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Biomedical subjects

F Christopher Holsinger

Publications and source records attributed to F Christopher Holsinger.

At least 19 recordsLinked to original sources
PubMed2026

Toward a Better Paradigm for Head and Neck Cancer Treatment Applying AI (HNC-TACTIC): Protocol for an International Cohort Study of Electronic Health Records.

BACKGROUND: Head and neck squamous cell carcinomas (HNSCCs) cause considerable morbidity and mortality. Multimodal treatment strategies can cause significant toxicity, and therapy options are limited for recurrent disease. Immunotherapy has emerged as a promising approach. However, patient response variability underscores the need for better predictive markers. OBJECTIVE: This study aims to use artificial intelligence to develop two predictive models in patients with HNSCC to assess (1) progression or recurrence following primary curative treatment and (2) long-term survival after immunotherapy schemes in recurrent and metastatic disease. This study will also describe the characteristics of patients with early, locally advanced, and recurrent or metastatic cancers. METHODS: This is a retrospective, observational study of data captured in electronic health records (EHRs) from participating hospitals between January 1, 2014, and December 31, 2021. This study's population comprises adults diagnosed with HNSCC at any stage. Study variables, including demographics, comorbidities, clinical variables, treatments, and outcomes, will be extracted using EHRead, a technology that applies natural language processing and machine learning to extract and analyze structured and unstructured clinical information in deidentified EHRs. Predictive models based on dynamic risk stratification for treatment response and progression or recurrence will be developed using multivariable logistic regressions, decision tree classifiers, and random forest approaches. Descriptive and outcome analyses will be shown for different anatomic subsites and stratified by stage and treatment. RESULTS: This study began enrolling sites in July 2021 and is currently ongoing. By December 2025, data from 10 centers has been collected, comprising a total of 151,934,990 EHRs from 2,159,719 patients. CONCLUSIONS: Development of predictive models using artificial intelligence will advance clinical understanding of HNSCC to improve patient outcomes.

Humans↗
PubMed2007

Primary adrenal natural killer/T-cell nasal type lymphoma: first case report in adults.

We report the first case of a primary adrenal natural killer (NK)/T-cell nasal type lymphoma in adults. The patient presented with an enlarging left adrenal mass and the initial concern was for adrenocortical carcinoma. Surgical resection revealed NK/T-cell lymphoma. Rapid recurrence in the contralateral adrenal gland was treated with a single cycle of chemotherapy before he died due to infectious complications and progressive disease. This case demonstrates the aggressive presentation of a novel subset of primary adrenal lymphoma that should be considered in the differential diagnosis of a rapidly enlarging adrenal mass.

Adrenal Gland Neoplasms↗
PubMed2006

Resection of selected invasive squamous cell carcinoma of the pyriform sinus by means of the lateral pharyngotomy approach: the partial lateral pharyngectomy.

BACKGROUND: Although the lateral pharyngotomy is a well-known surgical procedure, to our knowledge, no published reports have described the results achieved with a lateral pharyngectomy approach in patients with isolated and previously untreated selected invasive squamous cell carcinoma of the lateral wall of the pyriform sinus. METHODS: The medical files and operative charts of 30 patients with an isolated, and previously untreated, squamous cell carcinoma of the pyriform sinus, treated for cure by lateral partial pharyngectomy and primary closure, as well as postoperative radiotherapy (n = 22), and preoperative chemotherapy (n = 8), were retrospectively studied. Sixteen tumors were classified as T1 and 14 as T2. All patients but one were followed until death. RESULTS: Three patients (9%) died in the immediate postoperative period (two from medical complications and one from a surgery-related complication). Overall, 29 patients died, resulting in a 77.7%, 40%, 23.3%, and 15% 1-, 3-, 5- and 10-year Kaplan-Meier actuarial survival estimate, respectively. Only one patient had a serious postoperative complication develop. All patients were decannulated. No patients required a gastrostomy and/or completion total laryngectomy for functional reasons. Local recurrence occurred in four patients (13%). The 3-and 5-year Kaplan-Meier actuarial local control estimates were 88.5% and 79.6%, respectively. The use of a platin-based induction chemotherapy (p = .05) regimen was the only variable that was significantly statistically related to local recurrence. Overall, a 93.3% laryngeal preservation rate was achieved. CONCLUSION: Partial pharyngectomy by means of the lateral pharyngotomy combined with postoperative radiation therapy is an efficient and function-sparing approach to control selected invasive squamous cell carcinomas of the lateral wall of the pyriform sinus.

Aged↗
PubMed2006

Conservation laryngeal surgery versus total laryngectomy for radiation failure in laryngeal cancer.

BACKGROUND: Total laryngectomy is the standard of care for surgical salvage of radiation failure in laryngeal cancer. However, the role of conservation laryngeal surgery in this setting remains unclear. The objective was to compare the efficacy of conservation versus total laryngectomy for salvage of radiation failure in patients who initially presented with T1 or T2 squamous cancer of the larynx. METHODS: A 21-year retrospective analysis of patients who received surgery at a single comprehensive cancer center after definitive radiation therapy is reported. At recurrence, the patients were reevaluated and then underwent a total laryngectomy or, if possible, a conservation laryngeal procedure. The charts of 105 patients who failed radiation treatment for primary laryngeal cancer and who subsequently underwent surgical salvage were reviewed for this study. Eighty-nine were male (84.8%). The mean age was 60.3 years. The median follow-up time after surgery was 69.4 months. Most patients with recurrence after radiotherapy required total laryngectomy (69.5%; 73/105). Conservation laryngeal surgery was performed for 32 patients (31.5%). Concomitant neck dissections were performed on 45 patients (45.5%). RESULTS: In 14 patients, local or regional recurrence developed after salvage surgery: 9 patients after total laryngectomy (12.3%; 9/73), and 5 patients (15.6%; 5/32) after conservation laryngeal surgery. This difference was not statistically significant, nor was there a difference in disease-free interval for the two procedures (p = .634, by log-rank test). Distant metastasis developed in 13 patients. Most developed in the setting of local and/or regional recurrence, but distant metastasis occurred as the only site of failure in 6 of the patients who had undergone total laryngectomy but in 1 of the conservation surgery patients treated for a supraglottic laryngeal cancer. The overall mortality for patients who underwent total laryngectomy was also higher: 73.74% (54/73) versus 59.4% (19/32) for patients who underwent a conservation approach (p = .011 by log-rank test). CONCLUSIONS: Although conservation laryngeal surgery was possible in a few patients with local failure after radiotherapy, conservation laryngeal surgery is an oncologically sound alternative to total laryngectomy for these patients.

Adult↗
PubMed2006

Sternocleidomastoid myofascial flap for reconstruction after composite resection of invasive squamous cell carcinoma of the tonsillar region: technique and outcome.

OBJECTIVE: To present the surgical technique and determine the efficacy of sternocleidomastoid myofascial (SCMF) flap reconstruction after composite resection with intent to cure. STUDY DESIGN: Retrospective review of 73 consecutive patients with a previously isolated and untreated moderately to well-differentiated invasive squamous cell carcinoma of the tonsillar region and a minimum of 3 years follow-up, managed at a tertiary referral care center during the years 1970 to 2002, with an ipsilateral superiorly based SCMF flap after composite resection. METHODS: The surgical procedure is presented in detail. Potential technical pitfalls are highlighted. Survival, mortality, and morbidity are documented. Univariate analysis for potential correlation between the incidence for postoperative flap complications and various variables is also performed. RESULTS: The 1, 3, and 5 year Kaplan-Meier actuarial survival estimates were 82.2%, 64.4%, and 49.3%, respectively. Death never appeared to be related to the completion of the SCMF flap. Thirty-three (45.2%) patients had some kind of significant postoperative surgical complication, and nine (12.3%) patients had some kind of significant postoperative medical complication. The most common significant postoperative complication was partial SCMF flap necrosis and pharyngocutaneous fistula noted in 30.1% and 10.9% of patients, respectively. Complete SCMF flap necrosis was never encountered. No patient developed carotid artery rupture or died as a result of the SCMF flap, and none required additional surgery. In univariate analysis, no significant statistical relation was noted between the significant postoperative surgical complications related to the use of the SCMF flap and the variables under analysis. CONCLUSIONS: The superiorly based SCMF flap appears to be simple to perform and useful for reconstruction of defects after composite resection.

Adult↗
PubMed2005

Mortality risk from squamous cell skin cancer.

PURPOSE: To identify nonmelanoma skin cancer patients with squamous cell carcinoma (SCC) who are at greatest risk of disease-specific mortality. PATIENTS AND METHODS: Prospectively enrolled patients with a minimum of one pathologically confirmed skin SCC lesion, definitive treatment of the SCC lesion(s) resulting in no evidence of disease, and at least 2 months of follow-up after definitive treatment were eligible for the present longitudinal analysis. They received comprehensive clinical, pathologic evaluations and follow-up for patterns of failure and mortality. RESULTS: We enrolled 210 patients (187 men and 23 women) with a total of 277 skin SCC lesions and a median enrollment age of 68 years (range, 34 to 95 years). Median follow-up of surviving patients was 22 months. Three-year overall and disease-specific survival (DSS) rates were 70% and 85%, respectively. In univariate analyses, the clinical-pathologic factors associated with adverse DSS were local recurrence at presentation (P = .05), invasion beyond subcutaneous tissues (P = .009), perineural invasion (P = .002), lesion size (P = .0003), and depth of invasion (P = .05). Statistical models identified a homogeneous high-risk group of patients with lesions > or = 4 cm, perineural invasion, and deep invasion beyond subcutaneous structures. Three-year DSS was 100% for patients with no risk factors versus 70% for patients with at least one risk factor. CONCLUSION: Lesion size > or = 4 cm and histologic evidence of perineural invasion and deep invasion beyond subcutaneous structures were the clinical-pathologic factors most significantly associated with disease-specific mortality in skin SCC.

Adult↗
PubMed2005

Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: I. Technique, complications, and functional results.

OBJECTIVES: To describe the surgical technique for transoral lateral oropharyngectomy (TLO) and its safety, postoperative management, complications, and functional outcomes. DESIGN: A 20-year retrospective case series review. Mean follow-up was 10 years. All but 10 patients were followed up until the fifth postoperative year or death. SETTING: Academic, tertiary referral center. PATIENTS: A total of 191 patients who underwent TLO for selected invasive squamous cell carcinoma of the tonsil and/or tonsillar fossa. INTERVENTIONS: Ten patients had received preoperative radiation therapy. Induction chemotherapy was used in 153 patients (80.3%). An associated neck dissection was performed in 148 patients (77.5%). Postoperative radiation therapy was administered to 52 patients (28.7%). MAIN OUTCOME MEASURES: Overall survival rate, intraoperative mortality, and perioperative mortality were determined. The need for and length of nasogastric tube feeding and tracheotomy were calculated. The incidence of significant postoperative surgical and medical complications was recorded. RESULTS: No intraoperative mortality occurred, but 5 patients (2.6%) died in the immediate postoperative period, 3 from medical complications and 2 from unknown causes. In this series, the internal carotid artery was never injured, and no cutaneous-oropharyngeal fistulas were apparent. The incidence of significant surgical complications from the oropharynx was 6.3%. Nasopharyngeal reflux and severe rhinolalia were the most common complications, occurring in 9 patients. Increasing tobacco use was statistically correlated with an increase in postoperative pneumonia from aspiration (P = .05) but no surgical complications. Seven patients (3.7%) had a temporary tracheotomy for a mean of 5 days. One hundred twelve patients (58.6%) had a nasogastric tube inserted for a mean of 6 days. No patients had a permanent gastrostomy or tracheotomy tube. The mean duration of hospitalization was 9 days. The duration of hospitalization was statistically correlated with the need for nasogastric tube placement and its duration (P<.001) or tracheotomy (P<.001). CONCLUSIONS: From a functional standpoint, the TLO is a safe surgical approach for treating selected carcinoma of the tonsillar fossa. It is a reliable technique that should be considered for treatment of appropriate squamous cell carcinoma of the tonsil.

Adult↗
PubMed2005

Transoral lateral oropharyngectomy for squamous cell carcinoma of the tonsillar region: II. An analysis of the incidence, related variables, and consequences of local recurrence.

OBJECTIVES: To determine the incidence of local and regional failure, distant metastasis, and overall survival following transoral lateral oropharyngectomy (TLO) and to determine factors associated with local recurrence. DESIGN: Retrospective case series throughout 20 years; mean follow-up of 10 years. SETTING: Academic center. PATIENTS: A total of 166 previously untreated patients with squamous cell carcinoma of the tonsil. INTERVENTIONS: A total of 131 (81.9%) of the 166 patients received preoperative induction chemotherapy. Fifty-one patients (30.7%) underwent postoperative radiation therapy. MAIN OUTCOME MEASURES: Local and regional recurrence, distant metastasis, second primary tumors, and survival. RESULTS: The 1- and 5-year Kaplan-Meier local control estimates were 91.2% and 82.1%, respectively. The 1- and 5-year Kaplan-Meier local control estimates were 98.3% and 89.0% for T1, 88.9% and 81.7% for T2, and 78.9% and 62.7% for T3 lesions, respectively (P = .02). In univariate analysis, 7 variables were significantly associated with an increased risk of local failure: increasing T classification; positive margins of resection; poor clinical response to induction chemotherapy; tumor spread to the posterior pillar, posterior pharyngeal wall, and contralateral soft palate; and invasion of the junction between the tonsil and soft palate. In a logistic regression model, spread to the posterior pillar was the only variable statistically associated with local failure (P = .02). The 1-, 3-, and 5-year Kaplan-Meier survival estimates were 87.9%, 67.2%, and 57.7%, respectively. The Kaplan-Meier survival estimate was significantly reduced (P = .009) in patients with local failure. CONCLUSIONS: Selected tonsillar squamous cell carcinoma can be managed with TLO with local control comparable to radiotherapy. Patient selection is critical and TLO is best suited for patients with anterior T1 to T2 squamous cell carcinoma of the tonsil, without posterior anatomic spread.

Adult↗
PubMed2005

Thyroplasty type I with Montgomery implant among native French language speakers with unilateral laryngeal nerve paralysis.

OBJECTIVE: To document the long-term results achieved with the Montgomery implant in 96 French speakers with a unilateral laryngeal nerve paralysis (ULNP). STUDY DESIGN: Retrospective series, inception cohort of 96 patients. METHODS: Data regarding morbidity and functional results were obtained at regular visits to our clinic. All patients were followed for a minimum of 6 months or until death. Forty-two patients had a minimum of 12 months of follow-up. Early in the study, 36 patients were prospectively recorded under similar conditions before placement of the Montgomery implant and at 1, 3, 6, and 12 months postoperatively. RESULTS: None of the 96 patients died in the immediate postoperative period. The perioperative course was unremarkable in 94.8% of cases. Perioperative problems included failure to obtain a satisfactory phonatory result in three patients, difficulty to stabilize the implant posteriorly in one patient, and fracture of the inferior rim of the thyroid cartilage window in another patient. The primary immediate postoperative problem (within the first postoperative month) was laryngeal dyspnea, noted in four patients. According to the patient's subjective assessment, speech and voice was always improved in the immediate postoperative period. However, three patients had secondary degradation of speech and voice. Revision surgery under local anesthesia resulted in a 97.9% ultimate speech and voice success rate. According to the patient's subjective assessment, adequate swallowing in the immediate postoperative period was achieved in 94.2% of cases that had swallowing problems preoperatively. A significant statistical increase in the duration parameters (phonation time, phrase grouping, speech rate) together with a statistical significant decrease in both the jitter and shimmer values was noted when comparing the preoperative and the postoperative values at 1 month. Analysis of the evolution of the speech and voice parameters at 1, 3, 6, and 12 months postoperatively showed a significant decrease in the fundamental frequency and noise-to-harmonic ratio values but did not demonstrate any significant differences for the other speech and voice parameters. CONCLUSIONS: From the reported data, we conclude that the type I thyroplasty with Montgomery implant insertion is a safe and reproducible method to treat ULNP. Furthermore, this system achieves very good and stable phonatory results. Finally, the use of this technique and implant system appears safe in patients from various cultures with ULNP from a variety of causes and severe comorbidity. Over the past decade at our department, this procedure progressively replaced the use of the intracordal injection of autologous fat injection that was initially advocated in patients with ULNP.

Adult↗
PubMed2005

Lymph node metastases from cutaneous squamous cell carcinoma of the head and neck.

OBJECTIVE/HYPOTHESIS: Cutaneous squamous cell carcinoma (CSCC) has been reported to metastasize to parotid and cervical lymph nodes. Few prospective investigations of associated clinical and histopathologic findings and their effect on patient outcomes exist. We seek to identify risk factors for nodal metastases in CSCC and determine the impact of lymphatic spread on survival and recurrence. STUDY DESIGN: Subset analysis of a prospective, longitudinal database of patients with CSCC at a comprehensive cancer center. METHODS: Eligible patients with nonmelanoma skin cancer were consecutively enrolled in a prospective database from July 1996 through June 2001; this cohort was then followed to the key endpoints of recurrence and mortality. RESULTS: Two hundred ten patients were enrolled, and 193 patients with CSCC of the head and neck are included in this analysis. The incidence of nodal metastases in this population was 20.7% at study entry. Median follow-up was 20 months in patients with lymph node metastases and 24 months in patients without metastases. Nodal metastases were significantly associated with recurrent lesions (P = .002) and the following histopathologic features: lymphovascular invasion (P < .0001), inflammation (P = .010), poorly differentiated histology (P = .001), invasion into the subcutaneous tissues (P = .0001), perineural invasion (P = .005), and larger size (P = .0007). Metastases to the cervical nodes were not clinically apparent in 42% of patients with parotid metastases. Combination surgery and radiation therapy resulted in regional control rates of 95%, although local recurrence and distant metastases, along with second primary tumors, were the most frequent recurrent events. Kaplan-Meier survival analysis demonstrates a decrease in overall survival (P = .005), disease-free survival (P = .015), disease-specific survival (P = 0002), and time to recurrence (P = .012) in patients with nodal metastases compared with controls. CONCLUSIONS: Lymph node metastases from CSCC are common in our population and are associated with diminished survival. The presence of nodal spread occurs with other adverse histopathologic findings, and we recommend surgery and postoperative radiation therapy to control regional disease in the presence of nodal metastases and perineural invasion. New approaches in early identification of nodal metastases, treatment, and prevention of local recurrences and second primary malignancies are warranted.

Adult↗
PubMed2004

Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer.

PURPOSE: No effective treatment options currently are available to patients with anaplastic thyroid cancer (ATC), resulting in high mortality rates. Epidermal growth factor (EGF) has been shown to play a role in the pathogenesis of many types of cancer, and its receptor (EGFR) provides an attractive target for molecular therapy. EXPERIMENTAL DESIGN: The expression of EGFR was determined in ATC in vitro and in vivo and in human tissue arrays of ATC. We assessed the potential of the EGFR inhibitor gefitinib ("Iressa," ZD1839) to inhibit EGFR activation in vitro and in vivo, inhibit ATC cellular proliferation, induce apoptosis, and reduce the growth of ATC cells in vivo when administered alone and in combination with paclitaxel. RESULTS: EGFR was overexpressed in ATC cell lines in vitro and in vivo and in human ATC specimens. Activation of EGFR by EGF was blocked by the addition of gefitinib. In vitro studies showed that gefitinib greatly inhibited cellular proliferation and induced apoptosis in ATC cell lines and slowed tumor growth in a nude mouse model of thyroid carcinoma cells injected subcutaneously. CONCLUSIONS: ATC cells consistently overexpress EGFR, rendering this receptor a potential target for molecular therapy. Gefitinib effectively blocks activation of EGFR by EGF, inhibits ATC cellular proliferation, and induces apoptosis in vitro. Our in vivo results show that gefitinib has significant antitumor activity against ATC in a subcutaneous nude mouse tumor model and therefore is a potential candidate for human clinical trials.

Animals↗
PubMed2004

Detection of plasminogen activators in oral cancer by laser capture microdissection combined with zymography.

Plasminogen activation is believed to be critical to the progression of oral squamous cell carcinoma by facilitating matrix degradation during invasion and metastasis, and high levels of urokinase plasminogen activator (uPA) and plasminogen activator (PA) inhibitor-1 (PAI-1) in tumors predict poor disease outcome. We describe the development of a novel method for studying PA in oral cancer that combines the sensitivity and specificity of zymography with the spatial resolution of immunohistochemistry. Laser capture microdissection (LCM) was combined with plasminogen-casein zymography to analyze uPA, tissue PA (tPA), uPA-PAI-1 complexes, and tPA-PAI-1 complexes in 11 tumors and adjacent non-malignant epithelium from squamous cell carcinomas of the tongue, floor of mouth, larynx, and vocal cord. uPA was detectable in all tumor samples analyzed, uPA-PAI-1 complexes in three samples, and tPA in nine. PA was detectable in as little as 0.5 microg protein lysate from microdissected tumors. In all specimens, uPA expression was highly increased in tumor tissue compared to adjacent non-malignant tissue. In conclusion, LCM combined with zymography may be excellently suited for analyzing the prognostic significance and causal involvement of the plasminogen activation system in oral cancer.

Aged↗
PubMed2003

Epidermal growth factor receptor blockade potentiates apoptosis mediated by Paclitaxel and leads to prolonged survival in a murine model of oral cancer.

PURPOSE: Because survival for patients with oral cancer has not improved over the past 25 years, new approaches for treatment are needed. Targeted molecular therapy against epidermal growth factor receptor (EGFR) has shown promise as an adjuvant therapy in preliminary studies in several solid tumors, including head and neck cancer. The objective of this study was to determine the efficacy of paclitaxel and PKI166, a novel inhibitor of EGFR, against oral cavity cancer. EXPERIMENTAL DESIGN AND RESULTS: JMAR human oral cancer cells were pretreated for 1 h with PKI166 and then stimulated with epidermal growth factor. EGFR-specific tyrosine kinase autophosphorylation measured by Western immunoblotting was inhibited by PKI166 in a dose-dependent fashion at all doses tested (0.01-1 micro M). Next, the induction of apoptosis in JMAR cells treated with paclitaxel (0.001 to 0.1 micro M) with or without PKI166 (0, 1, or 2 micro M) was determined using a propidium iodide assay. The addition of 2.0 micro M PKI166 significantly increased tumor cell death, shifting the amount of paclitaxel needed to induce apoptosis in 50% of cells from 0.1 to 0.001 micro M. These in vitro findings were confirmed using an orthotopic model of oral cancer. JMAR oral cancer cells were implanted into the tongues of nude mice. After lingual tumors developed, mice were randomized into four groups (n = 10): (a) oral PKI166 (100 mg/kg); (b) i.p. paclitaxel (200 micro g/wk); (c) PKI166 and paclitaxel; or (d) placebo. Mice treated with PKI166/paclitaxel demonstrated a significant increase in survival (P = 0.028). After necropsy, all tongue tumors were evaluated for apoptosis by the terminal deoxynucleotidyl transferase-mediated nick end labeling assay. A greater apoptotic fraction of tumor cells was found in tumors of mice treated with paclitaxel and PKI166 as compared with the other treatment groups (136.4 versus 37.8; P = 0.016). CONCLUSIONS: Combination therapy with paclitaxel and PKI166 prolongs survival in an orthotopic preclinical model of tongue cancer by increasing programmed cell death of oral cancer.

Animals↗
PubMed2003

Squamous cell carcinoma of the buccal mucosa: one institution's experience with 119 previously untreated patients.

BACKGROUND: Squamous cell carcinoma (SCC) of the buccal mucosa is a rare, but especially aggressive, form of oral cavity cancer, associated with a high rate of locoregional recurrence and poor survival. We reviewed our institution's experience with 119 consecutive, previously untreated patients with buccal SCC. METHODS: We reviewed the charts of 250 patients who were seen at The University of Texas M. D. Anderson Cancer Center between January, 1974, and December, 1993. Of these, 119 were untreated and were subsequently treated exclusively at our institution. Patients who were previously treated elsewhere or whose lesions arose in other sites and only secondarily involved the buccal mucosa were excluded. RESULTS: Patients with T1- or T2-sized tumors had only a 78% and 66% 5-year survival, respectively. Muscle invasion, Stensen's duct involvement, and extracapsular spread of involved lymph nodes were all associated with decreased survival (p <.05). Surgical salvage for patients with locoregional recurrence after radiation therapy was rarely successful. CONCLUSIONS: SCC of the buccal mucosa is a highly aggressive form of oral cavity cancer, with a tendency to recur locoregionally. Patients with buccal mucosa SCC have a worse stage-for-stage survival rate than do patients with other oral cavity sites.

Academic Medical Centers↗