Inferred drought-induced plant allocation shifts and their impact on drought legacy at a tropical forest site.

While droughts predominantly induce immediate reductions in plant carbon uptake, they can also exert long-lasting effects on carbon fluxes through associated changes in leaf area, soil carbon, etc. Among other mechanisms, shifts in carbon allocation due to water stress can contribute to the legacy effects of drought on carbon fluxes. However, the magnitude and impact of these allocation shifts on carbon fluxes and pools remain poorly understood. Using data from a wet tropical flux tower site in French Guiana, we demonstrate that drought-induced carbon allocation shifts can be reliably inferred by assimilating Net Biosphere Exchange (NBE) and other observations within the CARbon DAta MOdel fraMework. This model-data fusion system allows inference of optimized carbon and water cycle parameters and states from multiple observational data streams. We then examined how these inferred shifts affected the duration and magnitude of drought's impact on NBE during and after the extreme event. Compared to a static allocation scheme analogous to those typically implemented in land surface models, dynamic allocation reduced average carbon uptake during drought recovery by a factor of 2.8. Additionally, the dynamic model extended the average recovery time by 5 months. The inferred allocation shifts influenced the post-drought period by altering foliage and fine root pools, which in turn modulated gross primary productivity and heterotrophic respiration for up to a decade. These changes can create a bust-boom cycle where carbon uptake is enhanced some years after a drought, compared to what would have occurred under drought-free conditions. Overall, allocation shifts accounted for 65% [45%-75%] of drought legacy effects in modeled NBE. In summary, drought-induced carbon allocation shifts can play a substantial role in the enduring influence of drought on cumulative land-atmosphere CO2 exchanges and should be accounted for in ecosystem models.

Zonally contrasting shifts of the tropical rainbelt in response to climate change.

Future changes in the position of the intertropical convergence zone (ITCZ; a narrow band of heavy precipitation in the tropics) with climate change could affect the livelihood and food security of billions of people. Although models predict a future narrowing of the ITCZ, uncertainties remain large regarding its future position, with most past work focusing on zonal-mean shifts. Here we use projections from 27 state-of-the-art (CMIP6) climate models and document a robust zonally-varying ITCZ response to the SSP3-7.0 scenario by 2100, with a northward shift over eastern Africa and the Indian Ocean, and a southward shift in the eastern Pacific and Atlantic Oceans. The zonally-varying response is consistent with changes in the divergent atmospheric energy transport, and sector-mean shifts of the energy flux equator. Our analysis provides insight about mechanisms influencing the future position of the tropical rainbelt, and may allow for more robust projections of climate change impacts.

Association of Preoperative Calcium and Calcitriol Therapy With Postoperative Hypocalcemia After Total Thyroidectomy.

Importance: Hypocalcemia is the most common complication after total thyroidectomy and can result in prolonged hospital admissions and increased hospital charges. Objective: To determine the effectiveness of preoperative calcium and calcitriol supplementation in reducing hypocalcemia following total thyroidectomy. Design, Setting, and Participants: A retrospective cohort study was conducted at a tertiary care center in 65 patients undergoing total thyroidectomy by a single surgeon. Patients were divided into 2 groups: those receiving preoperative as well as postoperative supplementation with calcium carbonate, 1000 to 1500 mg, 3 times daily and calcitriol, 0.25 to 0.5 µg, twice daily, and those receiving only postoperative supplementation with those agents at the same dosages. Data on patients who underwent surgery between January 1, 2008, and December 31, 2011, were acquired, and data analyses were conducted from March through June 2012, and from October through December 2016. Interventions: Calcium and calcitriol therapy. Main Outcomes and Measures: Postoperative serum calcium levels and development of postoperative hypocalcemia. Results: Of the 65 patients who underwent total thyroidectomy 27 (42%) were men; mean (SD) age was 49.7 (16.7) years. Thirty-three patients received preoperative calcium and calcitriol supplementation, and 32 patients received only postoperative therapy. In the preoperative supplementation group, 15 of 33 (45%) patients underwent complete central compartment neck dissection and 11 of 33 (33%) had lateral neck dissection, compared with 16 of 32 (50%) and 12 of 32 (38%), respectively, patients without preoperative supplementation. The mean measured serum calcium level in those without preoperative supplementation vs those with supplementation are as follows: preoperative, 9.6 vs 9.4 mg/dL (absolute difference, 0.16; 95% CI, -0.12 to 0.49 mg/dL); 12 hours postoperative, 8.3 vs 8.6 mg/dL (absolute difference, -0.30; 95% CI, -0.63 to 0.02 mg/dL); and 24 hours postoperative, 8.4 vs 8.5 mg/dL (absolute difference, -0.13; 95% CI, -0.43 to 0.16 mg/dL). In patients not receiving preoperative supplementation, 5 of 32 (16%) individuals became symptomatically hypocalcemic vs 2 of 33 (6%) in the preoperative supplementation group; an absolute difference of 10% (95% CI, -6.6% to 26.3%). Compared with the group not receiving preoperative supplementation, the mean [SD] length of stay was significantly shorter in the preoperative supplementation group (3.8 [1.8] vs 2.9 [1.4] days; absolute difference, -0.9; 95% CI, -1.70 to -0.105 days). Preoperative supplementation resulted in an estimated $2819 savings in charges per patient undergoing total thyroidectomy. Conclusions and Relevance: Preoperative calcium and calcitriol supplementation, in addition to routine postoperative supplementation, was associated with a reduced incidence of symptomatic hypocalcemia, length of hospital stay, and overall charges following total thyroidectomy.

Rigid Esophagoscopy for Head and Neck Cancer Staging and the Incidence of Synchronous Esophageal Malignant Neoplasms.

IMPORTANCE: Rigid esophagoscopy (RE) was once an essential part of the evaluation of patients with head and neck squamous cell carcinoma (HNSCC) due to the high likelihood of identifying a synchronous malignant neoplasm in the esophagus. Given recent advances in imaging and endoscopic techniques and changes in the incidence of esophageal cancer, the current role for RE in HNSCC staging is unclear. OBJECTIVE: To analyze the current role of RE in evaluating patients with HNSCC, and to determine the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective study performed at an academic tertiary care center, 582 patients were studied who had undergone RE for HNSCC staging from July 1, 2004, through October 31, 2012. To assess the incidence of synchronous esophageal malignant neoplasms, a literature review was performed, and the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) data set was queried. MAIN OUTCOMES AND MEASURES: The primary outcome measure was the incidence of synchronous esophageal malignant neoplasms, as measured by retrospective review at our institution, SEER data set analysis, and literature review. Secondary outcome measures were RE complications and nonmalignant findings during RE. RESULTS: A total of 601 staging REs were performed in 582 patients. The mean age was 60.2 years and 454 (78.0%) were men. There were 9 complications (1.5%), including 1 esophageal perforation (0.2%). Rigid esophagoscopy was aborted in 50 cases. Of the 551 completed REs, no abnormal findings were noted in 523 patients (94.9%), and nonmalignant pathologic findings were identified in 28 patients (5.1%). No synchronous primary esophageal carcinomas were detected. The incidence of synchronous esophageal malignant neoplasms found on screening endoscopy based on literature review and on SEER data set analysis was very low and has decreased from 1980 to 2010 in North America. The incidence reported in South America and Asia was relatively high. CONCLUSIONS AND RELEVANCE: Rigid esophagoscopy is safe, but the utility is low for cancer staging and for detection of nonmalignant esophageal disease. Review of the literature and analysis of a large national cancer data set indicate that the incidence of synchronous esophageal malignant neoplasms in patients with HNSCC is low and has been decreasing during the past 3 decades. Thus, screening esophagoscopy should be limited to patients with HNSCC who are at high risk for synchronous esophageal malignant neoplasms.

Histopathologic margin distance in survival in resection of cutaneous melanoma of the head and neck.

OBJECTIVES/HYPOTHESIS: Treatment of cutaneous melanoma involves surgical excision with wide clinical margins. No guidelines regarding safe histopathologic margin distance exist. This study examines the impact of histopathologic margin, measured from closest cut edge of the specimen, on overall survival in resection of cutaneous melanoma of the head and neck. We hypothesize that close histopathologic margins (<2 mm) are associated with decreased survival. STUDY DESIGN: Retrospective chart review. METHODS: A total of 637 patients were treated for cutaneous melanoma of the head and neck between 2001 and 2011. Demographics, tumor characteristics, histopathologic margin distance (from a pathology database), and survival data from state health registries and health system clinical data repositories were used to create a dataset. Cox regression models and Kaplan-Meier curves were used to analyze data, adjusting for age, tumor location, ulceration, and depth of invasion (DOI). RESULTS: When analyzing for overall survival, Cox multivariate regression analysis showed age (hazard ratio [HR] = 1.0-1.1), DOI (HR = 1.2-1.5), ulceration (HR = 1.3-3.8), and subsite (ear, HR = 1.0-3.9) were significant predictors of survival. Histopathologic margin distance was not significant for predicting survival. Three percent of histopathologic margins were <1 mm. CONCLUSIONS: In a large dataset of head and neck cutaneous melanoma, known factors associated with overall survival (age, DOI, ulceration, subsite) proved significant, validating the dataset. Examining the effect of histopathologic margin distance on survival, while controlling for these factors, we failed to reject the null hypothesis. Margin distance as measured by histopathology does not affect survival. LEVEL OF EVIDENCE: 4.

Accuracy of MRI for the diagnosis of metastatic cervical lymphadenopathy in patients with thyroid cancer.

PURPOSE: The aim of this study was to systematically compare a comprehensive array of magnetic resonance (MR) imaging features in terms of their sensitivity and specificity to diagnose cervical lymph node metastases in patients with thyroid cancer. MATERIALS AND METHODS: The study included 41 patients with thyroid malignancy who underwent surgical excision of cervical lymph nodes and had preoperative MR imaging ≤4weeks prior to surgery. Three head and neck neuroradiologists independently evaluated all the MR images. Using the pathology results as reference, the sensitivity, specificity and interobserver agreement of each MR imaging characteristic were calculated. RESULTS: On multivariate analysis, no single imaging feature was significantly correlated with metastasis. In general, imaging features demonstrated high specificity, but poor sensitivity and moderate interobserver agreement at best. CONCLUSIONS: Commonly used MR imaging features have limited sensitivity at correctly identifying cervical lymph node metastases in patients with thyroid cancer. A negative neck MR scan should not dissuade a surgeon from performing a neck dissection in patients with thyroid carcinomas.

Prognostic significance of p16 and its relationship with human papillomavirus in pharyngeal squamous cell carcinomas.

IMPORTANCE: The prognostic significance of p16 in squamous cell carcinoma (SCC) of the hypopharynx (HP) and nasopharynx (NP) and relationship between human papillomavirus (HPV) and p16 is unclear. OBJECTIVES: To evaluate the prognostic significance of p16 in pharyngeal subsites (oropharynx [OP], HP, and NP) and assess the relationship between HPV and p16 in the HP and NP. DESIGN, SETTING, AND PARTICIPANTS: Retrospective medical record review of 172 patients with SCC of the pharynx treated with definitive radiation therapy from 2002 to 2013 at a university tertiary referral center, with tissue available for immunohistochemical analysis. The median follow-up was 30.1 months. INTERVENTIONS: A total of 118 patients were treated with chemoradiation, and 54 patients were treated with radiation alone. Immunohistochemical analysis for p16 was performed for all tumors. Hypopharynx and NP tumors were tested for HPV using in situ hybridization, and NP tumors were tested for Epstein-Barr virus. MAIN OUTCOMES AND MEASURES: Overall survival, locoregional control, and disease-free survival were analyzed according to p16, HPV, and Epstein-Barr virus status. RESULTS: Thirty-two patients had HP SCC, 127 had OP SCC, and 13 had NP SCC. p16 Was positive in the HP (34%), OP (66%), and NP (46%). Prevalence of HPV was 14% in the HP and 50% in the NP. As a test for HPV, p16 had a positive predictive value of 38% (HP) and 67% (NP) and a negative predictive value of 100% in HP and NP tumors. p16 Status was a significant predictor of all clinical outcomes for patients with OP SCC (P<.001), but not for patients with HP or NP SCC. Patients with Epstein-Barr virus- or HPV-associated NP SCC had improved clinical outcomes. CONCLUSIONS AND RELEVANCE: p16 Was not associated with improved outcomes in patients with HP or NP SCC. The positive predictive value of p16 as a test for HPV is too low for p16 testing alone in the HP and NP. However, p16 negativity is sufficient to rule out HPV. As a research approach, we recommend p16 immunohistochemistry as a screening test for HPV in NP SCC and HP SCC followed by confirmatory HPV in situ hybridization when p16 positive.

Utility of abdominal imaging to assess for liver metastasis in patients with head and neck cancer and abnormal liver function tests.

PURPOSE: To determine the utility of abdominal imaging to further evaluate abnormal pre-operative liver function tests (LFTs) in patients with head and neck squamous cell carcinoma (HNSCC). METHODS: Records of patients evaluated by the head and neck surgery service from January 2004 through December 2009 were reviewed. For patients with abnormal alkaline phosphatase, alanine transaminase, or aspartate transaminase, subsequent abdominal imaging was assessed. RESULTS: Of the 862 patients with HNSCC who had documented LFTs, 109 (12.6%) had one or more abnormal values. In the same time period, LFTs were also obtained on 361 patients with benign head and neck tumors; of these, 40 (11.1%) had abnormalities. Of the 109 patients with HNSCC and abnormal LFTs, 78 (71.6%) underwent abdominal imaging (ultrasound, CT, MRI, or PET/CT). Overall, liver metastasis was demonstrated in only 1 of 109 patients with abnormal LFTs (0.92%) and in only 1 of 862 patients with HNSCC (0.12%). CONCLUSIONS: While HNSCC patients rarely present with liver metastasis, they often have abnormal LFTs. Although the presence of liver metastasis can dramatically change patient management, the yield of follow-up liver imaging for all patients with elevated LFTs is exceedingly low. Thus, the use of risk-stratified abdominal imaging may be prudent and cost effective in a select group of patients in whom distant metastasis is more likely. However, characteristics of this group are difficult to define given the rarity of liver metastasis in HNSCC.

Predicting positive margins in resection of cutaneous melanoma of the head and neck.

OBJECTIVES/HYPOTHESIS: Head and neck melanoma surgeons must achieve negative margins before performing margin compromising reconstructions such as a local flap closure. This often necessitates staged operations, including further margin resection. Peripheral sampling is often used before definitive resection to help guide the extent of the resection. If melanoma margin status could be predicted based on lesion characteristics, the surgeon could be more confident in performing definitive closure immediately after resection of some lesions or confident in the need to take larger margins in predictably extensive lesions. STUDY DESIGN: Retrospective review and logistic regression analysis. METHODS: Institutional review board approval was obtained. Out of 637 patients treated for head and neck melanoma by the Department of Otolaryngology-Head and Neck Surgery in the last 10 years, 409 patients had primary resection with available histopathologic margin status used as the outcome variable. Predictor variables of demographics, lesion size, pathologic subtype, location on face, and depth of invasion were collected. RESULTS: Histopathologic margin status could be predicted by age but not by the other predictor variables. CONCLUSIONS: In this large series of head and neck melanomas excised using National Comprehensive Cancer Network-recommended margins, histopathologic margin status could be predicted based on age but not on lesion characteristics. This finding is surprising given the published data showing that melanoma in situ has a higher rate of positive margin compared to subtypes of invasive melanoma. It reinforces the need for delaying reconstruction until margins are clear or performing reconstruction at a time of resection that does not compromise the ability to resect margins further (e.g., skin graft).

p16, Cyclin D1, and HIF-1α Predict Outcomes of Patients with Oropharyngeal Squamous Cell Carcinoma Treated with Definitive Intensity-Modulated Radiation Therapy.

We evaluated a panel of 8 immunohistochemical biomarkers as predictors of clinical response to definitive intensity-modulated radiotherapy in patients with oropharyngeal squamous cell carcinoma (OPSCC). 106 patients with OPSCC were treated to a total dose of 66-70 Gy and retrospectively analyzed for locoregional control (LRC), disease-free survival (DFS), and overall survival (OS). All tumors had p16 immunohistochemical staining, and 101 tumors also had epidermal growth factor receptor (EGFR) staining. 53% of the patients had sufficient archived pathologic specimens for incorporation into a tissue microarray for immunohistochemical analysis for cyclophilin B, cyclin D1, p21, hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase, and major vault protein. Median followup was 27.2 months. 66% of the tumors were p16 positive, and 34% were p16 negative. On univariate analysis, the following correlations were statistically significant: p16 positive staining with higher LRC (P = 0.005) and longer DFS (P < 0.001); cyclin D1 positive staining with lower LRC (P = 0.033) and shorter DFS (P = 0.002); HIF-1α positive staining with shorter DFS (P = 0.039). On multivariate analysis, p16 was the only significant independent predictor of DFS (P = 0.023). After immunohistochemical examination of a panel of 8 biomarkers, our study could only verify p16 as an independent prognostic factor in OPSCC.