Samer G. Hakim

Radiochemotherapy including cisplatin alone versus cisplatin + 5-fluorouracil for locally advanced unresectable stage IV squamous cell carcinoma of the head and neck.

Background and Purpose:The optimal radiochemotherapy regimen for advanced head-and-neck cancer is still debated. This nonrandomized study compares two cisplatin-based radiochemotherapy regimens in 128 patients with locally advanced unresectable stage IV squamous cell carcinoma of the head and neck (SCCHN).Patients and Methods:Concurrent chemotherapy consisted of either two courses cisplatin (20 mg/m2/d1–5 + 29–33; n = 54) or two courses cisplatin (20 mg/m2/d1–5 + 29–33) + 5-fluorouracil (5-FU; 600 mg/m2/d1–5 + 29–33; n = 74).Results:At least one grade 3 toxicity occurred in 25 of 54 patients (46%) receiving cisplatin alone and in 52 of 74 patients (70%) receiving cisplatin + 5-FU. The latter regimen was particularly associated with increased rates of mucositis (p = 0.027) and acute skin toxicity (p = 0.001). Seven of 54 (13%) and 20 of 74 patients (27%) received only one chemotherapy course due to treatment-related acute toxicity. Late toxicity in terms of xerostomia, neck fibrosis, skin toxicity, and lymphedema was not significantly different.The 2-year locoregional control rates were 67% after cisplatin alone and 52% after cisplatin + 5-FU (p = 0.35). The metastases-free survival rates were 79% and 69%, respectively (p = 0.65), and the overall survival rates 70% and 51%, respectively (p = 0.10). On multivariate analysis, outcome was significantly associated with performance status, T-category, N-category, hemoglobin level prior to radiotherapy, and radiotherapy break > 1 week.Conclusion:Two courses of fractionated cisplatin (20 mg/m2/day) alone appear preferable, as this regimen resulted in similar outcome and late toxicity as two courses of cisplatin + 5-FU, but in significantly less acute toxicity.Hintergrund und Ziel:Das optimale Radiochemotherapieregime bei der Behandlung fortgeschrittener Kopf-Hals-Tumoren ist nicht hinreichend geklärt. Diese nichtrandomisierte Studie vergleicht zwei cisplatinbasierte Regimes in einer Serie von 128 Patienten (Tabelle 1) mit lokal fortgeschrittenem (Stadium IV) nichtresektablem Plattenepithelkarzinom der Kopf-Hals-Region (SCCHN).Patienten und Methodik:Die simultan zur Strahlentherapie applizierte Chemotherapie bestand aus zwei Kursen Cisplatin (20 mg/m2/d1–5 + 29–33; n = 54) oder zwei Kursen Cisplatin (20 mg/m2/d1–5 + 29–33) + 5-Fluorouracil (5-FU; 600 mg/m2/ d1–5 + 29–33; n = 74).Ergebnisse:Mindestens eine Grad-3-Toxizitat trat bei 25 von 54 Patienten (46%) unter alleiniger Cisplatingabe und bei 52 von 74 Patienten (70%) unter Cisplatin + 5-FU auf. Das letztgenannte Regime war insbesondere mit hoheren Raten an Mukositis (p = 0,027) und akuter Hauttoxizitat (p = 0,001) assoziiert (Abbildung 1). Sieben von 54 (13%) und 20 von 74 Patienten (27%) erhielten toxizitatsbedingt nur einen Kurs Chemotherapie. Die Spattoxizitat (Xerostomie, Halsfibrose, Hauttoxizitat, Lymphodem) war in beiden Gruppen vergleichbar (Abbildung 2).Die Raten fur die lokoregionale Kontrolle nach 2 Jahren betrugen 67% nach alleiniger Cisplatingabe sowie 52% nach Cisplatin + 5-FU (p = 0,35; Abbildung 3). Die Raten fur das metastasenfreie Uberleben lagen bei 79% und 69% (p = 0,65; Abbildung 4), die Raten für das Gesamtüberleben bei 70% und 51% (p = 0,10; Abbildung 5). In der Multivarianzanalyse waren die Therapieergebnisse signifikant mit dem Allgemeinzustand, der T-Kategorie, der N-Kategorie, dem Hamoglobinwert vor Strahlentherapie und einer Radiotherapiepause > 1 Woche assoziiert (Abbildung 3, Tabelle 2).Schlussfolgerung:Das aus alleiniger fraktionierter Cisplatingabe (20 mg/m2/d) bestehende Regime scheint besser geeignet zu sein als die Kombination Cisplatin + 5-FU. Das erstgenannte Regime führte zu vergleichbaren Therapieergebnissen, war allerdings mit signifikant geringerer Akuttoxizitat assoziiert als die Kombination Cisplatin + 5-FU.

TOXICITY OF TWO CISPLATIN-BASED RADIOCHEMOTHERAPY REGIMENS FOR THE TREATMENT OF PATIENTS WITH STAGE III/IV HEAD AND NECK CANCER

This nonrandomized study compared 2 radiochemotherapy regimens for toxicity in 128 patients with stage III/IV head and neck cancer.

High-molecular tenascin-C as an indicator of atypical cells in oral brush biopsies

Tumour-invasion like wound healing is characterised by the formation of an extracellular matrix with a high tenascin-C content. The tenascin-C molecule undergoes alternative splicing. Analysis using antibody BC2 indicates that especially the high-molecular tenascin-C (hm tn-C) variants are typically tumour-associated, while distribution in normal tissue is restrictive. This study investigated whether hm tn-C is a suitable indicator of atypical cells with invasive potential in oral brush biopsies. One hundred fifty nine consecutive oral brush biopsies with histopathological diagnoses were analysed for the identification of atypical cells. A standardised haematoxylin and eosin staining plus standardised immunocytochemistry using the monoclonal anti-hm tn-C antibody was performed. The bound hm tn-C antibodies were detected with the streptavidine/alkaline phosphatase technique in the autostainer. Conventional cytology produced four false-positives when identifying atypical cells in brush biopsies of inflammatory/benign hyperproliferative mucosa (specificity 96%), while 10 in 52 carcinomas and three of eight recurrences were not identified (sensitivity 78%). Ten of these 13 non-identified tumours could be marked when adding the hm tn-C assay (increasing specificity to 99%). Combining the two assays also reduced the false-positive outcomes from four to one (increasing sensitivity to 95%). The positive and negative predictive values were 92 and 88% for conventional cytology vs 98 and 97% for the dual assay. (1) A 95%-sensitivity proves hm tn-C assisted conventional cytology to be a suitable means of identifying atypical cells in oral brush biopsies. (2) The positive (98%) and negative (97%) predictive values obtained approximate hm tn-C assisted conventional cytology to laminin-5 (100/97%).

Altered expression of cell–cell adhesion molecules β-catenin/E-cadherin and related Wnt-signaling pathway in sporadic and syndromal keratocystic odontogenic tumors

Differential diagnosis of the keratocystic odontogenic tumor (KCOT) still represents a challenging problem especially if compared with the dentigerous cyst, which is similar in clinical and radiological course. Histological assessment of this entity may therefore draw crucial attention since various radical procedures are recommended for such lesions in contrast to dentigerous cysts. Since recent reports could prove the involvement of wingless(Wnt)-signaling pathway and β-catenin in the pathogenesis of many odontogenic and neoplastic lesions indicating impairment of cell–cell adhesion, we investigated the expression of two Wnt-signaling pathways, Wnt-1 and Wnt-10A as well as β-catenin and E-cadherin along with other related proteins in both lesions. We found a significant down-regulation in the expression of cell adhesion proteins β-catenin and E-cadherin along with alteration of Wnt-1 and Wnt-10A expression in the epithelium of KCOT. We assessed a specific focal distribution pattern of p63 in the suprabasal cell layer and a significant up-regulation of cyclin D1. Furthermore, laminin α-2 was a characteristic marker labelling only the basement membrane of dentigerous cysts. These results provide a new hypothesis explaining a molecular mechanism to understand initiating and development of KCOTs and an alternative therapeutic approach, especially for syndromal patients, where these multilocal lesions may involve and destroy wide orofacial bony structures.

Oral acantholytic squamous cell carcinoma shares clinical and histological features with angiosarcoma

Backgroundacantholytic squamous cell carcinomas (ASCC) and intraoral angiosarcoma share similar histopathological features. Aim of this study was to find marker for a clear distinction.MethodsFour oral acantholytic squamous cell carcinomas and one intraoral angiosarcoma are used to compare the eruptive intraoral growth-pattern, age-peak, unfavourable prognosis and slit-like intratumorous spaces in common histological staining as identical clinical and histopathological features. Immunohistochemical staining for pancytokeratin, cytokeratin, collagen type IV, γ2-chain of laminin-5, endothelial differentiation marker CD31 and CD34, F VIII-associated antigen, Ki 67-antigen, β-catenin, E-cadherin, α-smooth-muscle-actin and Fli-1 were done.ResultsCytokeratin-immunoreactive cells can be identified in both lesions. The large vascularization of ASCC complicates the interpretation of vascular differential markers being characteristic for angiosarcoma. Loss of cell-cell-adhesion, monitored by loss of E-cadherin and β-catenin membrane-staining, are indetified as reasons for massive expression of invasion-factor ln-5 in ASCC and considered responsible for unfavourable prognosis of ASCC. Expression of Fli-1 in angiosarcoma and cellular immunoreaction for ln-5 in ASCC are worked out as distinguishing features of both entities.ConclusionFli-1 in angiosarcoma and ln-5 in ASCC are distinguishing features.

Comparison of Four Cisplatin-Based Radiochemotherapy Regimens for Nonmetastatic Stage III/IV Squamous Cell Carcinoma of the Head and Neck

PURPOSE To compare the outcomes of four cisplatin-based radiochemotherapy regimens in 311 patients with Stage III/IV squamous cell carcinoma of the head and neck. METHODS AND MATERIALS Concurrent chemotherapy consisted of three courses of cisplatin 100 mg/m(2) on Day 1 (Group A, n = 74), two courses of cisplatin 20 mg/m(2) on Days 1-5 plus 5-fluorouracil 1,000 mg/m(2) on Days 1-5 (Group B, n = 49), two courses of cisplatin 20 mg/m(2) on Days 1-5 plus 5-fluorouracil 600 mg/m(2) on Days 1-5 (Group C, n = 102), or two courses of cisplatin 20 mg/m(2) on Days 1-5 (Group D, n = 86). The groups were retrospectively compared for toxicity and outcomes, and 11 additional factors were evaluated for outcomes. RESULTS No significant difference was observed among the groups regarding radiation-related acute oral mucositis and radiation-related late toxicities. Acute Grade 3 skin toxicity was significantly more frequent in Group B than in the patients of the other three groups (p = .013). The chemotherapy-related Grade 3 nausea/vomiting rate was 24% for Group A, 8% for Group B, 9% for Group C, and 6% for Group D (p = .003). The corresponding Grade 3 nephrotoxicity rates were 8%, 1%, 2%, and 1% (p = .019). The corresponding Grade 3-4 hematologic toxicity rates were 35%, 41%, 19%, and 21% (p = .027). Chemotherapy could be completed in 50%, 59%, 74%, and 83% of the Group A, B, C, and D patients, respectively (p = .002). Toxicity-related radiotherapy breaks occurred in 39%, 43%, 21%, and 15% of Groups A, B, C, and D, respectively (p = .005). The 3-year locoregional control rate was 67%, 72%, 60%, and 59% for Groups A, B, C, and D, respectively (p = .48). The corresponding 3-year metastasis-free survival rates were 67%, 74%, 63%, and 79% (p = .31), and the corresponding 3-year survival rates were 60%, 63%, 50%, and 71% (p = .056). On multivariate analysis, Karnofsky performance status, histologic grade, T/N category, preradiotherapy hemoglobin level, completion of chemotherapy, and radiotherapy breaks were associated with the outcome. CONCLUSION The four compared radiochemotherapy regimens were not significantly different regarding treatment outcomes. Two courses of cisplatin 20 mg/m(2) on Days 1-5 were better tolerated than the other three regimens.

Superficial ulnar artery: Curse or blessing in harvesting fasciocutaneous forearm flaps

Superficial ulnar artery is a well‐known vascular anomaly that may cause special risks because of possible impairment of the vessel by mistake during harvesting fasciocutaneous forearm flaps.

A Comparative Study on the Protection Profile of Lidocaine, Amifostine, and Pilocarpin on the Parotid Gland during Radiotherapy

The aim of this study was to evaluate the individual and the synergetic radioprotective effect of lidocaine, amifostine, and pilocarpin on the parotid gland. Forty-nine rabbits were randomized into seven groups (n = 7)--control, irradiated sham-treated, irradiated/lidocaine-pretreated, irradiated/amifostine-pretreated, irradiated/pilocarpin-pretreated, irradiated/lidocaine + pilocarpin-pretreated, and irradiated/amifostine + pilocarpin-pretreated groups. One week before irradiation (15 Gy) and 72 hours as well as 1 month afterward, the parotid gland was investigated morphologically, sialoscintigraphically, and immunohistochemically with the use of tenascin-C and alpha smooth muscle actin. Compared with control animals, there was a significant reduction of the salivary ejection fraction in the irradiated untreated group 72 hours following radiation. Only animals pretreated with lidocaine or amifostine (alone or combined with pilocarpin) showed a slight nonsignificant reduction of salivary ejection fraction. Immunohistochemically, we observed a significant loss of alpha smooth muscle actin and an up-regulation of tenascin-C expression in irradiated/untreated glands. These changes were less evident in animals pretreated with lidocaine or lidocaine + pilocarpin. Amifostine and pilocarpin did not show any influence on tenascin-C or alpha smooth muscle actin expression. Ultrastructural damage was observed in irradiated untreated and pilocarpin-pretreated glands. In contrast, lidocaine and amifostine could largely preserve the glandular ultrastructure. One month postradiation, all changes were regressive regardless of treatment protocol. Potential radioprotective agents show different effects on both morphology and function of the parotid gland. Associated immunohistochemical and ultrastructural findings could prove the prevailed protection profile of lidocaine. This may provide a prophylactic approach in the field of radioprotection of salivary glands.

Rare facial clefts : Treatment during charity missions in developing countries

During 10 charity missions in developing countries, 14 patients of a total of 374 children with cleft lip and palate deformities were treated for rare facial clefts. There were three midline clefts (Tessier no. 0 cleft, n = 1; Tessier no. 14 cleft, n = 2), four oblique facial clefts (Tessier no. 3 cleft, n = 2; Tessier no. 5 cleft, n = 2), and seven lateral facial clefts (Tessier no. 7 cleft). Surgical treatment focused on cleft repair by soft-tissue reconstruction apart from two Tessier no. 14 clefts, in which the bony gap was also closed using bone grafts from the iliac crest. The postoperative course was uneventful except for one local wound infection that was treated successfully using oral antibiotics. This article summarizes the authors’ experience with the surgical management of these malformations and considers the limitations under conditions of charity missions in developing countries. Furthermore, some rare forms of cleft formation are added to the existing literature.

Subcutaneous fat layer in different donor regions used for harvesting microvascular soft tissue flaps in slender and adipose patients.

The aim of this study is to provide valid data concerning the thickness of the subcutaneous fat layer in seven donor regions which are most commonly used for soft tissue replacement in the head and neck region. Furthermore the study focuses on differences in thickness of this layer depending on the nutritional status and sex. In 100 volunteers the thickness of the subcutaneous fat layer was evaluated using ultrasound in seven potential donor regions: radial and ulnar forearm, lateral upper arm, scapular and parascapular region, abdominal/supra-umbilical region and the lateral calf. Volunteers were divided into 4 groups: male and female, slender (body mass index [BMI] < 25) and adipose (BMI > 30). Data obtained was compared and differences were proven to be statistically significant (Students t-test, P<0.05). The largest thickness was found in the supra-umbilical region followed by the lateral upper arm whereas the ulnar forearm region had the smallest thickness. Depending on the BMI the supra-umbilical and the lateral upper arm regions showed the most wide variation. Depending on sex the most noticeable variation in thickness of the subcutaneous layer was seen in the lateral calf region with a significant larger tissue layer in females.