A pilot study of perilymphatic leukocyte cytokine mixture (IRX-2) as neoadjuvant treatment for early stage cervical carcinoma.

Clinical and experimental data demonstrate that local cytokines are able to induce tumor regression and in some cases antitumor systemic immune response. IRX-2 is a cell-free mixture of cytokines obtained from unrelated donor lymphocytes with demonstrated ability to induce immune mediated regression of squamous cell carcinomas of head and neck. The objective of this study was to evaluate the antitumor activity and toxicity of IRX-2 in untreated early stage cervical cancer patients. Ten consecutive patients clinically staged IB1, IB2 and IIA were treated with a neoadjuvant immunotherapy regimen that consisted in a single IV dose of cyclophosphamide at 300 mg/m2 on day 1, oral indomethacin or ibuprofen and zinc sulfate were administered from days I to 21 and 10 regional perilymphatic injections of IRX-2 on days 3 to 14. All patients were scheduled for radical hysterectomy on day 21. The clinical and pathological responses, toxicity and survival were evaluated. Clinical response was seen in 50% of patients (three partial responses, two minor responses). Seven patients underwent surgery and pathological tumor reduction associated with tumor fragmentation was found in five cases. Histological studies demonstrated a rather heterogeneous cell type infiltrating pattern in the tumor which included lymphocytes, plasma cells, neutrophils, macrophages and eosinophils. Immunohistochemical analysis of the surgical specimens demonstrated an increase of tumor infiltrating CD8+ cells. The treatment was well tolerated except for mild pain and minor bleeding during injections and gastric intolerance to indomethacin. At 31 months of maximum follow-up (median 29), eight patients are disease-free. Our results suggest that the immunotherapy approach used induces tumor responses in cervical cancer patients. Further studies are needed to confirm these results as well as to elucidate the mechanisms underlying these effects.

Tumor angiogenesis as a prognostic factor in oral cavity carcinomas.

Currently, lymph node metastasis and thickness of the tumor are the gold standard as a predictor of survival in patients with oral cavity squamous cell carcinoma (OSCC). However, there is a significant correlation between microvessel density and the development of cervical metastases or recurrence. Previous studies have demonstrated that head and neck cancers are able to induce an angiogenic response in experimental models. This factor shows a strong correlation with regional recurrence. In this study we propose to use angiogenesis as an independent prognostic indicator of recurrence. We evaluated the expression of tumor angiogenesis in OSCC and determinated its possible usefulness as a prognostic factor. Thirty-three cases with diagnosis of OSCC were identified from January 1985 to January 1997 in the Head and Neck Department of the Instituto Nacional de Cancerología in Mexico City. These cases were analyzed retrospectively for a minimum period of six months. All of them received a conventional complete treatment to the primary tumor and lymph node metastasis. Paraffin-embedded tumor specimens were available in all patients. The tumors were scanned and the areas of highest microvessel density (MVD) were immunostained for CD-34 using QBEnd/10 antibody. Statistical analysis included descriptive statistics, Wilcoxon test curves, and Cox's proportional hazards model for multivariate analysis. We identified 33 patients with OSCC, 16 were men and 17 women. The mean age among all patients was 58.9 years old. Based on tumor size 33.3% were T1, 27.3% T2, 12.1% T3, and 27.3% T4. The median microvessel count was 32.5. The mean percentage of MVD was 37 in patients with regional recurrence and in those patients without regional metastasis was 29 (p<0.05). 57.9% of the patients who presented recurrence had vessel counts over the median (p<0.01). In fact, 6 patients (46%) who showed more than 20% of angiogenesis expression and higher MVD presented with recurrence. Only 3 patients (23%) who had less than 20% of angiogenesis expression and lower MVD developed recurrence (p<0.01). Higher MVD was seen with increasing T and N stages; however, it did not show correlation with survival. In this study, angiogenesis expression demonstrated to be an independent factor of recurrence in patients with OSCC. It is suggested that it should be used as an independent prognostic indicator. In concordance with previous reports, we observed a significant correlation between MVD determination and recurrence of the tumor, followed by lymph node metastases and tumor size.

Radial forearm free tissue transfer for head and neck reconstruction: versatility and reliability of a single donor site.

Since its description as a free flap, the radial forearm flap has undergone numerous modifications for reconstruction of various defects in the head and neck region. Fasciocutaneous, adipofascial, osteocutaneous, tendinofasciocutaneous, or osteotendinofasciocutaneous flaps may be designed and transferred from the radial forearm. This article illustrates the versatility and reliability of this donor site in 15 patients with a variety of head and neck oncologic defects who underwent immediate (12 patients) and delayed (3 patients) reconstruction using different free flaps from the radial forearm. Skin flaps were used in 11 patients (73.3%) with floor of mouth (4 cases), hemiglossectomy (2 cases) and partial maxillectomy (2 cases) defects, and for scalp (1 case), lower lip (1 case) and a central face (anterior maxilla/upper lip/nasal) (1 case) defect. Osteocutaneous flaps were used in four patients (26.6%) for reconstruction of bilateral subtotal maxillectomy defects (2 cases), a complex forehead and nasal defect (1 case), and for mandible reconstruction (1 case). In addition, the palmaris longus tendon was included with the flap in the two patients that required oral sphincter reconstruction. One patient required reexploration due to vein thrombosis, and no flap failures were detected in this series. The donor site healed uneventfully in all patients, except one, who had partial skin graft failure. Because of their multiple advantages, free flaps from the radial forearm have a definite role for reconstruction of head and neck defects. New applications of composite flaps from this donor site may continue to emerge, as illustrated in some of our patients.

Inmunoterapia en cáncer epidermoide de lengua recurrente, asociado a epidermólisis bulosa distrófica. Reporte de un caso / Immunotherapy for recurrent tongue epidermoid carcinoma associated to dystrophic epidermolysis bullosa. Case report

La epidermólisis bulosa distrófica (EBD) es una patología cutánea, que frecuentemente se asocia a la presencia de cánceres epidermoides cutáneos de conducta agresiva. El tratamiento quirúrgico constituye la principal modalidad de tratamiento, debido a la presencia de metástasis en forma temprana, debe consolidarse con quimioterapia o radioterapia. El uso de estas modalidades se dificulta, debido a la patología cutánea de base. Se presenta el manejo con inmunoterapia utilizando una mezcla de citocinas naturales (IRX-2), en un paciente de 27 años con cáncer epidermoide de lengua recurrente, metastásico a cuello, en quien, por sus condiciones generales, no fue posible administrar otras modalidades terapéuticas. El uso de inmunoterapia indujo una respuesta objetiva parcial y paliación sintomática sin toxicidad. El uso de este tratamiento pudiera ser considerado como manejo paliativo en pacientes con cáncer epidermoide (CE) asociado a EBD.

[Indications and results of hepatic resection in benign and malignant tumors]. / Indicaciones y resultados de la resección hepática en tumores benignos y malignos.

OBJECTIVE: The authors analyze the indications and results in 75 consecutive liver resections. BACKGROUND: In recent years, the morbidity and mortality of this procedure have been reduced at specialized centers due to better control of intraoperative bleeding and improved perioperative management. METHODS: The clinical records of 72 patients who had a liver resection over a 4-year period were reviewed. RESULTS: Fifty-two were females and 23, males. Ages ranged between 15 and 88 years (X: 50 +/- 22 years). The indications for surgery were liver, secondary in 28, gallbladder or bile duct cancer in 17, benign liver tumors in 16, and primary malignant liver tumors in 14. Forty-seven major liver resections were performed and included 25 right hepatectomies, 13 left hepatectomies, five right trisegmentectomies, and four left trisegmentectomies. Additionally, 28 minor resections included 12 resections of the left lateral segment, nine bisegmentectomies, five segmentectomies and two resections of the caudate lobe. Operative time ranged from 60-540 min (X: 260 +/- 97 min); the mean operative bleeding was 1439 +/- 660 mL (range 20-5,000 mL). The pringle maneuver was used in 63 patients and ranged from 20-100 min (X: 42 +/- 25 min). Twenty-five patients presented complications (33%), the most frequent being hepatic failure, postoperative bleeding, ascitis and bilomas. Six patients died (8%) due to hepatic and multiorganic failure in four pneumonia and myocardial infarct in one, and systemic sepsis in the other. CONCLUSIONS: Liver resection is an excellent therapeutic alternative in patients with benign and malignant liver focal lesions.

Repeat hepatic resection for recurrent metastatic melanoma.

We present an unusual case of a recurrent metastatic hepatic melanoma that had undergone a repeat hepatic resection. A 62 year-old female patient was diagnosed with a plantar melanoma and was managed with resection and regional lymphadenectomy. Eight months later, a solitary liver metastasis was diagnosed and a right hepatectomy performed. Sixteen months later, a recurrent solitary metastasis was diagnosed in the caudate lobe and resection was performed. She has since been asymptomatic with no evidence of recurrence of the disease at a 2-year follow up. We recommend surgical removal of hepatic metastatic melanoma in selected cases where the disease is confined to the liver and surgery can be performed without unacceptable risk.