Case report of a huge lower lip cancer successfully treated with intra-arterial infusion chemotherapy.

INTRODUCTION: We present a difficult case of huge squamous cell carcinoma (SCC) of lower lip that was successfully treated by intra-arterial infusion with methotrexate (MTX). PRESENTATION OF CASE: This 42-year-old female patient present with a fungating lower lip SCC of approximately 10 × 5 cm in size. MTX 25 mg was infused continuously to each side of external carotid artery every 24 h using two portable pumps. Totally, MTX 300 mg was given over 6 days. After treatment initiation, the tumor shrank dramatically and disappeared completely 2 months after the therapy. The patient was now recurrence-free at the recent follow-up 4 and half years after therapy. DISCUSSION: Intra-arterial infusion chemotherapy has the advantage of delivering a high concentration of anticancer drug to the lesion to induce a rapid shrinkage of the tumor and the side effects are limited. Intra-arterial infusion with MTX achieves good tumor response to lower lip cancer with excellent anatomical and functional preservation. CONCLUSION: This therapy may be a treatment option in lower lip cancers with unresectable lesions, or in those patients who are unwilling to undergo resection.

Transanal inside-out rectal resection for ultra-low rectal cancer.

Two major issues encountered in the surgical resection of low rectal cancers (tumor located <6 cm from anal verge) are tumor-free surgical resection margin and adequate fields of colo-anal pull-through anastomosis. The clinical consequences of ensuring gross tumor-free surgical resection margin by transanal inside-out rectal resection technique were assessed for ultra-low rectal cancer patients. From February 2009 to September 2011, ultra-low anterior resection with a new method of eversion of the rectum through the anal canal after resecting the distal rectum and colo-anal anastomosis extracorporally performed in 30 patients (age range, 41-80 years) was reviewed. All patients received preoperative neoadjuvant concurrent chemoradiotherapy (CCRT) before the surgical resection. The median operating time was 265 min (range, 220-400 min), and the median intraoperative blood loss was 325 ml (range, 80-855 ml). No in-hospital mortality was noted among these patients. R0 resection (tumor-free margin range, 0.9-2.5 cm) was confirmed in all patients by pathologic reports, except one patient with 0.5 cm tumor-free margin. The new surgical technique of transanal inside-out rectal resection and colo-anal pull-through anastomosis for selected patients with ultra-low rectal cancers seems to be a safe and alternative procedure.

High preoperative ratio of blood urea nitrogen to creatinine increased mortality in gastrointestinal cancer patients who developed postoperative enteric fistulas.

Development of an enteric fistula after surgery is a major therapeutic complication. In this study, we retrospectively examined the potential relationship between preoperative laboratory data and patient mortality by collecting patient data from a tertiary medical center. We included patients who developed enteric fistulas after surgery for gastrointestinal (GI) cancer between January 2005 and December 2010. Patient demographics and data on preoperative and pre-parenteral nutritional statuses were compared between surviving and deceased patients. Logistic regression analysis and receiver operating characteristic (ROC) curves were used to determine the predictors and cut-off values, respectively. Patients with incomplete data and preoperative heart, lung, kidney, and liver diseases were excluded from the study; thus, out of 65 patients, 43 were enrolled. Logistic regression analysis showed that blood urea nitrogen-to-creatinine (BUN/Cr) ratio [p = 0.007; OR = 0.443, 95% confidence interval (CI), 0.245-0.802] was an independent predictor of mortality in patients who developed enteric fistulas after surgery for GI cancer. In conclusion, the results of our study showed that a high preoperative BUN/Cr ratio increases the risk of mortality in patients who develop enteric fistulas after surgery for GI cancer.

Association between HLA-DQA1, HLA-DQB1 and oral cancer.

Cancer is one of the most common causes of morbidity and mortality. Genes whose products play a critical role in regulation of the immune response include the HLA antigen and cytokine families of genes. Oral cancer is common in men in developing countries, and its frequency is increased by using betel-quid, tobacco, and alcohol. The association between certain HLA Class I and Class II haplotypes and cancer has been documented in a variety of tumors. There was no previous data concerning the association of specific HLA Class II DQA1, DQB1 alleles, or haplotypes with oral cancer patients. In this study, we enrolled 134 Taiwanese patients with histologically confirmed oral cancer and 268 age- and gender-matched healthy Taiwanese adults as control group to investigate the association between HLA-DQA1, HLA-DQB1 allele frequencies and oral cancer patients by using polymerase chain reaction with sequence-specific primers. We found that both HLA-DQA1* and HLA-DQB1* allele frequencies in oral cancer patients revealed no significant difference from those of control groups. Haplotype frequencies of HLA*DQA1-0103-DQB1*0601 in oral cancer patients were significantly lower than those of the control group (odds ratio: 0.18, 95% confidence interval: 0.054-0.583, p(c)=0.02). Our data suggest that HLA DQA1*0103-DQB1*0601 haplotype may be protective with regard to the development of oral cancer.

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.

Effective eradication of oral verrucous carcinoma with continuous intraarterial infusion chemotherapy.

BACKGROUND: We evaluated the effectiveness of intraarterial methotrexate infusion as a primary therapy for oral verrucous carcinoma (VC). METHODS: Fifteen male patients (mean age, 55 years) were included. By using an implantable port-catheter system and a portable pump, methotrexate was continuously infused to the external carotid artery for a mean period of 7.5 days (50 mg/day), followed by weekly bolus of methotrexate (25 mg) via intraarterial route for a mean period of 10 weeks. RESULTS: The tumor regressed dramatically and disappeared completely after treatment within a mean period of 2.5 months. All patients obtained complete remission and recovered without disfigurement. All patients were alive without disease recurrence at a median follow-up of 43 months. The side effects were tolerable. CONCLUSIONS: The results of our treatment modality for oral VC appear to compete favorably with the results of surgical series and even more with those of radiotherapy series.

Continuous intraarterial infusion chemotherapy for early lip cancer.

Most lip cancers are usually diagnosed and can be treated with good prognosis at an early stage. This study reports our experience of treating seven, previously untreated, patients with lip cancer in stage I or II using intraarterial infusion chemotherapy with a single agent. They were all males with ages ranging from 37 to 69 years. An implantable port-catheter system was used for catheterization. Methotrexate 50mg was infused continuously to the external carotid artery every 24h using a portable pump. Methotrexate was given continuously for a mean period of 7 days (range, 4-10 days) and the total administrated dose of methotrexate for intraarterial infusion ranged from 200 to 500 mg (mean, 350 mg). These seven patients were then given weekly bolus of methotrexate (25mg) via intraarterial route for a range of 6-12 weeks. In every case the tumor regressed dramatically and disappeared completely after treatment within a mean period of 2.5 months. Only one patient died, of non-disease related pneumonia 3 years after infusion therapy. The remaining patients are still alive and no recurrence of carcinoma has been observed at a median follow-up period of 28 months. There was no catheter-related complication. The side effects of infusion chemotherapy were mild and tolerable. Our technique of continuous intraarterial infusion therapy for treatment of early lip cancers seems to be as effective as other standard techniques such as surgery or radiation therapy. This modality achieves good tumor response rates, an excellent cosmetic result, preservation of function and minimal side effects.

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.

WOX1 is essential for UVB irradiation-induced apoptosis and down-regulated via translational blockade in UVB-induced cutaneous squamous cell carcinoma in vivo.

PURPOSE: We investigated the role of candidate tumor suppressor and proapoptotic WOX1 (also named WWOX, FOR, or WWOXv1) in UVB-induced apoptosis and formation of cutaneous squamous cell carcinomas (SCC). EXPERIMENTAL DESIGN: Expression of WOX1 and family proteins (WWOX) in human primary cutaneous SCCs was examined by immunohistochemistry, in situ hybridization, and reverse transcription-PCR. UVB irradiation-induced WOX1 activation (Tyr33 phosphorylation and nuclear translocation), apoptosis, and cutaneous SCC formation were examined both in vitro and in vivo. RESULTS: Up-regulation of human WOX1, isoform WOX2, and Tyr33 phosphorylation occurred during normal keratinocyte differentiation before cornification and death. Interestingly, significant reduction of these proteins and Tyr33 phosphorylation was observed in nonmetastatic and metastatic cutaneous SCCs (P < 0.001), but without down-regulation of WWOX mRNA (P > 0.05 versus normal controls), indicating a translational blockade of WWOX mRNA to protein. During acute exposure of hairless mice to UVB, WOX1 was up-regulated and activated in epidermal cells in 24 hours. In parallel with the clinical findings in humans, chronic UVB-treated mice developed cutaneous SCCs in 3 months, with significant reduction of WOX1 and Tyr33 phosphorylation and, again, without down-regulation of WWOX mRNA. Human SCC-25 and HaCaT cells were transfected with small interfering RNA-targeting WOX1 and shown to resist UVB-induced WOX1 expression, activation, and apoptosis. CONCLUSIONS: WOX1 is essential for UVB-induced apoptosis and likely to be involved in the terminal differentiation of normal keratinocytes. During UVB-induced cutaneous SCC, epidermal cells have apparently prevented the apoptotic pressure from overexpressed WOX1 by shutting down the translation machinery for WWOX mRNA.

Subungual verrucous carcinoma of the thumb treated by intra-arterial infusion with methotrexate.

BACKGROUND: For preservation of integrity of appearance and function in a 66-year-old male with an extremely rare case of verrucous carcinoma developing from the subungium of his right thumb, intra-arterial infusion with methotrexate was used. OBJECTIVE: To evaluate the effectiveness of arterial infusion with methotrexate in this unusual nail bed cancer. METHODS: Right brachial arterial catheterization and infusion with methotrexate (50 mg) were used every 24 hours together with simultaneous intramuscular injection of 6 mg of leucovorin every 6 hours for 10 days. RESULTS: At 4 years, 8 months after therapy, the patient was in sustained complete remission with a functionally normal right thumb. CONCLUSION: This case study suggests that intra-arterial infusion chemotherapy is a simple and effective method for thumb subungual verrucous carcinoma with the unique advantage of preservation of morphology and functional conditions. It can be considered an effective treatment option.

Squamous cell carcinoma of the big toe successfully treated by intra-arterial infusion with methotrexate.

BACKGROUND: For preservation of integrity of appearance and function in a 57-year-old male with a squamous cell carcinoma of his left big toe who had refused amputation, intra-arterial infusion with methotrexate was used. OBJECTIVE: To evaluate the effectiveness of arterial infusion with methotrexate in this uncommon big toe cancer. METHODS: Left external iliac arterial catheterization and infusion with methotrexate (50 mg) were used every 24 hours plus simultaneous intramuscular injection of 6 mg of leucovorin every 6 hours for 8 days. RESULTS: At 7 years and 3 months after therapy, the patient was in sustained complete remission with a functionally normal left foot. CONCLUSION: This case study suggests that intra-arterial infusion chemotherapy is a simple and effective method for big toe squamous cell carcinoma with the unique advantage of preservation of organ and function. It can be considered as an effective alternative treatment.

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.

Bile duct cancer 25 years after choledochoduodenostomy: a case report.

We describe a 65-year-old man who had undergone choledochoduodenostomy (CDS) for choledocholithiasis 25 years prior to admission to our hospital for cholangitis. Abdominal sonography and computerized tomography (CT) scan revealed a tumor mass at the hilar region with bilateral intrahepatic duct dilatation. Upper gastrointestinal endoscopic examination indicated the site of the CDS. Biopsy was taken from the mucosa of the bile duct, and pathology revealed well-differentiated adenocarcinoma. CT scan and angiography further confirmed unresectable hilar bile duct cancer. Conservative treatment with intra-arterial chemotherapy was arranged. After briefly reviewing the hypothesized pathogenesis and radiographic diagnosis of this rare case, we recommend that chronic cholangitis consequent to CDS should be closely followed for late development of biliary tract malignancy.