provided by hospice services can provide valuable support to patients with end-stage disease. If local control is not achieved, salvage surgery may still be curative, and therefore in a subset of men with penile cancer radiation as an initial strategy represents a reasonable treatment strategy. Both external-beam radiotherapy and interstitial brachytherapy are currently used in treating the primary penile tumor. Before radiation therapy, circumcision is necessary to expose the lesion, to allow resolution of any surface infection, and to prevent preputial edema and subsequent phimosis. Brachytherapy As an alternative to external-beam radiotherapy, interstitial brachytherapy using a variety of radioisotopes but most commonly iridium-192 has been reported. Gerbaulet and Lambin (1992), using percutaneously placed interstitial iridium-192 implants, reported successful local control in 82% of 109 patients, with long-term survival rates of 75% to 80% in patients with tumorfree regional lymph nodes. Rozan and associates (1995) reviewed 259 patients from multiple centers, with 5- and 10-year diseasefree survival rates of 78% and 67%, respectively. Twenty-two percent of patients also had surgery ranging from circumcision or local excision (75% of procedures) to total penectomy (4%). For noninvasive or very superficial tumors, a surface mold containing iridium-192 wires can be constructed. The plastic mold is worn in close apposition to the penile shaft for 12 hours or so daily for a period of 7 to 10 days for a total tumor dose of 60 Gy (El-Demiry et al, 1984; Akimoto et al, 1997). Because the depth of tumor invasion can be difficult to ascertain by clinical examination or imaging, and because a margin of full dose (comparable to the required surgical margin) is required beyond the macroscopic disease, the mold technique is rarely appropriate. Such superficial disease may now be treated more appropriately with laser or organ-sparing surgical techniques. Crook and associates (2009) initially reported a cohort (19892000) of 30 men with cT1 to cT3 squamous cell carcinoma treated with iridium-192 delivered by 17- to 19. With a median six needles (range 2 to 9), a prescribed dose of 60 Gy (range 55 to 65 Gy) was delivered during an average of 93 hours. With a median 34 months of follow-up, there were four local failures and four regional failures, and 1 patient required partial penectomy for radionecrosis. The 2-year actuarial local failure-free rate was 85%, and successful penile conservation was 83%. Obviously, tumors could only be clinically staged, and the External-Beam Radiotherapy External-beam radiotherapy has several advantages: It is widely available, delivers a homogeneous dose, and does not require the same expertise with respect to technical skills required for delivery of effective brachytherapy. In a review, Crook and coworkers (2009) described contemporary doses and fractions as ranging from 60 Gy in 25 fractions delivered over 5 weeks to 74 Gy in 37 fractions over 7. This contrasts with lower doses of 50 to 55 Gy cited in older series (McLean et al, 1993; Neave et al, 1993). One of the challenges of external-beam radiotherapy is to consistently position the penis in such a way as to be accessible by the radiation beam while not implicating adjacent normal tissues and structures. This is achieved by positioning the patient supine on the treatment couch and encasing the penis in a vertical position in a block of wax or Perspex with a central cylindric chamber. The block is bivalved for ease of application, which admittedly becomes more difficult as the course of radiotherapy progresses. The second consideration involves the physical nature of megavoltage radiation beams, which spare the skin surface and deliver the radiation dose at a depth in tissue. Penile cancer is of cutaneous origin and requires full treatment of the skin surface. Kiltie and associates (2000), however, found local failures in 60% of tumors larger than 4 cm compared with 14% of tumors smaller than 4 cm. Mazeron and colleagues (1984) and Soria and coworkers (1997) both demonstrated more local failure as the tumor invaded the corpora and with tumor size larger than 4 cm. In the initial Crook series, prophylactic lymph node dissections were not routinely performed, and as one would expect, 50% of moderately or poorly differentiated tumors recurred regionally or distally (Crook et al, 2002).
Bilateral orchiectomy is required because of the risk of bilateral tumors (40%) (Scully skin care doctors buy generic aknesil canada, 1970) acne jeans sale buy aknesil 40mg on-line. Given the rarity of these tumors skin care vitamin c cost of aknesil, they are often not suspected preoperatively skin care yang aman buy aknesil with a mastercard, and most patients undergo radical orchiectomy. Benign lesions are usually small, yellow to brown, and well circumscribed, without areas of necrosis or hemorrhage. Reinke crystals are present in 25% to 40% of cases and appear as densely eosinophilic, needlelike or rhomboid structures within the cytoplasm. Metastatic Leydig cell tumors are resistant to chemotherapy and radiation therapy, and survival is poor (Mosharafa et al, 2003). Surveillance is recommended for patients without clinical or pathologic features suggestive of malignancy. Persistent Leydig cell dysfunction and hypogonadism may occur after excision of the primary tumor, and 40% of men may require testosterone supplementation postoperatively (Conkey et al, 2005). MiscellaneousTestisNeoplasms Dermoid and Epidermoid Cyst Dermoid and epidermoid cysts are rare benign neoplasms that are thought to arise from benign germ cells with retained embryonic properties or from displaced metaplastic mesothelial cells (Ye and Ulbright, 2012). Grossly, they are well-circumscribed, unilocular cystic masses filled with keratinized debris that may have a laminated appearance, which gives them the characteristic "onion peel" appearance on ultrasound scan. Dermoid cysts are differentiated from epidermoid cysts by the presence of adnexal structures such as glandular elements, adipose tissue, and cartilage. Sertoli Cell Tumor Sertoli cell tumors constitute less than 1% of testis neoplasms. The median age at diagnosis is 45 years, but rare cases in boys have been reported. Rarely, these tumors are associated with Peutz-Jeghers syndrome and androgen insensitivity syndrome and are frequently bilateral (either synchronous or metachronous). As for Leydig cell tumors, testis-sparing surgery can be considered for tumors less than 3 cm given the high incidence of benign histology (90%). Microscopically, the tumors contain epithelial elements resembling Sertoli cells with varying amounts of stroma organized into tubules. These tumors may be misinterpreted as seminomas leading to errors in the selection of treatment. Diagnostic workup; staging studies; and criteria for treatment, surveillance, and follow-up are similar to Leydig cell tumors. Adenocarcinoma of the Rete Testis Adenocarcinoma of the rete testis is a rare but highly malignant neoplasm arising from the collecting system of the testis. More than 50% of patients present with metastatic disease, and the overall median survival is 1 year. SecondaryTumorsoftheTestis Lymphoma Primary testicular non-Hodgkin lymphoma is a rare tumor representing only 1% to 2% of all cases of lymphoma. Most commonly, lymphoma involves the testis through dissemination from extratesticular sites (Ulbright, 2004). Non-Hodgkin lymphoma is the most common testicular neoplasm in men older than age 50. Approximately 25% of men have systemic symptoms (fever, night sweats, weight loss). Men with testicular non-Hodgkin lymphoma should be referred to a hematologist-oncologist for staging investigations and subsequent therapy. Most cases are associated with systemic disease, and the overall prognosis is poor. The juvenile type is benign and is the most frequent congenital testis tumor (most frequently occurring in infants <6 months old), accounting for 7% of all prepubertal testicular neoplasms. Testis-sparing surgery may be considered for tumors less than 3 cm if the diagnosis is suspected preoperatively. Treatment of the primary tumor is curative because these tumors appear to have limited metastatic potential. Leukemic Infiltration the testis is a frequent site of relapse in boys with acute lymphocytic leukemia. Overall, the prognosis is poor because most patients have associated systemic disease. Although treatment is largely dictated by the primary tumor, orchiectomy may be considered for palliative reasons. AdenomatoidTumor Adenomatoid tumor is the most common paratesticular tumor, most commonly involving the epididymis (although these tumors may also arise within the testicular tunicae or the spermatic cord). These tumors are benign and managed by inguinal exploration and surgical excision. On microscopic examination, tumors are composed of epithelial-like cells that contain vacuoles and fibrous stroma. Sarcomas should be managed initially through an inguinal approach with wide excision of the spermatic cord and testis with high ligation. Patients with an initial incomplete resection should undergo repeat wide excision (Coleman et al, 2003). The primary pattern of failure is local, particularly for liposarcoma (Ballo et al, 2001; Montgomery and Fisher, 2003; Khandekar et al, 2013). Some authors have advocated for postoperative radiation therapy for all paratesticular sarcomas, particularly for liposarcomas and for tumors for which the adequacy of local control is in doubt (Ballo et al, 2001; Hazariwala et al, 2013). However, the efficacy of this approach is debated (Fagundes et al, 1996; Coleman et al, 2003; Khandekar et al, 2013). Systemic chemotherapy should be given to patients with evidence of retroperitoneal or distant metastases. Given that the lymphatic drainage of the spermatic cord includes the ipsilateral pelvis, inguinal, and retroperitoneal lymph nodes, treating these areas with lymphadenectomy or radiation therapy should be considered.
The authors concluded that in patients with normal penile hemodynamics but without adequate rigidity acne jensen boots sale discount generic aknesil uk, structural causes should be investigated (Udelson et al acne 8 days before period purchase aknesil 5 mg overnight delivery, 1998) acne 24 cheap 30mg aknesil with mastercard. Tunica Albuginea the tunica affords great flexibility acne 4 dpo buy 20 mg aknesil with mastercard, rigidity, and tissue strength to the penis (Hsu et al, 1992). The tunical covering of the corpora cavernosa is a bilayered structure with multiple sublayers. Inner-layer bundles support and contain the cavernous tissue and are oriented circularly. Radiating from this inner layer are intracavernous pillars that act as struts to augment the septum and provide essential support to the erectile tissue. Penile measurements in normal adult Jordanians and in patients with erectile dysfunction. The tunica is composed of elastic fibers that form an irregular, latticed network on which the collagen fibers rest. The detailed histologic composition of the tunica varies with anatomic location and function. Emissary veins run between the inner and outer layers of the tunica for a short distance, often piercing the outer bundles obliquely. However, the cavernous artery and the branches of the dorsal artery that give additional blood supply to the corpus cavernosum take a more direct route and are surrounded by a periarterial soft-tissue sheath, which protects the arteries from occlusion by the tunica albuginea during erection. The outer tunical layer appears to play an additional role in compression of the emissary veins during erection. It also determines, to a large extent, the variability in tunical thickness and strength (Hsu et al, 1992). The strength and thickness of the tunica correlate in a statistically significant fashion with location. The elastin content allows tunical expansion and helps to determine stretched penile length. External penile support consists of two ligamentous structures: the fundiform and suspensory ligaments. The fundiform ligament arises from Colles fascia and is lateral, superficial, and not adherent to the tunica albuginea of the corpora cavernosa. The suspensory ligament arises from Buck fascia and consists of two lateral bundles and one median bundle, which circumscribe the dorsal vein of the penis. In these men, the accessory pudendal was the dominant blood supply in 54% and the only corporeal blood supply in 11%. The importance of accessory pudendal artery preservation during radical prostatectomy was demonstrated by Mulhall and colleagues (2008), who reported more rapid recovery of sexual function in men who underwent artery-sparing radical prostatectomy. The internal pudendal artery becomes the common penile artery after giving off a branch to the perineum. The three branches of the penile artery are the dorsal, bulbourethral, and cavernous. Distally, they join to form a vascular ring near the albuginea of the corpora cavernosa to the pubis, and it provides support for the mobile portion of the penis (Hoznek et al, 1998). In patients with congenital deficiency or in whom this ligament has been severed in "penile elongation" surgery, the erect penis may be unstable or droop. Corpora Cavernosa, Corpus Spongiosum, and Glans Penis the corpora cavernosa comprise two spongy, paired cylinders contained in the thick envelope of the tunica albuginea. Their proximal ends, the crura, originate at the undersurface of the puboischial rami as two separate structures but merge under the pubic arch and remain attached up to the glans. The septum between the two corpora cavernosa is incomplete in men but is complete in some species such as dogs. The corpora cavernosa are supported by a fibrous skeleton that includes the tunica albuginea, the septum, the intracavernous pillars, the intracavernous fibrous framework, and the periarterial and perineural fibrous sheath (Goldstein and Padma-Nathan, 1990; Hsu et al, 1992). Within the tunica are the interconnected sinusoids separated by smooth muscle trabeculae surrounded by elastic fibers, collagen, and loose areolar tissue. The terminal cavernous nerves and helicine arteries are intimately associated with the smooth muscle. Each corpus cavernosum is a conglomeration of sinusoids, larger in the center and smaller in the periphery. In the flaccid state, the blood slowly diffuses from the central to the peripheral sinusoids, and the blood gas levels are similar to those of venous blood. During erection, the rapid entry of arterial blood to both the central and the peripheral sinusoids changes the intracavernous blood gas levels to those of arterial blood (Sattar et al, 1995). The structure of the corpus spongiosum and glans is similar to that of the corpora cavernosa except that the sinusoids are larger. The tunica is thinner in the spongiosum (with only a circular layer [see earlier]) and is absent in the glans (Table 26-2). In many instances, however, accessory arteries exist, arising from the external iliac, obturator, and vesical and femoral arteries, and they may constitute the dominant or only arterial supply to the corpus cavernosum in some men (Breza et al, 1989). The cavernous artery effects tumescence of the corpus cavernosum and enters it at the hilum of the penis, where the two crura merge. It gives off many helicine arteries along its course, which supply the trabecular erectile tissue and the sinusoids. These helicine arteries are contracted and tortuous in the flaccid state and become dilated and straight during erection. Diallo and associates (2013) noted that in four of their five cadaveric specimens, the dorsal artery sent two to four penetrating branches to join the cavernous artery and supply blood to the distal one third of the penis. The bulbourethral and urethral arteries are situated outside the tunica albuginea of the corpus spongiosum on the lateral and dorsal sides. Anastomosis of the cavernous and urethral arteries occurs outside the tunica of the spongiosum.
Studies suggest that neoplastic cells mimic normal tissue development and may arise from and are dependent on a small population of stem cells acne hyperpigmentation treatment buy aknesil 40 mg on-line. The cancer stem cell hypothesis argues that cancers arise from transformation of stem or progenitor cells that are capable of multilineage differentiation skin care for swimmers generic aknesil 40 mg without a prescription. Cancer stem cells may account for only a small percentage of any tumor acne 8 year old boy purchase aknesil 40 mg fast delivery, but this Alternative Regulators of Apoptosis in Genitourinary Malignancies In addition to the classic regulators of apoptosis acne definition generic 5mg aknesil overnight delivery, numerous other pathways for cell survival and death have been uncovered that play key roles in urologic cancer. The Vancouver group mapped out a detailed gene profile of prostate tumors treated with neoadjuvant hormonal ablation therapy to identify key regulators of cell death and survival after castration. In addition to Bcl-2, which is upregulated in surviving cancer cells, they also reported on clusterin and Hsp27. Initiator caspases start caspase proteolytic cascades terminating in the activation of executioner caspases that target several cellular proteins. In the intrinsic pathway, Bcl-2 family members modulate the release of cytochrome c from the mitochondria, which participates in the activation of initiator caspases. The extrinsic pathway activates caspases in response to signals from extracellular "death receptors. The most readily accepted experimental demonstration of cancer stem cells relies on serial transplantation of tumor cell populations isolated based on one or numerous putative cancer stem cell markers into immune-deficient mice or three-dimensional culture systems and recapitulation of the heterogeneous primary tumor. Using this experimental strategy, initial evidence to support the cancer stem cell hypothesis was discovered in leukemia, breast cancer, and neurologic cancers. One challenge in cancer stem cell research is the lack of any one marker that is exclusively expressed by cancer stem cells. For any given tumor type, typically many different markers can be identified that confer a cancer stem cell phenotype, and absence of the marker does not always imply that a cell is not a cancer stem cell. High levels of phosphorylated form of Akt-1 in prostate cancer and non-neoplastic prostate tissues are strong predictors of biochemical recurrence. Caveolin-1 levels are down-regulated in human colon tumors, and ectopic expression of caveolin-1 in colon carcinoma cell lines reduces cell tumorigenicity. Implication of cell kinetic changes during the progression of human prostatic cancer. Sequence analysis of the protein kinase gene family in human testicular germ-cell tumors of adolescents and adults. Aneuploidy and aneusomy of chromosome 7 detected by fluorescence in situ hybridization are markers of poor prognosis in prostate cancer. A common variant associated with prostate cancer in European and African populations. Promoter deletion and loss of retinoblastoma gene expression in human prostate carcinoma. Methylation of the E-cadherin gene in bladder neoplasia and in normal urothelial epithelium from elderly individuals. Independent origin of multiple foci of prostatic intraepithelial neoplasia: comparison with matched foci of prostate carcinoma. Microsatellite instability, mismatch repair deficiency, and genetic defects in human cancer cell lines. Genetic variants and prostate cancer risk: candidate replication and exploration of viral restriction genes. Constitutional short telomeres are strong genetic susceptibility markers for bladder cancer. Loss of chromosome 17 loci in prostate cancer detected by polymerase chain reaction quantitation of allelic markers. The retinoblastoma protein is phosphorylated during specific phases of the cell cycle. Initiation of bladder cancer may involve deletion of a tumour-suppressor gene on chromosome 9. Frequent loss of heterozygosity on chromosome 10q in muscle-invasive transitional cell carcinomas of the bladder. A signature of chromosomal instability inferred from gene expression profiles predicts clinical outcome in multiple human cancers. Decreased levels of the cellcycle inhibitor p27Kip1 protein: prognostic implications in primary breast cancer. Identification, molecular characterization, clinical prognosis, and therapeutic targeting of human bladder tumor-initiating cells. Hypermethylation of multiple genes in tumor tissues and voided urine in urinary bladder cancer patients. Projecting the performance of risk prediction based on polygenic analyses of genome-wide association studies. The deficiency of Akt1 is sufficient to suppress tumor development in Pten+/- mice. Laser capture microdissection analysis reveals frequent allelic losses in papillary urothelial neoplasm of low malignant potential of the urinary bladder. Genetic alterations in untreated metastases and androgen-independent prostate cancer detected by comparative genomic hybridization and allelotyping. Gene panel model predictive of outcome in men at high-risk of systemic progression and death from prostate cancer after radical retropubic prostatectomy. Fibroblast growth factor receptor 3 induces gene expression primarily through Ras-independent signal transduction pathways.
