Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma.

BACKGROUND: We performed a randomized phase 3 study of trabectedin versus dacarbazine in previously-treated patients with liposarcoma/leiomyosarcoma (LPS/LMS). METHODS: Patients were randomized 2:1 to trabectedin (n = 384) or dacarbazine (n = 193) administered intravenously every 3 weeks. The primary objective was overall survival (OS). Secondary objectives were progression-free survival, objective response rate, safety, and patient-reported outcomes, all previously reported and demonstrating superior disease control with trabectedin. Results of the final OS analysis in preplanned subgroups of patients with LPS/LMS are presented. RESULTS: At the time of the final OS analysis, 577 patients had been assigned randomly, including 423 (73%) with LMS and 154 (27%) with LPS. The median duration of treatment exposure was higher in the trabectedin arm compared with the dacarbazine arm (4 vs 2 cycles), as was the proportion of patients receiving an extended number of therapy courses (≥6 cycles: 42% vs 22%). This pattern was consistent across histological subgroups: the median number of treatment cycles (4 vs 2 for both subgroups) and proportion of patients with ≥6 treatment cycles (LMS, 43% vs 24%; LPS, 40% vs 16%). Despite improved disease control by trabectedin, no improvement in OS was observed; the final median OS for trabectedin versus dacarbazine was 13.7 versus 13.1 months (P = .49). Sensitivity analyses of OS suggest confounding by post-study anticancer therapies, which were utilized in most patients in both treatment arms (71% vs 69%, respectively). CONCLUSION: The final OS results demonstrated comparable survival between LPS/LMS patients receiving trabectedin or dacarbazine, which is consistent with the interim analysis results. Both LPS and LMS demonstrated improved disease control with trabectedin.

Can Early Dental Extractions Reduce Delays in Postoperative Radiation for Patients With Advanced Oral Cavity Carcinoma?

PURPOSE: This study sought to evaluate the effect of early extractions on the timing of postoperative radiation (PORT) for patients with advanced oral cavity squamous cell carcinoma. MATERIALS AND METHODS: All patients with oral cavity squamous cell carcinoma who required resection, free flap reconstruction, and dental extractions in a 10-year period were retrospectively reviewed. The study included patients who preoperatively had advanced disease that indicated the need for adjuvant radiation as defined by an advanced clinical T category (T3 or T4a) or clinical N category (N2a or above). Multivariate logistic regression models were created to estimate the risk factors for initiation of PORT greater than 6 weeks after surgery. RESULTS: Thirty-four patients were included. Thirteen patients underwent early extractions (before or at the time of surgery). Twenty-one patients underwent extractions after surgery. Extractions included all teeth with periodontal disease within the expected field of radiation. Most patients underwent full-mouth extractions (91.1%). PORT was initiated at greater than 6 weeks in 30.8% of patients in the early cohort, whereas 72.4% of patients in the late group experienced a delay (P = .02). Early extractions were significantly associated with a decreased risk of PORT delay. No increase in operating room time occurred for patients who underwent same-day extractions. CONCLUSIONS: Early involvement of the dental oncology department and oral-maxillofacial surgeons can aid in the timely delivery of care for patients with advanced oral cavity cancer.

When it is not just DKA; diabetic ketoacidosis as a first presentation of pancreatic adenocarcinoma.

Pancreatic cancer is the fourth leading cause of cancer related-deaths in the United States. Early symptoms of pancreatic cancer are nonspecific, and most cases are diagnosed at an advanced stage. DKA as a first presentation of pancreatic adenocarcinoma is a seldom reported condition. We present a case of a 59 year old female with type 2 diabetes, who presented to the emergency department with confusion, abdominal pain, polyuria and polydipsia. Laboratory workup showed a high anion gap metabolic acidosis and a blood glucose level of 419 mg/dl with positive serum ketones. She was diagnosed with DKA and admitted to the ICU. A CT abdomen/pelvis was performed to assess for pancreatic pathology as her DKA took longer time to resolve, it showed a pancreatic mass with multiple lesions in the liver. She had biopsies done which were positive for poorly differentiated pancreatic ductal adenocarcinoma. DKA occurs less commonly in patients with type 2 diabetes. Common precipitating factors for DKA in type 2 diabetes include medication noncompliance, infection, or possibly treatment with SGLT2 inhibitors. DKA as a first presentation of pancreatic cancer has been reported more with endocrine islet cell tumors but rarely with adenocarcinoma of the exocrine pancreas. Studies have shown that diabetes is an independent risk factor for development of pancreatic cancer. Other studies suggested that diabetes might be a result of pancreatic cancer or a paraneoplastic effect. One study suggested that diabetes associated with pancreatic cancer occurs at a resectable stage of the disease.

Shorter interval between radiation therapy and salvage laryngopharyngeal surgery increases complication rates following microvascular free tissue transfer.

PURPOSE: To evaluate how the interval between radiation and salvage surgery for advanced laryngeal cancer with free tissue transfer reconstruction influences complication rates. MATERIALS AND METHODS: This is a retrospective series of 26 patients who underwent salvage laryngectomy or laryngopharyngectomy with vascularized free tissue reconstruction (anterolateral thigh or radial forearm) following radiation or chemoradiation between 2012 and 2017 at a single academic center. The primary outcome was incidence of postoperative complications, including pharyngocutaneous fistula. Secondary outcomes included the need for a second procedure, time to resumption of oral feeding, feeding tube dependence, and hospital length of stay. RESULTS: Salvage surgery was performed for persistence (7/26, 27%), recurrence/new primary (12/26, 46%), and dysfunctional larynges (7/26, 27%). Twenty-two (85%) defects were reconstructed with an anterolateral thigh free flap and 4/26 with a radial forearm free flap (15%). There were no flap failures. There were significantly more complications in patients undergoing surgery within 12 months of completion of radiation therapy (7/12, 58%) versus those undergoing surgery after 12 months (1/14, 7%; p = .02). Patients experiencing complications more often required a second procedure (4/7 vs. 0/1; p = .02), experienced a longer delay to initiation of oral diet (61 vs. 21 days; p = .04), and stayed in the hospital longer (28 vs. 9 days; p = .01). CONCLUSIONS: Shorter intervals between definitive radiation and salvage laryngopharyngeal surgery with free tissue reconstruction increases postoperative complications, hospital length of stay, and the likelihood of feeding tube dependence. Reconstructive surgeons can use these findings to help guide preoperative patient counseling and assess postoperative risk.

Does a Standalone Cancer Center Improve Head and Neck Microsurgical Outcomes?

Objectives To evaluate the role of hospital setting (standalone cancer center vs. large multidisciplinary hospital) on free tissue transfer (FTT) outcomes for head and neck reconstruction. Methods Medical records were reviewed of 180 consecutive patients undergoing FTT for head and neck reconstruction. Operations occurred at either a standalone academic cancer center (n = 101) or a large multidisciplinary academic medical center (n = 79) by the same surgeons. Patient outcomes, operative comparisons, and hospital costs were compared between the hospital settings. Results The cancer center group had higher mean age (65.2 vs. 60 years; p = 0.009) and a shorter mean operative time (12.3 vs. 13.2 hours; p = 0.034). Postoperatively, the cancer center group had a significantly shorter average ICU stay (3.45 vs. 4.41 days; p < 0.001). There were no significant differences in medical or surgical complications between the groups. Having surgery at the cancer center was the only significant independent predictor of a reduced ICU stay on multivariate analysis (Coef 0.73; p < 0.020). Subgroup analysis, including only patients with cancer of the aerodigestive tract, demonstrated further reduction in ICU stay for the cancer center group (3.85 vs. 5.1 days; p < 0.001). A cost analysis demonstrated that the reduction in ICU saved $223,816 for the cancer center group. Conclusion Standalone subspecialty cancer centers are safe and appropriate settings for FTT. We found both reduced operative time and ICU length of stay, both of which contributed to lower overall costs. These findings challenge the concept that FTT requires a large multidisciplinary hospital. Level of Evidence 4.

Sternocleidomastoid contour restoration: an added benefit of the anterolateral thigh free flap during facial reconstruction.

PURPOSE: To demonstrate the potential of the anterolateral thigh free flap for neck contour restoration. STUDY DESIGN: Retrospective chart review at a tertiary care medical center of patients who underwent radical parotidectomy with sternocleidomastoid sacrifice, with or without temporal bone resection, and reconstruction of both facial and cervical contour with the anterolateral thigh free flap between November 2011 and March 2015. Seven patients were included and demographics, flap viability, pathology and tumor staging, surgical intervention, adjunctive reanimation procedures, ischemia time, and pre-operative and post-operative photos were recorded and analyzed. RESULTS: There were no flap failures and the mean ischemia time was 82 minutes. There were 2 recipient site complications. Post-operative neck symmetry was improved for all 7 patients. CONCLUSIONS: The adipofascial anterolateral thigh flap is useful for improving the aesthetic contour of the neck among patients undergoing sternocleidomastoid muscle resection/disinsertion following total parotidectomy with/without temporal bone resection. Contour restoration may be performed with minimal added morbidity and with relatively little additional operative time. This technique may be adapted for other complex facial and neck defects caused by ablative surgery. LEVEL OF EVIDENCE: 4.

Benefits of Immediate Extubation Following Free Tissue Transfer for Head and Neck Reconstruction.

Background Immediate postprocedure extubation (cessation of mechanical ventilation) after free tissue transfer for head and neck reconstruction may improve outcomes, reduce intensive care unit and hospital length of stay, and reduce overall cost compared with delayed extubation in the intensive care unit. Methods Medical records of 180 consecutive patients undergoing free tissue transfer for head and neck reconstruction were reviewed. Patients immediately extubated in the operating room (immediate group, N = 63) were compared with patients who were extubated in the intensive care unit (delayed group, N = 117) by univariate and multivariate analysis. Results Medical complication rates and intensive care unit length of stay were significantly higher in the delayed extubation group (55.5 vs. 12.7%, p < 0.001, and 4.4 vs. 2.9 days, p < 0.001, respectively). Although the rate of preoperative alcohol use was similar between the two groups, significantly fewer patients underwent treatment for alcohol withdrawal or agitation in the immediate extubation group (3.2 vs. 27.4%, p = 0.001). There were no significant differences in surgical complication rates. Conclusion Immediate postprocedure extubation is associated with shorter intensive care unit length of stay, reduced medical complications, and reduced incidence of treatment for agitation/alcohol withdrawal for patients undergoing free tissue transfer for head and neck reconstruction.

Safety of cyanoacrylate-based adhesives in creating layered septal cartilage grafts during open structure septorhinoplasty.

PURPOSE: Patients having suffered severe nasal trauma or having undergone prior septal surgery present particular problems during open structure septorhinoplasty. Septal cartilage deficient noses often require costal or conchal cartilage grafting or the use of allograft material, resulting in secondary donor site morbidity, longer operative times and variable results. The present study evaluated the utility of cyanoacrylate-based adhesives (CBA) in creating layered septal cartilage grafts from remnant septal cartilage for L-strut reconstruction during open septorhinoplasty. STUDY DESIGN: A retrospective clinical review was performed at a university-based facial plastic and reconstructive surgical practice, identifying patients undergoing open structure septorhinoplasty performed by the senior authors. Procedures involved construction of a layered caudal or dorsal L-strut graft from at least two smaller autologous septal cartilage grafts. The grafts were adhered together with CBA with 5-0 polydioxanone suture (Ethicon, Somerville, NJ) used for reinforcement. Stability of the final construct was assessed postoperatively. RESULTS: Fifteen patients were included with mean age of thirty-nine years (range: 15-65). Fifty-three percent of the patients had undergone prior nasal surgery: Seven had undergone at least one prior external septorhinoplasty and one had undergone prior endonasal septoplasty. Median follow-up was 144 days (range: 45-405). Postoperatively, one local infection was noted and two patients complained of post-operative columellar deviation. No other complications were encountered. CONCLUSION: CBAs provide a safe technique in the crafting of layered grafts to provide reliable tip/dorsal support when performing open structure septorhinoplasty among patients with cartilage deficient or severely traumatized septa.

Microbiomic subprofiles and MDR1 promoter methylation in head and neck squamous cell carcinoma.

Clinical observations and epidemiologic studies suggest that the incidence of head and neck squamous cell carcinoma (HNSCC) correlates with dental hygiene, implying a role for bacteria-induced inflammation in its pathogenesis. Here we begin to explore the pilot hypothesis that specific microbial populations may contribute to HNSCC pathogenesis via epigenetic modifications in inflammatory- and HNSCC-associated genes. Microbiomic profiling by 16S rRNA sequencing of matched tumor and adjacent normal tissue specimens in 42 individuals with HNSCC demonstrate a significant association of specific bacterial subpopulations with HNSCC over normal tissue (P < 0.01). Furthermore, microbial populations can separate tumors by tobacco status (P < 0.008), but not by alcohol status (P = 0.41). If our subhypothesis regarding a mechanistic link from microorganism to carcinogenesis via inflammation and consequent aberrant DNA methylation is correct, then we should see hypermethylation of relevant genes associate with specific microbiomic profiles. Methylation analysis in four genes (MDR1, IL8, RARB, TGFBR2) previously linked to HNSCC or inflammation shows significantly increased methylation in tumor samples compared with normal oral mucosa. Of these, MDR1 promoter methylation associates with specific microbiomic profiles in tumor over normal mucosa. Additionally, we report that MDR1 methylation correlates with regional nodal metastases in the context of two specific bacterial subpopulations, Enterobacteriaceae and Tenericutes (P < 0.001 for each). These associations may lead to a different, and potentially more comprehensive, perspective on the pathogenesis of HNSCC, and support further exploration of mechanistic linkage and, if so, novel therapeutic strategies such as demethylating agents and probiotic adjuncts, particularly for patients with advanced or refractory disease.

Functional and Cosmetic Considerations in Gender-Affirming Feminization Rhinoplasty.

Gender-affirming facial surgery is increasing in prevalence, and rhinoplasty plays an integral role in its success. The nose displays considerable gender dimorphism, and maneuvers performed during gender-affirming rhinoplasty may differ considerably from those performed during cis-gender surgery. During feminization rhinoplasty in particular, cosmetic goals often rely on reductive techniques such as osteotomies, dorsal reduction, sidewall narrowing, tip narrowing, and alar base narrowing. These maneuvers collectively have important ramifications when considering the functional aspects of the nose. Herein, we outline the status of feminization rhinoplasty, and the interplay of cosmetic and functional considerations of the field.

Systemic Therapy for Melanoma: ASCO Guideline Update Q and A.

This Q&A answers questions regarding ASCO's recent Systemic Therapy for Melanoma guideline.

Through a New Lens: Skin-Grafted Free Flaps and Objective Facial Skin Color Matching.

Background: Head and neck ablative surgery can impose aesthetic disfigurement, particularly when severe color mismatch exists between native and reconstructed facial skin. To date, the accuracy, objectivity, and modifiability of facial skin color matching remains poorly understood. Objective: To measure skin color match outcomes after head and neck reconstruction using handheld colorimetry. Methods: Patients undergoing complex head and neck reconstruction involving facial skin were included. A variety of skin paddle donor sites were studied, including split-thickness skin graft (STSG) placement over myocutaneous or adipofasciocutaneous free flaps after de-epithelization. Skin color match (deltaE) was measured during follow-up using a handheld colorimeter. Results: Forty-seven patients were included, with median age 69. The most common flap type was the anterolateral thigh (n = 31, 66%). Twenty patients underwent STSG to the skin paddle. DeltaE measurements among the patients with STSGs demonstrated better color match (lowest deltaE), compared with patients with unaltered skin paddles (3.4 ± 1.0 vs. 6.5 ± 2.5, p < 0.0001). Conclusion: We found the use of STSGs over de-epithelialized myogenous or adipofasciocutaneous flaps improves color match, as measured by handheld colorimetry.

Increasing Pedicle Reach with Musculocutaneous Perforator Dissection in Anterolateral Thigh Free Flaps.

OBJECTIVE: To measure the increase in effective pedicle reach with microdissection of musculocutaneous perforators during anterolateral thigh (ALT) free tissue harvest. METHODS: A review of our institution's free flap database was performed to identify ALT free tissue transfers. The distance from pedicle vessel origin to its perforator's insertion at the fascia lata (effective pedicle length [EPL]) was measured prior to and following intramuscular dissection of musculocutaneous perforators. Pertinent clinicopathologic variables were abstracted from the electronic medical record. RESULTS: A total of 314 ALT free flaps were performed between February 2017 and August 2022. Of these, 85 had documentation of EPL before and after musculocutaneous perforator dissection. ALT reconstruction was primarily performed for reconstruction of oncologic ablative defects (66, 78%). The mean EPL prior to perforator microdissection was 8.8 cm (standard deviation, SD 2.8 cm; range 3-15 cm). Following perforator dissection, mean EPL significantly increased to 14.0 cm (SD 3.0 cm; range 7-22 cm) with a mean net gain of 5.2 cm in distance (95% confidence interval 4.8-5.6 cm; p < 0.001). Nine patients (11%) required operating room take-back for anastomosis revision (3, 3.5%), recipient site hematoma evacuation (4, 4.7%), and wound dehiscence (2, 2.3%); one complete flap loss due to venous thrombosis was observed. CONCLUSION: Dissection of musculocutaneous perforators during ALT free flap harvest can increase effective pedicle reach by 5.2 cm or nearly 60%. This harvest technique can facilitate the performance of tension-free anastomoses when substantial vascular pedicle length or vascular pedicle tunneling is required. LEVEL OF EVIDENCE: 4 Laryngoscope, 134:666-670, 2024.

The Impact of Venous Anastomosis Technique on Outcomes of Free Tissue Transfer to the Head and Neck.

Objectives: To evaluate the impact of different techniques of microvascular venous anastomosis on the outcome of free tissue transfer to the head and neck. Methods: Retrospective case series of patients undergoing microvascular free tissue transfer (MFTT) from January 2006 to September 2021. Chi-square tests and t-tests were utilized to identify differences in flap outcomes by technique, and log-binomial regression analyses were utilized to identify differences in flap outcomes by technique. Results: A total of 1055 consecutive MFTTs were analyzed. One hundred four cases required a return to the operating room for any reason, and 19 were attributed to venous compromise (18.0%). Ultimately, there were 22 FTT failures requiring complete revision (2.1%). In total, 1055 MFTTs involved 1352 venous anastomoses, ranging from 1 to 3 anastomoses in each case. End-to-end (ETE) was used 1040 times (76.9%) and end-to-side (ETS) 204 times (15.0%). The calculated risk ratio for venous complication for ETS compared with ETE was 1.17 (0.34-3.98). A microvascular coupler was used in 355 cases (33.6%). The calculated risk ratio for coupler compared with suture anastomoses was 0.92 (0.35-2.39). Conclusions: There were no significant difference in regard to outcomes of MFTT when comparing ETE with ETS, nor when comparing coupler with suture anastomoses.

Ultrasonic Shears Decrease Postoperative Hematomas in Head and Neck Microvascular Reconstruction.

OBJECTIVE: To evaluate postoperative hematoma and takeback rates in a large series of microvascular reconstructions. We sought to determine whether the use of ultrasonic shears reduced these rates. STUDY DESIGN: Retrospective cohort study. SETTING: Tertiary referral hospital. METHODS: A total of 2288 patients undergoing free flap reconstruction for head and neck defects between 1995 and 2022 were reviewed. Patients undergoing dissection with and without ultrasonic shears were compared to determine postoperative hematoma and takeback rates. RESULTS: The overall hematoma rate was 1.3% (29/2288) for the entire cohort. The postoperative hematoma rates with and without ultrasonic shears were 0.63% (9/1418) and 2.3% (20/870), relative risk = 0.28, P = .0015. Of 870 patients undergoing surgery without ultrasonic shears, 14 (1.61%) were taken back to the operating room for control of bleeding compared to 8 of 1418 (0.56%) in the ultrasonic shears cohort. CONCLUSION: Our large series of patients undergoing microvascular reconstruction shows a decrease in postoperative hematoma rate and takeback for bleeding with the adoption of ultrasonic shears. Ultrasonic shears are an effective tool that can help decrease perioperative morbidity secondary to hematoma after head and neck tumor resection and microvascular reconstruction.

Objective Photoanalysis of Feminizing Frontal Cranioplasty Outcomes.

Study Design: Retrospective analysis at a tertiary care center. Objective: This study describes a method of analyzing postoperative results using lateral view clinical photographs to create normalized projection ratios of the glabella and radix. Methods: We reviewed preoperative and postoperative photographs of 15 patients. All photographs were in the lateral view Frankfort horizontal plane. We calculated the distances between the (a) tragus and cornea, (b) cornea and radix, (c) cornea and glabella, and the (θ) nasofrontal angle. Results: Fifteen sets of patient photographs were analyzed and found that there was a favorable 14% reduction at the radix and an even greater reduction (78.9%) at the glabella. The nasofrontal angle was improved to a more feminine range from 131.84° preoperatively to 145.86° postoperatively. Conclusions: Normalized projection ratios of the glabella and radix, along with the nasofrontal angle, can be used to objectively measure outcomes of frontal feminizing cranioplasty.

Postoperative inpatient surgical complications following head and neck microvascular free tissue transfer.

BACKGROUND: Complications following head and neck microvascular free tissue transfer (MFTT) are common. Less is known about when they occur. METHOD: Retrospective study of patients with primary or recurrent head and neck cancer undergoing MFTT reconstruction at a tertiary care institution. MFTT reconstructions with inpatient postoperative complications were included. The Kruskal-Wallis test was used to compare median postoperative day (POD) onset of complication by flap type. RESULTS: Of 1090 patients undergoing MFTT reconstruction, 126 (11.6%) patients experienced inpatient complications including fibula (n = 35), anterolateral thigh (n = 60), or radial forearm (n = 31) MFTTs. POD onset was shortest for surgical site hematoma (median = 1 [IQR 1-5]), and longest for donor site infection (median = 11.5 [IQR 8-15]). There was no significant difference between flap types and POD onset of complications (p > 0.05). CONCLUSION: Hematoma formation and flap failure occur earliest during hospitalization, while dehiscence, infection, and fistula occur later. There is no difference in complication timing between flap types.

Ultrasound characterization of middle ear effusion.

PURPOSE: To further enhance and assess the ability to characterize middle ear effusion (MEE) using non-invasive ultrasound technology. MATERIALS AND METHODS: This is a prospective unblinded comparison study. Fifty-six children between the ages of 6 months and 17 years scheduled to undergo bilateral myringotomy with pressure equalization tube placement were enrolled. With the child anesthetized, the probe was placed into the external ear canal after sterile water was inserted. Ultrasound recordings of middle ear contents were analyzed by computer algorithm. Middle ear fluid was collected during myringotomy and analyzed for bacterial culture and viscosity. RESULTS: Ultrasound waveforms yielded a computer algorithm interpretation of middle ear contents in 66% of ears tested. When a result was obtained, the sensitivity and specificity for successfully characterizing middle ear fluid content as either void of fluid, thick fluid (mucoid), or thin fluid (serous or purulent) were at least 94%. Mucoid effusions had higher measured viscosity values (P=.002). Viscosity measures were compared to culture result, and those with low viscosity (thin consistency) had a higher likelihood of having a positive culture (P=.048). CONCLUSION: The device sensitivity and specificity for fluid detection were 94% or greater among interpretable waveforms (66% of those tested). Although this technology provides important information of the middle ear effusion presence and characteristic, further technological improvements are needed.

Outcomes Associated with Multiple Free Tissue Transfers Performed in a Single Day.

Background: Although microvascular free tissue transfer (MFTT) remains technically challenging, surgeons may need to perform >1 MFTT operations in a given day. Objective: To compare MFTT outcomes in cases where surgeons completed one versus two flaps per day by measuring flap viability and complication rates. Methods: A retrospective review was conducted of MFTT cases from January 2011 to February 2022 with >30-day follow-up. Outcomes, including flap survival and operating room takeback, were compared using multivariate logistic regression analysis. Results: Of 1096 patients meeting inclusion criteria (1105 flaps), there was a male predominance (n = 721, 66%). Mean age was 63.0 ± 14.4 years. Complications requiring takeback were identified in 108 flaps (9.8%) and were greatest for double flaps in the same patient (SP) (27.8%, p = 0.06). Flap failure occurred in 23 (2.1%) cases and was also greatest for double flaps in the SP (16.7%, p = 0.001). Takeback (p = 0.06) and failure (p = 0.70) rates were not different between days with one versus two unique patient flaps. Conclusions: Among patients undergoing MFTT, those treated on days in which surgeons perform two unique cases compared with single cases will demonstrate no difference in outcomes, as measured by flap survival and takeback, whereas patients with defects requiring multiple flaps will experience greater takeback and failure rates.