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The submandibular glands (SMGs), along with the parotid and sublingual glands, generate the majority of saliva and play critical roles in maintaining oral and systemic health. Despite their physiological importance, long-term therapeutic options for salivary gland dysfunction remain limited, highlighting the need for a deeper molecular understanding of SMG biology, particularly in humans. To address this knowledge gap, we have performed transcriptomic- and epigenomic-based analyses and molecular characterization of the human SMG. Our integrated analysis of multiorgan RNA-sequencing datasets has identified an SMG-enriched gene expression signature comprising 289 protein-coding and 75 long non-coding RNA (lncRNA) genes that include both known regulators of salivary gland function and several novel candidates ripe for future exploration. To complement these transcriptomic studies, we have generated chromatin immunoprecipitation sequencing (ChIP-seq) datasets of key histone modifications on human SMGs. Our epigenomic analyses have allowed us to identify genome-wide enhancers and super-enhancers that are likely to drive genes and regulatory pathways that are important in human SMG biology. Finally, comparative analysis with mouse and human SMG and other tissue datasets reveals evolutionary conserved gene and regulatory networks, underscoring fundamental mechanisms of salivary gland biology. Collectively, this study offers a valuable knowledge-based resource that can facilitate targeted research on salivary gland dysfunction in human patients.

Pneumatosis intestinalis is a rare but known potential complication of treatment with cetuximab. Here we present two cases of pneumatosis intestinalis occurring in patients who were receiving cetuximab as treatment for advanced head and neck cancer. In both cases, cetuximab was discontinued after discovery of the pneumatosis intestinalis.

Percutaneous endoscopic gastrostomy (PEG) tubes are often placed in head and neck cancer patients to provide nutritional support, but studies have found the complication rates to be higher than other subsets of patients who undergo PEG placement. Complication rates as high as 50% have been reported, with the bulk of these complications being PEG site issues (i.e., cellulitis, abscess, fascitis, and tumor implantation). Because the pull technique has been the primary technique used, the theory is that the transoral tube passage is the source of the complications in these patients. Alternatively, the introducer technique uses a transabdominal approach to place the device, avoiding any tube contamination by upper aerodigestive organisms or tumor cells. At our institution, this technique has been used exclusively for head and neck cancer patients and this article reports our experience. One hundred forty-nine head and neck cancer patients who had a prophylactic PEG tube placed were reviewed from January 1, 1999 to December 31, 2003. The rates of placement success, morbidity, and complications were determined. Successful placement was achieved in 148 (99%) patients without any PEG-related deaths. Overall, 17 complications (11%) occurred, with only one major complication (0.7%) identified. PEG site infections were uncommon with only five cases (3.4%) and all were mild cellulitis. The introducer technique is the safest method for PEG tube placement in head and neck cancer patients. The overall rate of complications is low and PEG site infectious complications are rare. The introducer technique should be the method of choice for PEG tubes in head and neck cancer patients.

The initial presentation of distant metastases in patients with differentiated thyroid cancer is a rare event. Interestingly, if managed appropriately, the long-term survival in this group of patients is approximately 43%. We intend to review our experience of patients presenting initially with distant metastatic disease in a large series of differentiated thyroid cancer patients. In the entire series of 1,038 consecutive patients treated at Memorial Sloan-Kettering Cancer Center from 1930 to 1985, 44 patients presented initially with distant metastases (4%). There were 22 male and 22 female patients ranging in age from 7 to 75 years with a mean age of 51 years. Patients were analyzed for their prognostic factors, and the survival curves were drawn by the Kaplan-Meier method. Univariate and multivariate analyses were performed by the Cox regression model. There were 19 patients presenting with distant metastases in 810 patients presenting with papillary thyroid cancer (2.3%). The incidence was high in patients with follicular thyroid cancer (11%). It is interesting to note that the highest incidence of presentation with distant metastatic disease was in patients above the age of 45 and with follicular thyroid carcinoma. The long-term survival in this group is 43% compared with 86% in patients presenting without distant metastasis ( P < 0.001). There was no statistical difference in survival of patients below or above the age of 45. Even though the presence of distant metastasis at the time of initial presentation in other cancers is considered to be of grave prognosis, for patients with differentiated thyroid cancer, the long-term survival is still 43%. The incidence of distant metastasis is highest in patients with follicular thyroid cancer. Appropriate initial evaluation and treatment will lead to satisfactory long-term survival.

We describe a brief staff training program to improve the delivery of tobacco cessation services to patients with head and neck cancers. This study utilized a quasi-experimental design to compare the delivery of smoking cessation components and outcomes among patients exposed to either usual care (UC) or an enhanced cessation (EC) program implemented following a 1-h staff education program. Of the 179 subjects enrolled, 112 were recontacted by phone 1 month after their clinic visit. More patients in EC compared to UC reported that they were asked about their smoking status (94.2% vs. 76.6%, p  = 0.01), advised to quit (92.3% vs. 72.3%, p  = 0.01), prescribed cessation medications (30.8% vs. 3.3%, p  < 0.001), and received a support call (53.8% vs. 11.7%, p  < 0.001) at the 1-month follow-up. Quit attempts and quit rates between groups were similar. The EC intervention improved the delivery of cessation services in a busy clinical setting, but this failed to increase cessation rates after 1 month.

The well recognized prognostic factors in differentiated carcinoma of the thyroid are age, grade, extracapsular extension, distant metastasis, and size of the tumor. Based on these prognostic factors, we have divided patients into low-, intermediate-, and high-risk categories. Clearly, there are significant differences in these three groups. This article analyzes in depth our data on low-risk thyroid cancer patients. A retrospective review of 1,038 patients with differentiated carcinoma of the thyroid was undertaken. Various prognostic factors and risk groups were analyzed. Univariate and multivariate analyses were performed, and the survival curves were plotted by the Kaplan-Meier method. The inclusion criteria for the low-risk group were age younger than 45 years, tumors < 4 cm in size, low-grade histology, absence of distant metastasis, and absence of extrathyroidal extension. There were 465 patients in the low-risk group. Four hundred three patients had papillary and 62 patients had follicular thyroid cancer. There were 120 male and 354 female patients. Two hundred seventy-eight patients (60%) presented with clinically apparent lymph node metastasis. With a median follow-up of 20 years, the 10- and 20-year survival in this select group was 99%. The local, regional, and distant recurrence rates were 5, 9, and 2% in this series. The analysis of the data showed statistical difference in local recurrence rate between partial lobectomy and total lobectomy (27 vs. 4%; p = 0.005). There was no statistical difference in local recurrence rate between total lobectomy compared with total thyroidectomy (4 vs. 1%; p = 0.10). The overall failure rate between partial lobectomy and total thyroidectomy (27 vs. 8%) was statistically significant (p = 0.04). There was no statistical difference in the overall failure rate between total lobectomy and total thyroidectomy (13 vs. 8%; p = 0.06). There was no survival difference between various histologies or nodal status. Patients with low-risk tumors have excellent long-term survival. Nodulectomy or partial lobectomy should be avoided. The intraoperative decisions regarding the extent of thyroidectomy should be based on gross clinical findings and risk group analysis.

The objective of this study was to describe the clinicopathologic manifestations of disease and outcomes of treatment among individuals without a history of smoking tobacco or consuming alcohol who develop head and neck cancer. Of 1648 invasive head and neck cancer cases treated between 1970 and 2001 at Roswell Park Cancer Institute, 40 patients were identified as never having smoked tobacco or consumed alcohol during their lifetime. These cases were reviewed to gather data on multiple clinicopathologic variables. Mean age at presentation of nonsmoker/nondrinker head and neck cancer patients was 60 years (range, 27 to 90 years), and 78% (n = 31) of the patients were women. The distributions of tumor sites were 75.0% oral cavity (n = 30), 20.0% oropharynx (n = 8), and 5.0% larynx (n = 2). Sixteen patients (40%) experienced a recurrence of disease during the follow-up period, and 10 patients (25.0%) developed a second primary tumor a median of 6 years after their initial diagnosis. The nonsmoker/nondrinker head and neck cancer patient tends to be elderly and female, have oral cavity primary tumors, and be predisposed to second primary tumor development.

Human papillomavirus 16 (HPV-16) infection and tobacco use are associated with human oropharyngeal cancers. We conducted a study of the role of HPV and tobacco use in base of the tongue (BOT) cancers. DNA from 34 such cancers was subjected to HPV-16 and HPV-18-specific polymerase chain reaction analysis. Demographic and clinicopathologic data were obtained from each patient's medical record. HPV-16 was detected in 68% of tumors. Tobacco use was the only factor found to be significantly associated with HPV status. Tumors from 100% of patients who had never use d tobacco tested positive for HPV, compared with only 56% of those who had ever used tobacco (Fisher exact test, p = 0.024). All tumors were associated with either tobacco use or HPV infection. These findings are consistent with the hypothesis that either tobacco use or HPV infection is necessary to the etiology of BOT tumors, and they suggest that tongue base carcinoma may be prevented by combining HPV vaccination with tobacco avoidance.