Immunotherapy utilization in stage IIIA melanoma: less may be more.

Background: Immunotherapy agents are approved for adjuvant treatment of stage III melanoma; however, evidence for survival benefit in early stage III disease is lacking. Current guidelines for adjuvant immunotherapy utilization in stage IIIA rely on clinician judgment, creating an opportunity for significant variation in prescribing patterns. This study aimed to characterize current immunotherapy practice variations and to compare patient outcomes for different prescribing practices in stage IIIA melanoma. Study design: Patients with melanoma diagnosed from 2015-2019 that met American Joint Committee on Cancer 8th edition criteria for stage IIIA and underwent resection were identified in the National Cancer Database. Multiple imputation by chained equations replaced missing values. Factors associated with receipt of adjuvant immunotherapy were identified. Multivariable Cox proportional hazards regression compared overall survival across groups. Results: Of 4,432 patients included in the study, 34% received adjuvant immunotherapy. Patients had lower risk-adjusted odds of receiving immunotherapy if they were treated at an academic center (OR=0.48, 95%CI=0.33-0.72, p<0.001 vs. community facility) or at a high-volume center (OR=0.69, 0.56-0.84, p<0.001 vs. low-volume). Immunotherapy receipt was not associated with risk-adjusted survival (p=0.095). Moreover, patients treated at high-volume centers experienced longer overall risk-adjusted survival than those treated at low-volume centers (HR=0.52, 0.29-0.93, p=0.030). Risk-adjusted survival trended toward being longer at academic centers than at community centers, but the difference was not statistically significant. Conclusion: Academic and high-volume centers utilize significantly less adjuvant immunotherapy in stage IIIA melanoma than community and low-volume centers without compromise in overall survival. These findings suggest that this population may benefit from more judicious immunotherapy utilization.

Immunotherapy Initiation at the End of Life in Patients With Metastatic Cancer in the US.

Importance: While immunotherapy is being used in an expanding range of clinical scenarios, the incidence of immunotherapy initiation at the end of life (EOL) is unknown. Objective: To describe patient characteristics, practice patterns, and risk factors concerning EOL-initiated (EOL-I) immunotherapy over time. Design, Setting, and Participants: Retrospective cohort study using a US national clinical database of patients with metastatic melanoma, non-small cell lung cancer (NSCLC), or kidney cell carcinoma (KCC) diagnosed after US Food and Drug Administration approval of immune checkpoint inhibitors for the treatment of each disease through December 2019. Mean follow-up was 13.7 months. Data analysis was performed from December 2022 to May 2023. Exposures: Age, sex, race and ethnicity, insurance, location, facility type, hospital volume, Charlson-Deyo Comorbidity Index, and location of metastases. Main Outcomes and Measures: Main outcomes were EOL-I immunotherapy, defined as immunotherapy initiated within 1 month of death, and characteristics of the cohort receiving EOL-I immunotherapy and factors associated with its use. Results: Overall, data for 242 371 patients were analyzed. The study included 20 415 patients with stage IV melanoma, 197 331 patients with stage IV NSCLC, and 24 625 patients with stage IV KCC. Mean (SD) age was 67.9 (11.4) years, 42.5% were older than 70 years, 56.0% were male, and 29.3% received immunotherapy. The percentage of patients who received EOL-I immunotherapy increased over time for all cancers. More than 1 in 14 immunotherapy treatments in 2019 were initiated within 1 month of death. Risk-adjusted patients with 3 or more organs involved in metastatic disease were 3.8-fold more likely (95% CI, 3.1-4.7; P < .001) to die within 1 month of immunotherapy initiation than those with lymph node involvement only. Treatment at an academic or high-volume center rather than a nonacademic or very low-volume center was associated with a 31% (odds ratio, 0.69; 95% CI, 0.65-0.74; P < .001) and 30% (odds ratio, 0.70; 95% CI, 0.65-0.76; P < .001) decrease in odds of death within a month of initiating immunotherapy, respectively. Conclusions and Relevance: Findings of this cohort study show that the initiation of immunotherapy at the EOL is increasing over time. Patients with higher metastatic burden and who were treated at nonacademic or low-volume facilities had higher odds of receiving EOL-I immunotherapy. Tracking EOL-I immunotherapy can offer insights into national prescribing patterns and serve as a harbinger for shifts in the clinical approach to patients with advanced cancer.

Combined Tripier and V-Y Advancement Flaps for Reconstruction of Large Lid-cheek Junction Defects.

Reconstruction of lid-cheek junction defects has a known risk of ectropion. Cervicofacial flaps require significant dissection and can still be prone to ectropion. V-Y advancement flaps have been described as less morbid, but their use is limited to moderate-size defects that do not involve the lid margin. The authors present a technique of combined Tripier and V-Y advancement flaps for reconstruction of large defects of the lid-cheek junction involving the lower eyelid. A retrospective review of patients undergoing the authors' technique was performed. A facial artery perforator flap was designed in a V-Y fashion and advanced into the cheek. An orbicularis oculi myocutaneous flap (Tripier flap) was elevated from the upper eyelid and rotated into the lower eyelid/upper cheek to meet the superior edge of the V-Y flap. A separate review of patients undergoing cervicofacial flap reconstruction was also performed. Demographics, operative details, and complications were recorded and compared. This technique was applied to five patients with large-size (19.9 ± 5.6 cm2) defects of the lid-cheek. In all cases, healing was achieved without ectropion, hematoma, infection, dehiscence, flap necrosis, or facial nerve injury. Twenty-four patients separately underwent cervicofacial flap reconstruction for defects of comparable size (15.8 ± 10.7 cm2). Two patients developed ectropion, one patient developed a hematoma, and two patients developed an infection. Combined Tripier and V-Y advancement flaps is a useful technique to reconstruct lid-cheek junction defects. This method allows for the reconstruction of large lid-cheek junction defects that involve the lid margin.

Predictive accuracy of elevated mitotic rate on lymph node positivity and recurrence in thin melanomas.

Background: Mitotic rate (MR) is considered an important prognostic factor for melanoma but is not currently used for staging because its nuanced effect is not yet well-delineated. We sought to determine if T category-specific MR is predictive of sentinel lymph node (SLN) positivity, recurrence, and melanoma-specific mortality (MSM). Methods: A retrospective review of patients with primary cutaneous melanoma from 1994 to 2020 at a single academic center was performed. Patient demographics and tumor characteristics were recorded. MR was considered elevated for each AJCC8-defined T category if it was ≥2 mitoses/mm2 for T1, ≥4 mitoses/mm2 for T2, ≥6 mitoses/mm2 for T3, or ≥7 mitoses/mm2 for T4. Statistical analysis was performed to assess the predictive accuracy of MR on selected outcomes while controlling for ulceration. Results: Data from 2,984 patients with complete records were analyzed. Along with Breslow thickness and ulceration, elevated MR was associated with higher risk of MSM (HR 1.816, P=0.0001). There was no difference among patients with ulcerated T1 or T2 tumors regardless of MR, but those with non-ulcerated T1 or T2 tumors and elevated MR were more likely to have positive SLNs (P<0.0001 and P=0.0043, respectively) and recurrence (P=0.0007 and P=0.0004, respectively) compared to counterparts with low MR. There were no notable differences for T3 or T4 tumors based on MR. Conclusions: Elevated MR is associated with SLN positivity and recurrence in thin melanomas, independent of ulceration. SLN biopsy should therefore be strongly considered for patients with non-ulcerated lesions <0.8 mm thick if the MR is ≥2 mitoses/mm2.

Thumb Amputations in Children: Classification and Reconstruction by Microsurgical Toe Transfers.

PURPOSE: Traumatic amputations of the thumb are rare in children compared with adults, but hand surgeons remain reticent to consider microsurgical reconstruction with toe-to-thumb transfers. This study reports the functional outcomes and complications of children with traumatic thumb amputations who underwent toe-to-thumb reconstruction. METHODS: A retrospective review of children who sustained thumb amputations and whose parents elected for their child to undergo reconstruction by toe-to-thumb transfer was performed. Details of the level of thumb amputation, whether other fingers were also amputated, which toe was transferred on which vascular pedicle, survival of the transfer, and complications, were collected. Opposition, sensation, and growth of the toe-to-thumb transfers was measured. Functional and psychosocial outcomes were evaluated by both the parents and the older children using the Pediatric Outcomes Data Collection Instrument questionnaire. RESULTS: Twenty-one thumb amputations in 19 children between the ages of 2 and 17 years were referred for secondary reconstruction. Ten were isolated thumb amputations and 11 were combined thumb and multiple finger amputations. Two children had bilateral thumb amputations. Twenty-one toe-to-thumb transfers were performed: 14 second toe transfers and 7 great toe transfers (3 great toe and 2 trimmed and 2 Morrison wraparound variations). There were no immediate postoperative reexplorations of the microsurgical anastomoses and all toe transfers survived completely. All children regained pinch and grasp function and sensation. There were no gait problems in the donor feet. CONCLUSIONS: Microsurgical toe-to-thumb transfers should be offered as an alternative option to the traditional techniques of distraction lengthening and pollicization, for posttraumatic thumb reconstruction in children for any level of amputation from just distal to the carpometacarpal joint to the interphalangeal joint. Toe-to-thumb transfer provides length, opposition, and sensation without disturbing ambulation and is associated with excellent psychosocial outcomes as evaluated by both parents and older children. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

The Repair of International Clefts in the Current Surgical Landscape.

Cleft lip and palate (CLP) constitute a significant global disease burden. There are two general models that exist to deliver cleft care: surgical missions and comprehensive cleft centers (CCC). While surgical missions offer high quality surgical care to patients who would be unlikely to ever receive treatment, they may fail to provide sustainable solutions. The development of CCC is growing in popularity worldwide. CCC are permanent centers that offer a multidisciplinary team approach to the treatment of cleft lip and palate. Operation Smile has adopted the concept of specialized surgical care centers. These centers are shown to be safe, cost-effective, and provide sustainable solutions for cleft care. The authors discuss some of the benefits and drawbacks of the classic mission-based model and highlight why there may be a paradigm shift towards CCC.

Disseminating surgery effectively and efficiently in Haiti.

The need for surgical care in Haiti remains vast despite the enormous relief efforts after the earthquake in 2010. As the poorest country in the Western hemisphere, Haiti lacks the necessary infrastructure to provide surgical care to its inhabitants. In light of this, a multidisciplinary approach led by Partners In Health and Dartmouth-Hitchcock Medical Center is improving the access to surgical care and offering treatment of a broad spectrum of pathology. This article discusses how postearthquake Haiti partnerships involving academic institutions can alleviate the surgical burden of disease and, in the process, serve as a profound educational experience for the academic community. The lessons learned from Haiti prove applicable in other resource-constrained settings and invaluable for the next generation of surgeons.

Effect of calvarial burring on resorption of onlay cranial bone graft.

Variable resorption occurs whenever calvarial bone graft is used for onlay cranioplasty. The recipient ectocortex may be burred to expose vessels and osteocytes to maximize healing. The purpose of this study was to determine whether abrading the recipient site improves the volume of onlay graft. The parietal bones of 17 rabbits were sectioned into split-thickness and full-thickness grafts. The right frontal cortex was abraded with a bur to punctate bleeding. Pairs of split-thickness (n = 48) or full-thickness (n = 20) grafts were onlayed to the burred right frontal bone and to the nonburred left frontal bone. Micro-computed tomography was used to determine graft volume immediately postoperatively and 16 weeks later. Histology, including tartrate-resistant acid phosphatase staining, was performed to quantify vascular channels and osteoclasts per high-power field 10 days postoperatively. Split-thickness graft volume decreased 58.0% when placed on the burred calvarial site, compared with grafts on the nonburred cortex (28.4%) (P = 0.01). Full-thickness grafts showed a similar trend: greater resorption (39.1%) when onlayed onto abraded calvaria compared with nonburred ectocortex (26.0%) (P = 0.11). Split-thickness graft orientation (cortical vs cancellous side in contact with the recipient site) did not affect resorption (P = 0.67). Onlay grafts placed on the burred recipient site had more vascular channels (11.8) and osteoclasts (5.7), compared with grafts over nonabraded cortex (3.4 and 4.2, respectively) (P < 0.05). Burring the recipient site cortex before onlay cranial bone grafting promotes resorption, possibly by increasing vascularization and osteoclastic activity. This technique cannot be recommended.

Cranial particulate bone graft ossifies calvarial defects by osteogenesis.

BACKGROUND: Cranial particulate bone graft heals inlay calvarial defects and can be harvested as early as infancy. The purpose of this study was to test the hypothesis that particulate bone promotes ossification primarily by osteogenesis. METHODS: Freshly harvested particulate bone, devitalized particulate bone, and high-speed drilled bone dust from rabbit calvaria were assayed for metabolic activity (resazurin) and viable osteoblasts (alkaline phosphatase). A rabbit cranial defect model was used to test the effect of devitalizing particulate bone on in vivo ossification. A parietal critical-size defect was created and managed in three ways: (1) no implant (n = 6); (2) particulate bone implant (n = 6); and (3) devitalized particulate bone implant (n = 6). Micro-computed tomographic scanning was used to measure ossification 16 weeks later; histology also was studied. RESULTS: Particulate bone contained more viable cells (0.94 percent transmittance per milligram) compared with devitalized particulate bone (0.007 percent) or bone dust (0.21 percent) (p = 0.01). Particulate bone had greater alkaline phosphatase activity (0.13 µU/µg) than devitalized particulate bone (0.000) or bone dust (0.06) (p = 0.01). Critical-size defects treated with particulate bone had more ossification (99.7 percent) compared with devitalized particulate bone implants (42.2 percent) (p = 0.01); no difference was found between devitalized particulate bone and the control (40.8 percent) (p = 0.9). CONCLUSIONS: Particulate bone graft contains living cells, including osteoblasts, that are required to heal critical-size cranial defects. These data support the hypothesis that particulate bone promotes ossification primarily by osteogenesis.

On Bernard Sarnat's 100th birthday: pathology and management of craniosynostosis.

The focus on nonsyndromic craniosynostosis, the most common type of isolated craniosynostosis, is sagittal, followed by unilateral coronal, bilateral coronal, metopic, and lambdoid, in order of decreasing frequency. Certain forms of craniosynostosis display a sex predilection. For example, boys outnumber girls in a 4:1 ratio in sagittal synostosis, but girls outnumber boys in a 3:2 ratio in unilateral coronal synostosis. Other forms, such as metopic, lambdoid, and bilateral coronal synostosis, demonstrate no sex dominances tract.

Autologous cranial particulate bone graft: an experimental study of onlay cranioplasty.

The purpose of this study was to determine whether particulate bone graft maintains its volume when used for onlay cranioplasty. Twenty-five adult, male, New Zealand white rabbits were divided into 5 groups (n = 5/group). Groups 1 to 3 were controls: group 1, untreated; group 2, sham procedure; and group 3, burring the cortical surface. Group s 4 and 5 had augmentation of the parietal bones with particulate graft harvested from the frontal bone with a brace and bit. The particulate graft was placed on native parietal bone (group 4) or on parietal bone that had been abraded to punctuate bleeding with an electric burr (group 5). Volume maintenance and osseointegration of the grafts were determined by micro-computed tomography and histology. At 16 weeks postoperatively, the mean (SD) volumes of the parietal bones in control groups 1, 2, and 3 were 555.8 (29.2), 550.8 (36.8), and 539.0 (39.0) mm, respectively. Immediately after cranioplasty, the mean (SD) volumes of augmented parietal bone were 846.0 (10.8) mm for group 4 and 831.8 (11.8) mm for group 5. Sixteen weeks postoperatively, 100% of the group 4 grafts had resorbed (551.8 [SD, 24.0] mm), and parietal volume was no different from controls (P = 0.89). Group 5 maintained 54.2% of volume (695.6 [SD, 22.0] mm), which was greater than those of the controls (P < 0.0001). Particulate graft may be used for onlay cranioplasty if the recipient site is burred. Approximately one half of the onlay graft is resorbed, and its original shape is not maintained.

Inlay cranioplasty: an experimental comparison of particulate graft versus bone dust.

BACKGROUND: Cranioplasty in children is difficult because autologous bone is limited. To expand the calvarial donor site, surgeons have used bone dust harvested with a power drill and particulate bone taken with a bit and brace. The purpose of this study was to compare bone dust and particulate bone for inlay cranioplasty. METHODS: A critical-size defect was made in the parietal bone of rabbits and managed in three ways: group I (n = 5), no implant; group II (n = 6), bone dust implant; and group III (n = 6), particulate graft implant. Bone dust and particulate graft were obtained using a power burr or brace and bit, respectively. Bone dust and particulate graft volume was calculated using a micrometer. Computed tomography was performed 4, 8, and 16 weeks after cranioplasty to determine ossification; histology also was studied. RESULTS: The average volume of particulate bone fragments (6.2 × 10 mm) was 344-fold greater than bone dust particles (1.8 × 10 mm) (p < 0.0001). Four weeks postoperatively, the filled volume of the experimental defect was 6.8 ± 4.9 percent in group I, 8.4 ± 7.4 percent in group II, and 43.0 ± 7.2 percent in group III. Eight weeks postoperatively, the filled volume was 22.3 ± 3.9 percent in group I, 29.1 ± 6.7 percent in group II, and 80.0 ± 8.9 percent in group III. Sixteen weeks postoperatively, the defect was closed 38.6 ± 11.1 percent in group I, 41.3 ± 11.2 percent in group II, and 99.3 ± 1.5 percent in group III (p < 0.0001). CONCLUSIONS: Particulate bone graft ossifies full-thickness cranial defects. Bone dust is ineffective and resorbs, possibly because of its smaller particle size and/or thermal injury during harvesting. Particulate graft, and not bone dust, is suitable for inlay cranioplasty.

Perioperative corticosteroid reduces hospital stay after fronto-orbital advancement.

Facial swelling is common after fronto-orbital advancement. Edema and closure of the palpebral fissures can lead to prolonged hospitalization. The purpose of this study was to determine if perioperative corticosteroid shortens hospital stay after this procedure.We retrospectively studied consecutive children younger than 2 years who underwent primary fronto-orbital advancement between 1990 and 2008. Patients were categorized into 2 groups: group 1 patients were not given corticosteroid; group 2 patients received tapered perioperative dexamethasone. Primary outcome variables included length of hospital stay and infection rate.A total of 161 patients were included in the study. Hospitalization was significantly shorter (P = 0.008) for group 2 (n = 65; median duration, 3.0 d) than group 1 (n = 96; median duration, 5.0 d). Infection rates did not differ between groups (group 1, 2.1%; group 2, 1.5%; P = 0.8).Perioperative corticosteroid shortens hospitalization after fronto-orbital advancement without increasing the incidence of postoperative infection. The cost of postoperative hospital care was reduced by 27.2%.