Pure Laparoscopic Radical Heminephrectomy for a Large Renal-Cell Carcinoma in a Horseshoe Kidney

Introduction Horseshoe Kidneys are the most common renal fusion anomaly. When surgery is contemplated for renal-cell carcinoma in such kidneys, aberrant vasculature and isthmusectomy are the major issues to consider. We describe a case of a pure laparoscopic radical heminephrectomy with hand-sewn management of the isthmus for a 11 cm tumour in a horseshoe kidney. Presentation A 47-year-old man complaining of palpable left flank mass for two months. Magnetic resonance of the abdomen revealed a 11 cm renal mass arising from the left moiety of an incidentally discovered horseshoe kidney. Preoperative CT angiography revealed a dominant anterior renal artery feeding the upper and midpole, with two other arteries feeding the lower pole and isthmus. The patient was placed in a modified flank position. A four-port transperitoneal technique was used, the colon was reflected. Renal pedicle was dissected and the renal arteries and renal vein were secured with polymer clips. The kidney was fully mobilized and a Satinsky clamp was placed on the isthmus for its division. A running 2-0 vicryl hand-sewn was used for parenchyma hemostasis. The specimen was extracted intact in a plastic bag through an inguinal incision. Results The operative time was 220 minutes, and the estimated blood loss was 200 mL. There were no immediate or delayed complications. The patient resumed oral intake on postoperative day 1 and was discharged on postoperative day 2. Pathologic examination of the specimen confirmed a 11 cm organ-confined chromophobe renal-cell carcinoma, with negative margins. Discussion Laparoscopic oncologic surgery in patients with horseshoe kidneys can be technically challenging. The presence of a large cancer in a horseshoe kidney should not preclude a purely laparoscopic approach. With the aid of a Satinsky clamp, the isthmus can be sharply divided and sutured in a fashion similar to the open technique. To our knowledge, this report represents the largest cancer (11 cm) removed laparoscopically in the context of a horseshoe kidney

Rational Design of Superoxide Dismutase (SOD) Mimics: The Evaluation of the Therapeutic Potential of New Cationic Mn Porphyrins with Linear and Cyclic Substituents

Our goal herein has been to gain further insight into the parameters which control porphyrin therapeutic potential. Mn porphyrins (MnTnOct-2-PyP⁵⁺, MnTnHexOE-2-PyP⁵⁺, MnTE-2-PyPhP⁵⁺, and MnTPhE-2-PyP⁵⁺) that bear the same positive charge and same number of carbon atoms at <i>meso</i> positions of porphyrin core were explored. The carbon atoms of their <i>meso</i> substituents are organized to form either linear or cyclic structures of vastly different redox properties, bulkiness, and lipophilicities. These Mn porphyrins were compared to frequently studied compounds, MnTE-2-PyP⁵⁺, MnTE-3-PyP⁵⁺, and MnTBAP^3–. All Mn­(III) porphyrins (MnPs) have metal-centered reduction potential, <i>E</i>_1/2 for Mn^IIIP/Mn^IIP redox couple, ranging from −194 to +340 mV versus NHE, log <i>k</i>_cat(O₂^•–) from 3.16 to 7.92, and log <i>k</i>_red(ONOO^–) from 5.02 to 7.53. The lipophilicity, expressed as partition between n-octanol and water, log <i>P</i>_OW, was in the range −1.67 to −7.67. The therapeutic potential of MnPs was assessed via: (i) <i>in vitro</i> ability to prevent spontaneous lipid peroxidation in rat brain homogenate as assessed by malondialdehyde levels; (ii) <i>in vivo</i> O₂^•– specific assay to measure the efficacy in protecting the aerobic growth of SOD-deficient <i>Saccharomyces cerevisiae</i>; and (iii) aqueous solution chemistry to measure the reactivity toward major <i>in vivo</i> endogenous antioxidant, ascorbate. Under the conditions of lipid peroxidation assay, the transport across the cellular membranes, and in turn shape and size of molecule, played no significant role. Those MnPs of <i>E</i>_1/2 ∼ +300 mV were the most efficacious, significantly inhibiting lipid peroxidation in 0.5–10 μM range. At up to 200 μM, MnTBAP^3– (<i>E</i>_1/2 = −194 mV vs NHE) failed to inhibit lipid peroxidation, while MnTE-2-PyPhP⁵⁺ with 129 mV more positive <i>E</i>_1/2 (−65 mV vs NHE) was fully efficacious at 50 μM. The <i>E</i>_1/2 of Mn^IIIP/Mn^IIP redox couple is proportional to the log <i>k</i>_cat(O₂^•–), <i>i.e</i>., the SOD-like activity of MnPs. It is further proportional to <i>k</i>_<i>r</i>ed(ONOO^–) and the ability of MnPs to prevent lipid peroxidation. In turn, the inhibition of lipid peroxidation by MnPs is also proportional to their SOD-like activity. In an <i>in vivo S. cerevisiae</i> assay, however, while <i>E</i>_1/2 predominates, lipophilicity significantly affects the efficacy of MnPs. MnPs of similar log <i>P</i>_OW and <i>E</i>_1/2, that have linear alkyl or alkoxyalkyl pyridyl substituents, distribute more easily within a cell and in turn provide higher protection to <i>S. cerevisiae</i> in comparison to MnP with bulky cyclic substituents. The bell-shape curve, with MnTE-2-PyP⁵⁺ exhibiting the highest ability to catalyze ascorbate oxidation, has been established and discussed. Our data support the notion that the SOD-like activity of MnPs parallels their therapeutic potential, though species other than O₂^•–, such as peroxynitrite, H₂O₂, lipid reactive species, and cellular reductants, may be involved in their mode(s) of action(s)