ABSTRACT
Thoracotomy is a common surgical procedure performed worldwide for lung disease. Despite major advances in analgesia, patients still experience severe shoulder, central back and surgical incision site pain in the postoperative period. This study aimed to assess whether intraoperative phrenic nerve infiltration reduces the incidence of postoperative pain and improves peak flow volume measurements during incentive spirometry. 90 patients undergoing open lobectomy were randomly assigned to have phrenic nerve infiltration (nâ¯=â¯46) or not (nâ¯=â¯44). The phrenic nerve infiltration group received 10 mL of 0.25% bupivacaine into the periphrenic fat pad. Preoperative assessments of spirometry and pain scores were recorded (at rest and with movement). Postoperative assessments included peak flow and pain measurements at intervals up to 72 hours. Less shoulder pain was experienced with phrenic nerve infiltration up to 6 hours postsurgery at rest (P = 0.005) and up to 12 hours with movement (P < 0.001). Reduced back pain was reported in the phrenic nerve infiltration group up to 6 hours after surgery both at rest (P = 0.001) and with movement (P = 0.00). Phrenic nerve infiltration reduced pain at the incision site for up to 3 hours both at rest (P < 0.001) and with movement (P = 0.001). Spirometry readings dropped in both groups with consistently lower readings at baseline and follow-up in the PNI group (Pâ¯=â¯0.007). Lower analgesic usage of patient controlled analgesia morphine (P < 0.0001), epipleural bupivacaine (Pâ¯=â¯0.001), and oramorph/zomorph (Pâ¯=â¯0.0002) were recorded. Our findings indicate that the use of phrenic nerve infiltration significantly reduced patient pain scores during the early postoperative period, particularly during movement. We believe that each technique has advantages and disadvantages; however, further studies with large sample size are warranted.
Subject(s)
Anesthetics, Local/administration & dosage , Back Pain/prevention & control , Bupivacaine/administration & dosage , Nerve Block/methods , Pain, Postoperative/prevention & control , Phrenic Nerve , Pneumonectomy , Shoulder Pain/prevention & control , Thoracotomy , Aged , Aged, 80 and over , Anesthetics, Local/adverse effects , Back Pain/diagnosis , Back Pain/epidemiology , Bupivacaine/adverse effects , England , Female , Humans , Incidence , Male , Middle Aged , Nerve Block/adverse effects , Pain Measurement , Pain, Postoperative/diagnosis , Pain, Postoperative/epidemiology , Pneumonectomy/adverse effects , Shoulder Pain/diagnosis , Shoulder Pain/epidemiology , Spirometry , Thoracotomy/adverse effects , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND: Pulmonary carcinoid (PC) tumours are classified as either typical (TC) or atypical (AC) according to mitotic index (MI) and presence of necrosis. The aim of this study was to analyse the diagnostic and prognostic values of the Ki-67 index in PC. METHODS/PATIENTS: Between January 2001 and March 2015, we evaluated 94 consecutive patients with a confirmed diagnosis of TC (n = 75) or AC (n = 19) at our institution. Diagnostic histology was centrally reviewed by a local expert neuroendocrine pathologist, with assessment of Ki-67, MI, and necrosis. RESULTS: Median patient follow-up was 35 months. Eighty-four patients who underwent curative surgical resection were included in the survival analysis for identification of prognostic factors. Ki-67 index showed high diagnostic accuracy to predict histological subtype when assessed by receiver operator characteristic curves with an area under the curve of 0.923 (95% CI 0.852-0.995, p < 0.001). Multivariate analysis showed that MI, Ki-67 index, and the presence or absence of necrosis were independent prognostic factors for relapse-free survival. Combination of MI, Ki-67, and necrosis led to the classification of patients into four different prognostic groups (very low, low, intermediate, and high risks of relapse). CONCLUSIONS: The current study proposes the incorporation of Ki-67 index in the prognostic classification of PC tumours. Due to the limited number of patients and length of follow-up, the current model needs validation by larger cohort studies. Nevertheless, our results suggest that Ki-67 index and MI have continuous effect on prognosis. Prognostic models incorporating multiple cutoffs of Ki-67 and MI might better predict outcome and inform clinical decisions.
Subject(s)
Biomarkers, Tumor/analysis , Carcinoid Tumor/diagnosis , Ki-67 Antigen/analysis , Lung Neoplasms/diagnosis , Adult , Aged , Aged, 80 and over , Area Under Curve , Carcinoid Tumor/mortality , Carcinoid Tumor/pathology , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Lung Neoplasms/mortality , Lung Neoplasms/pathology , Male , Middle Aged , Mitotic Index , Prognosis , Proportional Hazards Models , ROC Curve , Sensitivity and Specificity , Young AdultABSTRACT
Iatrogenic injury accounts for the second most common cause of acquired diaphragmatic hernias after penetrating trauma. An increased incidence of these hernias has been observed with the widespread use of laparoscopic surgery. We present the case of a 65-year-old woman who initially underwent sigmoid resection for an adenocarcinoma and a subsequent liver resection for metastasis. She was noted to have a left lower lobe pulmonary nodule on surveillance computed tomography, for which she underwent a mini-thoracotomy for a planned resection. At the time of surgery, the pulmonary nodule was discovered to be a diaphragmatic hernia, most probably of iatrogenic origin. We discuss the difficulty in diagnosis given her history and the location of such a lesion.
Subject(s)
Hernia, Diaphragmatic/diagnosis , Hernia, Diaphragmatic/etiology , Iatrogenic Disease , Adenocarcinoma/pathology , Adenocarcinoma/secondary , Adenocarcinoma/surgery , Aged , Diagnosis, Differential , Female , Humans , Liver Neoplasms/secondary , Liver Neoplasms/surgery , Lung Neoplasms/diagnosis , Sigmoid Neoplasms/pathology , Sigmoid Neoplasms/surgeryABSTRACT
BACKGROUND: Despite the advances made in immunosuppression therapy, episodes of acute cellular rejection may affect graft function and survival. We investigated the role of RANTES in cellular recruitment and in cardiac allograft rejection. METHODS: Endomyocardial biopsies (n = 65) from 30 patients were taken at various times after transplantation. In 4 subjects who died of acute cellular rejection, the profile of RANTES expression was monitored in all biopsy specimens and in postmortem tissue. Myocardial tissue from 10 other transplants was also analyzed. Sections were stained with an anti-human RANTES antibody with the streptavidin-biotin technique. RANTES-positive cells were related to macrophage, CD45RO "memory" T-cell, and eosinophil infiltration. RESULTS: RANTES-positive cells were identified within the cellular infiltrate in 95% of biopsies with moderate/severe rejection and 28% with mild rejection. RANTES-positive, CD45RO-positive, and macrophage cell numbers were higher in subjects who died of acute cellular rejection than of other causes. A highly significant difference in RANTES-positive cell number was observed between moderate/severe, mild, and nonrejection groups (p = .0001) and correlated significantly with macrophage number in both right and left ventricles (r = .693, p < .01; r = .599, p < .05, respectively) and with the number of "memory" T cells (r = .829, p < .001; r = .779, p < .01, respectively). CONCLUSIONS: These findings suggest that local release of RANTES is important in the recruitment of both macrophages and CD45RO T cells in cardiac allograft rejection. RANTES may be an important chemokine to target for therapeutic intervention in heart rejection.
Subject(s)
Chemokine CCL5/physiology , Graft Rejection/immunology , Heart Transplantation , Leukocyte Common Antigens/analysis , Macrophages/immunology , T-Lymphocytes/immunology , Adolescent , Adult , Antigens, CD/analysis , Antigens, Differentiation, Myelomonocytic/analysis , Chemokine CCL5/analysis , Female , Humans , Immunohistochemistry , Immunologic Memory , Macrophages/chemistry , Male , Middle Aged , T-Lymphocytes/chemistrySubject(s)
Cyclosporine/blood , Cyclosporine/therapeutic use , Heart Transplantation/immunology , Heart-Lung Transplantation/immunology , Immunosuppressive Agents/therapeutic use , Lung Transplantation/immunology , Administration, Oral , Adolescent , Adult , Aged , Cyclosporine/administration & dosage , Cyclosporine/pharmacokinetics , Heart Transplantation/physiology , Heart-Lung Transplantation/physiology , Humans , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/blood , Infusions, Intravenous , Kidney Function Tests , Lung Transplantation/physiology , Metabolic Clearance Rate , Middle Aged , Time FactorsSubject(s)
Graft Rejection/epidemiology , Heart Transplantation/physiology , Actuarial Analysis , Adolescent , Adult , Antilymphocyte Serum/therapeutic use , Azathioprine/therapeutic use , Child , Cyclosporine/therapeutic use , Drug Therapy, Combination , Female , Heart Transplantation/immunology , Heart Transplantation/mortality , Humans , Male , Middle Aged , Multivariate Analysis , Prednisolone/therapeutic use , Retrospective Studies , Risk Factors , Survival Rate , Time FactorsSubject(s)
Graft Survival/physiology , Heart Transplantation/physiology , Hemodynamics , Adolescent , Adult , Azathioprine/therapeutic use , Child , Cyclosporine/therapeutic use , Drug Therapy, Combination , Graft Rejection/epidemiology , Heart Transplantation/immunology , Heart Transplantation/mortality , Humans , Immunosuppressive Agents/therapeutic use , Middle Aged , Prednisolone/therapeutic use , Retrospective Studies , Survival Rate , Tissue and Organ Procurement/methods , Waiting ListsSubject(s)
Heart Transplantation/physiology , Histocompatibility Testing , Adolescent , Adult , Antilymphocyte Serum/therapeutic use , Azathioprine/therapeutic use , Child , Coronary Artery Disease/epidemiology , Cyclosporine/blood , Cyclosporine/therapeutic use , Drug Therapy, Combination , Female , Follow-Up Studies , Graft Rejection/epidemiology , Graft Rejection/immunology , Graft Rejection/pathology , Heart Function Tests , Heart Transplantation/immunology , Humans , Immunosuppressive Agents/blood , Immunosuppressive Agents/therapeutic use , Incidence , Male , Middle Aged , Postoperative Complications/epidemiology , Prednisone/therapeutic use , Retrospective Studies , Treatment OutcomeABSTRACT
BACKGROUND & AIMS: Tachykinins mediate nonadrenergic, noncholinergic excitation in the gastrointestinal tract, but their role in esophageal peristalsis remains unclear. METHODS: We used muscle strips from the distal third of human esophagus, obtained from patients undergoing esophagectomy for cancer, to investigate the contribution of tachykinins to nerve-mediated contractions. Isometric tension responses to agonists or electrical field stimulation were recorded in circular and longitudinal muscle strips. RESULTS: Tachykinins produced concentration-dependent increases in tension in circular and longitudinal muscle strips, with the following order of potency: beta-Ala(8)-neurokinin (NK) A (4-10) > NKB > substance P, suggesting NK(2) receptor involvement. The NK(2) receptor antagonist, SR48968 (1 micromol/L), inhibited responses to tachykinins in both muscles. Nerve activation produced on- and off-contractions in circular muscle and a duration-contraction in longitudinal muscle. Atropine (10 micromol/L)-insensitive nerve-evoked contractions were identified for the 3 types of responses. SR48968 produced concentration-dependent inhibition of atropine-insensitive on- and off-contractions but had no effect on the duration-contraction. At low stimulus frequency (1 Hz), on-contractions showed greater sensitivity to SR48968 than off-contractions. CONCLUSIONS: Nerve-mediated contractions in the human esophagus have a significant atropine-insensitive component. Tachykinins acting on NK(2) receptors can account for some, but not all, of this response, suggesting that other excitatory mechanisms also contribute.
Subject(s)
Esophagus/innervation , Esophagus/physiology , Muscle Contraction/drug effects , Tachykinins/pharmacology , Atropine/pharmacology , Autonomic Nervous System/drug effects , Autonomic Nervous System/physiology , Benzamides/pharmacology , Dose-Response Relationship, Drug , Humans , In Vitro Techniques , Muscle, Smooth/innervation , Muscle, Smooth/physiology , Neurokinin A/analogs & derivatives , Neurokinin A/pharmacology , Neurokinin B/pharmacology , Parasympatholytics/pharmacology , Peptide Fragments/pharmacology , Piperidines/pharmacology , Receptors, Neurokinin-2/antagonists & inhibitors , Substance P/pharmacologyABSTRACT
Esophageal peristalsis is dependent on activation of muscarinic receptors, but little is known about the roles of specific receptor subtypes in the human esophagus. We examined muscarinic receptor expression and function in human esophageal smooth muscle obtained from patients undergoing resection for cancer. [(3)H]Quinuclidinyl benzylate (QNB)-specific binding was similar in longitudinal muscle (B(max) = 106 +/- 22 fmol/mg of protein, K(d) = 68 +/- 9 pM) and circular muscle (B(max) = 81 +/- 16 fmol/mg of protein, K(d) = 79 +/- 15 pM). Subtype-selective antagonists inhibited [(3)H]QNB similarly in muscle from both layers. Further analysis of antagonist inhibition of [(3)H]QNB binding showed a major site (60-70%) with antagonist affinity profile consistent with the M2 subtype and a second site that could not be classified. Reverse transcription-polymerase chain reaction and immunoblotting demonstrated the presence of all five known muscarinic receptor subtypes, and immunocytochemistry on acutely isolated smooth muscle cells confirmed the expression of each subtype on the muscle cells. Subtype-selective antagonists had similar inhibitory effects on carbachol-evoked contractions in longitudinal muscle and circular muscle strips with pA(2) values of 9.5 +/- 0.1 and 9.6 +/- 0.2 for 4-diphenylacetoxy-N-methylpiperidine methiodide, 7.1 +/- 0.1 and 7.0 +/- 0.2 for pirenzepine, and 6.2 +/- 0.2 and 6.4 +/- 0.2 for methoctramine, respectively. We conclude that human esophageal smooth muscle expresses muscarinic receptor subtypes M1 through M5. The antagonist sensitivity profile for muscle contraction is consistent with activation of the M3 subtype.
Subject(s)
Esophagus/chemistry , Muscle, Smooth/chemistry , Receptors, Muscarinic/classification , Esophagus/physiology , Humans , Immunoblotting , Immunohistochemistry , In Vitro Techniques , Muscle Contraction , Muscle, Smooth/physiology , Quinuclidinyl Benzilate/metabolism , Receptors, Muscarinic/analysis , Receptors, Muscarinic/physiology , Reverse Transcriptase Polymerase Chain ReactionABSTRACT
Receptor characterization in human esophageal smooth muscle is limited by tissue availability. We used human esophageal smooth muscle cells in culture to examine the expression and function of muscarinic receptors. Primary cultures were established using cells isolated by enzymatic digestion of longitudinal muscle (LM) and circular muscle (CM) obtained from patients undergoing esophagectomy for cancer. Cultured cells grew to confluence after 10-14 days in medium containing 10% fetal bovine serum and stained positively for anti-smooth muscle specific alpha-actin. mRNA encoding muscarinic receptor subtypes M(1)-M(5) was identified by RT-PCR. The expression of corresponding protein for all five subtypes was confirmed by immunoblotting and immunocytochemistry. Functional responses were assessed by measuring free intracellular Ca(2+) concentration ([Ca(2+)](i)) using fura 2 fluorescence. Basal [Ca(2+)](i), which was 135 +/- 22 nM, increased transiently to 543 +/- 29 nM in response to 10 microM ACh in CM cells (n = 8). This response was decreased <95% by 0.01 microM 4-diphenylacetoxy-N-methylpiperidine, a M(1)/M(3)-selective antagonist, whereas 0.1 microM methoctramine, a M(2)/M(4)-selective antagonist, and 0.1 microM pirenzepine, a M(1)-selective antagonist, had more modest effects. LM and CM cells showed similar results. We conclude that human smooth muscle cells in primary culture express five muscarinic receptor subtypes and respond to ACh with a rise in [Ca(2+)](i) mediated primarily by the M(3) receptor and involving release of Ca(2+) from intracellular stores. This culture model provides a useful tool for further study of esophageal physiology.