Mario Bussi

Pharyngocutaneous Fistula as a Complication of Total Laryngectomy: Review of the Literature and Analysis of Case Records:

Pharyngocutaneous fistula is the most common complication of total laryngectomy. The management of this problem increases hospitalization time and delays initiation of postoperative radiotherapy, where indicated. To identify factors predisposing to the development of pharyngocutaneous fistula, we reviewed the postoperative courses of 293 patients who underwent total laryngectomy at our clinic. General factors taken into account were concurrent diseases such as diabetes, liver diseases, or chronic anemia; local factors included radiotherapy before and after surgery, preoperative tracheostomy, type of cervical lymph node removal, and method of pharyngeal closure. We then compared our data with those reported in the literature by other authors. Last, we applied the Fisher exact test to a correlation we found between the higher incidence of fistula in patients with diabetes, liver diseases, or anemia. The local factor that turned out to be statistically most significant for the development of fistula was preoperative radiotherapy.

Staging of head and neck squamous cell carcinoma using the MET oncogene product as marker of tumor cells in lymph node metastases.

In head and neck squamous cell carcinomas (HNSCC), metastasis to cervical lymph nodes is a major determinant of patient outcome. To detect metastases, we used the MET oncogene as marker, which encodes the receptor for hepatocyte growth factor/scatter factor, mediating epithelial cell motility and invasiveness. The MET gene is expressed in epithelia and over‐expressed in carcinomas of specific histotypes, but not in lymphatic tissue. A total of 151 lymph nodes from 20 squamous cell carcinomas were studied with both in‐depth histology and end‐point and real‐time quantitative RT‐PCR. MET‐encoded sequences were found in 61 of 151 nodes (40%), of which 24 (16%) were found metastatic by in‐depth histopathology. Parallel routine histopathologic analysis of 654 lymph nodes from the same cases identified 36 metastases (5%). Real‐time quantitative RT‐PCR was used to measure MET gene‐specific mRNA in normal tissues, primary tumors and lymphatic metastases and showed a 2–8‐fold increased expression in tumor cells which metastasize. RT‐PCR for 3 cytokeratins expressed in HNSCC (K4, K10 and K13) proved to be less sensitive in detecting occult lymphatic metastases. Western blot analysis demonstrated the presence of the full‐size MET receptor in primary tumors and lymph node metastases; immunohistochemistry showed receptor localization in tumor cells. Altogether, these data demonstrate that the MET gene product is a valuable marker with which to detect occult tumor cells in lymph nodes, thanks to its high expression in metastatic cells. After RT‐PCR analysis we were able to attribute a more advanced stage to 10 out of 20 HNSCC cases, including 5 cases classified as tumor‐free after routine histopathology. Int. J. Cancer 89:286–292, 2000.

Improved survival with perilymphatic interleukin 2 in patients with resectable squamous cell carcinoma of the oral cavity and oropharynx.

The current randomized, multicenter, Phase III trial was conducted to determine whether the disease free interval and overall survival of patients with T2–T4,N0–N3,M0 squamous cell carcinoma (SCC) of the oral cavity or oropharynx could be extended through the combination of surgery (and radiotherapy, if required) with perilymphatic recombinant IL‐2 (rIL‐2).

Results of hypofractionated stereotactic re-irradiation on 13 locally recurrent nasopharyngeal carcinomas

Thirteen patients with locally recurrent, previously-irradiated nasopharyngeal carcinoma were treated with linac-based hypofractionated stereotactic radiotherapy (24 Gy in two or four fractions). One- and 3-year overall survival were 54 and 31%. Three patients were free of disease at 30, 34 and 65 months. No severe acute or late complications were seen.

Prognostic factors of cervical lymph node metastasis in head and neck squamous cell carcinoma.

Aims and background The metastatic spread of squamous cell carcinoma of the head and neck (SCCHN) to the cervical lymph nodes is a negative prognostic factor in terms of survival. We have used multivariate analysis to identify the possible prognostic significance of a number of clinical and pathological characteristics in relation to possible involvement of the cervical lymph nodes in a series of 396 patients. Method 396 patients with SCCHN were studied. Variables regarding the patient, the carcinoma and histology were analysed by multivariate analysis using BMDPs PLR programme. Results Some variables appear to represent predisposing factors for tumor spread to the lymph nodes: tumor site (supraglottic larynx: P=0.005; base of the tongue: P=0.02; hypopharynx: P=0.02), grading (P=0.001), and a number of histological parameters (lower degree of histological differentiation: P=0.001; vascular permeation: P=0.04; perineural invasion: P<0.05; prevalently plasmocytic infiltrate: P<0.05). Conclusion The identification of cases at risk for metastasis can be improved by the assessment of prognostic factors, with a consequent improvement in treatment strategies.

Is Transposed Skin Transformed in Major Head and Neck Mucosal Reconstruction

We used histological and histochemical methods to investigate the possible changes with time in skin transposed into the oropharynx and oral cavity of patients whose surgical wounds were reconstructed with the classic pectoralis major flap. We found histological evidence that skin morphology was maintained (keratinization with reduced, but the desquamating layer, hair follicles, sweat and sebaceous glands were identifiable), and noted an intense inflammatory reaction in the dermis. Histochemical studies confirmed the progressive flattening of the basal interdigitations between the epithelium and dermis, and the gradual reconstruction of the basement membrane. Although skin-mucosa continuity developed fairly quickly without scar reactions, the two epithelia maintained their original patterns of keratin production, i.e., their textural peculiarities. We propose an original method for the transposition of muscular flaps implanted with autologous culture of keratinocytes, an approach developed in an attempt to ensure more satisfactory rehabilitation of the removed mucosal structures.

Results of Chemotherapy Plus External Reirradiation in the Treatment of Locally Advanced Recurrences of Nasopharyngeal Carcinoma

Between 1982 and 1991, 16 patients with recurrent cancer of the nasopharynx were treated with chemotherapy (CT) and radiotherapy (RT). All patients had received prior RT (45-69, 30 Gy). According to rTNM there were three rT2, one rT3 and 12 rT4. 5 patients were N1. Reirradiation (12-46 Gy, mean: 28) started 3-4 weeks after CT (2-6 cycles of different combinations), but 2 cases involved concomitant therapy. Out of 16 patients 7 had complete response (CR) (43.7%), 7 partial response and 2 no response. Statistically significant prognostic factors for obtaining CR were time of relapse and response to initial CT. Median duration of CR was 22+ months (9-64+). Failures at primary site occurred in 3 patients, 2/2 of those receiving CT without platinum compounds and 1/5 of other ones, with statistically significant difference in local recurrence free-survival between the two groups. Two- and 3-year actuarial overall survival were 28% and 10%. Rates of disease-free survival were 17% and 8%, respectively. The acute toxicity was generally mild. No central nervous system damage or radiation-induced myelitis were observed in survivors.

The Effect of Preoperative Local Interleukin-2 (IL-2) Injections in Patients with Head and Neck Squamous Cell Carcinoma: An Immunological Study

Clinical, immunological, immunophenotypical, pathological and molecular biological studies were performed on tumor infiltrating lymphocytes (TIL) and lymph node lymphocytes (LN-ly) of 8 patients with squamous cell carcinoma of the oral cavity and oropharynx treated with 10 daily locoregional injections of low doses of IL-2 before surgery. No complications were seen during or after surgery. In 3 cases the LN-ly showed a moderate LAK activity, higher in the LN-ly omolateral to the tumor and near the IL-2 injection site; in 2 of these 3 patients a good LAK activity was induced after 6-day culture with IL-2. The LN-ly derived from nodes next to the tumor showed a decreased NK activity and proliferative ability both in basal conditions and after in vitro lymphokine challenging. LN-ly of 2 IL-2 treated patients showed high levels of mRNA encoding for IL-2-R, while it was absent in 2 untreated cases. Immunophenotypical studies on TIL showed statistically improved levels of CD25+ and LAK1+ cells in treated cases. Clusters of CD11c+ (macrophages) cells were seen close to the neoplastic sheets.

Primary malignant melanoma arising in the parotid gland: case report and literature review.

Melanoma of the head and neck is an extremely rare disease, characterized by difficult and late diagnosis and poor prognosis; moreover, the definition of primary melanomas of the salivary glands remains controversial. In this paper we describe an unusual case of primary melanoma arising in the parotid gland. A 60-year-old woman presented to us for the persistence of a parotid neoplasm diagnosed as carcinoma by fine-needle aspiration and treated with radiation therapy. Wide destructive surgery was performed and immunohistochemical analysis of the surgical specimen led to a diagnosis of melanoma. Complete screening excluded other primary tumor sites. After five years of follow-up the patient is alive and free of disease. Here we report the diagnostic procedures leading to the diagnosis along with a critical analysis of the literature, emphasizing the difficulties in the diagnosis and classification of melanoma as a primary tumor in the parotid gland and the need for destructive surgery.

Problems in reconstructive surgery in the treatment of carcinoma of the hypopharyngoesophageal junction

Thirty percent of carcinomas of the pyriform sinus manifest generally with infiltrations in the cervical esophagus. In recent years, progress in reconstructive surgery has broadened surgical indications to include tumors previously managed with palliative measures alone. In some cases, radical surgery has been extended to creating safer resection margins, with more and more indications for circular pharyngectomy. Lesions involving the hypopharyngoesophageal junction pose particular problems; furthermore, the high rate of synchronous or metachronous tumors warrants the indication for total esophagectomy, which requires complex reconstructive techniques.