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2,3-Pyridinedicarboxylate Is Associated with Shorter Recurrence-Free Survival in Patients with Hypopharyngeal Squamous Cell Carcinoma.
UNLABELLED: Introduction: Metabolites are associated with the biology of cancer; however, no metabolites related to prognosis have been identified in head and neck cancer. This study aimed to identify metabolites associated with prognosis in patients with hypopharyngeal squamous cell carcinoma (HPSCC). METHODS: Fifty-two patients who underwent surgery for HPSCC were included and randomly divided into test and validation cohorts of 26 patients each for further metabolome analysis using capillary electrophoresis/mass spectrometry on tumor and non-tumor tissues of the hypopharynx. Twenty-two patients who received adjuvant therapy after surgery were included. The receiver operating characteristic (ROC) and univariate and multivariate analyses were used to explore the relationship between recurrence-free survival (RFS), clinicopathological factors, and differentiated metabolites. RESULTS: ROC analysis revealed six metabolites significantly associated with RFS in both cohorts, and multivariate analysis indicated that 2,3-pyridinedicarboxylate was a significantly independent poorer prognostic factor in the cohorts including patients with HPSCC without any adjuvant therapies (p = 0.017). CONCLUSION: 2,3-Pyridinedicarboxylate, involved in NAD+ metabolism and genomic stability, suggests the possibility of developing molecular-targeted drugs for the production of metabolites related to prognosis. This study identifies novel prognostic metabolites and their associated metabolic pathways in HPSCC, highlighting potential therapeutic targets for treatment. .
Treatment of carcinoma of the hypopharynx.
In a review of 80 patients with hypopharyngeal squamous-cell carcinoma, 43 patients were found to have had lesions arising in the pyriform sinus, 34 had lesions arising on the postcollateral wall of the hypopharynx, and 3 had lesions in the postcricoid area. Therapeutic modalities included radical radiation therapy in 56 patients, radiation plus surgery in 13 patients, and planned combined therapy in 11 patients. The five-year determinate survival rate of all the patients was 20%. Patients with posterolateral wall tumors had a 23% rate of cure, but those with pyriform sinus tumors had only a 13% rate of cure. The five-year determinant survival rate was 12.5% for patients undergoing radical radiation therapy, 15.4% for those undergoing unplanned radiation and surgery (salvage therapy), and 55.6% for those with planned combined therapy. Over 40% of the patients had a recurrence of their disease; an additional 20% developed distant metastatic spread which usually occurred within the first year. The type of therapy did not alter the rate of recurrence but did affect the rate of distant metastatic spread, with planned combined therapy greatly improving control of the primary lesion. This study suggests that, even with advanced disease, the most effective therapy for hypopharyngeal carcinoma is planned combined radiation therapy and surgery.
Multi-omics insights into the molecular signature and prognosis of hypopharyngeal squamous cell carcinoma.
Approximately two-thirds of hypopharyngeal squamous cell carcinoma (HPSCC) cases are diagnosed at advanced stages, with the worst prognosis among head and neck squamous cell carcinomas (HNSCCs). Identifying biomarkers for high-risk patients requiring aggressive treatment is crucial. We present mutational, transcriptomic, and proteomic studies of 103 Chinese HPSCC patients and observe a higher prevalence and poorer prognosis in males. Estrogen response pathways are up-regulated, and proteins phosphorylated by protein kinase C (PKC) and cyclin-dependent kinases (CDKs) are aberrantly regulated in HPSCC. We identify aberrant copy number regions including SOX2(3q26.33), FGFR(8p11.23), CCND1(11q13.3), CDKN2A/2B(9p21.3), and MYC(8q24.21). Human papillomavirus (HPV) status combined with highly mutated genes, such as SYNE1 in HPV(-) and MUC4 in HPV(+) patients, were assessed as prognosis markers. A predictive model involving clinical factors and expression of six genes was established and cross-site validated. These findings open new opportunities for stratifying high-risk patients and molecular targets for personalized therapeutic strategies.
Case reports: Dumbbell-shaped thyroglossal cyst masquerading as hypopharyngeal-mass lesion.
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[Covering of hypopharyngeal defects using deltopectoral flaps following total laryngeal exstirpation and preoperative irradiation].
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Oesophageal papillomata in the child.
This is a case report of a 6-year-old female child with asymptomatic multiple squamous papillomatosis involving the hypopharynx and the entire length of the oesophagus. Total spontaneous regression of the papillomata occurred within 2 years of presentation. Associated asymptomatic laryngeal papillomata were removed by suction diathermy under general anaesthesia. The diagnosis was confirmed by direct microlaryngoscopy, oesophagoscopy, barium swallow and histology. The laryngeal hypopharyngeal and oesophageal lesions were identical histologically and macroscopically.
[Preoperative irradiation of larynx and hypopharynx carcinoma].
30 patients with carcinoma of the larynx or hypopharynx were irradiated preoperatively with a dosis of 1,500 to 4,500 rads. The results are compared with those of an identical group of patients who were only operated. The operation was mostly partial (20 cases). In laryngeal cancer the cure rate after two years was 69% and 47%, in hypopharyngeal cancer 43% and 28% respectively.
Surgical management of hypopharyngeal cancer. Particular reference to the gastric "pull-up" operation.
Between the years 1965 to 1977, 58 patients with advanced hypopharyngeal squamous carcinoma were treated by pharyngolaryngoesophagectomy and total thyroidectomy. Operative mortality for potentially curable cases was 8.6%, with a crude three-year survival rate of 29% for all cases. Mortality was 37% for patients with postcricoid tumors. Long-term management was uncomplicated except for calcium metabolism; two patients died from nephrocalcinosis secondary to return of circulating parathyroid hormone. I discuss the role of this operation in the successful treatment of hypopharyngeal cancer.
Reconstruction after pharyngolaryngo-oesophagectomy using delto-pectoral flap.
Fifty patients with hypopharyngeal cancer treated with total pharyngolaryngectomy and staged reconstruction using delto-pectoral flaps in the years from 1967-1976 were studied. The main complications were fistulae and stricture formation; these are described. The hospital mortality was low, and postoperative deaths only occurred in previously irradiated patients. The crude 5-year survival was 35%.
Complications of high dose preoperative irradiation for advanced laryngeal-hypopharyngeal cancer.
The authors studied 162 patients with advanced cancer of the laryngopharynx who were treated over the same period of time by standard techniques. High dose preoperative supervoltage irradiation to 5000 rads/5 weeks through large opposed lateral fields and a lower anterior neck field is not accompanied by a prohibitive increase in mortality or morbidity for patients with stage III-IV largynogopharyngeal cancer. Rescue surgery for recurrence after definitive irradiation can be accomplished.
[Reconstruction following surgical removal of extensive malignant tumors of the mouth and pharynx].
Large tumors in the oral and hypopharyngeal areas require wide surgical excision with closure either by simple direct means or with replacement of soft tissue and the use of local mucosal flaps, regional skin flaps or visceral transplantation. Five examples have been chosen to explain the proposed methods of treatment with special emphasis on the use of the Bakamjian flap. A detailed description of a combined procedure using part of the colon as an oesophageal replacement is given.
Rehabilitation problems after pharyngogastric anastomosis.
Fifty-three patients had pharyngolaryngoesophagectomy during the years 1965 to 1976 for lower hypopharyngeal or cervical esophageal cancer. The operative mortality--defined as the percent of patients who died within seven days of operation--was 7.5%, which is reduced to 5.6% if one patient with inoperable disease is excluded. Twenty-eight percent of patients survived for longer than one year, and there have been no problems with swallowing. Communication is possible in every patient who possesses good motivation, but the problems of long-term management of calcium metabolism still require attention.
High dose preoperative irradiation for advanced laryngeal-hypopharyngeal cancer.
Combined therapy, consisting of 5000 rads delivered in five weeks by total laryngectomy +/- radical neck dissection, was compared with treatment by irradiation (6000-7000 rads) with surgical salvage when clinically possible for radiation failure. Patients were categorized according to site of primary cancer (glottic, supraglottic and pyriform sinus) and staged (T, N, M). Survival was equally good in the two programs for glottic and supraglottic lesions, N0 or N1. The combined treatment program was judged superior for supraglottic and pyriform sinus lesions, N2 or N3.
Late recurrence of cancer in the larynx and hypopharynx after irradiation.
11 cases of recurrent laryngeal or hypopharyngeal carcinoma, occurring 5 or more years after radiotherapy for carcinoma, are reported. The possible pathological mechanisms involved include persistence of the original carcinoma, second primary due to the original factors, and radiation-induced carcinoma. The last-mentioned possibility is of vital importance and requires further investigation. If radiation-induced carcinoma is as common as some recent series suggest, then primary treatment of T1 laryngeal carcinoma must be re-thought. However, this author believes that convincing evidence is lacking that irradiation is a common cause of late recurrent carcinoma.
Laryngocele.
Laryngocele occurs more commonly than the literature indicates. Until recently, most were diagnosed clinically in the symptomatic patient. Although laryngocele is usually asymptomatic, greater numbers are being diagnosed because more patients suspected of head and neck cancer are undergoing sophisticated diagnostic radiographic procedures. Of 2,068 patients studied at M.D. Anderson Hospital and Tumor Institute for suspected laryngeal or hypopharyngeal cancer, 87 (4.2%) had laryngoceles. Three types of laryngocele are recognized: internal, external, and combined. They may be congenital or acquired and occur at any age. The coexistence of carcinoma and laryngocele has been discussed often enough in the literature to suggest a direct relationship; however, this series yielded no substantive evidence to implicate laryngocele as a precursor of carcinoma. The radiographic procedures currently used which readily establish the presence of laryngoceles are lateral soft tissue radiography of the neck, anteroposterior tomography of the larynx, and contrast laryngography.
Levamisole versus placebo as an adjunct to primary therapy of laryngopharyngeal epidermoid carcinoma. Evaluation of the immune status.
Twenty-four patients, with a biopsy-proven laryngeal or hypopharyngeal carcinoma, received as an adjunct to their primary treatment (surgery and/or radiotherapy), levamisole (150 mg daily during three consecutive days, every fortnight) or placebo, following a single-blind, but randomized method. At the end of the follow-up, an investigation of the immune status was done, and compared with that of a healthy control-group. It is concluded that the immunity is disturbed in patients with laryngo-pharyngeal cancer, but that this disturbance does not clearly correlate with the clinical state of the disease. Also, the immunological measures did not appear relevant to the significantly favourable effect of levamisole on the prognosis.
Recessive FANCM cancer syndrome with high cancer risks, chemotherapy toxicity, chromosome fragility, and gonadal failure.
PURPOSE: Heterozygous FANCM variants have been associated with breast cancer. Only a few studies have examined other cancer types. Biallelic truncating variants have been linked to a Fanconi anemia (FA)-like cancer prone syndrome in case reports; however, the range of cancers and the risk estimates are lacking. METHODS: We studied the association of Finnish-enriched variants c.5101C>T p.(Gln1701Ter) and c.5791C>T p.(Arg1931Ter) with risk of any cancer and FA-related conditions in the FinnGen data with 500,348 individuals. RESULTS: Heterozygous c.5101C>T (N = 10,940) was associated not only with an increased risk of breast cancer (odds ratio = 1.24, P = 2.7 × 10-6) but also with risks of other cancer types, including hypopharyngeal (odds ratio = 3.98, P = 3.6 × 10-7), suggesting a risk effect wider than previously described. Homozygous c.5101C>T (N = 76) was associated with a high risk of breast, head and neck, gastrointestinal, gynecological, hematologic, skin, and lung cancer, whereas c.5791C>T was rare. Additionally, high recessive risks of ovarian dysfunction and hematologic side effects after cancer treatment were detected, but no risks of bone marrow failure or physical features of FA. CONCLUSION: Based on the pattern of risks associated with biallelic variants, we suggest a novel FANCM cancer syndrome that is separate from FA and other characterized cancer susceptibility syndromes.