Combination cisplatin, 5-fluorouracil and radiation therapy for locally advanced unresectable or medically unfit bladder cancer cases: a Southwest Oncology Group Study

PURPOSE: Patients with locally advanced bladder cancer or who are not medically fit for surgery are a therapeutic dilemma. Radiotherapy with or without single agent cisplatin has been the major therapeutic modality. A phase II Southwest Oncology Group trial investigated the efficacy and feasibility of 5-fluorouracil, cisplatin and radiation in this patient subset. MATERIALS AND METHODS: Eligible patients had muscle invasive bladder cancer (clinical stages T2-T4) with nodal involvement at or below the level of bifurcation of the iliac vessels, were medically or surgically inoperable, or refused cystectomy. Patients underwent pretreatment cystoscopy and detailed tumor mapping, and were treated with 75 mg. /m.2 cisplatin on day 1 and 1 gm./m.2 daily, 5-fluorouracil on days 1 to 4 and definitive radiotherapy. Chemotherapy was repeated every 28 days, twice during and twice after radiation. RESULTS: From October 1993 to April 1998, 60 patients were enrolled in study. Of the 56 eligible patients 34% had unresectable tumors, 21% were not medically fit for surgery and 45% refused cystectomy. Overall, 68% of the patients had clinical T3 tumors or greater and 22% had nodal metastasis. Treatment was completed as planned in 32 of 56 (57%) patients. The most frequent grade 3 or 4 toxicities were neutropenia, stomatitis or mucositis, diarrhea, neuropathy and nausea. There were 53 patients who were evaluable for response, although response was not determined for 18. The overall response rate was 51% (95% confidence interval [CI] 37 to 65) based on intent to treat with a complete response rate of 49% (95% CI 35 to 63). Estimated median survival of the 56 patients was 27 months (95% CI 21 to 40 months) with an overall 5-year survival of 32%. The 5-year survival of the 25 patients who refused surgery was 45%. CONCLUSIONS: Concurrent 5-fluorouracil, cisplatin and radiation therapy is feasible. Despite a promising complete response rate, the overall 5-year survival suggests the need for more effective systemic therapy. The 5-year survival of patients who refused cystectomy suggests that this combined modality may provide another alternative to cystectomy for these patients.     

Venous air embolism during the use of a Nd YAG laser

We report a case of a 47-year-old female who suffered a cardiac arrest during sub-mucosal diathermy of the inferior turbinate using a Nd YAG laser. The possible causes of the cardiac arrest are discussed. Venous air embolism due to Nd YAG laser was thought to be the most likely cause in this case. Although venous air embolism has previously been reported during nasal sinus surgery and choanal atresia when using a Nd YAG laser, the occurrence of this complication during a relatively minor surgical procedure has not previously been reported. It is important, therefore, to raise the awareness of this life threatening complication during use of a Nd YAG laser regardless of the duration of surgery. We recommend the use of appropriate methods and techniques to avoid this life threatening complication during the use of Nd YAG laser even for relatively short procedures.     

Compound palmar ganglion with carpal tunnel syndrome

Compound palmer ganglion is an uncommon condition characterized by a swelling in the distal part of volar aspect of wrist and communicating with another swelling over palm across the flexor retinaculum. It commonly results from tuberculous tenosynovitis. It may lead to carpal tunnel syndrome and need surgical excision with division of flexor retinaculum.     

Spilled gallstones during laparoscopic cholecystectomy

Introduction

Incidental gallbladder cancer is found in 0.6–2.1% of patients undergoing laparoscopic cholecystectomy for symptomatic gallstones. Patients with Tis or T1a tumours generally undergo no further intervention. However, spilled stones during surgery may have catastrophic consequences. We present a case and suggest aggressive management in patients with incidental gallbladder cancer who had spilled gallstones at surgery.

Case History

A 37-year-old woman underwent a laparoscopic cholecystectomy for symptomatic gallstones, during which some stones were spilled into the peritoneal cavity. Subsequent histological examination confirmed incidental pT1a gallbladder cancer. Hepatopancreatobiliary multidisciplinary team discussion agreed on regular six-monthly follow-up. The patient developed recurrent pain two years after surgery. Computed tomography revealed a lesion in segment 6 of the liver. At laparotomy, multiple tumour embedded gallstones were found on the diaphragm. Histological examination showed features (akin to the original pathology) consistent with a metastatic gallbladder tumour.

Conclusions

This case highlights the potential for recurrence of early stage disease resulting from implantation of dysplastic or malignant cells carried through spilled gallstones. It is therefore important to know if stones were spilled during original surgery in patients with incidental gallbladder cancer following a laparoscopic cholecystectomy. Aggressive and early surgical management should be considered for these patients.     

A Meta-Analysis to Determine the Effect of Primary Tumor Resection for Stage IV Colorectal Cancer with Unresectable Metastases on Patient Survival

Background

Approximately 20 % of patients diagnosed with colorectal cancer will have distant metastases at first presentation (stage IV disease). The effect of removing the primary tumor on survival for patients with stage IV disease with unresectable metastases remains unclear. To address this a meta-analysis of all studies comparing primary tumor resection with chemotherapy alone in cases of stage IV colorectal cancer with unresectable metastases was performed.

Methods

A comprehensive search for published studies examining the effect of primary tumor resection in the setting of colorectal cancer with unresectable metastases was performed. Each study was reviewed and data extracted. Random-effects methods were used to combine data.

Results

There were 21 studies including a total of 44,226 patients that met the inclusion criteria. Resection of the primary tumor in patients with unresectable metastases compared with chemotherapy alone was associated with a lower mortality risk (OR 0.28; 95 % CI 0.165–0.474; P < 0.001), translating into a difference in mean survival of 6.4 months in favor of resection (95 % CI 5.025–7.858, P < 0.001). Patients who underwent resection of the primary tumor were more likely to have liver metastasis only (OR 1.551; 95 % CI 1.247–1.929; P < 0.001), were less likely to have ≥2 metastasis (OR 0.653; 95 % CI 0.508–0.839; P = 0.001), and were less likely to have rectal cancer (OR 0.495; 95 % CI 0.390–0.629; P < 0.001). There was significant cross-study heterogeneity.

Conclusions

Resection of the primary tumor may confer a survival advantage in stage IV colorectal cancer with unresectable metastases but significant selection bias exists in current studies. Randomized controlled trials are essential to validate these findings.     

Electroporation enhances transfection efficiency in murine cutaneous wounds

Transfection of wounds with DNA-encoding growth factors has the potential to improve healing, but current means of nonviral gene delivery are inefficient. Repeated high doses of DNA, necessary to achieve reliable gene expression, are detrimental to healing. We assessed the ability of in vivo electroporation to enhance gene expression. Full-thickness cutaneous excisional wounds were created on the dorsum of female mice. A luciferase- encoding plasmid driven by a CMV promoter was injected at the wound border. Following plasmid administration, electroporative pulses were applied to injection sites. Pulse parameters were varied over a range of voltage, duration, and number. Animals were euthanized at intervals after transfection and the luciferase activity measured. Application of electric pulses consistently increased luciferase expression. The electroporative effect was most marked at a plasmid dose of 50 micro g, where an approximate tenfold increase was seen. Six 100- micro s-duration pulses of 1750 V/cm were found to be the most effective in increasing luciferase activity. High numbers of pulses tended to be less effective than smaller numbers. This optimal electroporation regimen had no detrimental effect on wound healing. We conclude that electroporation increases the efficiency of transgene expression and may have a role in gene therapy to enhance wound healing.