Optimization of treatment parameters for Foscan-PDT of basal cell carcinomas

BACKGROUND AND OBJECTIVE: Basal cell carcinomas (BCCs) are the most common form of skin cancers with high and increasing incidence rates. Photodynamic therapy (PDT) with mTHPC (Foscan) has shown to be a promising treatment alternative with good cosmetic results. The current study was aimed to determine optimal treatment parameters for this indication. STUDY DESIGN/MATERIALS AND METHODS: mTHPC-PDT was performed in 117 patients with a total of 460 BCCs with diagnosis confirmed by scratch cytology. Treatment parameters were altered as follows: Foscan dose 0.03-0.15 mg/kg, drug-light interval (DLI) 1-96 hours, total energy density 20-120 J/cm(2). Outcomes were assessed 8 weeks post-PDT following WHO guidelines. RESULTS: The overall rate of complete remissions (CR) was 96.7% and the cosmetic outcome was very good. In the largest subgroup (n=80) where low-dose Foscan was applied (0.05 mg/kg mTHPC; 48 hours DLI; 50 J/cm(2) total energy density), a CR rate of 100% with a high and narrow 95% Confidence Interval of 0.955-1.000 was achieved. Smaller variations of the treatment parameters (i.e., reducing the photosensitizer dose to 0.04 mg/kg or shortening the DLI to 24 hours) yielded similarly good results. Side effects were encountered in 52 out of 133 PDT sessions. They were more common in patients who had received high drug doses (0.06-0.15 mg/kg) and comprised mostly pain and phototoxic reactions. Three patients developed severe sunburns with subsequent scarring at the injection site following bright sunlight exposure 15-19 days after photosensitizer administration. CONCLUSIONS: The presented data suggest that mTHPC-PDT with the treatment parameters mentioned above seems to be an effective treatment option for BCCs. If sensibly applied, it is well tolerated and provides mostly excellent cosmetic results. Long-term results are yet to be evaluated.     

Cryosurgical treatment of basal cell carcinoma of the skin

Cryosurgical method was used for the treatment of 102 patients with basal cell carcinoma of the skin. A portable cryosurgical apparatus with a set of applicators was used. Liquid nitrogen was used as the cold agent. The method is simple and accessible and gives good long-term results: recidivation is not more than 2%, rough cicatricial keloids are not formed.     

The development of squamous cell carcinomas in split-thickness skin graft donor sites

The development of squamous cell carcinoma in the donor site of a split-thickness skin graft is rare having only been described in ten previous cases. We describe one further case and review this along with the previous cases. Possible aetiologies are discussed along with advice on how to reduce the chances of this complication occurring and how to manage it should it occur. Level of Evidence: Level V, diagnostic study     

Ultrapulse CO2 used for the successful treatment of basal cell carcinomas found in patients with basal cell nevus syndrome.

BACKGROUND: Basal cell nevus syndrome (BCNS) is an inherited condition marked by multiple basal cell carcinomas (BCCs) associated with several other abnormalities. Various treatment modalities have been used to eradicate these tumors. However, recurrences and scarring limit their use. OBJECTIVE: To evaluate the treatment of multiple BCCs associated with BCNS. METHODS: We describe three cases of BCNS in which multiple BCCs were effectively treated with ultrapulse CO2 laser. Postoperative Mohs micrographic surgical sections (thin sections looking for residual tumor) verified complete histologic clearance of the tumors. RESULTS: All three patients were effectively treated with ultrapulse CO2 laser. Minimal scarring was noted at follow-up. CONCLUSION: Ultrapulse CO2 laser can be used to effectively treat small BCCs in low-risk areas associated with BCNS with minimal posttreatment scarring.     

A reliable frozen section technique for basal cell carcinomas of the head and neck

Basal cell carcinomas (BCCs) of the head and neck treated by conventional techniques of surgical excision, curettage, cryotherapy and radiation therapy have recurrence rates of up to 42%. Mohs micrographic surgery (MMS) decreases the recurrence rate but can be expensive, delay definitive reconstruction and is limited in its availability.The authors report a series of 50 patients with head and neck BCCs treated by a surgeon-directed ‘en face’ frozen section technique that immediately evaluates the entire peripheral and deep margins during BCC resection, and potentially offers a more efficient and equally effective alternative to MMS.Patient demographics, pathology results, operative time, technique and outcomes are all reported. With a mean follow-up of three years, there was only one recurrence (1.7%). Mean total operative time was 1 h 47 min. The authors conclude that this surgeon-directed ‘en face’ frozen section technique does not require any specialized training, enables more rapid and reliable results than standard frozen section techniques that are currently used, and provides outcomes equivalent to MMS in the surgical treatment of head and neck BCCs.     

The stromal reaction in basal cell carcinomas. A prerequisite for tumour progression and treatment strategy.

Specimens of basal cell carcinomas collected from 28 patients were classified into three groups: superficial, nodular, and infiltrative, according to their microarchitecture. The specimens were then subjected to histological characterization by means of a biotinylated hyaluronan-binding probe (HABP). By using Ki-67 and PCNA the proliferative activity of the BCC tumours was evaluated with immunohistological techniques. In superficial BCC the tumour islands displayed moderate hyaluronan (HA) staining. Feeble proliferation, denoted by modest mitotic activity and weak Ki-67 and PCNA immunoreactivity, occurred within the tumour islands. The surrounding connective tissue resembled normal skin, and no differentiated tumour stroma was observed. In nodular BCC, the HA staining of the tumour strands was weak to moderate, denoting increased proliferative activity. The differentiated surrounding tumour stroma stained strongly for HA. Tumour islands of infiltrative BCC stained weakly to moderately to HA and evidenced intense proliferation. The intensely HA-stained tumour stroma ended abruptly and the adjacent areas were almost devoid of HA. This study showed that the proliferative activity of BCC cells is associated with increased expression of HA in the tumour stroma. Modification of tumour-associated connective tissue indicates a close relationship between the tumour cells and the adjacent matrix. In particular, in infiltrative BCC, such alterations include degeneration and possible modification and remodelling of the surrounding extracellular matrix. These processes involving areas of probable importance for tumour progression, should be considered when deciding the extent of intended surgical resection.     

Preliminary evaluation of two fluorescence imaging methods for the detection and the delineation of basal cell carcinomas of the skin

BACKGROUND AND OBJECTIVE: Fluorescence techniques can provide powerful noninvasive means for medical diagnosis, based on the detection of either endogenous or exogenous fluorophores. The fluorescence of delta-aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) has already shown promise for the diagnosis of tumors. The aim of the study was to investigate the localization of skin tumors after the topical application of ALA, by detecting the PpIX fluorescence either in the spectral or in the time domain. STUDY DESIGN/MATERIALS N AND METHODS: Two fluorescence imaging systems were used to identify basal cell carcinomas of the skin in humans, after topical application of 20% ALA ointment. Both systems rely on the comparison between the exogenous and the endogenous fluorescence, performed either in the spectral domain or in the time domain. The first system works by using three images acquired through different spectral filters, whereas the second one measures the spatial map of the average fluorescence lifetime of the sample. RESULTS: A clear demarcation of skin malignancies was successfully performed in vivo noninvasively with both fluorescence imaging systems. CONCLUSION: The two complementary approaches considered in the present study show promise for skin tumor detection and delineation based on specific fluorescence features.     

Possible indication for surgical treatment of squamous cell carcinomas of the esophagus that involve the stomach

BACKGROUND: The caudal spread of esophageal squamous cell carcinoma (ESCC) frequently involves the stomach. An extended surgical treatment may provide a tumor-free margin; however, its clinical benefit has not been elucidated. METHODS: Sixty-three of 582 patients with ESCC (11%) had massive gastric involvement and underwent esophagectomy with combined resection of the stomach and other organs. The mode of gastric involvement was classified as direct invasion from primary tumor (PT invasion) or invasion from metastatic lymph nodes (LN invasion). RESULTS: In addition to the removal of either the proximal (83%) or the whole (17%) stomach, 46 patients (73%) underwent the combined resection of adjacent organs, including the diaphragm, pancreas, liver, lung, and pericardium. This surgical treatment resulted in a high rate (83%) of curative resection and a low rate (8%) of operative mortality. Postoperative survival rates were 53%, 33%, and 25% at 1, 2, and 5 years, respectively. The first tumor recurrence was frequently in the abdominal paraaortic lymph nodes (41%) and the liver (28%), followed by the mediastinal lymph nodes, local recurrence, the lung, and other organs. The mode of gastric involvement strongly affected clinical outcome, with a 5-year survival rate of 36% for those with PT invasion but of only 7% with LN invasion (P <.0086). No significant difference was seen in the number and location of metastatic lymph nodes between the 2 groups; however, the size of the largest metastatic lymph node was significantly smaller with PT invasion than with LN invasion (12 mm vs 37 mm in diameter; P <.0001). CONCLUSION: Surgical treatment of ESCC involving the stomach was considered safe and successful. A favorable prognosis can be expected for gastric invasion from the primary tumor but not from metastatic lymph nodes.     

Inverted papillomas and associated squamous cell carcinomas

Inverted papillomas of the nose and paranasal sinuses are found to be associated with squamous cell carcinomas in a small percentage of cases. The records of forty-six patients treated for inverted papillomas in these areas over a 10-year period were reviewed. Eleven patients (24%) were found to have squamous cell carcinoma, and one carcinoma in situ, in relationship to the inverted papillomas. This is a much higher percentage than generally reported. Four of these patients were found to have inverted papillomas coincidentally in surgical specimens resected for squamous cell carcinoma. Patients with squamous cell carcinoma were found to be in older age groups, were more likely to manifest epistaxis than the more common unilateral nasal obstructive symptoms, and had less time between the onset of symptoms and presentation than those with inverted papillomas alone. The clinical presentation, treatment, and outcome of inverted papillomas and squamous cell carcinomas in association with inverted papillomas are discussed.     

Mouse models for human head and neck squamous cell carcinomas

Mouse models of human cancer play an important role in understanding the mechanisms of carcinogenesis and have accelerated the search for finding new molecular targets for cancer therapy. However, genetically engineered mouse models for head and neck squamous cell carcinoma (HNSCC) have only recently overcome major technical obstacles and begun to be explored. Here we review the current progress in the development of mouse models for human HNSCC, with emphasis on conditional transgenic and knockout mouse models. These new models faithfully recapitulate human HNSCC at both the pathologic and molecular levels. These animal models will not only be useful to define the roles of specific genes in HNSCC development and progression but will also provide a unique tool for developing and testing new therapeutic approaches.     

Lectin histochemistry of laryngeal squamous cell carcinomas

A panel of five biotinylated lectins was applied to study the presence and distribution of membrane carbohydrate residues in the normal laryngeal epithelium and in laryngeal squamous cell carcinomas (SCCs) of 86 patients with the avidin-biotin peroxidase complex technique. The lectin-binding pattern of well-differentiated SCCs was comparable to that of the spinous cells of the normal laryngeal epithelium. In the less differentiated SCCs, staining of the keratinocyte plasma membrane with lectins was either reduced or absent, indicating a decline in the glycosylation of cell surface glycoconjugates. The lectins applied here could be used in the rapid assessment of less-differentiated areas within a laryngeal SCC, but they cannot be regarded as reliable markers of laryngeal keratinocytes undergoing malignant transformation. (Otolaryngol Head Neck Surg 1998;118:886-91.)     

Head and neck squamous cell carcinoma cell lines: established models and rationale for selection

BACKGROUND: Head and neck squamous cell carcinoma (HNSCC) cell lines are important preclinical models in the search for novel and targeted therapies to treat head and neck cancer. Unlike many other cancer types, a wide variety of primary and metastatic HNSCC cell lines are available. An easily accessible guide that organizes important characteristics of HNSCC cell lines would be valuable for the selection of appropriate HNSCC cell lines for in vitro or in vivo studies. METHODS: A literature search was performed. RESULTS: Cell growth and culture parameters from HNSCC cell lines were catalogued into tables or lists of selected characteristics. Methods for establishing cancer cell lines and basic cell culture maintenance techniques were reviewed. CONCLUSIONS: A compendium of HNSCC cell line characteristics is useful for organizing the accumulating information regarding cell line characteristics to assist investigators with the development of appropriate preclinical models.     

Metastatic basal cell carcinoma with squamous appearances in the naevoid basal cell carcinoma syndrome.

A patient with the naevoid basal cell carcinoma syndrome developed a secondary carcinomatous deposit in the pelvis. Persisting tumour in the skull and the secondary deposit in the pelvis contained areas of squamous differentiation. This confirms that the appearances of baso-squamous (or transitional or metatypical-cell) carcinoma can develop from typical basal cell carcinoma which had not been subjected to radiotherapy or to more than one surgical excision.     

Small cell squamous and mixed small cell squamous--small cell anaplastic carcinomas of the lung

Five patients are presented who had neoplasms which, by light microscopy and in two cases cytologically, appeared to be small cell anaplastic (polygonal and fusiform cell type) carcinomas of the lung. However, by electron microscopy, four of the carcinomas exhibited squamous characteristics including desmosomes and tonofilament bundles, and lacked demonstrable neurosecretory granules, suggesting that they were small cell squamous carcinomas. The fifth carcinoma contained cells with neurosecretory granules as well as cells demonstrating squamous differentiation. One patient died within 3 months of presentation. Three patients survived for approximately 18 months each; two received chemotherapy but one was treated by surgical resection alone. The fifth patient had a peripheral coin lesion which was treated by surgical resection only; he is alive without evidence of recurrent carcinoma 1 year after operation. We suggest that some carcinomas of the lung with the light-microscopic and cytologic appearance of small cell anaplastic carcinoma are actually small cell variants of squamous cell carcinoma and lack the characteristic neurosecretory granules of classic small cell carcinoma. The behavior of these tumors needs to be determined.