Biomedical subjects

M K Ferguson

Publications and source records attributed to M K Ferguson.

At least 19 recordsLinked to original sources

PubMed1998

Induction chemotherapy, surgery, and concomitant chemoradiotherapy for carcinoma of the esophagus: a long-term analysis.

PURPOSE: To define the activity and toxicity of preoperative chemotherapy and postoperative concomitant chemoradiotherapy in patients with carcinoma of the esophagus, and to determine the effect on survival in patients treated with this approach. PATIENTS AND METHODS: Patients were treated with two 21-day cycles of induction chemotherapy with cisplatin 100 mg/m2 on day 1, 5-fluorouracil (5-FU) 800 mg/m2/day continuous infusion on days 1-5, and leucovorin 100 mg/m2 every four hours on days 1-5. Surgical resection was performed if feasible (and could also be performed prior to chemotherapy). Patients then received radiotherapy (50 to 60 Gy) every other week x five to six weeks, concomitantly with 5-FU 800 mg/m2 continuous infusion daily and hydroxyurea 1 g twice daily x five days. RESULTS: Forty-six patients were treated. With a minimum follow-up of 58 months, the median survival for the entire group was 16 months; the median survivals for patients with squamous carcinoma and adenocarcinoma were 29 months and 12 months, respectively. Toxicities of induction chemotherapy were severe neutropenia and mucositis; there was one toxic death. Toxicities of concomitant chemoradiotherapy were neutropenia, mucositis and esophagitis. There were five cases of radiation pneumonitis, one fatal. CONCLUSION: Induction chemotherapy and postoperative concomitant chemoradiotherapy can be added to surgical resection for carcinoma of the esophagus. Combined modality therapy, as reported here, produces long-term survival benefit, particularly in patients with squamous carcinoma. However, similar outcome results have been reported with less toxic and shorter treatment regimens as tested in randomized studies.

Adult↗

PubMed1998

Phase I study of vinorelbine, cisplatin, and concomitant thoracic radiation in the treatment of advanced chest malignancies.

PURPOSE: The cisplatin-vinorelbine regimen has superior activity in advanced non-small-cell lung cancer (NSCLC). We conducted a phase I trial to identify the maximum-tolerated dose (MTD) and dose-limiting toxicities (DLTs) of this regimen with concomitant thoracic radiation (RT) in patients with advanced chest malignancies. PATIENTS AND METHODS: Patients with advanced chest malignancies that required RT were enrolled onto this phase I study of standard chest radiation (30 daily 2-Gy fractions for a total of 60 Gy) and concurrent chemotherapy with cisplatin starting at 100 mg/m2 every 3 weeks and vinorelbine starting at 20 mg/m2/wk. RESULTS: Thirty-seven patients were treated on this study. Two of three patients treated at the maximum-administered dose of cisplatin 100 mg/m2 per cycle and vinorelbine 25 mg/m2/wk experienced acute DLT (neutropenia), which required deescalation. The dose level of cisplatin 100 mg/m2 and vinorelbine 20 mg/m2/wk, although tolerated acutely, produced delayed esophagitis, which proved dose-limiting. The recommended phase II dose was cisplatin 80 mg/m2 every 3 weeks and vinorelbine 15 mg/m2 given 2 of every 3 weeks with concomitant chest RT. CONCLUSION: Concomitant chemoradiotherapy with cisplatin and vinorelbine is feasible. The recommended phase II dose is cisplatin 80 mg/m2 every 3 weeks with vinorelbine 15 mg/m2 given twice over 3 weeks on a day 1/day 8 schedule. Esophagitis is the DLT, with neutropenia occurring at higher dose levels. A Cancer and Leukemia Group B (CALGB) phase II trial is currently underway to evaluate further the efficacy and toxicities of this regimen in unresectable stage III NSCLC.

Adult↗

PubMed1997

Resection for Barrett's mucosa with high-grade dysplasia: implications for prophylactic photodynamic therapy.

OBJECTIVES: Optimal therapy for Barrett's mucosa is controversial. Photodynamic therapy has recently been introduced as a technique for eradicating Barrett's mucosa with high-grade dysplasia. We sought to determine the incidence of invasive cancer and the outcomes after resection for high-grade dysplasia and to compare these results with published results of photodynamic therapy. METHODS: We performed a retrospective review of patients who underwent esophagectomy for Barrett's esophagus from 1985 to 1996 and completed a metaanalysis of published results of surgery for Barrett's esophagus with high-grade dysplasia. RESULTS: Thirteen men and two women with a mean age of 63 years underwent resection for Barrett's esophagus with high-grade dysplasia. The operation was performed through a transhiatal approach in nine and a transthoracic approach in six patients. There was no operative mortality. The final pathologic study demonstrated dysplasia in four patients, carcinoma-in-situ in three, and invasive carcinoma in eight patients (53%). All patients are alive and none of the patients with invasive cancer has recurrent disease. A metaanalysis of published results of 119 patients undergoing resection demonstrated an operative mortality of 2.6%, an incidence of invasive cancer of 47%, and a 5-year survival in patients with invasive carcinoma of 82%. CONCLUSIONS: A substantial percentage of patients with Barrett's mucosa containing foci of high-grade dysplasia have invasive carcinoma at the time of diagnosis. Resection is accompanied by a low operative risk, achieves an excellent long-term outcome, and should remain the standard therapy for Barrett's esophagus with high-grade dysplasia.

Barrett Esophagus↗

PubMed1997

Management of giant paraesophageal hernia.

A retrospective review was performed of 51 patients operated on for giant paraesophageal hiatal hernia to compare the transthoracic and transabdominal approaches and to assess the value of a concomitant fundoplication. Operative repair was performed using open transthoracic, transabdominal, and thoracoabdominal approaches. Laparoscopic techniques were used in one patient. Fundoplication was performed in 45 patients. There was no operative mortality, but early postoperative complications occurred in 29% of patients. The presence of commonly associated symptoms was used to derive preoperative and postoperative symptom scores. Follow-up was available in 48 patients. Excellent results were reported in 69% of patients and 17% had good results. The symptom score improved significantly regardless of the operative approach selected or whether a fundoplication was performed. We conclude that outcome after open paraesophageal hiatal hernia repair is satisfactory in most patients, irrespective of the route chosen or techniques used for repair.

Abdomen↗

PubMed1997

Esophageal perforation and caustic injury: management of perforated esophageal cancer.

Perforation of esophageal cancer is an unusual complication that most often results from instrumentation. The management of this condition must be individualized on the basis of the patient's condition and the stage of the cancer. For patients who are otherwise well and have localized disease, a standard resection is performed. Stent placement and esophageal exclusion are sometimes used for patients in good condition but in whom resection is not feasible. Supportive care alone is reserved for patients who have end-stage disease or are otherwise not candidates for aggressive therapy. Although the overall mortality rate is 50%, the risk for patients who undergo resection is less than 10%. This risk is similar to that found in patients undergoing elective resection and supports the concept that aggressive therapy should be pursued in highly selected patients with perforated esophageal cancers.

Esophageal Neoplasms↗

PubMed1997

Pitfalls and complications of antireflux surgery. Nissen and Collis-Nissen techniques.

The outcome of total fundoplication surgery for GER disease is unsatisfactory in 15% of patients. The likelihood of an unsuccessful outcome can be reduced by careful patient selection, which includes making an accurate diagnosis, and by choosing an operation that is tailored to the patient's physiology. Intraoperative and acute postoperative complications fortunately are rare and can be avoided through the use of meticulous surgical techniques. Late complications, including dysphagia, recurrent reflux symptoms, and delayed gastric emptying, are common and have a rate of reoperation of up to 10%; a systematic evaluation usually discloses their underlying causes. A slipped fundoplication wrap, an excessively tight wrap, a paraesophageal hiatal hernia, and severe recurrent symptoms are common indications for reoperation.

Esophageal Diseases↗

PubMed1996

Endothelin-1 synthesis and receptor-mediated activity in porcine lymph vessels.

Endothelin-1 (ET-1) is a potent vasoconstrictor of blood vessels and interacts with nitric oxide (NO) to regulate vascular tone. We hypothesized that ET-1 may modulate lymph vessel tone via local synthesis, receptor-mediated vasoconstriction, and interaction with NO. Serial sections obtained from formalin-fixed porcine mediastinal tissue, incubated with either ET-1 or von Willebrand factor antibody and stained with avidin-biotin complex and peroxidase, demonstrated ET-1 in lymphatic vascular endothelium. Isometric tension was recorded in vitro in fresh porcine tracheo-bronchial lymph vessel rings in response to the cumulative addition of ET-1 (10(-11) to 10(-6) M). ET-1 induced a tonic contraction with peak tension at 3 x 10(-7) M (mean tension 3731 +/- 306 mg; 259 +/- 20 percent of response to 65 mM KCl). The addition of specific receptor antagonists (ET(A) (BQ-610), ET(B) (BQ-788), or both) blocked the contractile response seen in ET-1 stimulated controls (ET(A) + ET(B) > ET(A)>> ET(B). The response to ET-1 was increased by endothelial damage but was unaffected by the inhibition of NO synthesis by N (G)-monomethyl-L-arginine (L-NMMA) Endothelial damage altered the ET-1 response in the presence of ET(B) antagonist but not ET(A) antagonist. ET-1 is a potent endothelium-derived vasoconstrictor of lymph vessels. Its effects are mediated through specific receptors, are not importantly modulated by NO, but may be modified by release of other endothelium-derived relaxing factors. We conclude that lymph vessel tone may be regulated by ET-1.

Analysis of Variance↗

PubMed1996

Retroperitoneal placement of an ICD generator: a solution for a difficult problem.

A woman experienced multiple episodes of pocket erosion after placement of an implantable cardioverter defibrillator culminating in a pocket infection. The device was placed in a retroperitoneal location, and the patient has not developed further episodes of pocket erosion or infection. Interrogation of the device in this position and its subsequent replacement have been straightforward.

Adult↗

PubMed1996

Genetic analysis of the activation domain of bovine papillomavirus protein E2: its role in transcription and replication.

The bovine papillomavirus protein E2 serves dual functions in viral transcription and in the initiation of viral replication. As a transcription factor, E2 can cooperatively interact with cellular proteins such as SP1 and stimulate transcription of distal promoters. In replication, E2 and the helicase El are the only viral proteins required for accurate replication of templates containing the viral origin. The amino terminus of E2 is a functionally separable domain critical for activation of both replication and transcription; its primary sequence is conserved between many strains of papillomavirus. We targeted conserved residues spanning the activation domain and constructed a series of 30 amino acid substitution mutants. These mutant E2 genes were analyzed for the ability to activate DNA replication and gene expression in cells. The majority of the substitutions affected the ability of E2 to support both viral replication and transcriptional activation, revealing substantial overlap of the functional determinants for these two processes. Replication and transcription activities are genetically separable, however, as mutations at amino acids 73 and 74 retained replication function but failed to activate transcription. Additionally, a mutation at position 39 substantially reduced replication activity but left transcriptional activation intact. Interestingly, over two-thirds of the mutations analyzed reduced function and protein accumulation, many in a temperature-dependent manner. The correspondence between the replication and transcription phenotypes of mutations spanning the activation domain may indicate that the entire region is folded into a single domain required for both functions.

Amino Acid Sequence↗

PubMed1996

Characterization of the effects of histamine in porcine tracheobronchial lymph vessels.

We characterized the responses of lymphatic vascular smooth muscle to histaminergic-receptor stimulation and blockade and explored the mechanisms underlying the histamine-stimulated release of endothelium-derived relaxing factor (EDRF). Fresh porcine tracheobronchial lymph vessel rings mounted in organ baths were stimulated by the cumulative addition of histamine or H1, H2, and H3 receptor-specific agonists in the presence or absence of receptor-specific antagonists. Histamine had a contractile effect on lymphatic vascular smooth muscle that was H1 receptor mediated. No important effects were elicited by H2- or H3-receptor stimulation. Histamine also caused the release of EDRF as demonstrated by an increase in smooth muscle tone in the absence of endothelium and after inhibition of nitric oxide synthase. This effect was strong at high concentrations of histamine and was mediated by H1-receptor stimulation. The results suggest that histamine may contribute to the regulation of lymphatic vascular smooth muscle tone under pathological conditions, an effect that may be controlled through modification of H1-receptor activity.

Animals↗

PubMed1996

Transcervical thymectomy.

Transcervical thymectomy has been used in the management of myasthenia gravis for over 20 years. Contraindications to this operation include advanced age, poorly controlled neurologic symptoms, and evidence for a thymoma. The procedure is associated with negligible morbidity and requires only a brief hospitalization. Remission rates are comparable with those reported for more extensive thymectomy operations.

Cervical Vertebrae↗

PubMed1996

Results of myotomy and partial fundoplication after pneumatic dilation for achalasia.

BACKGROUND: We questioned whether results of myotomy for achalasia are influenced by previous pneumatic dilation and whether surgical outcome is influenced by a dilation-related perforation necessitating urgent operation. METHODS: We performed a retrospective analysis of 60 patients who underwent transthoracic myotomy and fundoplication from 1977 to 1995. Dysphagia, heartburn, pain, and regurgitation were scored on a scale of 0 to 3 and results were classified according to combined symptom score. RESULTS: Dilation was performed before myotomy once in 15 patients, twice in 25, 3 times or more in 9, and never in 11 patients. Operation was urgent due to perforation in 6 patients (10%). There was no postoperative leak or mortality. Overall symptom score at last follow-up (57 +/- 8 months; 90% of patients) was improved compared with preoperative score (2.1 +/- 0.3 months versus 5.1 +/- 0.2 months; p < 0.0001). Outcome was unrelated to whether or not a perforation occurred (excellent/good outcomes in 100% and 88%, respectively) or to whether or not preoperative dilations had been performed (excellent/good outcomes in 90% and 89%, respectively). CONCLUSIONS: Myotomy and partial fundoplication is an effective technique for management of achalasia. Results are unaffected by the need for urgent operation for perforation and are unrelated to whether pneumatic dilation is performed preoperatively.

Adolescent↗

PubMed1996

The current status of lung volume reduction operations for emphysema.

In the 1990s, the concept of surgical therapy was introduced once again for the treatment of end-stage emphysema. The earliest reports touted laser ablation of emphysematous lung as definitive therapy. Although some discernable benefit was reported, this was associated with significant operative morbidity. In 1993, the concept of parenchymal resection or "lung volume reduction" was reintroduced as treatment for end-stage lung disease. Over the ensuing 3 years, different techniques and approaches have evolved at different institutions. Lung volume reduction has been performed bilaterally and unilaterally through multiple approaches including sternotomy, thoracotomy, and thoracoscopy. The results of these various approaches are reviewed and compared. Lung volume reduction appears to be a beneficial procedure when performed in carefully selected patients by personnel and at institutions that are experienced in the care of patients with end-stage emphysema.

Humans↗

PubMed1995

A phase I trial of concomitant chemoradiotherapy with cisplatin dose intensification and granulocyte-colony stimulating factor support for advanced malignancies of the chest.

UNLABELLED: Concomitant chemoradiotherapy with cisplatin and combination chemotherapy in the neoadjuvant setting have both shown promising results. PURPOSE: To identify a locally and systemically active concomitant chemoradiotherapy regimen incorporating high-dose cisplatin, interferon alfa-2a (IFN), fluorouracil (5-FU), hydroxyurea (HU) and radiotherapy. METHODS: Phase I cohort design establishing the maximal tolerated dose (MTD) of cisplatin with and without granulocyte colony stimulating factor (GCSF). For the first six dose levels, a 4-week cycle consisted of escalating doses of cisplatin during weeks 1 and 2, IFN (week 1), and 5-FU and HU (week 2) with single daily radiation fractions of 200 cGy during days 1-5 of weeks 1-3 and no treatment in week 4. When dose-limiting neutropenia was encountered. GCSF was added during weeks 1, 3, and 4. Finally, to decrease esophagitis, the radiotherapy schedule was altered to 150 cGy twice daily during weeks 1 and 2, followed by a 2-week break (level 7). RESULTS: Forty-nine patients with refractory chest malignancies were treated. The MTD of this regimen without GCSF was cisplatin 50 mg/m2 in weeks 1 and 2, IFN 5 million Units (MU)/m2 per day on days 1-5 in week 1, 5-FU 800 mg/m2 per day for 5 days by continuous infusion, and HU 500 mg every 12 h for 11 doses during week 2. The addition of GCSF during weeks 1, 3, and 4 allowed for escalation of cisplatin to 100 mg/m2 during weeks 1 and 2, with a decreased dose of IFN at 2.5 MU/m2 per day to avoid renal toxicity. Dose-limiting toxicity (DLT) included severe neutropenia, thrombocytopenia, and esophagitis in 5 of 13 patients. Increased thrombocytopenia in patients receiving GCSF was not observed. During hyperfractionated radiotherapy (level 7) chemotherapy doses were as above except for a reduction of 5-FU to 600 mg/m2 per day. While severe esophagitis was reduced, grade 4 thrombocytopenia became more prevalent and was seen in 6 of 7 patients. In-field tumor responses were observed in 17 of 28 evaluated patients with non-small-cell lung cancer. The median times to progression and survival were 4 and 6 months, respectively. When only patients with all known disease confined to the radiotherapy field were considered the corresponding times were 6 and 15 months, respectively. Most treatment failures occurred outside of the irradiated field. CONCLUSIONS: (1) This intensive multimodality regimen can be given with aggressive supportive care incorporating GCSF. The recommended phase II doses for a 4-week cycle are cisplatin 50 mg/m2 week 1, and 100 mg/m2 week 2, IFN 2.5 MU, HU 500 mg every 12 h x 11 and 5-FU 800 mg/m2 per day with single fraction radiotherapy during weeks 1-3 and GCSF during weeks 1, 3, and 4. (2) GCSF can be safely administered and provides effective support of neutrophils when administered simultaneously with IFN, cisplatin, and chest radiotherapy. (3) There is synergistic renal toxicity when high doses of IFN and cisplatin are given together. (4) Hyperfractionated radiotherapy decreases the severity of esophagitis but increases thrombocytopenia. (5) Although highly toxic, response rates, time to progression and survival figures with this regimen are encouraging and support its investigation in the phase II setting.

Adult↗

PubMed1995

Intensive multimodality therapy for carcinoma of the esophagus and gastroesophageal junction.

BACKGROUND: We designed a trial of intensive multimodality therapy for carcinoma of the esophagus and gastroesophageal junction to assess tumor response and operability after neoadjuvant chemotherapy and to determine the impact of trimodality therapy on longterm survival. METHODS: Thirty-two patients with resectable (clinical stage IIa, n = 17; IIb, n = 1; III, n = 14) squamous cell cancer (n = 15) or adenocarcinoma (n = 17) were treated with neoadjuvant chemotherapy (cisplatin, 5-fluorouracil, leukovorin), resection, and postoperative chemoradiotherapy (hydroxyurea, 5-fluorouracil; 50-66 Gy). RESULTS: Use of neoadjuvant chemotherapy yielded the following results: a measurable clinical response in 22 patients, stable disease in eight patients, disease progression in one patient, and death in one patient. Thirty-one patients underwent resection, with the following results: two operative deaths (6.5%) and nonfatal morbidity in 17 (59%); the median hospital stay was 13 days. Pathologic staging was stage 0, n = 1; I, n = 2; IIa, n = 11; IIb, n = 5; III, n = 7; and IV, n = 5. Postoperative chemoradiotherapy was completed in 23 patients with one death, for an overall treatment-related mortality rate of 12.5% (four of 32). At a mean follow-up of 22.5 months, median survival is 19.7 months and 14 patients are alive and disease free. CONCLUSIONS: Neoadjuvant therapy for cancer of the esophagus and cardia results in good tumor response. Esophagectomy in this setting can be accomplished with acceptable morbidity and mortality. Results of an interim analysis of survival are encouraging and suggest that further investigation of this regimen is warranted.

Adenocarcinoma↗

PubMed1995

Recurrent spontaneous perforation of the esophagus.

Boerhaave's syndrome is uncommon and its precise etiology is unclear. Information regarding the long-term outcome of patients surviving this injury is lacking. We present the case of a patient who suffered two spontaneous perforations of the esophagus that occurred 30 years apart.

Aged↗

PubMed1995

Current results of therapy for esophageal perforation.

BACKGROUND: Prior reviews of esophageal perforation with delayed recognition have reported mortality rates as high as 66%. We performed a retrospective review of patients with nonmalignant esophageal perforation to assess the outcome of current management techniques. PATIENTS AND METHODS: Charts were reviewed of all patients who were treated for nonmalignant esophageal perforation between 1980 and 1993. They were 23 men and 10 women, mean age 49 +/- 3 years, 19 of whom were diagnosed early (< or = 24 hours) and 14 of whom were diagnosed late (> 24 hours). RESULTS: Perforations were due to instrumentation (16), operative injury (7), spontaneous rupture (4), trauma (4), and other causes (2). Pre-existing esophageal disease was identified in 23 patients (70%), including achalasia (9), stricture (7), varices (5), and other (2). Treatment included closure and fundoplication or muscle wrap (10), closure with or without pleural flap (7), resection only (7), resection and reconstruction (3), drainage only (4), and observation (2). Nonfatal complications included empyema (4), arrhythmia (3), persistent leak following attempted closure (2), and other (5). They occurred in 50% of both the early and late diagnosis groups and were of comparable severity in both. The overall mortality was 9% (3/33). Causes of death were sepsis (1) and multisystem organ failure (2). Mortality was 5% (1/19) in patients diagnosed early and 14% (2/14) of those diagnosed late. CONCLUSIONS: Current mortality rates in nonmalignant esophageal perforation are improved compared to previously published rates of 19% for all patients with the condition, 9% following early and 29% following late diagnosis (47 patients overall). We conclude that, despite a high incidence of associated complications, the survival rate following nonmalignant esophageal perforation is improving and the impact of delayed recognition is decreasing.

Adolescent↗

PubMed1995

Safety and efficacy of video-assisted thoracic surgical techniques for the treatment of spontaneous pneumothorax.

Video-assisted thoracic surgery has been widely used in the treatment of spontaneous pneumothorax despite a paucity of data regarding the relative safety and long-term efficacy for this procedure. We reviewed 113 consecutive patients (68 male and 45 female patients, aged 15 to 92 years, mean 35.1) who underwent 121 video-assisted thoracic surgical procedures during 119 hospitalizations from 1991 through 1993. Recurrent ipsilateral pneumothorax was the most frequent indication for surgery and occurred in 77 patients (65%). The most common method of management was stapling of an identified bleb in the lung, which was undertaken in 105 (87%) patients. No operative deaths occurred. Complications included an air leak lasting longer than 5 days in 10 (8%) patients, two of whom required second procedures for definitive management. No episodes of postoperative bleeding or empyema occurred. The postoperative stay ranged from 1 day to 39 days (median 3 days, average 4.3 days) and 99 patients (84%) were discharged within 5 days. Mean follow-up was 13.1 months and ranged from 1 to 34 months. Eleven patients (10%) were lost to follow-up. Ipsilateral pneumothorax recurred after five of 121 procedures (4.1%). Twelve perioperative parameters (age, gender, race, smoking history, site of pneumothorax, severity of pneumothorax, operative indications, number of blebs, site of blebs, bleb ablation, method of pleurodesis, and prolonged postoperative air leak) were entered into univariate and multivariate analysis to identify significant independent predictors of recurrence. The only independent predictor of recurrence was the failure to identify and ablate a bleb at operation, which resulted in a 23% recurrence rate versus a 1.8% rate in those with ablated blebs (p < 0.001). These data suggest that video-assisted thoracic surgery is a viable alternative to thoracotomy for the treatment of recurrent spontaneous pneumothorax. It results in a short hospital stay, low morbidity, high patient acceptance, and a low rate of recurrence.

Adult↗