Autologous cell salvage in off-pump coronary artery bypass surgery reduces post-operative complications: a retrospective weighted-matching analysis.

OBJECTIVES: Blood transfusion plays a crucial role in coronary artery bypass grafting (CABG). The choice between autologous cell saver (CS) and allogenic blood transfusion (ABT) has been a continuous debate in the medical community, especially within cardiac surgery. This study aimed to assess the outcomes of off-pump CABG (OPCAB) surgery in patients receiving blood solely via cell salvage compared to those receiving ABT or a combination of ABT and CS perioperatively. METHODS: A total of 414 patients who underwent isolated OPCAB surgery at our cardiovascular clinic were analyzed. Among them, 250 patients (60.4%) received blood via CS alone, while 164 patients (39.6%) received either ABT or a mix of ABT and CS. Stabilized inverse probability treatment weighted (IPTW) matching technique ensured balance in baseline covariates. RESULTS: We found no significant differences in 30-day mortality rates between the CS and ABT groups. The CS group displayed significantly lower rates of overall complications, encompassing stroke, acute kidney injury, atrial fibrillation, and pulmonary complications. Rates of sepsis, readmission, gastrointestinal complications, heparin-induced thrombosis, and deep venous thrombosis were comparable between the two groups. However, in contrast to the ABT group, the CS group exhibited significantly shorter median lengths of hospital stay (LOHS), ICU stay, and ventilation time, along with higher rates of discharge to home rather than acute care facilities. CONCLUSION: Our data suggest that autologous blood transfusion via CS results in fewer perioperative complications and faster recovery following OPCAB procedures as compared to ABT.

Risk of pneumonectomy after induction therapy for locally advanced non-small cell lung cancer.

BACKGROUND: Recent data from prospective multimodality trials have documented an unacceptable early mortality with pneumonectomy after induction chemotherapy. This finding has raised skepticism toward pneumonectomy as a surgical option for patients with regionally advanced nonsmall-cell lung cancer. In the current study, perioperative outcomes after pneumonectomy with or without neoadjuvant therapy are compared to determine the impact of induction therapy on perioperative mortality in this setting. Variables associated with increased perioperative risk are identified. METHODS: A review of 315 nonsmall-cell lung cancer patients (196 male [62%]) undergoing pneumonectomy over a 15-year period was undertaken. Patients were well matched for clinical variables other than receiving induction chemotherapy. Complications and operative mortality were analyzed for associations with laterality and induction chemotherapy. RESULTS: Median age was 64 years, (range, 25 to 82). Age was predictive of mortality in 13 of 86 patients (15%) more than 70 years old, compared with 16 of 229 patients (7%) less than 70 years old (hazard ratio = 1.77, p = 0.046). Overall operative mortality was 9.2% (29 of 315). There were 115 left-sided (37%) and 200 right-sided (63%) pneumonectomies. Sixty-eight patients (22% [left = 31, right = 37]) received induction chemotherapy. Surgery alone was performed in 247 patients. Mortality among patients undergoing induction chemotherapy was 21% (odds ratio = 4.01; p = 0.0007). After induction chemotherapy, postoperative bronchopleural fistula associated with respiratory failure was predictive of operative mortality (hazard ratio = 148, p = 0.0001). Left-side pneumonectomy did appear to a have a greater incidence of postoperative arrhythmia. CONCLUSIONS: Morbidity and mortality after pneumonectomy is substantial. Patients greater than 70 years old appear to be at increased risk. Induction chemotherapy also increases the risk of operative mortality after pneumonectomy. Patients should be advised of this increased operative risk, and the multidisciplinary team must consider this when pneumonectomy appears necessary after induction therapy for locally advanced nonsmall-cell lung cancer.

Survival among patients with platinum resistant, locally advanced non-small cell lung cancer treated with platinum-based systemic therapy.

BACKGROUND: Recent adjuvant chemotherapy trials after resection of stage II and III non-small cell lung cancer (NSCLC) have identified important survival differences among patients with immunohistochemical evidence suggesting platinum resistance. No clinical information exists regarding the impact upon survival of patients treated with platinum agents who exhibit cellular evidence of their tumors' resistance to platinum. We evaluated the utility of the extreme drug resistance (EDR) assay to predict mortality among a consecutive group of stage II through IV NSCLC patients receiving adjuvant or definitive platinum-based chemotherapy after resection or surgical biopsy. METHODS: The Extreme Drug Resistance (EDR) Assay is a clinically validated cellular proliferation assay used to test tumors for chemotherapy drug resistance. Based on response in the EDR assay, tumor specimens from stage II through IV NSCLC patients were segregated into three groups: extreme drug resistant (EDR), intermediate drug resistant (IDR), and low drug resistant (LDR). Patient survival was evaluated after platinum-based chemotherapy. RESULTS: Platinum IDR/EDR was statistically significant in predicting shorter overall survival (29.8 months vs. 15.6 months) among platinum IDR/EDR-resistant patients compared with LDR patients (P = 0.047). Median survival was 16.6 months for patients with IDR/EDR to platinum and any other second agent of doublet therapy compared with patients with LDR to any platinum-based doublet where median survival was not achieved (P = 0.0268). CONCLUSIONS: This is the first study to demonstrate the utility of the EDR assay to predict poor clinical outcome when platinum-based therapy is used to treat patients with biological evidence of tumor resistance to platinum. These data corroborate the finding of recent studies evaluating possible molecular correlates to poor response to specific chemotherapeutic agents.

Dosimetric evaluation of radiation exposure during I-125 vicryl mesh implants: implications for ACOSOG z4032.

BACKGROUND: Segmentectomy or wedge resection along with brachytherapy delivered via a vicryl mesh implant imbedded with 125I is a novel therapeutic modality to treat early stage lung cancer. This modality is being evaluated in a large national prospective randomized trial (ACOSOG Z4032). There has been concern that this method exposes physicians and staff to unacceptable amounts of radiation. In this prospective study, we measured the exposure to health care professionals during such a procedure. METHODS: Dosimetric readings using Special Microdosimeter thermoluminescent detectors (TLDs) (Landauer, Inc) were performed during 22 125I vicryl mesh implantations. Diodes were placed on the back of the each hand of the primary radiation oncologist and primary surgeon during the creation and implantation of the mesh. In addition, diodes were placed on the posterior shoulder of the patient to obtain a control reading. RESULTS: Patients had 40-60 125I seeds placed. Median activity per seed was 0.511 milli Curie (mCi), with a median total activity implanted of 23.0 mCi. Median radiation dose to the radiation oncologist was 1 milli rem (mrem), and that to the surgeon was 2 mrem. Median dose to the control diode on the patient was a median radiation dose to the outside of the patient of 5.4 mrem/h. CONCLUSIONS: There is very little radiation exposure to physicians and staff during a segmentectomy and 125I vicryl mesh implantation. This is a safe method of lung cancer treatment with respect to health care professionals, although the ALARA (As Low As Reasonably Achievable) principle should still be followed.

Laparoscopic clam shell partial fundoplication achieves effective reflux control with reduced postoperative dysphagia and gas bloating.

BACKGROUND: We describe a novel laparoscopic "clam shell" partial fundoplication, incorporating a modified Toupet with an anterior fundic flap for the management of medically recalcitrant gastroesophageal reflux disease. We hypothesize that this clam-shell-like mechanism allows a dynamic rather than rigid circumferential antireflux barrier allowing effective reflux control (compared with partial fundoplication) with reduced occurrence of postoperative dysphagia, gas bloating and vagal nerve injury (compared with Nissen fundoplication). METHODS: Between November 2002 and May 2006, 140 patients (82 female; mean age, 53 years) underwent this laparoscopic clam shell fundoplication procedure for medically recalcitrant gastroesophageal reflux disease (n = 94) or large paraesophageal hernias (n = 46). Preoperative invasive studies (endoscopy, manometry, pH monitoring) and noninvasive studies (barium swallow and radionuclide gastroesophageal motility) revealed esophageal dysmotility in 26 patients. Routine barium swallow and radionuclide studies were performed 6 months postoperatively and then at yearly intervals. RESULTS: There was no mortality or conversions to open procedures. Mean operative time was 45 minutes; median hospital stay was 1 day (range, 1 to 4). Overall control of reflux symptoms was seen in 95% of patients. Postoperative gas bloating and significant dysphagia occurred in only 11% and 6% of patients, respectively. Three patients (2%) experienced postoperative complications (pneumonia, 2; pleural effusion requiring drainage, 1). Postoperative studies demonstrated reflux in 8 patients (5%) and the presence of small hiatal hernias in 5 patients (4%) during a mean follow-up 19 months (range, 7 to 42). Twenty five patients (17%) underwent postoperative esophageal dilation (median dilations, 1; range, 1 to 3) for dysphagia (11 of these patients had preoperative esophageal dysmotility). Five patients underwent repeat fundoplication (recurrent reflux, 2; gas bloating, 1; dysphagia, 2). CONCLUSIONS: Clam shell near-circumferential fundoplication may be considered as an attractive alternative antireflux approach to Nissen fundoplication, particularly among patients at risk for postoperative dysphagia or gas bloating.

Anatomic segmentectomy in the treatment of stage I non-small cell lung cancer.

BACKGROUND: Segmentectomy for early-stage non-small cell lung cancer (NSCLC) remains controversial and has been previously associated with high local recurrence rates. We compared the outcomes of anatomic segmentectomy with lobectomy for stage I NSCLC and investigated the impact of surgical resection margins on recurrence. METHODS: From 2002 to 2006, 182 anatomic segmentectomies (114 open, 68 video-assisted thoracic surgery [VATS]), were performed for stage 1A (n = 109) or IB (n = 73) NSCLC. These were compared with 246 lobectomies (1A, 114; 1B, 132). Variables analyzed included hospital course, mortality, and patterns of recurrence and survival. RESULTS: All segmentectomy surgical margins were free of tumor (average margin, 18.2 mm). Operative time (147 versus 216 minutes; p < 0.0001) and estimated blood loss (185 versus 291 mL; p = 0.0003) were significantly reduced after segmentectomy compared with lobectomy. Thirty-day mortality (1.1% versus 3.3%), total complications, disease-free recurrence, and survival were similar between segmentectomy and lobectomy at a mean follow-up of 18.1 and 28.5 months, respectively. There were 32 recurrences after segmentectomy (17.6%) at a mean of 14.3 months (14 locoregional [7.7%], 18 distant [9.9%]), and 89% of recurrences were seen when tumor margins were 2 cm or less. Margin/tumor diameter ratios exceeding 1 were associated with a significant reduction in recurrence rates compared with ratios of less than 1 (25.0% versus 6.2%; p = 0.0014). CONCLUSIONS: Anatomic segmentectomy can be performed safely by an open or VATS approach. Segmentectomy outcomes compare favorably with standard lobectomy for stage I NSCLC. Margin/tumor ratios of less than 1 are associated with a higher rate of recurrence. Lobectomy should be considered as primary therapy when such margins are not obtainable with segmentectomy in the good-risk patient.

Adjuvant chemotherapy and the role of chemotherapy resistance testing for stage I non-small cell lung cancer.

The frequency of in vitro chemotherapy resistance in NSCLC is extraordinary: however, its clinical relevance remains unproved. Future studies on the use of the EDR assay and its integration into clinical trials is justified. To achieve the goal "to do no harm", the EDR has a role in eliminating some ineffective agents to avoid unnecessary toxicity, and when possible, in directing therapy. Empiric adjuvant chemotherapy for resected NSCLC may soon become passe as reproducible and generally available molecular testing becomes more common. Profiles from DNA and RNA expression analysis not only help define patients at risk for early recurrence and unresponsiveness to commonly used cytotoxic drugs, but also assist in the development of new assays that are less expensive, reliable, and can be used more commonly than arrays.

Minimally invasive resection of benign esophageal tumors.

OBJECTIVE: Benign tumors of the esophagus are uncommon. Traditionally, resection has required thoracotomy or laparotomy. In this study we present our experience with resection of these tumors using a minimally invasive approach. METHODS: A retrospective review of patients who underwent resection of benign esophageal tumors between 1990 and 2005 was conducted. Operative approach, tumor size, and outcomes after surgery were recorded. RESULTS: Twenty patients were identified (leiomyoma: n = 15; stromal tumor: n = 3; granular cell tumor, n = 1; schwannoma: n = 1). Four patients underwent an open approach (right thoracotomy); the remainder were resected using minimally invasive techniques (thoracoscopy, n = 9; laparoscopy, n =7). There were no postoperative leaks or other major complications after surgery. Two patients required repair of a mucosal injury during resection. Mean tumor size in the open group was 8.1 cm (range 7-10 cm) compared with 3.5 cm (range 0.9-8 cm) in the minimally invasive group. Median length of stay was 5.5 days in the open group compared with 2.75 days in the minimally invasive group. Five patients subsequently required fundoplication for worsening (n = 3) or new-onset (n = 2) gastroesophageal reflux disease after tumor resection. CONCLUSIONS: Minimally invasive resection of benign esophageal tumors is technically safe and associated with a shorter length of stay compared with open approaches. Although no specific cutoff for size could be identified, most tumors greater than 7 cm were removed by thoracotomy. The subsequent development of reflux may be related to the esophageal myotomy required for resection.

Chemotherapy resistance and oncogene expression in non-small cell lung cancer.

OBJECTIVES: Empiric chemotherapy for patients with non-small cell lung cancer who have undergone resection is recommended without knowledge of the tumor's specific biologic characteristics, and many patients may not benefit. In vitro chemotherapy resistance is associated with clinical unresponsiveness in some tumors, and in lung cancer, chemotherapy resistance is prevalent. Multiple-agent chemotherapy resistance and association of chemotherapy resistance with molecular markers are described. METHODS: Chemotherapy resistance to doublets--carboplatin and paclitaxel, cisplatin and navelbline, cisplatin and docetaxel, and cisplatin and gemcitabine--was analyzed in 4571 non-small cell lung cancer tumors with the extreme drug resistance assay. Chemotherapy resistance is defined as follows: extreme drug resistance, 1 SD above the median chemotherapy resistance; intermediate drug resistance, between the median and extreme drug resistances; and low drug resistance, 1 SD below the median. Chemotherapy resistance was compared with DNA ploidy measured by flow cytometry, and markers p53 and epithelial growth factor receptor were assayed by immunohistochemistry. RESULTS: Tumors with extreme or intermediate drug resistance were noted in 30% to carboplatin-paclitaxel, in 24% to cisplatin-navelbline, in 42% to cisplatin-gemcitabine, and in 27% to cisplatin-docetaxel. Extreme or intermediate drug resistance to at least one drug occurred in 74% to carboplatin-paclitaxel, in 68% to cisplatin-navelbline, in 88% to cisplatin-gemcitabine, and in 68% to cisplatin-docetaxel. More intermediate plus extreme chemotherapy resistances occurred in aneuploid tumors to etoposide (53% vs 36%, P = .0002) and topotecan (48% vs 36%, P = .0094), with less intermediate or extreme chemotherapy resistance to gemcitabine (88% vs 81%, P = .0345). p53-Positive tumors had more intermediate or extreme resistance to etoposide (57% vs 44%, P = .0009) and doxorubicin (73% vs. 58%, P = .0324) and less intermediate or extreme resistance to cisplatin (44% vs 54%, P = .0125), to carboplatin (47% vs 57%, P = .0129), to taxol (47% vs 57%, P = .0056), and to gemcitabine (78% vs 87%, P = .0108). Fewer epithelial growth factor receptor-positive tumors were extremely drug resistant to cisplatin (13% vs 26%, P = .0074) and carboplatin (13% v. 30%, P = .0008). CONCLUSIONS: Multi-drug chemotherapy resistance in non-small cell lung cancer tumor cultures is common, and associations between molecular markers and in vitro chemotherapy resistance are noted. Clinical validation through integration of such testing into clinical trials seems warranted.

Prevalence of in vitro extreme chemotherapy resistance in resected nonsmall-cell lung cancer.

BACKGROUND: Recent clinical trials suggest that adjuvant chemotherapy provides a survival advantage for patients with completely resected nonsmall-cell lung cancer (NSCLC) yet many patients receive chemotherapy without benefit. Tumor in vitro resistance to antineoplastic agents is highly predictive of clinical unresponsiveness to chemotherapy for some cancers; however, little is known of the prevalence of extreme chemotherapy drug resistance for human NSCLC tumors. Chemoresistance testing may be a way to predict treatment failure, choose alternative agents, and to avoid unnecessary chemotherapy toxicity. This study describes the prevalence of in vitro chemotherapy resistance in NSCLC patient tumor cultures. METHODS: A total of 3,042 NSCLC specimens were cultured in a proliferation assay and tested for resistance to carboplatin, cisplatin, doxorubicin, etoposide, gemcitabine, navelbine, paclitaxel, taxotere, or topotecan. The percentage of cell-growth inhibition measured by 3H-Thymidine uptake was used to determine extreme drug resistance, intermediate drug resistance, or low drug resistance. RESULTS: Extreme drug resistance or intermediate drug resistance to carboplatin was found in 1,056 of 1,565 NSCLC cultures (68%), to cisplatin in 1,409 of 2,227 (63%), to doxorubicin in 1,101 of 1,471 (75%), to etoposide in 1,581 of 2,505 (63%), to gemcitabine in 594 of 823 (72%), to navelbine in 603 of 1,444 (42%), to paclitaxel in 689 of 1,706 (40%), to taxotere in 273 of 521 (52%), and to topotecan in 280 of 896 (31%). CONCLUSIONS: Chemotherapy resistance is prevalent among NSCLC clinical cell cultures. This may account for the small survival seen with empiric adjuvant chemotherapy. The use of viable tumor culture for in vitro chemoresistance testing should be considered when formulating a plan of adjuvant therapy for resected NSCLC. Future trials comparing patient survival after tailored versus empiric adjuvant therapy appear justified.

A unique atrial primary cardiac lymphoma mimicking myxoma presenting with embolic stroke: a case report.

An immunocompetent 29-year-old male presented with an embolic stroke from an unusual primary cardiac lymphoma. The cardiac lesion consisted of a polypoid, left atrial, mural fibrin thrombus with anaplastic tumor cells lining the surface of the clot. Histologic, immunophenotypic, and molecular characterizations were consistent with a diagnosis of CD30+ large B-cell lymphoma with anaplastic cytology. While tumor emboli from invasive primary cardiac lymphomas have been reported, this noninvasive fibrin thrombus-associated lymphoma appears to be unique and previously unreported.