Bending the Arc of the Trilobed Flap Through External Interlobe Angle Inequality.

BACKGROUND: The trilobed flap is a useful repair option for distal nasal defects. In certain cases, however, the placement of its quaternary defect may risk compression of the internal nasal valve or induction of ectropion. In this study, we propose a modified design of the trilobed flap, which uses unequal external interlobe angles. OBJECTIVE: To present the design principles and results of our modified trilobed flap for the reconstruction of difficult distal nasal Mohs defects. MATERIALS AND METHODS: Mohs defects of 26 patients were reconstructed (21 with long-term follow-up) using our modified trilobed flap over 1 year. Two independent masked raters graded postoperative photographs for alar symmetry and overall cosmesis. RESULTS: Median alar symmetry scores were excellent and overall cosmesis grades were between excellent and very good. CONCLUSION: The modified trilobed flap with unequal external angles offers an excellent option for reconstruction of Mohs defect of the distal nose that may not be well-suited for other repairs. Over 1 year, 21 modified trilobed repairs were performed with overall excellent outcomes.

Association of Smoking and Other Factors With the Outcome of Mohs Reconstruction Using Flaps or Grafts.

IMPORTANCE: Smoking, a common lifestyle trait, is considered by many surgeons to be a major risk factor for postoperative complications. However, in the literature on local reconstruction, the association between smoking and the rate of postoperative complications after cutaneous tissue transfer is not well characterized. OBJECTIVE: To study the outcomes of flaps and grafts used in Mohs micrographic surgery reconstruction with respect to smoking status and patient-specific and surgery-specific variables. DESIGN, SETTING, AND PARTICIPANTS: This retrospective case-control study was conducted at a single tertiary referral center among 1008 patients who underwent Mohs reconstruction repaired by flap or graft between July 1, 2012, and June 30, 2016, and were selected via consecutive sampling. Cases with incomplete records or those in which a single flap or graft was used to repair multiple defects were excluded. Data analysis was performed from September 2017 to January 2018. MAIN OUTCOMES AND MEASURES: Postoperative acute and long-term complications. Acute complications included postsurgical infection, dehiscence, hematoma, uncontrolled bleeding, and tissue necrosis that required medical counseling or intervention. Long-term complications included functional or cosmetic outcomes that prompted the patient to request or the surgeon to offer additional intervention. RESULTS: Of the 1008 patients included in the study (396 women and 612 men), the median (SD) age was 70 (12) years (range, 21-90 years). A total of 128 patients (12.7%) were current smokers, 385 (38.2%) were former smokers, and 495 (49.1%) were never smokers. On multivariate logistic regression, current smoking (odds ratio [OR], 9.58; 95% CI, 3.63-25.3), former smoking (OR, 3.64; 95% CI, 1.41-9.38), larger defect size (OR, 2.25; 95% CI, 1.58-3.20), and the use of free cartilage graft (OR, 8.19; 95% CI, 2.02-33.1) were associated with increased risks of acute complications. For long-term complications, central face location (OR, 25.4; 95% CI, 6.16-106.5), use of interpolation flap or flap-graft combination (OR, 3.49; 95% CI, 1.81-6.74), larger flap size (OR, 1.42; 95% CI, 1.09-1.87), and basal cell carcinomas or other basaloid tumors (OR, 3.43; 95% CI, 1.03-11.5) were associated with an increased risk, whereas increased age (OR, 0.66 per 10-year interval; 95% CI, 0.54-0.80) was associated with decreased risk. CONCLUSIONS AND RELEVANCE: This study suggests that both current and former smokers are at increased risk for acute postsurgical complications but that smoking status is not associated with long-term complications. These findings may allow the surgeon to better quantify the magnitude of risk and provide helpful information for patient counseling. LEVEL OF EVIDENCE: 3.

Hedgehog pathway inhibition in chondrosarcoma using the smoothened inhibitor IPI-926 directly inhibits sarcoma cell growth.

Hedgehog (Hh) pathway inhibition in cancer has been evaluated in both the ligand-independent and ligand-dependent settings, where Hh signaling occurs either directly within the cancer cells or within the nonmalignant cells of the tumor microenvironment. Chondrosarcoma is a malignant tumor of cartilage in which there is ligand-dependent activation of Hh signaling. IPI-926 is a potent, orally delivered small molecule that inhibits Hh pathway signaling by binding to Smoothened (SMO). Here, the impact of Hh pathway inhibition on primary chondrosarcoma xenografts was assessed. Mice bearing primary human chondrosarcoma xenografts were treated with IPI-926. The expression levels of known Hh pathway genes, in both the tumor and stroma, and endpoint tumor volumes were measured. Gene expression profiling of tumors from IPI-926-treated mice was conducted to identify potential novel Hh target genes. Hh target genes were studied to determine their contribution to the chondrosarcoma neoplastic phenotype. IPI-926 administration results in downmodulation of the Hh pathway in primary chondrosarcoma xenografts, as demonstrated by evaluation of the Hh target genes GLI1 and PTCH1, as well as inhibition of tumor growth. Chondrosarcomas exhibited autocrine and paracrine Hh signaling, and both were affected by IPI-926. Decreased tumor growth is accompanied by histopathologic changes, including calcification and loss of tumor cells. Gene profiling studies identified genes differentially expressed in chondrosarcomas following IPI-926 treatment, one of which, ADAMTSL1, regulates chondrosarcoma cell proliferation. These studies provide further insight into the role of the Hh pathway in chondrosarcoma and provide a scientific rationale for targeting the Hh pathway in chondrosarcoma.

Hedgehog and Notch signaling regulate self-renewal of undifferentiated pleomorphic sarcomas.

Like many solid tumors, sarcomas are heterogeneous and include a small fraction of the so-called side population (SP) cells with stem-like tumor-initiating potential. Here, we report that SP cells from a soft tissue tumor of enigmatic origin termed undifferentiated pleomorphic sarcoma (also known as malignant fibrous histiocytoma or MFH sarcoma) display activation of both the Hedgehog and Notch pathways. Blockade to these pathways in murine xenograft models, this human cancer decreased the proportion of SP cells present and suppressed tumor self-renewal, as illustrated by the striking inability of xenograft tumors subjected to pathway blockade to be serially transplanted to new hosts. In contrast, conventional chemotherapies increased the proportion of SP cells present in tumor xenografts and did not affect their ability to be serially transplanted. SP cells from these tumors displayed an unexpectedly high proliferation rate which was selectively inhibited by Hedgehog and Notch blockade compared with conventional chemotherapies. Together, our findings deepen the concept that Hedgehog and Notch signaling are fundamental drivers of tumor self-renewal, acting in a small population of tumor-initiating cells present in tumors. Furthermore, our results suggest not only novel treatment strategies for deadly recurrent unresectable forms of this soft tumor subtype, but also potential insights into its etiology which has been historically controversial.