18F-FDG PET/CT for detecting nodal metastases in patients with oral cancer staged N0 by clinical examination and CT/MRI.

(18)F-FDG PET has a high accuracy in staging head and neck cancer, but its role in patients with clinically and radiographically negative necks (N0) is less clear. In particular, the value of combined PET/CT has not been determined in this group of patients. METHODS: In a prospective study, 31 patients with oral cancer and no evidence of lymph node metastases by clinical examination or CT/MRI underwent (18)F-FDG PET/CT before elective neck dissection. PET/CT findings were recorded by neck side (left or right) and lymph node level. PET/CT findings were compared with histopathology of dissected nodes, which was the standard of reference. RESULTS: Elective neck dissections (26 unilateral, 5 bilateral; a total of 36 neck sides), involving 142 nodal levels, were performed. Only 13 of 765 dissected lymph nodes harbored metastases. Histopathology revealed nodal metastases in 9 of 36 neck sides and 9 of 142 nodal levels. PET was TP in 6 nodal levels (6 neck sides), false-negative in 3 levels (3 neck sides), true-negative in 127 levels (23 neck sides), and false-positive in 6 levels (4 neck sides). The 3 false-negative findings occurred in metastases smaller than 3 mm or because of inability to distinguish between primary tumor and adjacent metastasis. TP and false-positive nodes exhibited similar standardized uptakes (4.8 +/- 1.1 vs. 4.2 +/- 1.0; P = not significant). Sensitivity and specificity were 67% and 85% on the basis of neck sides and 67% and 95% on the basis of number of nodal levels, respectively. If a decision regarding the need for neck dissection had been based solely on PET/CT, 3 false-negative necks would have been undertreated, and 4 false-positive necks would have been overtreated. CONCLUSION: (18)F-FDG PET/CT can identify lymph node metastases in a segment of patients with oral cancer and N0 neck. A negative test can exclude metastatic deposits with high specificity. Despite reasonably high overall accuracy, however, the clinical application of PET/CT in the N0 neck may be limited by the combination of limited sensitivity for small metastatic deposits and a relatively high number of false-positive findings. The surgical management of the N0 neck should therefore not be based on PET/CT findings alone.     

Der chirurgische Part im Rahmen multimodaler Therapiekonzepte in der Onkologie-Schilddrüse

29. Tagung der ?sterreichischen Gesellschaft für Chirurgie und Ihrer Assoziierten Fachgesellschaften Innsbruck, 2. bis 4. Juni 1988 Herausgeber: E. Bodner und G. Szinicz Abstracts

Der chirurgische Part im Rahmen multimodaler Therapiekonzepte in der Onkologie-Schilddrüse     

Identification of novel prognosticators of outcome in squamous cell carcinoma of the head and neck.

PURPOSE: The goal of this study was to identify chromosomal aberrations associated with poor outcome in patients with head and neck squamous cell carcinoma (HNSCC). PATIENTS AND METHODS: We assessed the global genomic composition of 82 HNSCCs from previously untreated patients with comparative genomic hybridization (CGH). The CGH data were subcategorized into individual cytogenetic bands. Only genomic aberrations occurring in more than 5% of cases were analyzed, and redundancies were eliminated. Each aberration was submitted to univariate analysis to assess its relationship with disease-specific survival (DSS). We used Monte Carlo simulations (MCS) to adjust P values for the log-rank approximate chi(2) statistics for each abnormality and further applied the Hochberg-Benjamini procedure to adjust the P values for multiple testing of the large number of abnormalities. We then submitted abnormalities whose univariate tests resulted in an adjusted P value of less than.15 together with significant demographic/clinical variables to stepwise Cox proportional hazards regression. We again verified and adjusted P values for the chi(2) approximation of the final model by MCS. RESULTS: CGH analysis revealed a recurrent pattern of chromosomal aberrations typical for HNSCC. Univariate analysis revealed 38 abnormalities that were correlated with DSS. After controlling for multiple comparisons and confounding effects of stage, five chromosomal aberrations were significantly associated with outcome, including amplification at 11q13, gain of 12q24, and losses at 5q11, 6q14, and 21q11 (MCS adjusted P =.0009 to P =.01). CONCLUSION: HNSCC contains a complex pattern of chromosomal aberrations. A sequential approach to control for multiple comparisons and effect of confounding variables allows the identification of clinically relevant aberrations. The significance of each individual abnormality merits further consideration.     

Angiogenesis inhibition by an oncolytic herpes virus expressing interleukin 12.

PURPOSE: Oncolytic herpes simplex viruses (HSVs) may have significant antitumor effects resulting from the direct lysis of cancer cells. HSVs may also be used to express inserted transgenes to exploit additional therapeutic strategies. The ability of an interleukin (IL)-12-expressing HSV to treat squamous cell carcinoma (SCC) by inhibition of tumor angiogenesis is investigated in this study. EXPERIMENTAL DESIGN: A replication-competent, attenuated, oncolytic HSV carrying the murine IL-12 gene (NV1042), its non-cytokine-carrying analog (NV1023), or saline was used to treat established murine SCC flank tumors by intratumoral injection. The expression of secondary antiangiogenic mediators was measured. Angiogenesis inhibition was assessed by in vivo Matrigel plug assays, flank tumor subdermal vascularity, and in vitro endothelial cell tubule formation assay. RESULTS: Intratumoral injections of NV1042 (2 x 10(7) plaque-forming units) into murine SCC VII flank tumors resulted in smaller tumor volumes as compared with NV1023 or saline. IL-12 and IFN-gamma expression in tumors was 440 and 2.2 pg/mg, respectively, at 24 h after NV1042 injection, but both IL-12 and IFN-gamma were undetectable (<0.2 pg/mg) after NV1023 or saline injections. Expression of two antiangiogenesis mediators, monokine induced by IFN-gamma and IFN-inducible protein 10, was elevated after NV1042 treatment. Matrigel plug assays of NV1042-transfected SCC VII tumor cells demonstrated significantly decreased hemoglobin content and microvessel density as compared with NV1023 and PBS. Excised murine flank tumors treated with NV1042 had decreased subdermal vascularity as compared with NV1023 and PBS. Both splenocytes and IL-12 expression by NV1042 were required for in vitro inhibition of endothelial tubule formation. CONCLUSIONS: IL-12 expression by an oncolytic herpes virus enhances therapy of SCC through antiangiogenic mechanisms. Strategies combining HSV oncolysis with angiogenesis inhibition merit further investigation for potential clinical application.     

Microbial keratitis following vegetative matter injury

The purpose of the present study was to analyze the microbiological profile of cases of keratitis following trauma with vegetative matter in a tertiary care center. A retrospective review of the medical records of 49 patients with keratitis following vegetative matter injury over a 3-month period was performed. All patients underwent corneal scraping for smears and inoculation onto various culture media. The microbiological profile was based on the smear and culture reports. For patients who were culture-negative, outcome after standard empirical antibacterial therapy as per hospital protocol was analyzed. Thirteen patients with corneal ulcers had fungal etiology, eight had bacterial etiology, and two had protozoal etiology, while 13 patients were polymicrobial and 13 were culture-negative. Polymicrobial infections were mainly bacterial (eight cases), and the remaining five cases had coexistent fungal and bacterial etiology. The treatment was directed to the specific organism and patients improved with medical or surgical therapy. Only a third of culture-negative cases showed fungal etiology on biopsy or histopathology after keratoplasty while a third showed improvement with therapy. Corneal infections following vegetative matter trauma show a varied etiological profile; however, bacterial and polymicrobial infections are more prevalent. Empirical anti-fungal therapy, as commonly practiced, must be avoided in cases with vegetative matter injury.     

Outcome of patients with systemic light chain amyloidosis with concurrent renal and cardiac involvement

Cardiac involvement in systemic light chain amyloidosis (AL) is generally associated with a worse outcome, especially if other organs are also involved. We sought to determine whether concurrent cardiac and renal involvement were associated with a worse outcome than either organ alone. We identified 129 patients with AL, who received high‐dose chemotherapy followed by autologous hematopoietic stem cell transplantation (auto‐HCT) at our institution between 1997 and 2014. Ninety‐nine patients had either renal (group 1: n = 62, 62%), cardiac (group 2: n = 20, 20%), or both cardiac and renal (group 3: n = 17, 17%) involvement. The overall hematological response rate (CR+VGPR+PR) post‐auto‐HCT in groups 1, 2, and 3 was 69%, 74% and 82%, respectively (P = 0.62). Overall, organ response in groups 1, 2, and 3 was 39%, 42%, and 70%, respectively. The median PFS from auto‐HCT in groups 1, 2, and 3 was not reached (NR), 13.3 and 21 months, respectively (P = 0.02). The median OS in groups 1, 2, and 3 was 120, 46, and 60 months, respectively (P = 0.1). In conclusion, median PFS and OS in patients with concurrent cardiac and renal AL were comparable to patients with cardiac AL only, but worse than patients with renal AL.