Juvady Leopairut’s research while affiliated with Ramathibodi Hospital and other places

Objective To evaluate the clinicopathologic findings and treatment outcome in laryngectomized patients with laryngeal cancer and hypopharyngeal cancer. Materials and Methods The authors retrospectively reviewed the medical records of 212 patients who had been newly diagnosed and treated with laryngectomy between January 2000 and December 2010. The age, gender, clinical manifestations, associated predisposing condition, tumor WHO grade, AJCC tumor stage, maximum tumor size, anatomical involvement, type of surgery, postoperative sequelae, treatment and therapeutic outcome were analyzed. Results The present study included laryngeal cancer (n = 155) and hypopharyngeal cancer (n = 57). The patients’ age ranged from 38 to 84 years, with the mean age of 62.08±9.67 years. The common clinical presentations were hoarseness (73.6%), cervical lymphadenopathy (35.8%), sorethroat (22.2%), and odynophagia (14.6%). The laryngeal cancer commonly involves true vocal cord (86.5%), anterior commissure (65.8%), false vocal cord (56.8%), laryngeal ventricle (53.5%), subglottis (47.1%), and paraglotic space (35.5%), respectively. Fifty-three percent of cases had stage IV cancer. The most common postoperative surgical sequela was hypothyroidism (77.8%). The overall 5-year survivals for laryngeal cancer and hypopharyngeal cancer were 55% and 9%, respectively. The 5-year survival for node-negative cases was 61.8% versus 17% for node-positive cases (p< 0.001). AJCC stage of laryngeal cancer and hypopharyngeal cancer was a significant predictor of 5-year survival (p< 0.001 and p = 0.004, respectively). Conclusions The advanced AJCC stage, advanced T stage, advanced N stage, extracapsular tumor spread, and tumor invasion of false vocal cord, epiglottis, preepiglottic space, paraglottic space, thyroid cartilage, cricothyroid membrane were found to significantly augment the decrease of 5-year survival in laryngeal cancer. Only advanced AJCC stage was significantly associated with 5-year survival rate in hypopharyngeal cancer.

Background: Early phase clinical studies showed promising activities of anti-PD1/PD-L1 antibody in squamous cell carcinoma of head and neck (SCCHN). PD-L1 expression is a potential biomarker of these drugs. Tumor Infiltrating Lymphocyte (TIL) was a prognostic marker of HPV+ SCCHN and potentially associated with response of immunomodulatory drugs. Most clinical trials of anti-PD1/PD-L1 often excluded nasopharyngeal carcinoma (NPC). We evaluated characteristics of PD-L1 expression and CD8+ TIL for a future development of anti-PD1/PD-L1 antibody in NPC. Methods: NPC patients were identified through the Ramathibodi Cancer Registry database between 1/2007 and 12/2012. PD-L1 and PD-1 expressions were characterized by immunohistochemistry (IHC) from formalin-fixed paraffin-embedded tumor samples. PD-L1 expression was defined by using a cut-off of ≥1% (≥1-9%=1+, 10-49%=2+, ≥50%=3+). Mean number of CD8+TILs following the analysis of 2-4 images was assessed quantitatively by 2 individual pathologists blinded to outcomes. Tumor EBV status was analyzed by using EBV encoded RNA (EBER) in situ hybridization. Results: 119 NPC samples were analyzed. Overall, PD-L1 expression was positive in 72% (13% IHC 3+). PD1+ was observed in 11% of patients. Most patients had EBER+ tumors (96%). Characteristics were summarized in the table. PD-L1+ was highly observed in male (p=0.02). Mean CD8+ TIL count was significantly deceased with stage at diagnosis (p=0.02). There was no significant correlation between PD-L1 and CD8+ TILs observed. Conclusions: More than 70% of EBV+ NPC expressed PD-L1. These results support future development of anti-PD1/PD-L1 antibody in NPC. Characteristics PD-L1 (%) P-value Mean CD8+ TIL count (±SD) P-value - + Median Age (range) <65 years ≥65 years 48 (24-69) 28(93) 2(7) 53.5 (17-81) 68(85) 12(15) 0.86 0.34 52 (17-81) 60±35 57±30 n/a 0.74 Male Female 15(50) 15(50) 59(74) 21(26) 0.02 62±34 55±34 0.35 Smoking Never Yes 15(63) 9(37) 29(52) 27(48) 0.38 54±30 59±34 0.45 EBV+ EBV- 32(97) 1(3) 82(95) 4(5) 1.00 59±34 47±19 0.44 PD1+ PD1- 3(9) 30(91) 10(12) 76(88) 1.00 71±47 57±31 0.14 Stage 1-2 3-4 5(18) 22(82) 12(15) 67(85) 0.68 77±40 56±31 0.02 Median OS (months) 44.2 54.0 0.76 n/a

The authors report four autopsy cases of previously healthy children with dengue shock syndrome complicated with infection-associated hemophagocytosis and invasive aspergillosis. Hemophagocytosis is confirmed by histopathology of autopsied reticuloendothelial organs. All four children were identified to have invasive aspergillosis by histopathology and three cases were positive on fungal culture for Aspergillus spp. Regarding the cause of death among the four children without pre-existing underlying disease, three cases were directly ascribable to invasive aspergillosis and the remaining case was ascribed to dengue shock syndrome. The transmigration of preexisting fungi from the respiratory mucosa damaged by the dengue shock process is postulated as the pathogenesis of invasive aspergillosis. The main predisposing factor was found to be prolonged dengue shock syndrome. We reviewed the clinicopathologic features and therapeutic management of infection-associated hemophagocytic syndrome in patients with dengue shock syndrome and invasive aspergillosis.

The diagnostic of malignancy in biopsy specimens is very important because it guides to selected treatment option and prognostic prediction. However biopsy specimens usually have small pieces leading to variations of the interpretation by anatomical pathologists. To detect and correct the errors or the significant discrepancies in the diagnosis of biopsy specimens before sign-out and to determine the frequency of anatomic pathology significant discrepancies. The application of the mutually agreed work instructions (record) for the detection of errors or the significant discrepancies and their process of sign-out. The record of biopsy specimen that received a secondary check (1959 cases, 2005-2007) was analyzed. After a secondary check, 53 cases of non-malignancy for any reason by a second pathologist were included. However when using our definition on significant discrepancies, only 37 cases were considered. Another seven cases with the opinions with malignancy that were of different cell types that do harm to the patients were added. Therefore, 44 cases (2.25%) had truly significant discrepancies. The truly significant discrepancy frequency was 2.25% during the process of pre-sign-out secondary check of malignancy of biopsy specimens. The project has been applied as a routine daily work. It can be an innovative safety program for patient in Thailand.

Rhinofacial entomophthoramycosis is an uncommon chronic mycotic disease caused by exposure to the organism Conidiobolus coronatus. The authors report a case series of 5 patients with rhinofacial entomophthoramycosis and review the literature. All patients had typical involvement of the rhinofacial area with formation of subcutaneous lesions causing a chronic granulomatous inflammatory response with tissue eosinophilia and Splendore-Hoeppli reaction. Diagnoses were made based on histopathologic examination in all cases and fungi were isolated and identified in one case. The clinicopathologic features and therapeutic management of rhinofacial entomophthoramycosis are described.

The objective of this study was to determine the clinicopathologic findings of invasive and non-invasive fungal rhinosinusitis and to compare the features of the two diseases. The medical records of patients with invasive and noninvasive fungal rhinosinusitis at Ramathibodi Hospital between July 1999 and June 2009 were analyzed. The criterion for the diagnosis of fungal rhinosinusitis was the evidence of fungal elements from histopathologic section on sinonasal specimens. The age, gender, clinical manifestations, duration of symptoms, associated diseases, laboratory data, results of mycotic culture and treatment outcomes were analyzed. The relationship between fungal rhinosinusitis and patient characteristics as well as clinical presentations were assessed. The fungus-attributable mortality rate was determined. The study included 43 cases of invasive fungal rhinosinusitis and 68 cases of non-invasive fungal rhinosinusitis. There were 44 male, and 67 female patients. The mean age at diagnosis was 54.6 years (range: 5 to 86 years). A total of 70 (63.1%) were attributed to aspergillosis, 8 (7.2%) to candidiasis, 6 (5.4%) to zygomycosis, 4 (3.6%) to phaeohyphomycosis, 1 (0.9%) to pseudallescheriasis, 1 (0.9%) to entomophthoromycosis and 21 (18.9%) to nonspecific fungi. Cultures from sinonasal tissues were positive for fungus in 37 of 87 cases (42.5%). The clinical presentations of fungal rhinosinusitis included nasal stuffiness (27.9%), nasal discharge (27.9%), facial pain (27.9%), fever (24.3%) and headache (19.8%). One-fifth of cases had an underlying hematologic malignancy. Invasive fungal rhinosinusitis was significantly associated with hematologic malignancy and neutropenia. Fungus-attributable mortality rate was 44.2% in invasive fungal rhinosinusitis. Early antifungal therapy and surgical drainage were associated with a survival advantage.

Metastasizing pleomorphic adenoma is an uncommon malignant tumor of the salivary gland demonstrating benign epithelial and modified myoepithelial elements intermingling with tissue of mucoid, myxoid, or chondroid appearance that inexplicably manifests local or distant metastasis. To determine the expression of hormonal receptor in the patients with metastasizing pleomorphic adenoma of the major salivary gland. Medical records, clinical and pathologic findings of three patients who were diagnosed as metastasizing pleomorphic adenoma were reviewed. The immunohistochemical stains for estrogen receptor, progesterone receptor, and Ki-67 were performed. Three cases of metastasizing pleomorphic adenoma, clinically presenting as painless, gradually enlarged cervical lymph nodes were reported. The pathologic examinations of the cervical lymph nodes are morphologically and immunohistologically identical to the sialoadenectomy specimen. Immunohistochemical stains show positive reactivity to progesterone receptor but negative reactivity to estrogen receptor in both mesenchymal and epithelial components of pleomorphic adenoma. These are the first reported cases of metastasizing pleomorphic adenoma of the major salivary glands associated with expression of progesterone receptor in both specimens of sialoadenectomy and lymph node biopsy. This finding supports the pathogenesis of benign metastasis of tumor. However, the role of hormonal receptor in the pathogenesis and treatment of salivary metastasizing pleomorphic adenoma should be further investigated.

To explore the effect of Ki-67 and vascular endothelial growth factor A (VEGF-A) expression on the risks of advanced T category (T3,4) and positive lymph node involvement (N+) in oral and pharyngeal squamous cell carcinoma (SCC) compared with laryngeal SCC. Immunohistochemical analysis of prospectively recruited patients. University-affiliated hospital. A total of 147 previously untreated patients with different stages of SCC in the oral cavity, pharynx, and larynx. Relative risks of T3,4 tumor and N+, a risk ratio comparing risks under high vs low marker expression. A significant association of Ki-67 and VEGF-A expression with tumor T category was observed for oral and pharyngeal SCC and for laryngeal SCC (P < or = .006). Regarding nodal status, Ki-67 expression was a significant risk factor for N+ in all tumors (P < or = .009), whereas VEGF-A expression was related to N+ in oral and pharyngeal SCC only (P < .03). Analytically, Ki-67 expression alone in oral and pharyngeal SCC was associated with a relative risk of N+ of 3.83 (95% confidence interval, 1.22-11.99; P = .009), and additional expression of VEGF-A raised the value to 6.12 (2.09-17.93; P < .001). Moreover, the combined expression of both markers was 3.25 times more effective in predicting N+ for T1,2 tumor compared with T3,4 tumor. Proliferative status was a common risk factor for N+ in all of the tumors in this series. Exploitation of VEGF-A in lymph node metastasis in addition to proliferation by oral and pharyngeal SCC but not by laryngeal SCC explains the clinical aggressiveness of oral and pharyngeal SCC, especially the early lymphatic invasion. In the management of cervical lymph nodes, combined expression of Ki-67 and VEGF-A may help identify patients at risk for occult metastases. This study suggests anti-VEGF-A therapy, an additional intervention to the classic antiproliferative regimen, for preventing lymphatic progression of oral and pharyngeal SCC.