Minimally invasive approach for retrorectal tumors above and below S3: a multicentric tertiary center retrospective study (MiaRT study).

BACKGROUND: Retrorectal tumors are uncommon lesions developed in the retrorectal space. Data on their minimally invasive resection are scarce and the optimal surgical approach for tumors below S3 remains debated. METHODS: We performed a retrospective review of consecutive patients who underwent minimally invasive resection of retrorectal tumors between 2005 and 2022 at two tertiary university hospital centers, by comparing the results obtained for lesions located above or below S3. RESULTS: Of over 41 patients identified with retrorectal tumors, surgical approach was minimally invasive for 23 patients, with laparoscopy alone in 19, with transanal excision in 2, and with combined approach in 2. Retrorectal tumor was above S3 in 11 patients (> S3 group) and below S3 in 12 patients (< S3 group). Patient characteristics and median tumor size were not significantly different between the two groups (60 vs 67 mm; p = 0.975). Overall median operative time was 131.5 min and conversion rate was 13% without significant difference between the two groups (126 vs 197 min and 18% vs 8%, respectively; p > 0.05). Final pathology was tailgut cyst (48%), schwannoma (22%), neural origin tumor (17%), gastrointestinal stromal tumor (4%), and other (19%). The 90-day complication rates were 27% and 58% in the > S3 and < S3 groups, respectively, without severe morbidity or mortality. After a median follow-up of 3.3 years, no recurrence was observed in both groups. Three patients presented chronic pain, three anal dysfunction, and three urinary dysfunction. All were successfully managed without reintervention. CONCLUSIONS: Minimally invasive surgery for retrorectal tumors can be performed safely and effectively with low morbidity and no mortality. Laparoscopic and transanal techniques alone or in combination may be recommended as the treatment of choice of benign retrorectal tumors, even for lesions below S3, in centers experienced with minimally invasive surgery.

Laparoscopic versus open resection of intrahepatic cholangiocarcinoma: nationwide analysis.

BACKGROUND: The relevance of laparoscopic resection of intrahepatic cholangiocarcinoma (ICC) remains debated. The aim of this study was to compare laparoscopic (LLR) and open (OLR) liver resection for ICC, with specific focus on textbook outcome and lymph node dissection (LND). METHODS: Patients undergoing LLR or OLR for ICC were included from two French, nationwide hepatopancreatobiliary surveys undertaken between 2000 and 2017. Patients with negative margins, and without transfusion, severe complications, prolonged hospital stay, readmission or death were considered to have a textbook outcome. Patients who achieved both a textbook outcome and LND were deemed to have an adjusted textbook outcome. OLR and LLR were compared after propensity score matching. RESULTS: In total, 548 patients with ICC (127 LLR, 421 OLR) were included. Textbook-outcome and LND completion rates were 22.1 and 48.2 per cent respectively. LLR was independently associated with a decreased rate of LND (odds ratio 0.37, 95 per cent c.i. 0.20 to 0.69). After matching, 109 patients remained in each group. LLR was associated with a decreased rate of transfusion (7.3 versus 21.1 per cent; P = 0.001) and shorter hospital stay (median 7 versus 14 days; P = 0.001), but lower rate of LND (33.9 versus 73.4 per cent; P = 0.001). Patients who underwent LLR had lower rate of adjusted TO completion than patients who had OLR (6.5 versus 17.4 per cent; P = 0.012). CONCLUSION: The laparoscopic approach did not substantially improve quality of care of patients with resectable ICC.

Laparoscopic versus open extended radical left pancreatectomy for pancreatic ductal adenocarcinoma: an international propensity-score matched study.

BACKGROUND: A radical left pancreatectomy in patients with pancreatic ductal adenocarcinoma (PDAC) may require extended, multivisceral resections. The role of a laparoscopic approach in extended radical left pancreatectomy (ERLP) is unclear since comparative studies are lacking. The aim of this study was to compare outcomes after laparoscopic vs open ERLP in patients with PDAC. METHODS: An international multicenter propensity-score matched study including patients who underwent either laparoscopic or open ERLP (L-ERLP; O-ERLP) for PDAC was performed (2007-2015). The ISGPS definition for extended resection was used. Primary outcomes were overall survival, margin negative rate (R0), and lymph node retrieval. RESULTS: Between 2007 and 2015, 320 patients underwent ERLP in 34 centers from 12 countries (65 L-ERLP vs. 255 O-ERLP). After propensity-score matching, 44 L-ERLP could be matched to 44 O-ERLP. In the matched cohort, the conversion rate in L-ERLP group was 35%. The L-ERLP R0 resection rate (matched cohort) was comparable to O-ERLP (67% vs 48%; P = 0.063) but the lymph node yield was lower for L-ERLP than O-ERLP (median 11 vs 19, P = 0.023). L-ERLP was associated with less delayed gastric emptying (0% vs 16%, P = 0.006) and shorter hospital stay (median 9 vs 13 days, P = 0.005), as compared to O-ERLP. Outcomes were comparable for additional organ resections, vascular resections (besides splenic vessels), Clavien-Dindo grade ≥ III complications, or 90-day mortality (2% vs 2%, P = 0.973). The median overall survival was comparable between both groups (19 vs 20 months, P = 0.571). Conversion did not worsen outcomes in L-ERLP. CONCLUSION: The laparoscopic approach may be used safely in selected patients requiring ERLP for PDAC, since morbidity, mortality, and overall survival seem comparable, as compared to O-ERLP. L-ERLP is associated with a high conversion rate and reduced lymph node yield but also with less delayed gastric emptying and a shorter hospital stay, as compared to O-ERLP.

Impact of cirrhosis in patients undergoing laparoscopic liver resection in a nationwide multicentre survey.

BACKGROUND: The aim was to analyse the impact of cirrhosis on short-term outcomes after laparoscopic liver resection (LLR) in a multicentre national cohort study. METHODS: This retrospective study included all patients undergoing LLR in 27 centres between 2000 and 2017. Cirrhosis was defined as F4 fibrosis on pathological examination. Short-term outcomes of patients with and without liver cirrhosis were compared after propensity score matching by centre volume, demographic and tumour characteristics, and extent of resection. RESULTS: Among 3150 patients included, LLR was performed in 774 patients with (24·6 per cent) and 2376 (75·4 per cent) without cirrhosis. Severe complication and mortality rates in patients with cirrhosis were 10·6 and 2·6 per cent respectively. Posthepatectomy liver failure (PHLF) developed in 3·6 per cent of patients with cirrhosis and was the major cause of death (11 of 20 patients). After matching, patients with cirrhosis tended to have higher rates of severe complications (odds ratio (OR) 1·74, 95 per cent c.i. 0·92 to 3·41; P = 0·096) and PHLF (OR 7·13, 0·91 to 323·10; P = 0·068) than those without cirrhosis. They also had a higher risk of death (OR 5·13, 1·08 to 48·61; P = 0·039). Rates of cardiorespiratory complications (P = 0·338), bile leakage (P = 0·286) and reoperation (P = 0·352) were similar in the two groups. Patients with cirrhosis had a longer hospital stay than those without (11 versus 8 days; P = 0·018). Centre expertise was an independent protective factor against PHLF in patients with cirrhosis (OR 0·33, 0·14 to 0·76; P = 0·010). CONCLUSION: Underlying cirrhosis remains an independent risk factor for impaired outcomes in patients undergoing LLR, even in expert centres.

ANTECEDENTES: El objetivo de este estudio fue analizar el impacto de la cirrosis en los resultados a corto plazo después de la resección hepática laparoscópica (laparoscopic liver resection, LLR) en un estudio de cohortes multicéntrico nacional. MÉTODOS: Este estudio retrospectivo incluyó todos los pacientes sometidos a LLR en 27 centros entre 2000 y 2017. La cirrosis se definió como fibrosis F4 en el examen histopatológico. Los resultados a corto plazo de los pacientes con hígado cirrótico (cirrhotic liver CL) (pacientes CL) y los pacientes con hígado no cirrótico (non-cirrhotic liver, NCL) (pacientes NCL) se compararon después de realizar un emparejamiento por puntaje de propension del volumen del centro, las características demográficas y del tumor, y la extensión de la resección. RESULTADOS: Del total de 3.150 pacientes incluidos, se realizó LLR en 774 (24,6%) pacientes CL y en 2.376 (75,4%) pacientes NCL. Las tasas de complicaciones graves y mortalidad en el grupo de pacientes CL fueron del 10,6% y 2,6%, respectivamente. La insuficiencia hepática posterior a la hepatectomía (post-hepatectomy liver failure, PHLF) fue la principal causa de mortalidad (55% de los casos) y se produjo en el 3,6% de los casos en pacientes CL. Después del emparejamiento, los pacientes CL tendieron a tener tasas más altas de complicaciones graves (razón de oportunidades, odds ratio, OR 1,74; i.c. del 95% 0,92-0,41; P = 0,096) y de PHLF (OR 7,13; i.c. del 95% 0,91-323,10; P = 0,068) en comparación con los pacientes NCL. Los pacientes CL estuvieron expuestos a un mayor riesgo de mortalidad (OR 5,13; i.c. del 95% 1,08-48,6; P = 0,039) en comparación con los pacientes NCL. Los pacientes CL presentaron tasas similares de complicaciones cardiorrespiratorias graves (P = 0,338), de fuga biliar (P = 0,286) y de reintervenciones (P = 0,352) que los pacientes NCL. Los pacientes CL tuvieron una estancia hospitalaria más larga (11 versus 8 días; P = 0,018) que los pacientes NCL. La experiencia del centro fue un factor protector independiente de PHLF (OR 0,33; i.c. del 95% 0,14-0,76; P = 0,010) pacientes CL. CONCLUSIÓN: La presencia de cirrosis subyacente sigue siendo un factor de riesgo independiente de peores resultados en pacientes sometidos a resección hepática laparoscópica, incluso en centros con experiencia.

Thoracoscopy in prone position with two-lung ventilation compared to conventional thoracotomy during Ivor Lewis procedure: a multicenter case-control study.

BACKGROUND: Intraoperative management based on thoracoscopy, prone position and two-lung ventilation could decrease the rate of postoperative pulmonary complications after esophagectomy. The aim of this study was to compare this multifaceted approach (MIE-PP) and conventional thoracotomy for Ivor Lewis procedure after a systematic laparoscopic dissection. METHODS: Data from 137 consecutive patients undergoing Ivor Lewis procedures between 2010 and 2017 at two tertiary centers was analyzed retrospectively. The outcomes of patients who underwent MIE-PP (n = 58; surgeons group 1) were compared with those of patients undergoing conventional approach (n = 79; surgeons group 2). Our primary outcome was major postoperative pulmonary complications. Our main secondary outcomes were anastomotic leak, quality of resection and mortality. RESULTS: Female patients were more prevalent in the MIE-PP group (p = 0.002). Other patient characteristics, cTNM staging and neoadjuvant treatment rate were not different between groups. Major postoperative pulmonary complications were significantly lower in the MIE-PP group compared to Conventional group (24 vs. 44%; p = 0.014). Anastomotic leak occurred in 31 versus 18% in MIE-PP group and Conventional groups, respectively (p = 0.103). Complete resection rate (98 vs. 95%; p = 0.303) and mean number of harvested lymph nodes (16 (4-40) vs. 18 (3-37); p = 0.072) were similar between the two groups. Postoperative mortality rates were 0 versus 2% at day 30 (p = 0.508) and 0 versus 7.6% at day 90 (p = 0.038). CONCLUSION: Short-term outcomes of minimally invasive Ivor Lewis using thoracoscopy, prone position and two-lung ventilation are at least equivalent to the hybrid approach. Anastomotic leak after MIE-PP remains a major concern.

[At-risk drinking screening by general practitioners: A survey of patients in primary care]. / Repérage de la consommation d'alcool à risque par les médecins généralistes : enquête auprès de patients en soins premiers.

BACKGROUND: The screening of patients who are at-risk drinkers, which means exceeding the thresholds defined by health authorities or associated with a specific situation (taking psychotropic drugs, having an organic pathology, driving a vehicle, drinking during pregnancy), represents a major issue in primary care. Few studies have offered perspective from the patients' standpoint. The main purpose of this study was to describe general practitioners at-risk drinking screening from their patients point of view. The secondary objective was to identify the factors associated with perception of satisfactory general practitioner knowledge about alcohol consumption. METHODS: A quantitative cross-sectional study was launched in 9 general practitioner offices over 6 months. Patients older than 18 were recruited to answer a questionnaire blinded from their general practitioner, indicating the level of their alcohol consumption and their perception regarding their general practitioner's screening methods. Descriptive, univariate and multivariate logistic regression analyses were performed. RESULTS: All in all, 445 patients were analyzed. Sixty-two at-risk drinkers were screened (13.9 %). Most of the patients declared they had not been interviewed about their alcohol consumption by their general practitioner either during initial consultations (86.1 %) or over time (83.3 %). Only 4.2 % of patients had previously initiated discussion about their consumption. Patients were not ashamed to talk about alcohol (99.2 %) and found their general practitioner to be competent on this topic (100 %). In multivariate analysis, independent factors associated with a good general practitioner knowledge about their patients' current consumption were the questions put forward by their general practitioner about alcohol consumption during their first visit (P<0.001) and during subsequent visits (P<0.001). CONCLUSION: This study showed a low general practitioner screening rate of their patients' at-risk drinking. Only a minority of patients, including at-risk drinkers, declared that their general practitioner was aware of their level of alcohol consumption. Screening could be improved by being systematized during initial consultations and regularly scheduled during subsequent visits, especially in at-risk situations.

'Green Apple' Heart Failure.

We report here the clinical case of an Afro-Caribbean patient referred for complete atrioventricular block for whom a diagnosis of hereditary cardiac amyloidosis was eventually confirmed. Hereditary cardiac amyloidosis is an emerging threat in the Caribbean, and the main goal of this report is to raise the awareness of the disease among physicians.

An adaptable, reusable, and light implant for chronic Neuropixels probes.

Electrophysiology has proven invaluable to record neural activity, and the development of Neuropixels probes dramatically increased the number of recorded neurons. These probes are often implanted acutely, but acute recordings cannot be performed in freely moving animals and the recorded neurons cannot be tracked across days. To study key behaviors such as navigation, learning, and memory formation, the probes must be implanted chronically. An ideal chronic implant should (1) allow stable recordings of neurons for weeks; (2) be light enough for use in mice; (3) allow reuse of the probes after explantation. Here, we present the "Apollo Implant", an open-source and editable device that meets these criteria and accommodates up to two Neuropixels 1.0 or 2.0 probes. The implant comprises a "payload" module that is attached to the probe and is recoverable, and a "docking" module that is cemented to the skull. The design is adjustable, making it easy to change the distance between probes, the angle of insertion, and the depth of insertion. We tested the implant across seven labs in head-fixed mice, freely moving mice, and freely moving rats. The number of neurons recorded across days was stable, even after repeated implantations of the same probe. The Apollo implant provides an inexpensive, lightweight, and flexible solution for reusable chronic Neuropixels recordings.

French legislation on retrospective clinical research: What to know and what to do.

The French legislation on human subject research known as the Jardé law of 5th March 2012 has been applicable since November 2016. It concerns all research involving human subjects (RIPH, in French) and is defined according to 3 categories: high-risk interventional RIPH, low-risk interventional RIPH and non-interventional RIPH. This recent development in the supervision of research on human subjects had several objectives: to redefine the various categories of research, to strengthen data protection and to effectively address the ethical guidelines of international journals. The levels of constraint differ between categories of research according to level of risk, the common objective being to ensure patient protection. Retrospective studies based on information drawn from medical records or other databases, which are widely used in the surgical field, are not covered by the Jardé law. However, they require approval by local ethics committees and compliance with European legislation on personal data protection. Simplified procedures have been set up by the research and innovation departments in our university hospitals. In this update, we shall synthesize the legal prerequisites applying to retrospective studies on data from medical files.

Comparative study of biological versus synthetic prostheses in the treatment of ventral hernias classified as grade II/III by the Ventral Hernia Working Group.

AIM OF THE STUDY: The implantation of biological prostheses in an at-risk environment has seen increasing use. Their markedly higher cost compared to synthetic prostheses makes it important to analyse their usefulness in terms of actual benefit and cost-effectiveness. This study aims to examine the relevance of bioprostheses during surgical repair of Grade II/III ventral hernias as classified by the Ventral hernia working group (VHWG). MATERIALS AND METHODS: This study analysed the data of 119 patients requiring non-emergency repair of VHWG II/III grade hernias between 2010 and 2017. The results of patients who were treated with a bioprosthesis (n=59) were compared to those receiving a synthetic prosthesis (n=60). The primary outcome was surgical site infection (SSI) at 90 days. The secondary endpoints were hernia recurrence rate, cost of the prosthesis, duration of hospital stay and re-hospitalisation rate. RESULTS: The two groups were shown to be comparable by analysis of demographic, pre- and intraoperative data. The SSI rate was significantly higher in the bioprosthesis group (20% vs. 7%; P=0.010), as was the recurrence rate (56% vs. 28%; P=0.003) with a median follow-up of 40 months. The cost of the bioprosthesis was significantly higher than that of the synthetic prosthesis (€3363 vs. €249; P<0.010). CONCLUSION: In this retrospective study, the use of a bioprosthesis for repair of VHWG II/III ventral hernias was associated with a higher rate of both SSI and hernia recurrence at a cost 13 times greater than the use of a synthetic prosthesis.

AFSOS-SFRO-SFH-SFNEP-SFCE-GFRP guidelines on radio-induced nausea and vomiting.

INTRODUCTION: The prevalence of radiation-induced nausea and vomiting varies between 40% and 80%. They have many consequences on treatment and comorbidities. This work thus aimed to define clinical practice guidelines for the management of radiation-induced nausea and vomiting. METHODS: XXXXX, XXXX, XXX, XXXXX, XXXX and XXXX compiled a working group who draft these recommendations. RESULTS: The assessment of the emetogenic risk found two main predictive factors: 1) the irradiated anatomical location, 2) an associated concomitant chemotherapy. In the case of exclusive radiotherapy, primary antiemetic prophylaxis depends on the emetogenic risk (the irradiated anatomical location). In the case of concomitant chemotherapy, the emetogenic risk is generally higher and the primary antiemetic prophylaxis corresponds to that of chemotherapy-induced nausea and vomiting. In cases where symptoms persist, remedial treatments are poorly codified. CONCLUSION: Radiation-induced nausea and vomiting remains underdiagnosed and undertreated, its rapid detection and treatment are essential to reinstate good clinical practice.

The allogeneic response and tumor immunity.

The strong allogeneic response to donor MHC molecules in transplantation and the weak response to tumor antigens represent two important and divergent but potentially interactive immune responses. A patient's response to allogeneic MHC molecules might promote an effective T-cell response to self MHC-restricted tumor peptides and the possibilities for this are discussed here. These allogeneic responses might successfully be harnessed to promote the immune eradication of metastatic cancer.

Decreased platelet aggregation, increased bleeding time and resistance to thromboembolism in P2Y1-deficient mice.

Platelet activation is characterized by shape change, induction of fibrinogen receptor expression and release of granular contents, leading to aggregation and plug formation. While this response is essential for hemostasis, it is also important in the pathogenesis of a broad spectrum of diseases, including myocardial infarction, stroke and unstable angina. Adenosine 5'-diphosphate (ADP) induces platelet aggregation, but the mechanism for this has not been established, and the relative contribution of ADP in hemostasis and the development of arterial thrombosis is poorly understood. We show here that the purinoceptor P2Y1 is required for platelet shape change in response to ADP and is also a principal receptor mediating ADP-induced platelet aggregation. Activation of P2Y1 resulted in increased intracellular calcium but no alteration in cyclic adenosine monophosphate (cAMP) levels. P2Y1-deficient platelets partially aggregated at higher ADP concentrations, and the lack of P2Y1 did not alter the ability of ADP to inhibit cAMP, indicating that platelets express at least one additional ADP receptor. In vivo, the lack of P2Y1 expression increased bleeding time and protected from collagen- and ADP-induced thromboembolism. These findings support the hypothesis that the ATP receptor P2Y1 is a principal receptor mediating both physiologic and pathological ADP-induced processes in platelets.

Technical requirements for effective regional hydrodynamic gene delivery to the left lateral lobe of the rat liver.

Hydrodynamic gene delivery to the liver is an attractive approach for clinical liver gene therapy, but critical aspects of technique remain uncertain. There has not been to date any report of high levels of hydrodynamic gene delivery to the liver, except in rodents. Regional hydrodynamic delivery to individual lobes/segments of the liver is being pursued in preclinical pig models, where reporter gene expression has been <1% of rodent levels, and in one clinical study, where there was no substantive evidence of gene expression. In none of these studies did surgical technique include outflow obstruction of the DNA solution. Here we report a novel technique for regional hydrodynamic gene delivery to the left lateral lobe of the rat liver. The technique gives high levels of gene delivery specific to the left lateral lobe with low volumes ( approximately 1.5 ml) of DNA solution, and permits an evaluation of hydrodynamic delivery in the presence and in the absence of outflow obstruction. We report that outflow obstruction is an absolute requirement for effective hydrodynamic gene delivery to individual lobes/segments of the liver, and therefore that minimally invasive techniques will not be possible in the clinic.

Identification with a monoclonal antibody of a predominantly B lymphocyte-specific determinant of the human leukocyte common antigen. Evidence for structural and possible functional diversity of the human leukocyte common molecule.

Initial studies with the monoclonal antibody F8-11-13 described in this paper showed that it reacted strongly with B lymphocytes, did not react at all with granulocytes, and reacted only weakly with a small subpopulation of thymocytes and peripheral T lymphocytes. This picture was entirely different from that seen with monoclonal antibodies to the leukocyte common (LC) antigen, where 100% of all the above-mentioned leukocyte populations were positive. Biochemical studies using detergent solubilized membranes labeled with 3H at the sialic acid residues showed that the molecule bearing the F8-11-13 determinant was a glycoprotein of 215,000 mol wt, and that the peak depleted by F8-11-13 monoclonal antibody affinity columns corresponded to the high molecular weight region of a broad peak previously shown to be completely depleted by monoclonal antibody (F10-89-4) affinity columns directed at the LC antigen. Proof that the F8-11-13 determinant was expressed on some LC molecules was established by cross-inhibition studies with affinity-column-purified and depleted material. This finding of a serologically identifiable conformational or other structural change selectively expressed on the LC molecule of a functionally discrete population of lymphocytes has interesting implications for the structure and function of the LC molecule, and might be relevant to functional consideration of other membrane molecules.

Identification and unusual tissue distribution of the canine and human homologues of Thy-1 (theta).

The tissue distribution of the canine and human homologues of Thy-1 were studied using quantitative absorption analyses of liver absorbed anti-brain xenosera assayed on thymus cells. Cross-reactivity studies with pure rat Thy-1 established that the assays were detecting the homologues of rat Thy-1. The results showed that the tissue distribution of Thy-1 varies remarkably between species. Canine Thy-1 was found in large amounts only on adult brain. It was present in much smaller amounts on thymus (8% compared with brain), and was also found on lymph node, spleen and bone marrow (3, 1 and 0.5%, respectively, compared with brain). Surprisingly, it was found on kidney in amounts equal to that on thymus. Studies with the fluorescence-activated cell sorter established that canine Thy-1 was present on all thymocytes and peripheral T lymphocytes. Neonatal thymus and kidney had adult levels of Thy-1, but only small amounts of Thy-1 were present on neonatal brain. In man, brain was again the only tissue to contain large amounts of Thy-1. Surprisingly, it was absent from human thymus, and present on human kidney in amounts roughly equivalent to that seen in the dog. It was absent from spleen, lymph node, bone marrow, liver, heart, erythrocytes, platelets, and serum. Cross-reactivity studies showed that dog and human Thy-1 showed extensive serological cross-reaction, and that the dog-rat and human-rat cross-reactive components were identical.

Kidney-specific alloantigen system in the rat. Characterization and role in transplantation.

The alloantibody response of LEW rats immunized with DA kidney homogenate or given vascularized DA kidney grafts was studied using an 125I-anti-Ig binding assay with kidney homogenate as the target tissue. A major component of the sera was found to be directed at a kidney-specific alloantigen. Analysis of LEW X (DA X LEW) F1 backcross rats showed that the locus coding for this antigen was not linked to the major histocompatibility complex (MHC). The use of these backcross rats, typed for both MHC and the kidney alloantigen, as kidney donors to LEW rats showed that the kidney alloantigen did not induce detectable graft damage and that only the DA MHC was involved in primary graft rejection of DA kidneys by LEW rats. Immunofluorescence studies localized the antigen to the basement membrane of proximal convoluted tubules, and to some Bowman's capsules. Strain distribution studies showed that only 2 of 11 strains were negative for the allele under study; these were the LEW and AS strains. Species cross-reactivity studies showed that rabbit, dog, and human kidneys could absorb this specificity, although more weakly than DA kidney.

Characterization of the tissue macrophage and the interstitial dendritic cell as distinct leukocytes normally resident in the connective tissue of rat heart.

Immunohistological studies with a mouse anti-rat macrophage mAb (BMAC-5) demonstrated the presence of numerous positive cells in the interstitial connective tissues of many organs. The pattern resembled that seen with anti-MHC class II antibodies, with the striking exception that BMAC-5+ cells were rare or absent in the portal triad, the islets of Langerhans, and the kidney. Double-labeling fluorescence studies were therefore performed in rat heart using the BMAC-5 mAb in combination with rabbit antisera to pure rat class II MHC antigens and pure rat leukocyte common (CD45) antigens. The tissue macrophages in heart were identified as BMAC-5+, MHC class II-negative, leukocyte common antigen-positive cells. They could be distinguished from the BMAC-5-, MHC class II-positive, leukocyte common antigen-positive interstitial dendritic cells. Moreover, 7 d after lethal irradiation, the class II-positive interstitial dendritic cells had completely disappeared from heart, whereas the BMAC-5+ macrophages were present in undiminished numbers. These studies strongly suggest that the interstitial dendritic cell and the tissue macrophage represent two distinct populations of leukocytes within the connective tissues of antigenically secluded organs such as the heart. They have potentially important implications for the physiology of the immune system, as well as for autoimmunity and transplantation.

Massive induction of donor-type class I and class II major histocompatibility complex antigens in rejecting cardiac allografts in the rat.

DA (RT1a) hearts were transplanted into PVG (RT1c) or DA recipients, excised on days 1, 3, 5, or 7 after grafting, and examined by immunohistological techniques and quantitative absorption analyses, using allospecific mouse anti-rat class I and class II major histocompatibility complex (MHC) monoclonal antibodies. Cryostat sections stained by the peroxidase technique demonstrated that, in the normal heart, class I antigens were largely restricted to vascular endothelium and interstitial cells, with no observable staining of the myocardial cells except at the intercalated discs. Class II antigens were found only on occasional interstitial dendritic cells. The picture at day 1 after transplantation was not noticeably different. By day 3, however, there was clear patchy induction of both class I and class II antigens on the myocardial cells, usually in the region of cellular infiltrates. By day 5, class I antigens had been strongly induced throughout the graft, with the myocardial cells being very strongly positive. Class II antigens were also uniformly expressed on myocardial cells at day 5, and at this stage the vascular endothelium was also strongly positive. Quantitative absorption analyses showed a 10-fold increase in class I antigen content in cardiac allografts at day 5 after transplantation when compared with normal DA heart. DA heart isografts showed no increase in class II antigens, but it was interesting that, by 5 d after grafting, there appeared to be some expression of class I antigens on the myocardial cells. Quantitative absorptions showed a threefold increase in class I antigens on 5-d isografts when compared with normal DA heart.