Paradigm Change for Intraoperative Surgical Margin Assessment for Oral Squamous Cell Carcinoma.

OBJECTIVE: Achieving clear surgical margins is one of the primary surgical goals in treating oral squamous cell carcinoma (OSCC) and thus aiming to improve overall and disease-specific survival. Therefore, we developed the Goal-Oriented Assessment for Intraoperative Margin ('GAIM') protocol, a novel intraoperative approach for margin assessment, and present here our 5-year experience and outcomes. METHODS: 'GAIM' is a 7-step procedure comprising systematic ruler-aided resection of labeled tumor-bed margins, frozen section (FS) co-produced by both pathologists and operating surgeons, and immediate extension of resection according to FS findings. Data from all patients operated using the 'GAIM' protocol at a single tertiary center between 2018 to 2022 were analyzed, including margin status on FS and final pathology (FP) records, recurrence, and mortality. RESULTS: A total of 196 patients were included, 56.6% (n = 111) stages I-II, and 43.4% (n = 85) stages III-IV. Using the 'GAIM' protocol, we achieved an overall 94.4% of clean and revised clean surgical margins. Patients with a 2-year and longer follow-up (n = 141) had local recurrence in 3.5% when both FS and final margins were clean, 8.1% when FP margins were clean, and 16.7% with close/positive final margins. CONCLUSIONS: The proposed 'GAIM' protocol is a novel, effective, reproducible, and safe approach for margin evaluation that can be systematically applied. It can increase the rate of final clean surgical margins and potentially improve patients' outcomes. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:1725-1732, 2024.

CDK 4/6 Inhibition Overcomes Acquired and Inherent Resistance to PI3Kα Inhibition in Pre-Clinical Models of Head and Neck Squamous Cell Carcinoma.

Activating alterations in PIK3CA, the gene coding for the catalytic subunit of phosphoinositide-3-kinase (PI3K), are prevalent in head and neck squamous cell carcinoma (HNSCC) and thought to be one of the main drivers of these tumors. However, early clinical trials on PI3K inhibitors (PI3Ki) have been disappointing due to the limited durability of the activity of these drugs. To investigate the resistance mechanisms to PI3Ki and attempt to overcome them, we conducted a molecular-based study using both HNSCC cell lines and patient-derived xenografts (PDXs). We sought to simulate and dissect the molecular pathways that come into play in PIK3CA-altered HNSCC treated with isoform-specific PI3Ki (BYL719, GDC0032). In vitro assays of cell viability and protein expression indicate that activation of the mTOR and cyclin D1 pathways is associated with resistance to PI3Ki. Specifically, in BYL719-resistant cells, BYL719 treatment did not induce pS6 and pRB inhibition as detected in BYL719-sensitive cells. By combining PI3Ki with either mammalian target of rapamycin complex 1 (mTORC1) or cyclin D1 kinase (CDK) 4/6 specific inhibitors (RAD001 and abemaciclib, respectively), we were able to overcome the acquired resistance. Furthermore, we found that PI3Ki and CDK 4/6 inhibitors have a synergistic anti-tumor effect when combined in human papillomavirus (HPV)-negative/PIK3CA-WT tumors. These findings provide a rationale for combining PI3Ki and CDK 4/6 inhibitors to enhance anti-tumor efficacy in HNSCC patients.

Acute Kidney Injury after Partial Nephrectomy: Role of Parenchymal Mass Reduction and Ischemia and Impact on Subsequent Functional Recovery.

BACKGROUND: Acute increase of serum creatinine (SCr) after partial nephrectomy (PN) is primarily due to parenchymal mass reduction or ischemia; however, only ischemia can impact subsequent functional recovery. OBJECTIVE: We evaluate etiologies of acute kidney injury (AKI) after PN and their prognostic significance. DESIGN, SETTING, AND PARTICIPANTS: From 2007-2014, 83 solitary kidneys managed with PN had necessary studies for detailed analysis of function and parenchymal mass before/after surgery. AKI was classified by Risk/Injury/Failure/Loss/Endstage classification and defined by either standard criteria (comparison to preoperative SCr) or proposed criteria (comparison to projected postoperative SCr based on parenchymal mass reduction). Subsequent recovery was defined as percent function preserved/percent mass saved. INTERVENTION: PN. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Predictive factors for AKI were evaluated by logistic regression. Relationship between AKI grade and subsequent functional recovery was assessed by linear regression. RESULTS AND LIMITATIONS: Median duration warm ischemia (n=39) was 20 min and hypothermia (n=44) was 29 min. Median parenchymal mass reduction was 11%. AKI occurred in 45 patients based on standard criteria and 38 based on proposed criteria, and reflected injury/failure (grade = 2/3) in 23 and 16 patients, respectively. On multivariable analysis, only ischemia time associated with AKI occurrence (p=0.016). Based on the proposed criteria, median recovery from ischemia was 99% in patients without AKI and 95%/90%/88% for patients with grades 1/2/3 AKI, respectively. The coefficient for association between AKI grade based on proposed criteria and subsequent functional recovery was -4.168 (p=0.018). Main limitation is limited patient cohort. CONCLUSIONS: Parenchymal mass reduction and ischemia both contribute to acute changes in SCr after PN. Classification of AKI by proposed criteria significantly associates with subsequent functional recovery. However, more robust numbers will be needed to further assess the merits of the proposed criteria. While AKI is associated with suboptimal recovery, even patients with grade 2/3 AKI reached 88-90% of recovery expected. PATIENT SUMMARY: Acute decline in function after partial nephrectomy associates with more prolonged ischemia time, and appears to impact subsequent functional recovery. However, most kidneys eventually recover strongly, even if their function is sluggish in the first few days after surgery.

Distant blunt forceps dissection in tissue expander insertion: A novel technique.

Tissue expansion using implantable expanders is a useful means of generating surplus tissue for reconstruction of defects such as scarring following burns. The authors describe their technique of incisions distant to the desired location of expander placement, and remote dissection of the expander pocket with hydrodissection and blunt forceps. A total of 81 expanders were placed in 30 consecutive patients, 81% of whom had burn scars due for reconstruction. During preparation, no complications, such as bleeding, were encountered, except one case with severe subdermal fibrosis, in which bleeding was stopped through brief application of pressure. Postoperatively, no complications were encountered in 76% of patients; however, 16.6% exhibited surgical site infection, which was managed conservatively and was correlated with a high number of expanders implanted at once. One patient experienced hematoma formation that resolved spontaneously, and one instance of expander extrusion and subsequent removal occurred. Receiving ≥2 expanders at the same time was statistically associated with higher risk for complication(s). The authors' complication rates were moderate and comparable with open or endoscopic approaches. Time of expansion is reduced compared with the open approach due to distant incision placement and immediate usability. Cost effectiveness appeared to be better using only inexpensive forceps, rather than elaborate and costly endoscopic equipment.

L'expansion tissulaire à l'aide d'implants produit un excédent de tissus utile pour reconstruire des lésions telles que des cicatrices consécutives à des brûlures. Les auteurs décrivent leur technique d'incisions éloignées du foyer de l'expanseur et leur méthode d'hydrodissection par pinces mousse à distance de la poche d'expanseur. Au total, ils ont inséré 81 expanseurs chez 30 patients consécutifs, dont 81 % pour reconstruire des cicatrices consécutives à des brûlures. Pendant la préparation, les chercheurs n'ont relevé aucune complication, telle qu'une hémorragie, à part un cas d'importante fibrose sous-cutanée dont l'hémorragie a été interrompue par une brève pression. Après l'opération, ils n'ont observé aucune complication chez 76 % des patients, mais 16,6 % ont présenté une infection au site chirurgical, liée à l'implantation de plusieurs expanseurs en une même intervention et traitée avec prudence. Un patient a présenté un hématome qui s'est résolu spontanément, et un autre, une extrusion de l'expanseur qu'il a fallu retirer. L'implantation simultanée d'au moins deux expanseurs s'associait statistiquement à un risque plus marqué de complication(s). Le taux de complications des auteurs était modéré et comparable à celui des chirurgies ouvertes ou des endoscopies. L'expansion était de plus courte durée que par chirurgie ouverte, grâce à l'incision à distance et à l'utilisabilité immédiate. Le rapport coût-efficacité semblait supérieur au moyen de pinces bon marché que de matériel endoscopique élaboré et coûteux.

Association of Vitamin B12 Deficiency with Homozygosity of the TT MTHFR C677T Genotype, Hyperhomocysteinemia, and Endothelial Cell Dysfunction.

BACKGROUND: Hyperhomocysteinemia is associated with increased cardiovascular risk, but treatment with folic acid has no effect on outcome in unselected patient populations. OBJECTIVES: To confirm previous observations on the association of homozygosity for the TT MTHFR genotype with B12 deficiency and endothelial dysfunction, and to investigate whether patients with B12 deficiency should be tested for 677MTHFR genotype. METHODS: We enrolled 100 individuals with B12 deficiency, tested them for the MTHFR C677T polymorphism and measured their homocysteine levels. Forearm endothelial function was checked in 23 B12-deficient individuals (13 with TT MTHFR genotype and 10 with CT or CC genotypes). Flow-mediated dilatation (FMD) was tested after short-term treatment with B12 and folic acid in 12 TT MTHFR homozygotes. RESULTS: Frequency of the TT MTHFR genotype was 28/100 (28%), compared with 47/313 (15%) in a previously published cohort of individuals with normal B12 levels (P = 0.005). Mean homocysteine level was 21.2 ± 16 µM among TT homozygotes as compared to 12.3 ± 5.6 µM in individuals with the CC or CT genotype (P = 0.008). FMD was abnormal ( 6%) in 9/13 TT individuals with B12 deficiency (69%), and was still abnormal in 7/12 of those tested 6 weeks after B12 and folic treatment (58%). CONCLUSIONS: Among individuals with B12 deficiency, the frequency of the TT MTHFR genotype was particularly high. The TT polymorphism was associated with endothelial dysfunction even after 6 weeks of treatment with B12 and folic acid. Based on our findings we suggest that B12 deficiency be tested for MTHFR polymorphism in order to identify potential vascular abnormalities and increased cardiovascular risk.

Treatment of wounds following breast reduction and mastopexy with subsequent wound dehiscence with charged polystyrene microspheres.

BACKGROUND: Lower T-junction wound dehiscence following breast reduction surgery or mastopexy constitutes a vexing and grievous complication both to the surgeon and the patient. Treatment modalities that can expedite wound healing and reepithelialization rates are highly craved. The objective of this study was to assess wound healing and epithelialization rates of open wounds following breast reduction and mastopexy wound dehiscence treated with charged polystyrene microspheres (CPM). MATERIALS AND METHODS: Five female patients with wound dehiscence and subsequent open wounds following breast reduction and mastopexy were treated with daily with CPMsoaked dressings. Wound closure rates were documented. RESULTS: The wounds showed both accelerated granulation tissue formation as well as swift epithelialization rates. No complications or side effects were encountered. CONCLUSIONS: Charged polystyrene microspheres may offer a new and efficacious way to heal open wounds due to wound dehiscence following aesthetic breast surgery. Further research with a larger patient population is still needed to verify these findings. .

Post-facelift flap necrosis treatment using charged polystyrene microspheres.

BACKGROUND: Flap necrosis following facial rhytidectomy constitutes a vexing and grievous complication to the patient and the surgeon. Treatment modalities that can expedite wound healing and re-epithelialization rates are highly desired. OBJECTIVES: To assess wound healing and re-epithelialization rates of open wounds following postrhytidectomy flap necrosis treated with commercially available charged polystyrene microspheres (Polyheal-1, Polyheal Ltd, Israel). METHODS: Flap necrosis following rhytidectomy with open wounds in three female patients were treated using dressings soaked with Polyheal-1. Wound closure rates were documented. RESULTS: The wounds demonstrated both accelerated granulation tissue formation and rapid re-epithelialization rates. No complications or side effects were encountered. CONCLUSIONS: Charged polystyrene microspheres may offer a new and efficacious way to treat open wounds due to flap necrosis following facial rhytidectomy. Further research with larger patient numbers is still needed to verify these findings.

HISTORIQUE: La nécrose d'un lambeau après une rhytidectomie du visage est une complication délicate et pénible pour le patient et le chirurgien. Des modalités thérapeutiques qui peuvent accélérer le taux de guérison et de réépithélialisation de la plaie sont fort souhaitables. OBJECTIFS: Évaluer le taux de guérison et de réépithélialisation de plaies ouvertes après la nécrose d'un lambeau de rhytidectomie traité à l'aide de microsphères chargées de polystyrène commerciales (Polyheal-1, Polyheal Ltd, Israël). MÉTHODOLOGIE: Les médecins ont traité la nécrose d'un lambeau après une rhytidectomie comportant des plaies ouvertes chez trois patientes à l'aide de pansements imbibés de Polyheal-1. Ils ont consigné le taux de fermeture des plaies. RÉSULTATS: Les plaies ont présenté à la fois la formation accélérée de tissu de granulation et un taux de réépithélialisation rapide. Cette guérison ne s'est pas accompagnée de complications, ni d'effets secondaires. CONCLUSIONS: Les microsphères chargées de polystyrène offrent peut-être un moyen nouveau et efficace de traiter des plaies ouvertes causées par la nécrose d'un lambeau après une rhytidectomie du visage. Des recherches plus approfondies auprès d'un plus grand nombre de patients s'imposent pour confirmer ces observations.

Are there predicting factors for burn patients that transfer to a rehabilitation center upon completion of acute care?

INTRODUCTION: Choosing the right burn patient that transfers to a rehabilitation facility following acute hospitalization is a difficult decision. In our study we characterize demographic, injury and hospitalization related variables that predict a burn patient's transfer to a rehabilitation facility. METHODS: We analyzed the data of 974 burn patients with burns of the second degree and deeper, spanning 20% TBSA (total body surface area) or more, that were admitted to all 5 hospitals that operate a burn unit in Israel, between the years 1998 and 2005. RESULTS: The results of the multivariate logistical regression model in which the predicted variable is discharge to rehabilitation showed that the most predictive variables were inhalation injury, surgical procedures and hospitalization period. Execution of a surgical procedure was the most influential factor over discharge to rehabilitation (odds ratio=6.202) followed by inhalation injury (OR=4.706) and finally, the hospitalization period (OR=1.026) (an increase of 1.026 times in the likelihood to be sent to rehabilitation with any additional day of hospitalization). DISCUSSION: In this study we examined patients who were sent to a rehabilitation facility upon completion of their acute care in an attempt to evaluate common initial clinical variables that assist in making an educated decision regarding the patient rehabilitation transfer. This is one of the first attempts at examining and revealing evidence based parameters that might determine the correct burn patient to send to rehabilitation after his hospitalization.

Synchronized real-time ultrasonography and three-dimensional computed tomography scan navigation during percutaneous renal cryoablation in a porcine model.

AIM: To investigate the accuracy of percutaneous cryoablation for kidney tumors performed under combined real-time ultrasonography (US) and three-dimensional (3D) CT scan navigation in a porcine model. MATERIALS AND METHODS: After percutaneously injecting 2 to 6 tumor mimic lesions in 11 pigs, a CT scan was performed and digital data were saved into a navigation system (Real-Time Virtual Sonography [RVS]) that allows 3D reconstruction and synchronization with real-time US images. The cryoprobe was guided percutaneously into the kidney tumor mimic, and ice ball formation was monitored continuously during cryoablation using the RVS system. Kidneys were harvested and sent for gross pathologic and histopathologic analysis at days 0, 15, and 30 postoperatively. RESULTS: Thirty-five renal tumor mimics were created and treated by percutaneous cryotherapy; tumor mimic locations were as follows: 16 tumors (46%) in the lower pole, 14 (40%) in the central region, and 5 (14%) in the upper pole. Eleven tumor mimics (31%) were intraparenchymal, and 24 (69%) subcapsular. The synchronization between the CT scan 3D reconstructed images and real-time US was successful in all cases. The mean tumor size was 2 cm (range, 1.2-4 cm). Mean cryonecrosis size was 3.3, 3.7, and 2.8 cm at days 0, 15, and 30, respectively. Three (8.5%) positive margins were found on the macroscopic and microscopic analysis. CONCLUSIONS: RVS imaging system synchronizing real-time US with preoperative CT scan is a feasible and safe technique for percutaneous probe ablation of kidney tumors.