Precision Adjuvant Therapy Based on Detailed Pathologic Risk Factors for Resected Oral Cavity Squamous Cell Carcinoma: Long-Term Outcome Comparison of CGMH and NCCN Guidelines.

PURPOSE: The evidence for adjuvant therapy of oral cavity squamous cell carcinoma (OCSCC) in National Comprehensive Cancer Network (NCCN) guidelines is derived from patients with head and neck cancer. Here, we examined whether adjuvant therapy should be guided by a detailed analysis of pathologic risk factors in patients with pure OCSCC. METHODS AND MATERIALS: Between 2004 and 2016, we retrospectively reviewed 1200 consecutive patients with OCSCC who underwent radical surgery and neck dissection in the Chang-Gung Memorial Hospital (CGMH). Patients were divided into 3 prognostic groups. High-risk patients were those with extranodal extension (ENE) and/or positive margins (ENE/margins+, n = 267). Intermediate-risk patients were further divided into 3 subgroups: (1) patients in whom adjuvant therapy was indicated according to the CGMH but not the NCCN guidelines (NCCN[-]/CGMH[+], n = 14); (2) patients in whom adjuvant therapy was indicated by the NCCN but not the CGMH guidelines (NCCN[+]/CGMH[-], n = 160); and (3) patients in whom adjuvant therapy was indicated according to both guidelines (NCCN[+]/CGMH[+], n = 411). Low-risk patients were those for whom adjuvant therapy was not suggested in light of either guideline (NCCN[-]/CGMH[-], n = 348). RESULTS: According to NCCN guidelines, postoperative adjuvant therapy was indicated in 69.8% of the participants. However, only 57.7% of patients were in need of adjuvant therapy by CGMH guidelines. The following 5-year outcomes were observed in the NCCN(-)/CGMH(-), NCCN(-)/CGMH(+), NCCN(+)/CGMH(-), NCCN(+)/CGMH(+), and ENE/margins+ subgroups: locoregional control, 88%/70%/83%/79%/68%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .576); distant metastases, 2%/7%/2%/9%/36%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P = .003); disease-specific survival, 97%/86%/94%/84%/56%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001); and overall survival, 92%/86%/87%/68%/42%, P < .001 (NCCN[+]/CGMH[-] vs NCCN[+]/CGMH[+], P < .001), respectively. CONCLUSIONS: Patients in the NCCN(+)/CGMH(-) subgroup, 28% (160/571[160 + 411]) of NCCN intermediate-risk patients, had more favorable 5-year disease-specific and overall survival (94% and 87%) than the NCCN(+)/CGMH(+) subgroup. The former are unlikely to derive clinical benefits from NCCN guidelines. The 70% adjuvant therapy rate required by NCCN guidelines after radical surgery might be too high, ultimately leaving room for improvement.

Ictus emeticus presenting as an unusual seizure type in chromosome 22q11.2 deletion syndrome.

We present a case study of a patient with chromosome 22q11.2 deletion syndrome presenting with ictus emeticus, together with a review of the relevant literature. The patient developed generalized tonic-clonic seizures at 3 months old, and seizures eventually remitted after calcium therapy. He then experienced vigorous vomiting that occurred during sleep, with glassy eyes and legs flexion. Video-EEG recordings exhibited a switch in background activity from organized reactivity during normal sleep to left lateralized temporal delta activity, which was bilaterally synchronized during an emetic attack. The ictal vomiting ceased following management with oxcarbazepine, high-dose phenobarbital, and a ketogenic diet. The unique seizure type and rare ictal EEG findings are the first reported in a child with chromosome 22q11.2 deletion syndrome. This case highlights that ictus emeticus without detectable epileptic discharge on EEG is one potential epileptic presentation in this genetic syndrome. [Published with video sequence on www.epilepticdisorders.com].

Clinical Outcomes of Taiwanese Patients with cT4 Oral Cavity Squamous Cell Carcinoma: Toward the Identification of the Optimal Initial Treatment Approach for cT4b Patients.

BACKGROUND: The National Comprehensive Cancer Network guidelines recommend that patients with oral cavity squamous cell carcinoma (OSCC) and cT4b disease should be either included in clinical trials or treated with a nonsurgical approach. However, surgery may be feasible in selected patients with adequate safety margins. Using the nationwide Taiwanese Cancer Registry Database, we examined the prognosis of cT4b OSCC patients in relation to their treatment approach. METHODS: Of the 18,910 patients with previously untreated first primary OSCC identified between 2004 and 2010, 492 (2.6 %) had cT4b tumors. Of them, 327 (66 %) received initial treatment with surgery, whereas 165 (34 %) were initially treated with a nonsurgical approach. Of the latter group, 78 patients subsequently underwent surgery. A 5-year disease-specific survival (DSS) ≥45 % was considered as a favorable outcome. RESULTS: Better 5-year DSS and overall survival (OS) rates were observed in cT4b patients initially treated with surgery (vs. nonsurgery; DSS, 51 vs. 38 %; OS, 43 vs. 27 %, respectively, p < 0.001). Of the participants initially treated with surgery, patients with cN0-2 disease had better 5-year survival rates (DSS: cN0, 59 %; cN1, 53 %; cN2, 46 %; OS: cN0, 49 %; cN1, 50 %; cN2, 37 %) than those with cN3 disease (DSS: 0 %; OS: 0 %). Among cT4b patients who initially received a nonsurgical treatment, subjects who subsequently underwent surgery showed better outcomes. CONCLUSIONS: Primary surgery is performed in approximately two-thirds of cT4b OSCC patients, with cN0-2 cases showing a good prognosis. Patients who initially received a nonsurgical approach can subsequently be treated with surgery and achieve favorable outcomes.

Clinical considerations and surgical approaches for low-grade gliomas in deep hemispheric locations: thalamic lesions.

BACKGROUND: Tumors with epicenter in the thalamus occur in about 4 % of pediatric brain tumors. The histological diagnosis is mainly gliomas. Among them, low-grade glioma (LGG) constituted of a significant entity of the tumors (Cuccia et al., Childs Nerv Syst 13:514-521, 1997; Puget et al., J Neurosurg 106:354-362, 2007; Bernstein et al., J Neurosurg 61:649-656, 1984; Bilginer et al., Childs Nerv Syst 30:1493-1498, 2014). Since Kelly's report in 1989, >90 % resection of thalamic tumors were achieved in reported series (Ozek and Ture, Childs Nerv Syst 18:450-6, 2002; Villarejo et al., Childs Nerv Syst 10:111-114, 1994; Moshel et al., Neurosurgery 61:66-75, 2007; Albright, J Neurosurg 100(5 Suppl Pediatrics): 468-472, 2004; Kelly, Neurosurgery 25:185-195, 1989; Drake et al., Neurosurgery 29: 27-33, 1991). MATERIALS AND METHODS: Sixty-nine cases of thalamic tumors in children were retrospectively reviewed. There were 25 cases of LGGs. We analyzed our experience and correlated it with reported series. RESULTS: Summing up of 4 reported series and the present series, there were 267 cases of thalamic tumors in children. Among these tumors, 107 (40.1 %) were LGGs and 91 (34.1 %) were low-grade astrocytomas (LGAs). In the present series, all of the 25 LGGs were LGAs that consisted of 11 pilocytic astrocytomas (PAs) and 14 diffuse astrocytomas (DAs). Six cases received biopsy sampling only. The remaining 19 cases received different degrees of surgical resection via several approaches. Radical (>90 %) resection was achieved better in PAs comparing with DAs. There was no operative mortality. Two patients had increased neurological deficits. In a mean follow-up period of 11.9 years, three patients died of tumor progression and one patient died of anaplastic change. The 5- and 10-year overall survival (OS) was 87.1 and 87.1 %, respectively. CONCLUSION: Thalamic LGGs are mainly LGAs and are indolent. The rate of >90 % resection was relatively low in the present series. By applying contemporary diagnostic MRI studies, surgical facilities, and appropriate approaches in selective cases, we may try maximum neuroprotective radical (>90 %) resection.

Influence of Chinese medicine on weight loss and quality of life during radiotherapy in head and neck cancer.

INTRODUCTION: The purpose of this study was to determine the influence of Chinese medicine in a Chinese medicine ward (CMW) on weight loss and quality of life in patients with head and neck (HN) cancers during radiotherapy (RT). METHODS: From 2006 to 2010, patients with HN cancers hospitalized in the CMW for ≥10 days during RT were included. Outpatients with HN cancers from the Department of Radio-oncology were also enrolled. Body weight was evaluated near the beginning and the end of RT. Quality of life was assessed near the end of RT. RESULTS: Sixty-nine inpatients and 74 outpatients with radiation doses ≥60 Gy were included. Inpatients had significantly lesser weight loss than outpatients (P = .016) during RT or chemoradiation. Patients hospitalized for ≥40 days had lesser weight reduction than those hospitalized for a shorter period (P = .025). In the quality-of-life assessment, inpatients had significantly lower score for the item "lack of appetite" on the M.D. Anderson Symptom Inventory than outpatients (P = .002). CONCLUSIONS: Patients with HN cancers receiving hospitalization and Chinese medicine in the CMW had lesser weight loss than outpatients. By monitoring the patient's condition to adjust the prescription of Chinese medicine, this treatment minimized the weight loss resulting from RT or chemoradiation potentially because of a better functioning of appetite. Patients receiving integrated medicine early showed better results than those starting this treatment later.

Candidate serological biomarkers for cancer identified from the secretomes of 23 cancer cell lines and the human protein atlas.

Although cancer cell secretome profiling is a promising strategy used to identify potential body fluid-accessible cancer biomarkers, questions remain regarding the depth to which the cancer cell secretome can be mined and the efficiency with which researchers can select useful candidates from the growing list of identified proteins. Therefore, we analyzed the secretomes of 23 human cancer cell lines derived from 11 cancer types using one-dimensional SDS-PAGE and nano-LC-MS/MS performed on an LTQ-Orbitrap mass spectrometer to generate a more comprehensive cancer cell secretome. A total of 31,180 proteins was detected, accounting for 4,584 non-redundant proteins, with an average of 1,300 proteins identified per cell line. Using protein secretion-predictive algorithms, 55.8% of the proteins appeared to be released or shed from cells. The identified proteins were selected as potential marker candidates according to three strategies: (i) proteins apparently secreted by one cancer type but not by others (cancer type-specific marker candidates), (ii) proteins released by most cancer cell lines (pan-cancer marker candidates), and (iii) proteins putatively linked to cancer-relevant pathways. We then examined protein expression profiles in the Human Protein Atlas to identify biomarker candidates that were simultaneously detected in the secretomes and highly expressed in cancer tissues. This analysis yielded 6-137 marker candidates selective for each tumor type and 94 potential pan-cancer markers. Among these, we selectively validated monocyte differentiation antigen CD14 (for liver cancer), stromal cell-derived factor 1 (for lung cancer), and cathepsin L1 and interferon-induced 17-kDa protein (for nasopharyngeal carcinoma) as potential serological cancer markers. In summary, the proteins identified from the secretomes of 23 cancer cell lines and the Human Protein Atlas represent a focused reservoir of potential cancer biomarkers.

Osteoradionecrosis of external auditory canal in nasopharyngeal carcinoma.

BACKGROUND: Osteoradionecrosis (ORN) is one of the most serious complications of radiotherapy of nasopharyngeal carcinoma (NPC). ORN rarely occurs in the external auditory canal. METHODS: This is a retrospective review of 11 NPC patients who had ORN in the external auditory canal. Exposed necrotic bone over the external auditory canal was the diagnostic hallmark. Three patients wore hearing aids and 2 had had previous otological surgery. ORN was detected between 2 and 15 years after radiation therapy (mean 8 years). The radiation dose ranged from 6480 to 8460 rads in 8 patients. RESULTS: The symptoms of external auditory canal ORN were crust (100%), otorrhea (91%), otalgia (91%), hearing impairment (73%), foul odor (45%) and retroauricular discharging fistula (9%), all of which mimicked those of chronic otitis media. After treatment, the diagnoses of 2 patients were rectified to external auditory canal malignancy and external auditory canal cholesteatoma, and the other 9 (82%) patients' diagnoses remained as ORN. After combined treatment with local cleansing, hyperbaric oxygen therapy, sequestrectomy and ear drops, resolution of symptoms was achieved in all the patients. Three patients who underwent sequestrectomy were free of disease. CONCLUSIONS: External auditory canal ORN is rare in NPC patients. The clinical presentation mimics that of chronic otitis media and differentiation is difficult. The disease is prone to occur in patients who wear hearing aids or have had previous surgery. A high index of suspicion is mandatory for early diagnosis. The disease may lead to disastrous complications and should never be neglected by clinicians.

Corpus callosotomy in children.

INTRODUCTION: For children of medical resistant epilepsy without resectable epileptogenic zone, corpus callosotomy and vagus nerve stimulation (VNS) therapy are the two commonly used palliative epilepsy surgeries that can be considered. Although their routes and mechanisms to control epilepsy are different, both surgeries have shown their efficacy in selected candidates. The most common candidates for palliative surgery are in infants and children with organic encephalopathic types of epilepsy including infantile spasms/West syndrome, Lennox-Gastaut syndrome (LGS), severe epilepsy with multiple independent spike foci (SE-MISF) and selected symptomatic partial epilepsy to relief seizures and to stabilize co morbidities (Hirsch and Arzimanoglou, Revue Neurologique [Hirsch E and Arzimanoglou A, Rev Neurol (Paris). 160 Spec No 1:5S210-S219, (2004); Ohtahara S and Yamatogi Y, J Clin Neurophysiol 20(6):398-407, (2003); Wheless JW and Epilepsia 45(Suppl 5):17-22, (2004); Trevathan E, J Child Neurol 17 Suppl 2:2S9-2S22, (2002)]. DISCUSSION: Callosotomy is a major and destructive but affordable surgical procedure as compare to the relative simple but costly extracranial procedure of VNS therapy. However, callosotomy is a safe and effective palliative operation in neurosurgeons familiar with the surgical procedure. Equipments for callosotomy can be as simple as headlight and binocular loupes, self-retention brain retractor, bipolar cauterization, and simple microinstruments.