A Complicated Case of Strangulated Inguinal Hernia of the Sigmoid Colon With Secondary Ischemic-Compromise of Scrotal Tissue: A Multi-Disciplinary Surgical Approach.

Inguinal hernia is amongst the most common acute abdominal disease that presents in the Emergency Department (ED). Pathologically, it involves the displacement and herniation of abdominal, pelvic, or groin tissue through weaknesses in the abdominal wall. Many inguinal hernias are simple and asymptomatic, managed conservatively without the need for surgical intervention. However, under rare circumstances, hernias are susceptible to significant complications requiring emergent surgery. This report follows the case of a 61-year-old Hispanic-American male presenting to the ED with signs of a complex strangulated inguinal hernia and consequent infarction of the testis with Fournier's Gangrene. Clinical evaluation elucidated a one-week worsening abdominal pain, non-reducible painful inguinal hernia, nausea, vomiting, constipation, groin discoloration, dysuria, and a history of failed primary hernia repair during childhood. The patient underwent emergent surgery to excise ischemic-necrotic portions of the sigmoid colon, creation of end-colostomy, non-mesh repair of inguinal hernia, and right-sided complete orchiectomy with the removal of adjacent scrotal-Dartos tissues and spermatic cord due to Fournier's Gangrene. This report provides both a report for a potentially preventable consequence in one of the most common surgical presentations and a review of the multi-disciplinary expertise that is required in the surgical management of complex inguinal hernias.

Dedifferentiated liposarcoma of the scrotum. Case report and literature review.

Malignant paratesticular and spermatic cord tumors are rare and often misdiagnosed preoperatively due to clinical presentations similar to other benign scrotal mass etiologies. Only a few cases regarding giant, paratesticular liposarcomas (>10 cm) have been reported. We report a unique case of an aggressive giant dedifferentiated liposarcoma of the scrotum with osteosarcoma features in a 70-year-old patient who initially presented with indolent scrotal swelling. A CT scan showed a large, complex, solid and cystic mass (12.0 x 15.5 x 19.0 cm) in the right scrotum. With a concern of a complex hydrocele, the patient was taken to the operating room for a scrotal approach to excise the hydrocele, but the spermatic cord was not traced to any discernible testicle as the entire mass was indurated and multilocular, and was excised. Pathology revealed a dedifferentiated liposarcoma, with MDM2 amplification. The patient's course was complicated due to metastatic disease.

Bladder Leiomyosarcoma: A Rare, but Aggressive Diagnosis.

It remains evident in the literature that leiomyosarcomas of the bladder have continuously been regarded as highly aggressive tumors associated with a poor prognosis. Immediate surgical therapy by radical cystectomy with wide margins is warranted as an effective treatment modality and has been associated with longer survival rates. Herein, we present the case of a high-grade leiomyosarcoma primarily treated with anterior pelvic exenteration and urinary diversion.

Initial experience with robot-assisted minimally-invasive nephroureterectomy.

PURPOSE: Various techniques have been described for laparoscopic nephroureterectomy. We reviewed our initial experience of laparoscopic nephroureterectomy with robot-assisted extravesical excision of the distal ureter and bladder cuff. MATERIALS AND METHODS: Nine consecutive patients aged 43 to 83 years underwent laparoscopic nephroureterectomy for transitional cell carcinoma (TCC) between August 2005 and March 2007. The first five patients were repositioned after laparoscopic nephrectomy from flank to lithotomy position to dock the robot for excision of the distal ureter and bladder cuff by a single surgeon. In contrast, the last four patients remained in flank position throughout the entire procedure, with the robot docked in flank position following laparoscopic nephrectomy. A two-layer closure re-approximated the cystotomy and a urethral catheter was left in place for a mean of 5 days. RESULTS: Eight men and one woman with a mean age of 64.2 years and mean body mass index (BMI) of 28.4 kg/m(2) underwent flexible cystoscopy and laparoscopic nephroureterectomy for five right-sided and four left-sided tumors. Mean operative time was 303 minutes (range 210-430 minutes), estimated blood loss was 211 mL (range 50-700 mL), and mean length of hospital stay was 2.3 days. Pathologic staging revealed T(3) for five (55.6%), T(a) for two (22.2%), carcinoma in situ (CIS) for two (22.2%) patients, and high-grade disease for seven (77.8%) patients. With a mean follow-up of 16.2 months (range 4.3-24.3 months), three patients with a history of bladder cancer have experienced recurrence in the bladder, and one of the three has also developed metastatic disease. CONCLUSIONS: Laparoscopic nephroureterectomy with robot-assisted extravesical excision of the distal ureter and bladder cuff appears to be a feasible alternative for patients with TCC of the upper urinary tract.

Postprenylation CAAX processing is required for proper localization of Ras but not Rho GTPases.

The CAAX motif at the C terminus of most monomeric GTPases is required for membrane targeting because it signals for a series of three posttranslational modifications that include isoprenylation, endoproteolytic release of the C-terminal- AAX amino acids, and carboxyl methylation of the newly exposed isoprenylcysteine. The individual contributions of these modifications to protein trafficking and function are unknown. To address this issue, we performed a series of experiments with mouse embryonic fibroblasts (MEFs) lacking Rce1 (responsible for removal of the -AAX sequence) or Icmt (responsible for carboxyl methylation of the isoprenylcysteine). In MEFs lacking Rce1 or Icmt, farnesylated Ras proteins were mislocalized. In contrast, the intracellular localizations of geranylgeranylated Rho GTPases were not perturbed. Consistent with the latter finding, RhoGDI binding and actin remodeling were normal in Rce1- and Icmt-deficient cells. Swapping geranylgeranylation for farnesylation on Ras proteins or vice versa on Rho proteins reversed the differential sensitivities to Rce1 and Icmt deficiency. These results suggest that postprenylation CAAX processing is required for proper localization of farnesylated Ras but not geranygeranylated Rho proteins.

Rap1 up-regulation and activation on plasma membrane regulates T cell adhesion.

Rap1 and Ras are closely related GTPases that share some effectors but have distinct functions. We studied the subcellular localization of Rap1 and its sites of activation in living cells. Both GFP-tagged Rap1 and endogenous Rap1 were localized to the plasma membrane (PM) and endosomes. The PM association of GFP-Rap1 was dependent on GTP binding, and GFP-Rap1 was rapidly up-regulated on this compartment in response to mitogens, a process blocked by inhibitors of endosome recycling. A novel fluorescent probe for GTP-bound Rap1 revealed that this GTPase was transiently activated only on the PM of both fibroblasts and T cells. Activation on the PM was blocked by inhibitors of endosome recycling. Moreover, inhibition of endosome recycling blocked the ability of Rap1 to promote integrin-mediated adhesion of T cells. Thus, unlike Ras, the membrane localizations of Rap1 are dynamically regulated, and the PM is the principle platform from which Rap1 signaling emanates. These observations may explain some of the biological differences between these GTPases.

Carboxyl methylation of Ras regulates membrane targeting and effector engagement.

Post-translational modification of Ras proteins includes prenylcysteine-directed carboxyl methylation. Because Ras participates in Erk activation by epidermal growth factor (EGF), we tested whether Ras methylation regulates Erk activation. EGF stimulation of Erk was inhibited by AFC (N-acetyl-S-farnesyl-L-cysteine), an inhibitor of methylation, but not AGC (N-acetyl-S-geranyl-L-cysteine), an inactive analog of AFC. AFC inhibited Ras methylation as well as the activation of pathway enzymes between Ras and Erk but did not inhibit EGF receptor phosphorylation, confirming action at the level of Ras. Transient transfection of human prenylcysteine-directed carboxyl methyltransferase increased EGF-stimulated Erk activation. AFC but not AGC inhibited movement of transiently transfected green fluorescent protein-Ras from the cytosol to the plasma membrane of COS-1 cells and depleted green fluorescent protein-Ras from the plasma membrane in stably transfected Madin-Darby canine kidney cells, suggesting that methylation regulates Erk by ensuring proper membrane localization of Ras. However, when COS-1 cells were transfected with Ras complexed to CD8, plasma membrane localization of Ras was unaffected by AFC, yet EGF-stimulated Erk activation was inhibited by AFC. Thus, Ras methylation appears to regulate Erk activation both through the localization of Ras as well as the propagation of Ras-dependent signals.

Ras signalling on the endoplasmic reticulum and the Golgi.

Current models evoke the plasma membrane (PM) as the exclusive platform from which Ras regulates signalling. We developed a fluorescent probe that reports where and when Ras is activated in living cells. We show that oncogenic H-Ras and N-Ras engage Raf-1 on the Golgi and that endogenous Ras and unpalmitoylated H-Ras are activated in response to mitogens on the Golgi and endoplasmic reticulum (ER), respectively. We also demonstrate that H-Ras that is restricted to the ER can activate the Erk pathway and transform fibroblasts, and that Ras localized on different membrane compartments differentially engages various signalling pathways. Thus, Ras signalling is not limited to the PM, but also proceeds on the endomembrane.