A systematic review on laparoscopic subtotal cholecystectomy for difficult gallbladders: a lifesaving bailout or an incomplete operation?

INTRODUCTION: Laparoscopic subtotal cholecystectomy (LSTC) is a bailout procedure that is undertaken when it is not safe to proceed with a laparoscopic total cholecystectomy owing to dense adhesions in Calot's triangle. The main aim of this review was to investigate the early (≤30 days) and late (>30 days) morbidity and mortality of LSTC. METHODS: A literature search of the PubMed® (MEDLINE®), Google Scholar™ and Embase® databases was conducted to identify all studies on LSTC published between 1985 and December 2020. A systematic review was then performed. RESULTS: Overall, 45 studies involving 2,166 subtotal cholecystectomy patients (51% female) were identified for inclusion in the review. The mean patient age was 55 years (standard deviation: 15 years). Just over half (53%) of the patients had an elective procedure. The conversion rate was 6.2% (n=135). The most common indication was acute cholecystitis (49%). Different techniques were used, with the majority having a closed cystic duct/gallbladder stump (71%). The most common closure technique was intracorporeal suturing (53%), followed by endoloop closure (15%). Four patients (0.18%) died within thirty days of surgery. Morbidity within 30 days included bile duct injury (0.23%), bile leak (18%) and intra-abdominal collection (4%). Reoperation was reported in 23 patients (1.2%), most commonly for unresolving intra-abdominal collections and failed endoscopic retrograde cholangiopancreatography to control bile leak. Long-term follow-up was reported in 30 studies, the median follow-up duration being 22 months. Late morbidity included incisional hernias (6%), symptomatic gallstones (4%) and common bile duct stones (2%), with 2% of cases requiring completion of cholecystectomy. CONCLUSIONS: LSTC is an acceptable alternative in patients with a "difficult" Calot's triangle.

Suprapatellar versus infrapatellar nailing for tibial shaft fractures: A comparison of surgical and clinical outcomes between two approaches.

BACKGROUND: Tibial shaft fractures are a relatively common injury and contemporary treatment includes on-axis fixation with a locked intramedullary nail in the majority of cases. The conventional technique is via an infrapatellar approach but currently there is a trend towards the use of a suprapatellar approach. We compared key variables including operative time, radiation exposure and early patient reported outcomes when adopting a suprapatellar approach to tibial nailing in our unit versus our previous experience of infrapatellar tibial nailing. METHOD: Twenty-eight consecutive patients with tibial fracture underwent tibial nailing via the suprapatellar (SPN) approach. Six patients in the study group were excluded due polytrauma and need for dual orthopaedic and plastic surgery management. We compared outcomes with our most recent 20 consecutive patients who had undergone tibial nailing via an infrapatellar (IPN) approach. Primary surgical outcomes were: operative time, radiation exposure and accuracy of entry point of the nail on both anteroposterior and lateral radiographs. Clinical outcomes included time to weightbearing, time to radiographic union and patient-reported outcome score (Lysholm score). RESULTS: Forty-eight consecutive patients underwent intramedullary nail fixation for tibial shaft fractures and 42 were eligible for inclusion in our study (22 SPN vs 20 IPN). There were no significant differences in patient demographics or injury patterns between the two groups. Operative time and radiation exposure were significantly lower in the SPN group when compared to the IPN group (115 min vs 139 min ± 12.5) (36 cGY/cm2 vs 76.33 cGY/cm2 +/- 20.1). Furthermore, patients in the SPN group reported superior outcome scores at a mean follow up of 3 months (8-24 weeks) There were no observed differences in complication rate between groups and time of final clinical follow up at a minimum of 6 months. CONCLUSION: Our study shows that adoption of the SPN approach requires minimal learning curve, and has the potential benefits of reduced operative time, radiation exposure and superior patient reported outcomes when compared to the conventional infrapatellar approach.

Acute resveratrol supplementation in coronary artery disease: towards patient stratification.

Objective: Resveratrol (RV) is a polyphenol with antioxidant, anti-inflammatory and cardio-protective properties. Our objective was to investigate whether acute supplementation with high doses of RV would improve flow-mediated dilation (FMD) and oxygen consumption (VO2) kinetics in older coronary artery disease (CAD) patients. Design: We employed a placebo-controlled, single-blind, crossover design in which ten participants (aged 66.6 ± 7.8 years) received either RV or placebo (330 mg, 3× day-1) during three consecutive days plus additional 330 mg in the morning of the fourth day with a seven-day wash-out period in-between. On the fourth day, FMD of the brachial artery and VO2 on-kinetics were determined. Results: RV improved FMD in patients who had undergone coronary artery bypass grafting (CABG; -1.4 vs. 5.0%; p = .004), but not in those who had undergone percutaneous coronary intervention (PCI; 4.2 vs. -0.2%; NS). Conclusion: Acute high dose supplementation with RV improved FMD in patients after CABG surgery but impaired FMD in patients who underwent PCI. The revascularization method-related differential effects of RV may be due to its direct effects on endothelial-dependent dilator responses. Our findings have important implications for personalized treatment and stratification of older CAD patients.

Investigation of the composition of arterial plaques based on arterial waveforms and material properties.

Stroke is mainly caused by a narrowing of the carotid artery from a build-up of plaque. The risk of plaque rupture and subsequent stroke is dependent on plaque composition. Advances in imaging modalities offer a non-invasive means to assess the health of blood vessels and detect damage. However, the current diagnosis fails to identify patients with soft lipid plaque that are more susceptible to fissure, resulting in stroke. The aim of this study was to use waveform analysis to identify plaque composition and the risk of rupture. We have investigated pressure and flow by combining an artificial blood flow circuit with tubing containing different materials, to simulate plaques in a blood vessel. We used fat and bone to model lipid and calcification respectively to determine if the composition of plaques can be identified by arterial waveforms. We demonstrate that the arterial plaque models with different percentages of calcification and fat, results in significantly different arterial waveforms. These findings imply that arterial waveform analysis has the potential for further development to identify the vulnerable plaques prone to rupture. These findings could have implications for improved patient prognosis by speed of detection and a more appropriate treatment strategy.

The distribution of cardiac macrophages in myocardial ischaemia and cardiomyopathy.

AIMS: Recent evidence has implicated the macrophage as an effector cell in the inflammatory processes in transplant rejection, as well as cardiac disease, including coronary atherosclerosis. Although the latter is a vascular disease, the entire myocardium is affected. We have previously demonstrated the presence and distribution of macrophages in the 'normal' human heart. In this paper the distribution of myocardial macrophages, in the various chambers of the failing human heart, from cases of coronary atheroma and cardiomyopathy undergoing heart transplantation is documented. METHODS AND RESULTS: Tissue blocks were removed at specific sites taken from six cases with ischaemic heart disease (IHD) (four males, two females, age range 54-62 years), and four cases with idiopathic dilated cardiomyopathy (IDCM) (three males, one female, age range 18-49 years). These were compared with hearts from five cases of sudden death, unrelated to heart disease. Sections were stained with a CD68 pan macrophage marker. Positive cells were enumerated in 20 random fields. Results were analysed using a generalized linear modelling method using a Poisson distribution. Macrophages were identified within the interstitium and often close to blood vessels in all hearts. Macrophages from IHD hearts demonstrated the most intense staining and were often larger and more elongated than those found in 'normal' control hearts. Macrophages were also often degranulated and staining was diffuse in the interstitium. Overall, there were significantly more macrophages in most areas from IHD hearts than from IDCM hearts or control hearts (P < 0.001). CONCLUSIONS: Significantly more macrophages were found in all four chambers in diseased hearts compared with controls. Macrophage numbers were higher in the atria than in ventricles in the diseased myocardium. This study suggests selective recruitment of macrophages into the atria in the disease states studied.

Tumor necrosis factor-alpha gene polymorphism and death due to acute cellular rejection in a subgroup of heart transplant recipients.

Irreversible acute rejection of the transplanted heart usually has a fatal outcome. Predicting which recipients are most likely to reject might allow closer monitoring and modification of treatment protocols to prevent graft loss. Recipients genetically predisposed to produce more TNF-alpha are those who suffer the most acute rejection episodes. Here we show that TNF-alpha genotype is strongly associated with death due to acute cell-mediated heart transplant rejection (Chi-square = 28.57, p < 0.0001). This subgroup of recipients should be given optimally tissue matched transplants and should be treated with the most effective immunosuppressive regimens.

TNF-alpha in acute cardiac transplant rejection.

Acute cardiac allograft rejection is an immune-mediated response, hallmarked by cellular infiltration and myocyte damage in the transplanted heart. Cardiac biopsy sampling has been the 'gold' standard for routinely monitoring episodes of acute rejection. As cardiac biopsy is invasive, attention has focused on other non-invasive methods, such as serum analysis, for monitoring purposes. Tumour necrosis factor alpha (TNF-alpha) is a lymphocyte- and macrophage-derived cytokine that is pleiotropic in its actions. Its proinflammatory functions suggest that it may play an important role in initiating and orchestrating the rejection response. Studies demonstrating a correlation in the expression of TNF-alpha with the severity of the rejection episode have placed TNF-alpha as a prime candidate marker of rejection, and have prompted further study to elucidate these findings. This review discusses the limitations of the methodologies used to identify TNF-alpha, and how intragraft expression of TNF-alpha is not reflected in the serum. Furthermore, we describe how other stimuli besides the rejection response can affect TNF-alpha production, arguing against its use as a 'rejection-specific' marker. Nevertheless, genetic studies suggest that TNF-alpha may influence transplant outcome, and offer a new tool for studying the role of TNF-alpha in acute transplant rejection

RANTES chemokine expression is related to acute cardiac cellular rejection and infiltration by CD45RO T-lymphocytes and macrophages.

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.

The excised preauricular sinus in 14 years of experience: is there a problem?

The congenital preauricular sinus is usually asymptomatic. However, if recurrent infection occurs, complete surgical excision of the sinus is required. If the sinus tracts are not entirely removed, recurrence is likely to follow. A retrospective study of the surgical results at The Hospital for Sick Children in Toronto, Ontario, was completed. One-hundred sixty-five primary preauricular excision procedures, performed in 146 patients between the years 1982 and 1996, were reviewed. All clinical, operative, and postoperative data were gathered. Patient outcome and epidemiologic issues were addressed. The overall recurrence rate of this series was 9.09 percent (15 of 165 sinuses). For the group of patients with active infection present at surgery, the recurrence rate was 15.79 percent, and when no infection was present, recurrence rate was 8.22 percent (p value = 0.32, odds ratio = 2.09). Moreover, in patients who underwent surgical drainage of an abscess before the procedure, 16.7 percent of the sinuses recurred, whereas in the patients who did not have an abscess, only 8.16 percent recurred (p value = 0.25, odds ratio = 2.25). In the group of patients in whom auricular cartilage was not excised from the base of the tract, 18.52 percent of the sinuses recurred; when cartilage was excised, the recurrence rate was 4.5 percent (p value = 0.006). A very high recurrence rate of 21.95 percent was found in the group of patients in whom no modality was used to demonstrate the sinus tract at surgery. A high recurrence rate of 10.87 percent was found in the group for whom probing with a cannula was used to identify the tract (p value = 0.17); a low recurrence rate of 2 percent was found in a group with dye injection only (p value = 0.015). In those patients in whom sinus probing and dye injection were used simultaneously, there were no recurrences (0 percent, p value < 0.05). In conclusion, a patient with an actively infected preauricular sinus or one with a previous abscess may have a tendency to experience a higher recurrence rate after excisional surgery. Excising a cartilage piece at the base of the tract and demonstrating the sinus with dye injection or with dye injection and probing at the time of surgery will reduce recurrence rates. In conclusion, we advise the excision of cartilage in the base of the tract as well as the use of methylene blue injection and probing of the sinus at surgery.

Distribution of myocardial macrophages in the normal human heart.

Macrophages are important in inflammatory processes in heart disease and in transplantation rejection. A resurgence of interest in the macrophage has emanated from recent evidence implicating it as an effector cell in atherosclerosis and transplantation rejection. The detailed distribution of the macrophage within the normal human heart is unknown. We quantified macrophage numbers in the different chambers of the heart. Large tissue blocks (1.5-2.0 cm3) were removed from specific sites in 5 'normal' control hearts (2 males, 3 females, age range 19-46 y). Paraffin-embedded sections were stained with a CD68 pan macrophage marker. Positive cells were enumerated within 20 random fields. Results were analysed using a generalised linear modelling method using the Poisson distribution. Macrophages were identified within septa, and often close to blood vessels, in the myocardium, and in the majority of areas in all hearts. Macrophage numbers varied significantly between areas (range 0-6 cells/high power field; P < 0.001), and between the 5 hearts analysed (P < 0.001). In general, there were significantly more macrophages in the ventricles (RV P < 0.01, LV P < 0.05), but these differences were affected by heart differences. This study provides a baseline for the range of macrophage numbers within normal hearts, thus enabling comparisons with macrophage numbers within diseased and transplanted hearts.

TNF alpha mRNA and protein in cardiac transplant biopsies: comparison with serum TNF alpha levels.

OBJECTIVES: To examine the role of TNF alpha (TNF alpha) in cardiac transplant rejection by simultaneous analysis of protein expression and its messenger RNA within serum and grafted tissue. METHODS: 54 endomyocardial biopsy specimens were taken from 19 patients at various times after transplantation. TNF alpha messenger RNA was localised using a digoxygenin labelled complementary DNA probe. An anti-TNF alpha antibody was used to immunohistochemically label the protein product. Serum TNF alpha levels at the time of biopsy were analysed using a specific enzyme-linked immunosorbent assay. RESULTS: TNF alpha mRNA was present in 22/34 endomyocardial biopsies. Eight also contained TNF alpha protein. None had protein alone. Expression did not relate to the grade of rejection in the present or subsequent biopsies. Serum TNF alpha was undetectable (assay sensitivity 30-330 pg/ml) for the majority of specimens. In the nine cases with elevated serum levels, eight samples were from cases within the first 30 days post transplant (r = -0.379; P < 0.05). CONCLUSIONS: Neither tissue TNF alpha mRNA, tissue protein, nor serum TNF alpha relate to the grade of rejection. Furthermore, TNF alpha expression within endomyocardial biopsies is not reflected in the serum. These findings argue against the use of serum analysis as an indicator of cytokine profiles within cardiac tissue allografts. The demonstration of a trend in the early expression of TNF alpha after transplantation suggests that its release may not be specific to the process of rejection.

Interleukin-10 in human heart transplantation: an in situ hybridization study. The Manchester Transplant Cytokine Group.

BACKGROUND: The role of interleukin-10 in graft acceptance and rejection was investigated by analysis of its messenger RNA expression within endomyocardial biopsy material from heart transplant recipients. METHODS: Forty-six biopsy specimens were analyzed from 19 patients (16 male, 3 female), with an age range of 15 to 62 years (mean = 47 years). Biopsy specimens were "snap" frozen in liquid nitrogen, and 10-microns thick sections were cut and postfixed in 4% paraformaldehyde. Messenger RNA for interleukin-10 was localized with nonradioactively (digoxigenin) labeled complementary DNA probes and detected immunoenzymatically with an antidigoxigenin polyclonal antibody. The histopathologic diagnosis of rejection was made according to the criteria of the Heart Rejection Study group. RESULTS: Interleukin-10 transcripts were detected in 12 of 36 rejecting biopsy specimens. None of the ten nonrejecting biopsy specimens were positive. Expression within the rejection infiltrate was more prominent in biopsy specimens from milder rejection episodes. By contrast, in biopsy specimens from moderate rejection, expression was mainly within areas of fibrosis. The expression of interleukin-10 transcripts did not relate to the number of previous rejection episodes nor to the histologic grade of the subsequent biopsy specimens. CONCLUSIONS: This study emphasizes the importance of in situ techniques in localizing cytokine expression in relation to tissue structure and suggests that interleukin-10 may serve a function in the immune regulation of the infiltrate at sites of inflammation, rather than in immune suppression of the rejection process. Further study is necessary to elucidate the precise role of interleukin-10 in transplantation in relation to the overall profile of cytokine expression within the rejection infiltrate.

Sequence and embryonic expression of the murine Hox-3.5 gene.

The murine Hox-3.5 gene has been mapped and linked genomically to a position 18 kb 3' of its most 5' locus neighbour, Hox-3.4, on chromosome 15. The sequence of the Hox-3.5 cDNA, together with the position of the gene within the locus, show it to be a paralogue of Hox-2.6, Hox-1.4 and Hox-4.2. The patterns of embryonic expression for the Hox-3.5 gene are examined in terms of three rules, proposed to relate a Hox gene's expression pattern to its position within the locus. The anterior boundaries of Hox-3.5 expression in the hindbrain and prevertebral column lie anterior to those of Hox-3.4 and all other, more 5'-located Hox-3 genes. Within the hindbrain, the Hox-3.5 boundary is seen to lie posterior to that of its paralogue, Hox-2.6, by a distance equal to about the length of one rhombomere. Patterns of Hox-3.5 expression within the oesophagus and spinal cord, but not the testis, are similar to those of other Hox-3 genes, Hox-3.3 and Hox-3.4.

T lymphocytes and activated eosinophils in airway mucosa in fatal asthma and cystic fibrosis.

With the use of monoclonal antibodies (mAb) and immunohistology, the numbers of phenotypically distinct cells infiltrating lung tissue from 15 postmortem (PM) cases of fatal asthma were quantified and compared with 6 cases of cystic fibrosis (CF) (three postmortem, three transplant) and 10 nonasthmatic cases of sudden death matched for age and sex. Tissue eosinophilia was significantly greater (p less than 0.001) in the fatal asthma group than in the CF or sudden death controls. In asthma, approximately 40% of the eosinophilic infiltrate was EG2 positive (an indication of eosinophil activation and secretion of eosinophil cationic protein). The numbers of eosinophils and EG2 positive cells were significantly elevated in the subjects with acute severe asthma who had had a duration of terminal illness exceeding, as compared with less than, 24 h (p less than 0.05). When compared with the sudden death controls, there were increases in the numbers of Dako L C positive cells (i.e., CD45 positive "total leukocytes") in both fatal asthma and CF (p less than 0.01 and 0.05, respectively). The mean number of MT-1 positive (T) cells in the asthma and CF groups was approximately twice that of the control (p less than 0.05 and 0.01, respectively). The mean number of MB2 positive (B) cells was similar for both the asthma and sudden death control groups but was significantly increased in CF (p less than 0.05). The average T:B cell ratios were 6:1, 1:1, and 2:1 in the fatal asthma, CF, and control groups, respectively. The results support a role for the T lymphocyte in the pathogenesis of fatal asthma and CF.(ABSTRACT TRUNCATED AT 250 WORDS)

Eosinophils, T-lymphocytes, mast cells, neutrophils, and macrophages in bronchial biopsy specimens from atopic subjects with asthma: comparison with biopsy specimens from atopic subjects without asthma and normal control subjects and relationship to bronchial hyperresponsiveness.

Bronchial biopsy specimens were obtained by fiberoptic bronchoscopy from 21 atopic subjects with asthma, 10 atopic subjects without asthma, and 12 normal healthy control subjects. With immunohistochemical techniques and a panel of monoclonal antibodies, inflammatory cells were identified and counted in the bronchial mucosa. The mean number of leukocytes (CD45+) and T-lymphocytes (CD3+, CD4+, and CD8+) at two airway levels in the subjects with asthma tended to be higher than in the other groups, but this difference did not achieve statistical significance. Similarly, there were no significant differences in the numbers of mucosal-type or connective tissue-type mast cells, elastase-positive neutrophils, or Leu-M3+ cells in the airway mucosa of subjects with asthma compared with atopic subjects without asthma and healthy control subjects. In contrast, significantly more interleukin-2 receptor-positive (CD25+) cells and "activated" (EG2+) eosinophils (EOSs) were present in the airways of subjects with asthma at both proximal and subsegmental biopsy sites. When the relationships between numbers of T-lymphocytes, activated (CD25+) cells, and EOSs were analyzed, there were positive correlations between CD3 and EG2, between CD3 and CD25, and between CD25 and EG2 positive cells in the airways of subjects with asthma. Furthermore, the ratio of EG2+ to CD45+ cells correlated with the provocative concentration of methacholine that caused a 20% decrease of FEV1 in hyperresponsive subjects. Although these associations do not prove a causal relationship, the results support the hypothesis that activated (CD25) T-lymphocytes release products which regulate recruitment of EOSs into the airway wall. In addition, our findings suggest that, in the large airways at least, asthma is not associated with hyperplasia of either mucosal-type or connective tissue-type mast cell.

Expression of mRNA for interleukin-5 in mucosal bronchial biopsies from asthma.

We have attempted to identify mRNA for IL-5 in endobronchial mucosal biopsies from asthmatics and controls, using the technique of in situ hybridization. Bronchial biopsies were obtained from 10 asthmatics and 9 nonatopic normal controls. A radio-labeled cRNA probe was prepared from an IL-5 cDNA and hybridized to permeabilized sections. These were washed extensively before processing for autoradiography. An IL-5-producing T cell clone derived from a patient with the hyper-IgE syndrome was used as a positive control. As a negative control, sections were also treated with a "sense" IL-5 probe. Specific hybridization signals for IL-5 mRNA were demonstrated within the bronchial mucosa in 6 out of the 10 asthmatic subjects. Cells exhibiting hybridization signals were located beneath the epithelial basement membrane. In contrast, there was no hybridization in the control group. No hybridization was observed with the sense probe. The six IL-5 mRNA-positive asthmatics tended to have more severe disease than the negative asthmatics, as assessed by symptoms and lung function, and showed a significant increase in the degree of infiltration of the bronchial mucosa by secreting (EG2+) eosinophils and activated (CD25+) T lymphocytes. Within the subjects who showed positive IL-5 mRNA, there was a correlation between IL-5 mRNA expression and the number of CD25+ and EG2+ cells and total eosinophil count. This study provides evidence for the cellular localization of IL-5 mRNA in the bronchial mucosa of asthmatics and supports the concept that this cytokine regulates eosinophil function in bronchial asthma.

Interleukin-5 mRNA in mucosal bronchial biopsies from asthmatic subjects.

Using in situ hybridization, we have investigated the expression of interleukin-5 (IL-5) mRNA in bronchial biopsies from asthmatics (n = 10) and controls (n = 9). The number of IL-5-nRNA-positive cells were compared with the number of CD25+ and EG2+ cells and total eosinophil counts. Specific hybridization signals for IL-5 mRNA were demonstrated in 6 out of the 10 asthmatic subjects but in none of the controls. The 6 IL-5-mRNA-positive asthmatics tended to have more severe disease and showed a significant increase in the degree of infiltration of the bronchial mucosa by activated T lymphocytes and eosinophils.