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M A Maddaus

Publications and source records attributed to M A Maddaus.

At least 19 recordsLinked to original sources
PubMed2006

Minimally invasive cancer surgery improves patient survival rates through less perioperative immunosuppression.

The import of the immune system to cancer survival is paramount. Immune effector cells are intimately involved in the patient's response to cancer. People with decreased immune function develop cancer more frequently. In the early stages of solid organ malignancies, surgery can potentially be curative. Surgical intervention, in and of itself, is immunosuppressive. Surgical resections are traditionally performed through large incisions. Technologic advances have allowed minimally invasive surgery (MIS) to evolve to the point it is now being used for cancer treatment. Recent minimally invasive series have reported improved survival and recurrence rates, as compared with historical data. We hypothesized that outcome differences for cancer patients undergoing open surgery vs. MIS are due to differential inhibition of immune effector cell function, in response to the different surgical stimulus. This increased immunosuppression after open surgery could potentially inhibit immune effector cell tumor surveillance as well as inhibit scavenging of any residual or micrometastatic disease or of tumor cells shed at the time of the operation. The less immunosuppressive MIS may leave immune function above a threshold level where remaining tumor is cleared. This difference would lead to less recurrence and to survival advantages. A deeper understanding of the integral components of the immune response to surgery would open the door for immunomodulation strategies and be of great clinical utility in guiding neoadjuvant, surgical, or adjuvant therapeutic decisions.

Carcinoma, Non-Small-Cell Lung↗
PubMed2004

Situs inversus totalis: giant hiatal hernia repair by laparoscopic Collis gastroplasty and Nissen fundoplication.

We report the repair of a giant hiatal hernia by laparoscopic Collis gastroplasty and Nissen fundoplication in a patient with situs inversus totalis, highlighting the unique anatomic challenges in this case. The 52-year old female patient had Kartageners syndrome, a giant hiatal hernia, and a history of chronic severe gastroesophageal reflux disease with uncontrolled regurgitation. The laparoscopic procedure was accomplished with five ports placed in a mirror-image configuration, reversed from our standard positions. After visual confirmation of the complete reversal of the intraabdominal anatomy, we performed a modified Collis gastroplasty and Nissen fundoplication. Significant technical challenges were encountered intraoperatively. To the best of our knowledge, this report is the first of its kind in the literature. The use of advanced laparoscopic techniques is highly adaptable to unusual anatomy. Laparoscopic hiatal hernia surgery is feasible in patients with situs inversus.

Female↗
PubMed2001

Postpneumonectomy syndrome after left pneumonectomy.

Postpneumonectomy syndrome, a late complication of pneumonectomy, is secondary to shift of the mediastinum and remaining lung toward the pneumonectomy side, leading to tracheobronchial compression between the vertebral body and the aorta or pulmonary artery. Obstructive airway symptoms are usually due to tracheobronchial tree compression, however, secondary airway malacia may develop. We report herein a case of postpneumonectomy syndrome with secondary bronchomalacia after left pneumonectomy in a patient with normal mediastinal vascular anatomy.

Adult↗
PubMed2001

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Biomarkers, Tumor↗
PubMed1998

Surgical therapy for pulmonary aspergillosis in immunocompromised patients.

BACKGROUND: Medical management for invasive pulmonary aspergillosis (IPA) is often unsatisfactory. Antifungal therapy may be unable to eradicate IPA in the immunocompromised or neutropenic patient. METHODS: We retrospectively reviewed the surgical management of IPA in 13 immunocompromised patients at our institution. Twelve patients underwent perioperative bone marrow transplantation (4 autologous, 8 allogenic). All 13 patients received antifungal therapy. Eleven patients were neutropenic at the time of operation. RESULTS: The mean interval from diagnosis of aspergillosis to operation was 42 days (range, 3 to 135 days). Eighteen operations were performed on the 13 patients. Seven patients had resections from multiple pulmonary sites, whereas 6 had a single lesion resected. The average lesion resected was 3.7 cm in greatest diameter (range, 1 to 9 cm). After a mean follow-up of 21 months (range, 0 to 9 years), 3 patients (23%) are alive with no evidence of aspergillosis, 6 patients (46%) died without evidence of aspergillosis, and 4 patients (31%) died secondary to aspergillus infection. All 4 patients who died of aspergillus infection received an allogenic bone marrow transplantation. Two patients with direct extrapulmonic extension of IPA at time of operation died of recurrent aspergillus infections. Three of 4 patients who died of aspergillus infection had an absolute neutrophil count less than 1,300 cells/microL at time of operation. The mean absolute neutrophil count of the patients who cleared the aspergillus infection was 5,538 cells/microL. The mean survival of allogenic bone marrow transplant recipients was 5.2 months, and for recipients of autografts was 51.4 months. CONCLUSIONS: In this series, surgical resection of IPA cleared the aspergillus infection in 69% of the patients. Neutropenia, extrapulmonic extension of IPA, and allogenic bone marrow transplantation may predict a worse prognosis. Surgical resection of IPA in immunocompromised patients is an effective form of therapy in a properly selected patient population.

Adolescent↗
PubMed1998

Primary esophageal lymphoma: a diagnostic challenge.

A 56-year-old man with primary esophageal lymphoma is presented. Diagnosis of this disease can present a challenge. Clinical characteristics, treatment principles, and a detailed discussion of diagnosis are presented. When primary esophageal lymphoma is diagnosed, combination chemotherapy and radiotherapy afford a significant chance of long-term survival.

Antineoplastic Combined Chemotherapy Protocols↗
PubMed1998

Serum carcinoembryonic antigen as an adjunct to preoperative staging of lung cancer.

OBJECTIVE: To determine whether measurement of preoperative serum carcinoembryonic antigen concentrations adds useful prognostic data to current preoperative staging of lung cancer by computed tomography, bronchoscopy, and mediastinoscopy. METHODS: A prospective cohort study of 130 consecutive patients was evaluated for suspected lung cancer from July 1991 through December 1992 at a university-affiliated Veterans Affairs Medical Center. Serum concentrations of carcinoembryonic antigen were measured before diagnosis, staging, or resection of cancer. RESULTS: Malignant disease was diagnosed by bronchoscopy, needle biopsy, mediastinoscopy, or resection in 111 of 130 patients. In the 50 patients undergoing resection with curative intent, multivariate analysis indicated that carcinoembryonic antigen was a significant predictor of survival independent of patient age, pathologic stage, histologic type, and tumor size (P=.0357). CONCLUSIONS: Elevated preoperative serum concentrations of carcinoembryonic antigen predict a poor prognosis for lung cancer independent of other conventional staging parameters and have an adjunctive role in the staging of lung cancer.

Adenocarcinoma↗
PubMed1998

Do molecular markers predict survival in non-small-cell lung cancer?

Patients with non-small-cell lung cancer (NSCLC) survive for variable lengths of time, even when adjustment is made for pathological stage. Numerous reports suggest that biological markers predict survival in patients undergoing surgery for NSCLC with curative intent, but many of these claims are unconfirmed or conflicting. We postulated that the use of multiple putative markers might provide greater power in predicting survival. We studied 101 consecutive patients with NSCLC who underwent exploratory thoracotomy and who were followed for at least 2 yr. We assessed mutations in the p53 tumor suppressor gene (exons 5-8) and the K-ras oncogene (codons 12 and 13) by polymerase chain reaction amplification and single strand conformation polymorphism of the product. We identified 19 K-ras mutations (all adenocarcinomas except for two) and 40 p53 mutations among the 101 cases. We also evaluated p53 protein, bcl-2 protein, c-erbB-1 protein, c-erbB-2 protein, and MIA-15-5 antigen by standard immunocytochemical techniques, and we found that all of these antigens were variably expressed. As expected, we found a strong inverse association between surgical tumor stage and survival. Of the molecular markers studied, only MIA-15-5 antigen expression correlated strongly with survival by univariate analysis (p = 0.001) and it remained a significant predictor by multivariate analysis (p = 0.01). However, in this study, overexpression of MIA-15-5 antigen predicted an improved survival, whereas the original report showed a worse prognosis (N. Engl. J. Med. 1992;327:14). We conclude the multiple cell markers are not clinically useful in predicting survival among patients undergoing surgery for NSCLC. Differences between our results and prior reports may be due to chance, to true population differences, or to other factors.

Adult↗
PubMed1998

Detection of occult micrometastases in non-small cell lung carcinoma by reverse transcriptase-polymerase chain reaction.

BACKGROUND: The 5-year survival rate following surgical resection of Stage I or Stage II non-small cell lung carcinoma (NSCLC) is 30% to 50%, probably because of undetected occult micrometastases (OMs) at the time of surgery. Other investigators have detected OMs in bone marrow and histologically negative lymph nodes from patients with NSCLC using immunohistochemical staining to cytokeratins and cell surface glycoproteins. STUDY OBJECTIVE: To develop and evaluate an assay based on the reverse transcriptase-polymerase chain reaction (RT-PCR) for the detection of OMs in NSCLC. PATIENTS: Twenty-eight patients with benign or malignant thoracic pathology. Samples of primary tumors and lymph nodes were collected at the time of surgical resection or mediastinoscopic lymph-node biopsy. RESULTS: Using RT-PCR to detect messenger RNA (mRNA) transcripts for MUC1 (a cell surface glycoprotein present in lung tissue but absent from normal lymph nodes), OMs were identified in 33 of 88 lymph nodes determined to be free of tumor by hematoxylin and eosin staining. Eleven of 11 control mediastinal lymph nodes from patients without malignancy failed to express detectable MUC1 transcripts. Dilutional experiments demonstrate that the assay can detect one MUC1-positive NSCLC cell in 1x10(7) MUC1-negative cells. A comparison of our RT-PCR assay to immunohistochemistry specific for the MUC1 glycoprotein suggests that RT-PCR may be more sensitive than immunohistochemistry for the detection of NSCLC OMs. CONCLUSIONS: This study demonstrates that RT-PCR for MUC1 mRNA can detect the presence of MUC1 mRNA in histologically negative lymph nodes from patients with NSCLC. The prognostic significance of these findings is currently unknown.

Adult↗
PubMed1996

Rb and p16INK4a expression in resected non-small cell lung tumors.

Inactivation of the cyclin-dependent kinase inhibitor p16INK4a (CDKN2/MTS1) is documented in a wide variety of cancer cell lines and tumors. We have shown that loss of p16INK4a protein expression is a common event in early stage non-small cell lung cancer (NSCLC), correlates with a significantly worse survival, and is more common in higher stage disease. One hundred NSCLC tumors from patients undergoing definitive thoracotomies at a single institution were examined for p16INK4a and retinoblastoma protein (pRB) expression. Abnormal pRB staining was identified in 15% of the tumors, whereas 51% possessed aberrant p16INK4a protein expression. Tumors with aberrant expression of p16INK4a by immunohistochemistry were associated with a significantly worse survival (P=0.04). Additionally, the inverse correlation of pRB and p16INK4a expression previously noted in lung cancer cell lines and tumors was confirmed in this large cohort of patients, with 65% of the tumors demonstrating inverse expression of pRB and p16INK4a (p=0.00019). A statistically significant increase in aberrant p16INK4a expression, as well as inverse expression of p16INK4a and pRB, was seen with increasing pathological stage of disease. These findings establish the prognostic significance (of the absence of p16INK4, in resected NSCLC and confirm the critical importance of disrupting the pathway of cyclin-dependent kinase-mediated phosphorylation of pRB in the molecular oncogenesis and progression of NSCLC.

Adenocarcinoma↗
PubMed1994

Alternative design for radiologic guidance in video thoracoscopic surgery.

RATIONALE AND OBJECTIVES: Easy dislodgment and a pneumothorax rate of up to 50% have been reported with the use of mammographic hookwires for radiologic guidance in thoracoscopic surgery. An alternative design is described and preliminary in vitro results are reported. METHODS: The new design is based on the T-fastener used in percutaneous gastrostomies and can be deposited with a 20-Fr guidance needle. In vitro measurements of the anchoring capability of this design were compared with the anchoring capability of the Hawkin's III (Meditech/Boston Scientific, Watertown, MA) mammographic hook wire system. RESULTS: Anchoring capabilities of the alternative anchoring design and the Hawkin's III mammographic hook wire localization system are comparable. Complete dislodgement of both anchors occurs at approximately 350 gm. CONCLUSIONS: Preliminary in vitro investigation demonstrated similar anchoring capabilities of the new design and mammographic hook wires. Potential advantages of this suture-based localization device over hook wires are discussed.

Equipment Design↗
PubMed1992

Selective gut decontamination reduces nosocomial infections and length of stay but not mortality or organ failure in surgical intensive care unit patients.

Suppression of the gut luminal aerobic flora to reduce nosocomial infections was tested in a prospective, randomized, double-blind, placebo-controlled clinical trial in patients in a surgical intensive care unit who had persistent hypermetabolism. Forty-six patients were randomized to receive either norfloxacin, 500-mg suspension every 8 hours, together with nystatin, 1 million units every 6 hours, or matching placebo solutions administered through a nasogastric tube within 48 hours of surgical intensive care unit admission. Selective gut decontamination with the experimental therapy or placebo solutions continued for at least 5 days or until the time of surgical intensive care unit discharge. Patients were monitored with routine surveillance cultures for the development of nosocomial infections, as defined by criteria from the Centers for Disease Control. All other therapy was given as clinically indicated, including systemic antibiotics. The selective gut decontamination group experienced a significant reduction in the incidence of nosocomial infections and a reduced length of stay. However, these results were not associated with a concomitant decrease in progressive multiple organ failure syndrome, adult respiratory distress syndrome, or mortality.

Adult↗
PubMed1992

Subglottic tracheal resection and synchronous laryngeal reconstruction.

Postintubation injury of the upper airway commonly results in stenotic lesions of the larynx, subglottis, and adjacent trachea. The traditional approach to surgical correction is laryngofissure for the laryngeal component and staged plastic reconstruction of the subglottic stenosis. Reported results are variable and unpredictable, and permanent extubation is impossible in a significant number of patients. We report experience with 15 patients with combined laryngeal, subglottic, and tracheal stenosis who were managed by a one-stage operation: circumferential resection of the subglottis and trachea with primary thyrotracheal anastomosis, combined with laryngofissure and laryngeal reconstruction. These procedures required the collaboration of the Departments of Otolaryngology and Thoracic Surgery of the Toronto General Hospital. Between 1972 and 1991, our thoracic surgical division did 53 circumferential subglottic tracheal resections with primary thyrotracheal anastomosis for benign disease. There were no operative deaths and 51 of 53 patients were successfully extubated. In 15 of these patients, a concomitant laryngofissure for laryngeal reconstruction was required. Laryngeal repair included excision or incision of interarytenoid scar (n = 13), interarytenoid mucosal graft (n = 6), or mobilization of cricoarytenoid joint (n = 3). A temporary laryngotracheal stent (usually a Montgomery T tube) was maintained after the operation in all cases (duration 3 to 42 months). Thirteen of these 15 patients are now permanently extubated and none has functionally significant restenosis. Vocal function is satisfactory to good in these patients. The approach described for these combined laryngotracheal lesions provides better results than those reported with traditional staged and plastic techniques of reconstruction. The collaboration of the departments of otolaryngology and thoracic surgery was essential to achieve these results.

Adolescent↗
PubMed1988

Role of intestinal anaerobic bacteria in colonization resistance.

The purpose of this study was to clarify the role of the intestinal anaerobe bacteria in colonization resistance. Germfree mice were associated with Escherichia coli C25 and either (a) no other species; (b) enterococcus; (c) Escherichia coli M14 and Proteus mirabilis, or (d) Bacteroides fragilis and Bacteroides vulgatus. All species colonized the cecum in high numbers, but only enterococcus significantly limited the translocation of Escherichia coli C25 to mesenteric lymph nodes. However, the overall translocation rates were similar in all groups and ranged from 60% to 100%, due to translocation of other intestinal flora in addition to Escherichia coli C25. Conventionally reared mice were given either streptomycin, bacitracin/streptomycin or metronidazole which selectively eliminated facultative gram-negative bacteria, nearly all bacterial species or strictly anaerobic bacteria respectively. Only metronidazole significantly increased the rates of translocation of normal intestinal bacteria into mesenteric lymph nodes. Cohort groups of mice were then orally inoculated with drug resistant Escherichia coli C25, which actively colonized the cecum of all drug treated mice and translocated to the mesenteric lymph nodes of approximately half the streptomycin and metronidazole treated mice and nearly all the bacitracin/streptomycin treated mice. These results indicate that anaerobic bacteria play a pivotal role in limiting the translocation of normal intestinal bacteria, but that other bacterial groups also have a role in preventing the intestinal colonization and translocation of potential pathogens.

Animals↗
PubMed1988

The role of intestinal flora on the interactions between nonparenchymal cells and hepatocytes in coculture.

Kupffer cells are exposed directly to a number of factors in the portal circulation that can modify or regulate their responses to septic stimuli. The gut represents a potential source of a number of these factors including endotoxin, lymphokines, and prostaglandins. We examined Kupffer cells from germfree rats and germfree rats exposed to endotoxin or bacteria via their GI tracts to determine the importance of the intestinal flora in maintaining or modulating Kupffer cell responses. Kupffer cells from germfree animals were reduced in numbers and failed to respond to LPS in Kupffer cell: hepatocyte coculture. When germfree rats were exposed to bacterial endotoxin or bacteria via the gastrointestinal tract their Kupffer cells increased in numbers to normal and the cells responded to LPS in culture. Intestinal overgrowth with Escherichia coli for 2 days activated the Kupffer cells and significantly increased Kupffer cell sensitivity to LPS. These data suggest that the environment of the gastrointestinal tract is important for normal Kupffer cell responses and that intestinal bacterial overgrowth can modify Kupffer cell responses to septic stimuli.

Animals↗