Chih-Fung Wu

Altered p-STAT3 (tyr705) expression is associated with histological grading and intratumour microvessel density in hepatocellular carcinoma

Background: Constitutive activation of signal transducer and activator of transcription 3 at tyrosine residue 705 (p-STAT3 (tyr705)) has been associated with many types of human cancers. However, its potential roles and biological effects in hepatocellular carcinoma (HCC) are not well established. Aim: To explore whether an altered p-STAT3 (tyr705) expression is associated with angiogenesis or proliferation and thereby plays a part in HCC development. Methods: Paraffin-wax-embedded sections from 69 patients with HCC were collected in this study. Using a semiquantitative immunohistochemical staining method, the expression patterns of p-STAT3 (tyr705) in both HCC lesions and the adjacent non-tumorous liver parenchyma were analysed. The results obtained were further correlated with intratumour microvessel density (MVD), Ki-67 expression, clinicopathological parameters and overall survival. Results: A strong p-STAT3 (tyr705) nuclear staining was observed in 49.3% of HCC lesions, but was reported only in 5.8% of the adjacent non-tumorous liver parenchyma (p<0.001). The expression of p-STAT3 (tyr705) in HCC lesions was significantly and positively correlated with the intratumour MVD (p = 0.002), but not with Ki-67 expression. No significant correlation of p-STAT3 (tyr705) was found in addition to histological grading (p = 0.019). Multivariate Cox regression analysis showed that p-STAT3 (tyr705) expression was a significant predictor of overall survival for HCC (p = 0.036), although the Kaplan–Meier survival curves showed no significant difference between the high and low p-STAT3 (tyr705) expression subgroups. Conclusions: The results showed that p-STAT3 (tyr705) expression was closely correlated with histological grading and intratumour MVD in HCC. Thus, the potential role of p-STAT3 (tyr705) in HCC development may be through these correlations.

Importance of Patient’s Cooperation in Surgical Treatment for Oral Submucous Fibrosis

PURPOSE The aim of this study was to investigate the results of surgical treatment for oral submucous fibrosis (OSF) in patients who did or did not cooperate with the rehabilitation regimen. PATIENTS AND METHODS There were 54 patients who had surgical treatment of trismus caused by OSF. Split-thickness skin grafts were used to repair surgical defects after surgery on the fibrous bands. According to postoperative collaboration in the rehabilitation regimen, patients were defined as non-cooperative patients (group I) and cooperative patients (group II). Group I (n = 28) and group II (n = 26) were analyzed separately for changes in preoperative, intraoperative, and postoperative interincisal distances (ID) for at least 6 months after surgery. RESULTS The mean preoperative ID was 18.9 mm (range, 8 to 25 mm) in group I and 18 mm (range, 7 to 25 mm) in group II. The intraoperative ID increased to an average of 39 mm in group I and 38.5 mm in group II. The mean final follow-up ID was 22 mm in group I and 36.1 mm in group II. When evaluating the changes of ID, only a statistically significant difference was found at final visit between groups. CONCLUSIONS In our study, we found the patients cooperation is the primary requirement for success in the treatment of OSF.

EFFECTIVE ERADICATION OF ORAL VERRUCOUS CARCINOMA WITH CONTINUOUS INTRAARTERIAL INFUSION CHEMOTHERAPY

We evaluated the effectiveness of intraarterial methotrexate infusion as a primary therapy for oral verrucous carcinoma (VC).

Penile verrucous carcinoma successfully treated by intra-aortic infusion with methotrexate.

OBJECTIVES Penile verrucous carcinoma is characterized by aggressive local growth and a low metastatic potential. Lower abdominal aortic infusion chemotherapy has the main advantage of delivering a very high concentration of an anticancer drug to the whole pelvic area, including the penis, and is especially suitable to treat penile verrucous carcinoma. METHODS From 1991 to 2000, 4 cases of penile verrucous carcinoma were treated by continuous intra-aortic infusion with methotrexate (50 mg) every 24 hours, for an average of 10 days. Citrovorum factor (6 mg) was given intramuscularly every 6 hours during the period of methotrexate infusion. RESULTS After treatment, 3 patients achieved complete remission. They were living disease free 10 years, 10 months, 6 years, 9 months, and 1 year, 8 months after therapy. CONCLUSIONS Intra-aortic infusion chemotherapy is a simple and effective method for penile verrucous carcinoma with the unique advantage of preserving cosmetic and functional integrity. It may be considered an effective alternative treatment for penile verrucous carcinoma. By using this simple method many unnecessary penectomies can be avoided.

Advanced Penile Verrucous Carcinoma Treated With Intra-Aortic Infusion Chemotherapy

PURPOSE Traditional treatment for advanced penile verrucous carcinoma is penectomy. This mostly leads to remarkable psychosexual problems and greatly affects quality of life, especially in young patients. To preserve the penis we used intra-aortic infusion chemotherapy for advanced verrucous carcinoma. MATERIALS AND METHODS From 1991 to 2009 we treated 6 men with penile verrucous carcinoma with continuous intra-aortic infusion of 50 mg methotrexate every 24 hours (average 550 mg, range 400 to 800). Citrovorum factor (6 mg) was given intramuscularly every 6 hours during methotrexate infusion. After continuous methotrexate infusion no further anticancer drug was given to complete responders. Partial responders subsequently received long-term, intermittent, intra-aortic infusion of 50 mg methotrexate or 2 mg mitomycin C plus 250 mg 5-fluorouracil every 1 to 2 weeks until tumors disappeared and all wounds healed. RESULTS After treatment 4 patients achieved a complete response and were disease-free 3 years 9 months to 17 years 10 months (median 11 years 3 months) after therapy. Two patients had a partial response. The patient with a shaft tumor subsequently underwent total penectomy due to unbearable penile pain 4 years after infusion with various drugs without an appreciable response. He has survived 12 years 5 months after initial treatment. The other patient with glans and prepuce tumors had progression with bilateral inguinal metastases despite 1 1/2 years of infusion therapy. Total penectomy was done. Histological examination of the glans mass revealed moderately differentiated squamous cell carcinoma. Patient condition progressed rapidly and he died 11 months after penectomy. CONCLUSIONS Intra-aortic infusion chemotherapy is a simple, effective method to treat penile verrucous carcinoma with the uniqueness of preserving the anatomical structure and sexual function in complete responders. For penile verrucous carcinoma, especially in younger patients, intra-aortic infusion chemotherapy may be considered organ sparing treatment before penectomy.

Continuous intra-arterial infusion chemotherapy as a palliative treatment for oral squamous cell carcinoma in octogenarian or older patients.

We intend to determine the potential benefits and analyze the outcomes of regional intra-arterial infusion chemotherapy (IAIC) for the octogenarian and older patients with oral cancer. Eighteen patients with oral squamous cell carcinoma were included. They were 12 males and six females with ages ranging from 80 to 96 years. An implantable port-catheter system was used for catheterization. Using a portable pump, methotrexate was given continuously through the external carotid artery for a mean period of 5.5 days (range, 4-7 days) followed by weekly bolus of low dose (25mg) of methotrexate until the clinical condition was stabilized. During the first week of IAIC, all tumors began to reduce in size. Of them 11 (61%) had a complete clinical response and 7 (39%) achieved a partial clinical response, after a mean follow-up period of 26 months (range, 8-72 months). The one- and three-year survival rates were 87% and 56%, respectively. There were no catheter-related complications. The side effects were mild and tolerable. IAIC might be specially indicated for oral cancer elderly with co-morbidity since a radical surgery or extensive radiotherapy can be avoided, and offers an acceptable palliative treatment in such patients.

Intraarterial chemotherapy: a valid option in the treatment of verrucous carcinoma?

More than sixty years have passed since Lauren V. Ackerman Wrst used the term “verrucous carcinoma” in 1948 [1]. This tumor is an unusual and indolent highly diVerentiated variant of squamous cell carcinoma. Currently, it is referred as a distinct clinicopathologic entity characterized by a favorable prognosis. Verrucous carcinoma is characterized by a high index of clinical suspicion of malignancy, but with a benign histological appearance and no tendency to metastasize neither into the regional lymphatics nor distant sites; it represents a unique diagnostic and therapeutic challenge [2]. Historically, surgery is advocated as the treatment of choice. Operative treatment should not include neck dissection, even though enlarged and tender lymph nodes may be palpated. In fact, histological examination of these lymph nodes has revealed only an inXammatory reaction. Patients receiving initial treatment with surgery enjoyed better survivals than did those treated with irradiation, especially for cases originating in the oral cavity, as suggested by the National Cancer Database records of 2,350 cases of verrucous carcinoma of the head and neck [3]. When deciding between treatment options, a favorable prognosis of verrucous carcinoma dictates two imperatives: the cure of cancer and the preservation of function and/or cosmetic appearance of the treated organ/region. As being local disease, the gold standard of treatment for verrucous carcinoma is surgery assuring high rates of permanent tumor control. However, surgery is limited to the medically Wt patients with an operable disease. In locally advanced tumors with locally destructive pattern of growth, often diagnosed in elderly patients, or in tumors extending to neighboring structures more mutilating surgical procedures are necessary or surgery is not an option any more. In such cases, radiotherapy—although being less eVective than surgery—is usually considered as a reasonable alternative [2, 3]. Recently, the concept of anaplastic transformation after treatment with irradiation, which reasoned many authors into avoiding radiotherapy in the past, was seriously challenged, and the opinion prevailed that it should not aVect the decision for this treatment approach. In more recent radiotherapy series, none of the patients with verrucous carcinoma that recurred after radiotherapy had features of anaplastic transformation. It would seem much more probable that the occurrence of a less diVerentiated lesion after the irradiation of verrucous carcinoma primarily evidences the foci of squamous cell carcinoma that were missed at the initial biopsy [4]. Thus, what therapy might have the potential for preserving the eVectiveness of surgery and, at the same time, keeping the organ-sparing capacity of irradiation? One of the strategies introduces chemotherapeutics, either as an upfront modality aimed at reducing the tumor size before surgery or in combination with radiotherapy. However, experience with chemotherapy in verrucous carcinoma is This paper was written by members and invitees of the International Head and Neck ScientiWc Group (http://www.IHNSG.com).

Continuous intra‐arterial chemotherapy for downstaging locally advanced oral commissure carcinoma

The purpose of this study was to assess the usefulness, safety, and efficacy of intra‐arterial (IA) infusion chemotherapy for patients with locally advanced oral commissure cancer.

Interval between Intra-Arterial Infusion Chemotherapy and Surgery for Locally Advanced Oral Squamous Cell Carcinoma: Impacts on Effectiveness of Chemotherapy and on Overall Survival

Background. The interval between intra-arterial infusion chemotherapy (IAIC) and surgery was investigated in terms of its effects on survival in patients with locally advanced oral squamous cell carcinoma (OSCC). Methods. This retrospective study analyzed 126 patients who had completed treatment modalities for stage IV OSCC. All patients were followed up for 3 years. Kaplan-Meier and Cox regression methods were used to determine how survival was affected by general factors, primary tumor volume, TNM stage, and duration of neoadjuvant chemotherapy. Results. In 126 patients treated for locally advanced OSCC by preoperative induction IAIC using methotrexate, multivariate analysis of relevant prognostic factors showed that an IAIC duration longer than 90 days was significantly associated with poor prognosis (hazard ratio, 1.77; P = 0.0259). Conclusions. Duration of IAIC is a critical factor in the effectiveness of multimodal treatment for locally advanced OSCC. Limiting the induction course to 90 days improves overall survival.

Retrospective Study of the Concurrent Intraarterial Chemo-Radiotherapy for Locally Advanced or al Cancers

Purpose: The aim of this study is to investigate the clinical outcomes and complications of intraarterial chemotherapy and concurrent radiation therapy (IACCRT) for locally advanced oral cancers. Materials and Methods: Between September, 2001 and July, 2006, 30 patients with locally advanced oral squamous cell carcinoma (stage Ⅳ: 22 patients and stage Ⅲ: 8 patients) received concurrent intraarterial chemo-radiotherapy in our department. The age ranged from 32 year-old to 63 year-old (median, 45 year-old). Each patient received a single bolus of 50 mg of methotrexate intraarterially every week while undergoing irradiation. The median irradiation dose was 64 Gy with 1.8-2.0 Gy daily fractions. The median follow-up period was 20 months (range, 6-52 months). Results: The response rate was evaluated by clinical examination and imaging study after IACCRT and the results were as follows: complete response, 53% (16/30); partial response, 23% (7/30); no response, 17% (5/30); progression, 7% (2/30). The major toxicities included grade 3 mucositis (10/30, 33.3%), grade 3 dysphagia (8/30, 26.6%), and grade 3 leukopenia (1/30, 3%). The estimated 1-year survival rate was 60.4%. Patients with complete or partial response were associated with better overall survival by Kaplan Meier survival analysis (log-rank test, p=0.05). Conclusion: Our preliminary data suggests IACCRT for locally advanced oral cancers is feasible. We have inferred a conclusion from the facts that tongue and gingival cancers have better response to IACCRT than buccal cancer does. Nevertheless, the result was not statistically significant. Further larger prospective study with detailed case selection is necessary.