Anti-tumor necrosis factor α: originators versus biosimilars, comparison in clinical response assessment in a multicenter cohort of patients with inflammatory arthropathies.

OBJECTIVE: To compare etanercept and adalimumab biosimilars (SB4 and ABP501) and respective bioriginators in terms of safety and efficacy in a real-life contest. METHODS: We consequently enrolled patients affected by rheumatoid arthritis, psoriatic arthritis, and ankylosing spondylitis, treated with SB4, and ABP501, or with corresponding originators, belonging to the main biological prescribing centers in the Lazio region (Italy), from 2017 to 2020. Data were collected at recruitment and after 4, 8, 12, and 24 months of therapy. RESULTS: The multicenter cohort was composed by 455 patients treated with biosimilars [SB4/ABP501 276/179; female/male 307/146; biologic disease-modifying anti-rheumatic drug (b-DMARD) naïve 56%, median age/ interquartile range 55/46-65 years] and 436 treated with originators (etanercept/adalimumab 186/259, female/ male 279/157, b-DMARD naïve 67,2%, median age/interquartile range 53/43-62 years). No differences were found about safety, but the biosimilar group presented more discontinuations due to inefficacy (p<0.001). Female gender, being a smoker, and being b-DMARD naïve were predictive factors of reduced drug survival (p=0.05, p=0.046, p=0.001 respectively). The retention rate at 24 months was 81.1% for bioriginators and 76.5% for biosimilars (median retention time of 20.7 and 18.9 months, respectively) (p=0.002). Patients with remission/low disease activity achievement at 4 months showed a cumulative survival of 90% to biosimilar therapy until 24 months (p=0.001); early adverse reactions instead represented a cause of subsequent drug discontinuation (p=0.001). CONCLUSIONS: Real-life data demonstrated a similar safety profile between biosimilars and originators, but a reduced biosimilar retention rate at 24 months. Biosimilars could be considered a valid, safe, and less expensive alternative to originators, allowing access to treatments for a wider patient population.

Major thoracic surgery in octogenarians: the video-assisted thoracic surgery (VATS) approach.

BACKGROUND: Thoracic surgery is associated with a high morbidity and mortality rate in the elderly patient population. Appropriate management of thoracic diseases is often avoided because of the inherent risks associated with the access thoracotomy. The purpose of this study was to evaluate the perioperative outcomes of octogenarians who underwent video-assisted thoracic surgery (VATS) for a variety of thoracic conditions. METHODS: A retrospective chart review was done on all patients who were between 80 and 90 years of age and underwent elective VATS between January 1995 and August 2001. RESULTS: A total of 162 consecutive VATS procedures were performed in 157 patients. Comorbid conditions consistent with their advanced age included chronic obstructive pulmonary disease, hypertension, coronary artery disease, and diabetes. The procedures included 96 lung resections (53 lobectomies, 42 wedge/segment resections), 46 pleurectomies, 8 decortications, 8 mediastinal biopsies, 3 pericardial windows, and 1 drainage of hemothorax. The pathology included 76 primary lung cancers, 35 metastatic diseases, 37 benign conditions, 9 nesotheliomas, and 3 carcinoid tumors. The average operative time and length of hospital stay after surgery were 51 min and 2.6 days, respectively. There were 3 (1.9%) mortalities, 2 from cardiac complications and 1 from pneumonia. Two (1.2%) patients required reexploration for bleeding. Four (2.5%) cases were converted to open thoracotomy thirteen (8.0%) cases had an air leak, of which 11 were managed on an outpatient basis with a Heimlich valve. They were discharged from the hospital an average of 3.3 days postoperatively. CONCLUSION: With VATS, surgical therapy can be offered to octogenarians with a low morbidity and mortality rate, as well as a short hospital stay.

CYP1A2 is expressed along with CYP1A1 in the human lung.

The expression and activity of CYP1A1 were examined in fresh, small-sized lung biopsy specimens from nine human subjects. CYP1A1 transcripts were detected by reverse transcription-polymerase chain reaction (RT-PCR) analysis of total lung RNA. CYP1A2 transcripts were detected in the RNA samples as well, and bioactivation of 2-aminofluorene (2-AF) or 2-amino-3,4-dimethylimidazo[4,5-f]quinoline (MeIQ), a CYP1A2-preferential activity, was catalyzed by the lung S(9) fractions also. Two major bands were detected in the whole homogenate by western blot analysis using CD3, a mouse anti rat CYP1A1 monoclonal that cross-reacts with rat CYP1A2 as well as with human CYP1A1 and CYP1A2. S(9) fractions from the tissues catalyzed the bioactivation of benzo[a]pyrene (B[a]P), a CYP1A1-preferential activity, to mutagens in the Ames assay. Our findings are in agreement with the known presence of CYP1A1 in the human lung, and provide strong evidence for the expression of catalytically functional CYP1A2 in the tissue.

Video-assisted thoracic surgery resection of chest wall en bloc for lung carcinoma.

A video-assisted thoracic surgery approach to en bloc resection of lung cancer invading the chest wall is described. Using a minimally invasive surgical approach combined with neoadjuvant external beam radiotherapy, complete resection of an upper lobe carcinoma invading two rib segments was performed in a manner that permitted complete resection with curative intent and allowed for rapid recovery.

Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy: a more patient-friendly oncologic resection.

OBJECTIVE: To evaluate the outcomes from a new surgical technique for lobectomy. PATIENTS: Two hundred fifty consecutive patients with an average age of 67.3 years underwent simultaneously stapled lobectomy. METHODS: Video-assisted thoracic surgical non-rib spreading lobectomy (VNSSL) is a new technique that has been evolving for approximately 6.5 years. During 1990, we began using video-assisted thoracic surgery (VATS) for simple, benign diseases. Throughout 1991, VATS was applied to malignant problems, ie, mediastinal masses, staging of lymph nodes, malignant effusions, and coin lesions. As experience was acquired, more complex procedures were attempted, such as lobectomy. On September 9, 1991, our first VATS lobectomy, using anatomic hilar dissection and lymph node sampling, was performed for primary carcinoma of the lung. One year later, we performed our first VNSSL using simultaneous stapling. RESULTS: Currently, 400 VNSSLs have been performed. In this entire series, there have been no surgical mortality, bronchopleural fistulas, port implantations, or transfusions. Bronchial stumps have averaged 4 mm in length, and all have been microscopically negative for neoplasm. In order to evaluate long-term survival for primary carcinoma of the lung in patients with an adequate duration of follow-up, the first 250 consecutive VNSSLs have been reviewed. There were 120 male and 130 female patients ranging in age from 20 to 92 years old who had 62 right upper lobe, 20 right middle lobe, 58 right lower lobe, 63 left upper lobe, and 33 left lower lobe lobectomies, and 14 bilobectomies. The lesions consisted of 214 primary carcinomas, 8 metastatic lesions, and 28 benign problems. Seven to 18 lymph nodes could be resected during staging of the primary neoplasms. The tumors ranged in size from 1 to 9 cm, and operating times averaged 78.6 min. Hospitalization averaged 2.83 days. No patient was admitted to the ICU. Intensive monitoring or narcotic analgesia were not needed. No epidural or intercostal anesthesia was used. Complications were infrequent and minor. Most patients returned to preoperative levels of physical activity within 7 to 10 days. Overall survival at a mean of 34 months, when all stages of neoplasms were combined, is 83%. For stage I, overall survival is 92%. The cost of VNSSL is approximately 50% less than the traditional open thoracotomy. CONCLUSIONS: VNSSL is an oncologic technique that has been clinically rewarding and economically beneficial for patients with malignant lesions. Long-term survival for primary carcinoma currently exceeds reports being published for the traditional open thoracotomy. Scientific reasons for this extraordinary survival are emerging. Complications, surgical mortality, pain, and length of stay have all been reduced. Patient recovery, comfort, and satisfaction have been extraordinary.

Video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy (VATS(n)SSL).

Two hundred consecutive patients underwent a video-assisted thoracic surgical non-rib spreading simultaneously stapled lobectomy (VATS(n)SSL). Ninety-three were males and 107 were females, ranging in age from 20 to 92 years. Lesions consisted of 171 primary lung carcinomas, 7 metastatic tumors, and 22 benign lesions. Resections included 47 right upper lobe, 18 right middle lobe, 46 right lower lobe, 52 left upper lobe, 26 left lower lobe and 11 bilobectomies, ie, 9 right upper and middle lobes and 2 right middle and lower lobes. Operating time averaged 79.5 minutes, and no patient received a transfusion. Tumors ranged from 1 cm to 9 cm, bronchial stumps were 4 to 5 mm, and length of hospitalization averaged 3.07 days. Complications were minimal, and there was no surgical mortality. No patient developed a bronchopleural fistula or neoplastic port implant. Twenty-four patients have died of metastases. At a median follow-up of 34 months for all stages of carcinoma, there is an overall survival rate of 86%. Survival rate is 92% for stage I. VATS(n)SSL is a new technique for lobectomy that has proven to be beneficial for patients needing resection.

[85 consecutive VATS non-rib spread simultaneously stapled lobectomies for malignancy]. / Videoassistierte simultane Stapler Lobektomie (VASSL) beim Bronchialkarzinom.

A new technique for pulmonary lobectomy has been utilized for malignant lesions. Eighty-five consecutive patients with pulmonary neoplasms underwent a VATS non-rib spread Simultaneously Stapled Lobectomy. There were 34 males and 51 females with 61 adeno, 21 squamous, 2 large cell and 1 carcinoid tumor who underwent 18 left upper, 13 left lower, 20 right upper, 7 right middle and 27 right lower lobectomies. Forty-one mediastinoscopies were negative. Patients with positive mediastinoscopies were not selected for curative resection. At VATS exploration, 10 patients had positive nodes. All resected nodes were negative in the other patients. Every bronchoscopy was negative. Operating times averaged 84.5 minutes. No patient received a transfusion. Lesions ranged from 1 cm to 8 cms with an average size of 3.62 cms. Post-operative length of stay averaged 3.38 days. There was no surgical mortality, no hemorrhage, no transfusion and no conversion to an open case in the entire series. No bronchial, vascular or broncho vascular fistula occurred. Complications were minor from which all patients recovered completely. Survival seems similar to patients resected by traditional open techniques.

One hundred video-assisted thoracic surgical simultaneously stapled lobectomies without rib spreading.

BACKGROUND: This study was performed to evaluate and determine the validity and benefits of video-assisted thoracic surgical simultaneously stapled pulmonary lobectomy without rib spreading. METHODS: Between September 1992 and August 1995, 100 consecutive video-assisted thoracic surgical simultaneously stapled lobectomies without rib spreading were performed. RESULTS: Forty-five male and 55 female patients had 24 right upper, 8 right middle, 29 right lower, 24 left upper, 15 left lower lobectomies for 66 adenocarcinomas, 20 squamous cell carcinomas, 4 large cell carcinomas, 8 benign lesions, and 2 metastatic lesions. Seventy-six patients had negative nodes. Nine patients had positive nodes. Every bronchoscopy was visually and cytologically negative. Forty-nine cervical mediastinoscopies were negative. Operating time for the series averaged 90.3 minutes. Hospitalization averaged 3.5 days for the entire group, but was 2.6 days for the last 20 patients. Lesions ranged from 1.5 to 8 cm, averaging 3.4 cm. There was no surgical mortality, no hemorrhage, no transfusion, and no urgent conversion to an open procedure. No bronchial fistula, vascular fistula, or bronchovascular fistula has occurred. Complications included 6 air leaks, 2 cerebrovascular accidents, 1 infected chest tube site, 2 cases of pneumonitis, and 1 subcutaneous emphysema. CONCLUSIONS: Video-assisted thoracic surgical simultaneously stapled lobectomy without rib spreading is a safe operation that can be combined with lymph node sampling. At this early stage, therapeutic outcomes (survival) for resected neoplasms appear similar to results obtained from traditional open techniques.

Does VATS favor seeding of carcinoma of the lung more than a conventional operation?

Seeding of carcinoma has always been of concern to surgeons. Recent reports have focused on possible implantation of tumor in the small wounds of minimally invasive procedures, i.e. VATS. A patient is presented who had a conventional open lobectomy for carcinoma and later developed tumor in the traditional thoracotomy wound. Although seeding or tumor implantation is accepted by thoracic surgeons, the exact mechanism of tumor implantation has never been scientifically explained or documented. Possibly, a rare and necessary pattern of genetic mutations could be responsible for this infrequent but serious problem.

VATS-Argon Beam Coagulator treatment of diffuse end-stage bilateral bullous disease of the lung.

Diffuse bullous disease of the lungs remains an unrelentless, debilitating, terminal disease. Intensive medical therapy can give transient relief of symptoms. Thoracotomy and resection has not always been successful and can be associated with an increased mortality and morbidity. Eight patients with end-stage bullous disease, unresponsive to medical therapy and not considered to be candidates for a thoracotomy, underwent unilateral video-assisted thoracic surgical ablation of bullae using the Argon Beam Coagulator. Six men and 2 women ranging in age from 28 to 71 years reported a decrease in dyspnea. Three patients restudied had an increase in forced expiratory volume in 1 second of 34%. Postoperatively, 7 patients had an air leak, pneumonia developed in 2 patients, and 3 patients had massive subcutaneous emphysema after parietal pleurectomy. Hospitalization averaged 13.6 days. All patients made a complete recovery, and each was subjectively improved. Steroid use decreased, oxygen requirements decreased, dyspneic episodes decreased, infections decreased, and endurance increased. In 3 patients with a limited follow-up evaluated postoperatively, video-assisted thoracic surgery and the Argon Beam Coagulator seemed to be beneficial for treating advanced, generalized bullous disease.

Endobag.

A simple method for placing specimens in a protective bag during video-assisted thoracic surgery has been developed. The equipment is readily available, and the technique is easy to perform.

Video-assisted thoracic surgical resection of malignant lung tumors.

Forty patients with malignant pulmonary disease underwent evaluation, staging, and a biopsy or resection by means of video-assisted thoracic surgery. There were 20 men and 20 women whose ages ranged from 27 to 82 years. Eight patients had a wedge resection for metastatic carcinoma, three a lobectomy for primary carcinoma, six exploration of the thorax, five biopsy of the aortopulmonary window, and eighteen a sublobar resection for primary carcinoma of the lung. There was no mortality. Three patients had air leaks that lasted an average of 8 days. Video-assisted thoracic surgery seems to be useful for more precise staging of carcinoma of the lung, and, in some patients, resectional operations can be performed.

One hundred consecutive patients undergoing video-assisted thoracic operations.

Video-assisted thoracic surgery is a new modality that allows visualization of and access to the intrathoracic organs without making a thoracotomy incision. One hundred consecutive patients underwent 113 thoracic procedures using this technique. Eight wedge resections for metastatic lesions, 6 pericardial windows, 1 bronchogenic cystectomy, 4 explorations of the aortopulmonary window, 1 decortication, 5 pleural scleroses, 8 bullous ablations, 25 lung biopsies, 19 wedge resections for carcinoma, 9 explorations of the thorax, 3 lobectomies, 1 esophageal cystectomy, 14 wedge resections for benign lesions, 4 pleurectomies, 1 excision of a neurogenic tumor, 3 mediastinal explorations, and 1 imaged axillary dissection were performed. There was no mortality. Ten patients had complications from which they recovered completely. Patients undergoing video-assisted thoracic operations seem to have reduced postoperative pain, shorter hospitalization, and quicker recovery times. Currently, this new modality appears to have beneficial value for patients; however, only further experience will determine its true merits.