Stephen Ariyan

Breast reconstruction in previously irradiated patients using tissue expanders and implants: a potentially unfavorable result.

There exists a paucity of definitive information on the suitability of implant reconstructions in previously irradiated breast cancer patients. This controversial topic prompted a review of our prosthetic reconstructions in this select group of patients. A retrospective study of patients treated between 1976 and 1993 with lumpectomy and radiation therapy for early breast cancer revealed 67 patients with local recurrences. Nine of these patients (10 breasts) underwent a two-stage prosthetic reconstruction following a salvage mastectomy. The average age was 47.9 years. The mean dose of irradiation was 6,070 cGy. The average interval from radiation therapy to placement of a tissue expander was 4.6 years. In one patient (10%) the tissue expander extruded. The average follow-up for 8 patients (9 breasts) who underwent exchange to a permanent prosthesis was 5.1 years. In four reconstructions (40%) there was an uneventful postoperative course. Two cases (20%) were difficult to expand and the final result lacked projection. One patient (10%) developed an infection requiring removal of the permanent prosthesis. Two patients (20%) developed Baker class III or IV capsular contractures. Overall, in our group of 10 implant reconstructions, 60% of the patients resulted in either a complication or an unfavorable result.

Abnormal Acidification of Melanoma Cells Induces Tyrosinase Retention in the Early Secretory Pathway

In tyrosinase-positive amelanotic melanoma cells, inactive tyrosinase accumulates in the endoplasmic reticulum. Based on studies described here, we propose that aberrant vacuolar proton ATPase (V-ATPase)-mediated proton transport in melanoma cells disrupts tyrosinase trafficking through the secretory pathway. Amelanotic but not melanotic melanoma cells or normal melanocytes display elevated proton export as observed by the acidification of the extracellular medium and their ability to maintain neutral intracellular pH. Tyrosinase activity and transit through the Golgi were restored by either maintaining the melanoma cells in alkaline medium (pH 7.4–7.7) or by restricting glucose uptake. The translocation of tyrosinase out of the endoplasmic reticulum and the induction of cell pigmentation in the presence of the ionophore monensin or the specific V-ATPase inhibitors concanamycin A and bafilomycin A1 supported a role for V-ATPases in this process. Because it was previously shown that V-ATPase activity is increased in solid tumors in response to an acidified environment, the appearance of hypopigmented cells in tyrosinase-positive melanoma tumors may indicate the onset of enhanced glycolysis and extracellular acidification, conditions known to favor metastatic spread and resistance to weak base chemotherapeutic drugs.

Arterial coupling for microvascular free tissue transfer

Objective The purpose of this study was to demonstrate the efficacy of arterial coupling. Study Design Retrospective data were collected in a consecutive series of 124 patients undergoing surgical resection of head and neck tumors followed by free tissue transfer (FTT). Methods And Measures The Unilink coupling device was used to perform arterial and venous anastomosis. Flap survival and thrombosis of the arterial anastomoses were determined. Results A total of 124 consecutive patients underwent a total of 127 microvascular FTTs. Reconstruction included 90 radial forearm, 26 fibula, 9 rectus abdominis, and 2 iliac crest myocutaneous free flaps. There were four (3.2%) complications related to arterial insufficiency in our series, three of which were salvageable. There were three (2.4%) flap failures, resulting in an overall free flap survival rate of 97.6 percent. Conclusion The flap survival with the Unilink Microvascular Anastomotic System is similar to that of standard suture techniques. Use of a coupler device is the preferred method in performing microvascular FTT at our institution.

Pectoralis major myocutaneous reconstruction of the anterior skull base.

It was once believed that prognosis for many patients with neoplasms of the anterior skull base was hopeless. Now, however, craniofacial resection of these lesions has been curative for many patients.

The hepatorenal syndrome: recovery after portacaval shunt.

Reversal of the morbid hepato-renal syndrome has been achieved in a cirrhotic patient with ascites following successful side-to-side portacaval shunt. The hepatorenal syndrome is defined as progressive unresponsive renal failure with previously normal kidneys in the presence of impaired hepatic function. Although the etiologic mechanism has not been defined, it is suggested the relationship of increased intrahepatic sinusoidal pressure on the thoracic duct and subsequent decreased lymph flow are interrelated to increased levels of aldosterone and manifested by (chylous) ascites. Laboratory and clinical evidence suggest that cirrhotics with ascites have remarkably high levels of aldosterone secretion via the rennin-angiotensin-adrenal cortex mechanism. This is the group that develops hepatorenal syndrome. Reduction of the intrahepatic pressure and decompression of the portal hypertension can be successfully achieved with a side-to-side shunt which should return the aldosterone-rennin-angiotensin axis to normal and subsequently reverse the hepatorenal syndrome.

End-to-Side Venous Anastomosis With an Anastomotic Coupling Device for Microvascular Free-Tissue Transfer in Head and Neck Reconstruction

Objective: The purpose of this study is to demonstrate the success rate of using a coupling device for end‐to‐side venous anastomosis in patients undergoing free‐tissue transfer (FTT) in head and neck reconstruction.

Use of the external pectoralis myocutaneous major flap in anterior skull base reconstruction

Despite the emergence of free tissue transfer, the pectoralis major myocutaneous flap (PMMF) still has a role in anterior base skull reconstruction (when free tissue transfer is not feasible). The aim of this study is to evaluate the results of external PMMF in anterior skull base reconstruction. A retrospective study from 1977 to 2006 was conducted at Yale New Haven Hospital. 16 patients (mean age 64 years), presenting with a malignant tumour of the anterior base skull, were included. The primary pathology was recurrent squamous carcinoma. Tumour resection resulted in orbital exenteration in 60%, and bone resection of the anterior skull base in 81% of patients. The initial skin defect was 49 cm(2) (range 16-100 cm(2)). The PMMF was the primary reconstructive choice in 87%, and utilized after free flap failure in two cases. Three minor complications were noted. Orbital exenteration and anterior base skull resection is a surgical procedure that leads to significant reconstructive challenges. The PMMF remains a safe and versatile reconstructive tool in anterior skull base tumour resection. The externalized pedicle allows this flap to reach periorbital and anterior skull base.

Comparison of the expression of vimentin and actin in spitz nevi and spitzoid malignant melanomas.

Introduction:The differentiation between Spitz nevi (SN) and Spitzoid malignant melanomas (SMM) represents a challenge to dermatopathologists. We recently demonstrated differential expression of vimentin and Actin in SN and SMM by mass spectrometry (MS). We sought to investigate whether this differential expression could be detected using conventional immunohistochemistry or automated quantitative analysis (AQUA) of histological sections. Methods:Cases of SN and SMM, which were previously studied by MS and have readily available blocks and enough material in the block, were selected from the Yale Spitzoid Neoplasm Repository. The cases were stained for vimentin and muscle-specific actin using standard protocols. H-scores were calculated by multiplying the percentage of cells staining and the intensity of staining. Selected cases were also studied for quantitative immunofluorescent staining using the AQUA method. Results:All 21 cases of SN showed strong and diffuse staining for vimentin; 19 of 21 (91%) cases had an H-score of 300 (average, 294). Similar staining results were observed in SMM; 13 of 14 (93%) cases had an H-score of 300 (average, 297). Muscle-specific actin was weakly and focally positive in 5 of 21 (24%) SN (H-score = 3.3) and 5 of 14 (39%) SMM (H-score = 3.5). The AQUA method showed no significant difference in the staining intensity of SN and SMM for both vimentin and actin. Conclusions:There was no difference in the expression of vimentin and actin in SN and SMM shown by conventional immunohistochemistry or the AQUA method. This study shows that MS has much grater sensitivity in detecting the differential expression of these proteins.

Skeletal muscle ventricles in continuity with the bloodstream.

Abstract Background and Aim of Study: The prevalence of end‐stage congestive heart failure and limitation of clinical alternative treatments present the need for creative new solutions. Formation of a ventricle from skeletal muscle (SMV) has shown promise in the animal laboratory. Two modes of the SMV for cardiac assistance, the counterpulsation (CP‐SMV) and the ventricular assist (VA‐SMV), using the latissimus dorsi muscle were applied in a canine model. Ability to augment arterial pressure was assessed. The effect of stimulation delay on the degree of augmentation was also evaluated. Methods and Results: Thirty‐five SMVs were connected in continuity with the bloodstream in the two modes: (1) CP‐SMV (aorta‐to‐aorta) (n =12); and (2) VA‐SMV (left ventricular [LV] apex‐to‐aorta) (n=23). In the CP‐SMV mode, designed to simulate the intra‐aortic balloon pump, the SMV was simply interposed into the path of the descending aorta (DAo) without prosthetic valves in either the inflow or the outflow conduit. In order to obligate blood flow through the SMV, the DAo was ligated between the two grafts. In the VA‐SMV mode, the connection was made with valved conduits from the LV apex (inflow) to the ascending aorta (outflow) (n = 11) or to the DAo (n = 12). The ascending aorta (AAo) was also ligated proximal to the outflow conduit for the same reason of obligating blood flow through the SMV. The SMV was timed to contract in diastole in both the CP‐SMV mode and the VA‐SMV mode. In the VA‐SMV mode, the average systolic pressure without stimulation was 101.6 ± 2.2 mmHg and with stimulation 118.21±4.78 mmHg (mean augmentation, 14.5±2.6 mmHg) (p < 0.01). In the CP‐SMV mode, the average systolic pressure without stimulation was 97±32 mmHg and with stimulation, 122±26 mmHg (mean augmentation, 25±8.6 mmHg) (p < 0.001). We also extended earlier work on timing of stimulation of isolated SMV by evaluating the effect of stimulation delay on the degree of augmentation in continuity with the bloodstream with the SMV in the VA‐SMV configuration. Delays of 50 msec to 225 msec were evaluated. SMV stimulation was via the thoracodorsal nerve at an amplitude of 1.5 V and a frequency of 25 Hz. The greatest augmentation occurred at a stimulation delay of 150 msec (p < 0.001). Conclusion: Both counterpulsation and assist configurations produced effective diastolic augmentation. Although diastolic augmentation occurred with all timing delays, the optimal delay was 150 msec. Complications in the survival animals include AAo problems, SMV rupture, respiratory insufficiency, intraoperative instability, and thrombosis (which occurred in 51% [18/35] of the animals). This high frequency of thrombosis in the canine model suggests the use of a less thrombogenic SMV lining, more aggressive or prolonged anticoagulation, or an alternative animal model.

Intratumoral multinucleated giant cells are not a prognostic pathologic feature in cutaneous melanoma.

Histopathologic diagnostic features such as tumor thickness, ulceration, mitoses, microsatellitosis and nodal metastases are principal pathologic staging components of cutaneous melanomas. We chose to focus on evaluating the presence of multinucleated giant cells in microscopic sections as a putative novel prognosticating diagnostic feature of melanoma.