Seromucinous hamartomas: a clinicopathological study of a sinonasal glandular lesion lacking myoepithelial cells

Aims:  To describe seven cases of sinonasal seromucinous hamartoma.
Materials and results:  The clinicopathological and immunohistochemical features of seven seromucinous hamartomas were analysed. There were four men and three women. Six lesions involved the posterior nasal septum and one the lateral wall. Size ranged from 6 to 40 mm. Four patients had no recurrences. One patient had local recurrences 24 and 60 months after diagnosis. The masses were covered by respiratory epithelium. Their stroma was oedematous to fibrous and contained invaginated respiratory epithelium forming glands and cysts, cysts with cuboidal to flat epithelium, and small serous glands, ducts and tubules with lobular and irregular haphazard patterns. One case had numerous glands surrounded by hyalinized basement membrane with features of respiratory epithelial adenomatoid hamartoma (REAH). One case had focal REAH-like changes. Both respiratory and serous components were positive for cytokeratin (CK) 7 and CK19. The serous component lacked myoepithelial cells when stained for CK14, p63, calponin and muscle-specific antigen in five cases.
Conclusions:  Seromucinous hamartomas show a broader histopathological appearance than previously reported. The serous proliferation in these lesions lacks myoepithelial cells. The presence of occasional REAH-like features and common location in the posterior nasal septum suggest a spectrum from pure seromucinous hamartoma to REAH.     

Nasal abnormalities in cystic fibrosis mice independent of infection and inflammation

It is not known whether the progressive airway changes in cystic fibrosis (CF) are all secondary to infection and inflammation. The CF mouse nose shares electrophysiologic and cellular properties with human CF airway epithelium. In the present work, we tested the hypothesis that structural abnormalities in the nasal mucosa of CF mice develop independent of infection and inflammation. We performed nasal lavage and subsequent serial coronal section through the nasal tissue of adult CF (mutations Cftr(TgHm1G551D) and Cftr(tm1Unc)-TgN((FABPCFTR))) and wild-type mice raised under normal housing conditions. Nasal tissue was also obtained from Day 17 embryos and newborn pups. Detailed histologic examination of the respiratory and olfactory epithelium within the nasal cavity was performed. Bacterial culture, cell count, and macrophage inflammatory protein-2 (MIP-2) concentration were assessed in nasal lavage fluid. Significantly thickened respiratory epithelium and increased mucous cell density was found in adult CF mice of both mutations compared with wild-type animals. In contrast, the olfactory epithelium was thinner, with a decreased cell density. Areas of lymphoid aggregates were found in CF mice but not in non-CF mice. There were no differences in bacterial growth, cell count, or MIP-2 concentrations. No genotype differences were observed in the embryonic or newborn periods. There are significant histologic changes in the nasal mucosa of adult CF mice, not associated with increased lumenal inflammation or bacterial content, and which are not present perinatally. These may be novel therapeutic targets.     

Cell and cytokine profiles in nasal secretions from patients with nasal polyposis: effects of topical steroids and surgical treatment

BACKGROUND: Nasal polyposis (NP), a chronic inflammatory disease of the paranasal sinus mucosa, is frequently associated with asthma. Previous reports showed that surgical treatment for nasal polyps may influence asthma evolution. We hypothesized that sinus surgery may alter the cytokine network in nasal secretions. METHODS: We evaluated the characteristics (cells and mediators) of nasal lavages in nine patients with untreated NP (group A), 17 patients treated with topical steroids (group B), 21 patients treated by nasal surgery endonasal ethmoidectomy associated with topical steroids (group C), and 12 healthy subjects (controls). RESULTS: Percentages of both eosinophils and neutrophils were higher in NP patients than in controls. Percentages of eosinophils and interleukin-5 (IL-5) level were higher in group A than in group C and controls. There was a positive correlation between IL-5 and eosinophils. In marked contrast, IL-8, IL-10, and IL-1beta levels were significantly higher in group C than in groups A and B and controls; TNF-alpha concentration was significantly lower in group C than in groups A and B and controls; and there was a negative correlation between IL-10 and TNF-alpha. The percentage of eosinophils was higher in asthmatic patients with NP than in nonasthmatic patients. In addition, in group C, asthmatic patients also had a significantly higher level of IL-10 than nonasthmatic patients. CONCLUSIONS: Our study demonstrates that percentages of eosinophils and neutrophils, and IL-5 level were increased in nasal secretions from untreated patients with NP. Topical steroid treatment is associated with a decrease of inflammatory cells and mediators. In marked contrast, nasal surgery is associated with marked changes, in cytokine profile in nasal secretions, that are clearly different from those of controls and topical steroid-treated NP patients.     

Clinical and pathologic methods to assess the long-term safety of nasal corticosteroids. French Triamcinolone Acetonide Study Group

BACKGROUND: The main objective of this long-term prospective local safety study was to evaluate endoscopic and histologic changes in nasal epithelium after 6-month treatment with triamcinolone acetonide (TAA). We describe here a method to measure quantitatively epithelium thickness. Results were compared with those seen with the use of cetirizine (an antihistamine) and another oral intranasal corticosteroid, beclomethasone dipropionate (BDP). METHODS: Patients were examined by an ENT specialist who first performed an endoscopic evaluation of the nasal cavities, assessing any morphologic abnormalities and the aspect of the mucosa. Biopsies were taken from the inferior turbinate before and after 24 weeks of treatment. Biopsies were immediately fixed in cold acetone (-20 degrees C) and embedded in glycolmethacrylate; sections of 2 microm were cut on an ultramicrotome. Morphometric evaluations were done in a blinded fashion by computerized image analysis to measure an epithelial area over a minimum length of 50 microm. The thickness was ascertained by the ratio of area to length. RESULTS: 1) For all three treatment groups, the nasal epithelium thickness decreased slightly from pretreatment to the end of treatment. 2) No statistically significant differences between the three treatment groups were found in epithelium thickness. 3) Macroscopically, nasal tissues in all treated groups were normal. CONCLUSIONS: These results clearly indicate that long-term treatment with TAA has no atrophic effect on nasal mucosa.     

Nasal seromucinous hamartoma (microglandular adenosis of the nose): a morphological and molecular study of five cases

Five cases of nasal seromucinous hamartoma were studied and their clinical, morphological, immunohistochemical and molecular data are reported. The patients, three females and two males, ranged in age from 49 to 66 years (mean 56 year, SD ± 7.91). All lesions were located in the nasal cavity. In four cases where follow-up was obtained, no recurrence was evident. In all cases, numerous small seromucinous tubules, embedded in a cellular stroma, were present in the lamina propria. Tubules were lined by one layer of cuboidal cells which displayed luminal phenotype positive for lysozyme and EMA in four, and S100 protein in all cases. Collagen IV and laminin positive basal lamina outlined the tubules which lacked basal cells. Stromal spindle cells present among tubules were immunoreactive for calponin in all cases and for alpha-smooth muscle actin in four cases. DNA mutation analysis of mitochondrial D-loop region was performed by direct sequencing in order to verify the mutation rate of these lesions. The tubules of the five seromucinous hamartomas showed a higher mutation rate especially in heteroplasmy (0.52% homoplasmy, 2.02% heteroplasmy) in comparison to normal seromucinous glands which exhibited a lower mutation frequency (0.83%). This is considered a sign of a low cellular proliferation rate consistent with a benign process. It is concluded that nasal seromucinous hamartomas are benign glandular proliferations that may resemble microglandular adenosis of the breast. Their distinction from benign and malignant mimics is discussed.     

Histologic and endoscopic studies before and after gastric bypass surgery

The purposes of this study were to establish a standardized multiparameter analysis system for histologic grading of gastritis and to compare histologic changes with endoscopic findings in the proximal and distal bypassed stomach in obese patients undergoing gastric bypass surgery. Three groups, comprising a total of 91 patients, were studied: a preoperative group (34 patients), a postoperative group at one year (33 patients), and a postoperative group at two years (24 patients). the biopsy specimens from the proximal and distal bypassed stomach were compared in all groups. Seventeen histologic variables were evaluated by three observers to classify the severity of gastritis. Forty percent of the patients in the postoperative group demonstrated histologic evidence of nonerosive, superficial gastritis, slightly more in the proximal stomach. Endoscopy showed significantly more bile reflux and inflammation in the distal stomach than the proximal stomach in nearly all patients. Our study demonstrates a significant discrepancy between bile reflux observed endoscopically and the histologic findings after gastric bypass surgery. No metaplastic or dysplastic changes were found up to two years postoperatively, but further studies are needed to determine the long-term endoscopic and histologic endoscopic and histologic sequelae of gastric bypass surgery.     

Comparison of intranasal and transdermal estradiol on nasal mucosa in postmenopausal women

OBJECTIVE: To compare nasal symptomatology and function and local concentrations of estradiol (E2), estradiol receptor (ERalpha), vasoactive intestinal peptide (VIP), substance P (SP) and neuropeptide Y (NPY) in nasal biopsies of 20 postmenopausal women complaining of paradoxical nasal stuffiness before and after treatment with intranasal or transdermal E2. DESIGN: Twenty healthy postmenopausal women willing to start hormone therapy (HT) were allocated to one of two groups, using a computer-generated randomization list.Ten postmenopausal women were treated with transdermal 17beta-estradiol 50 microg daily plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group A). Ten postmenopausal women were treated with intranasal 17beta-estradiol 300 microg/day (one spray delivery of 150 microg per nostril) plus nomegestrole acetate 5 mg/day for 12 days per 28-day cycle for 6 months (Group B). Fourteen fertile women undergoing nasal mucosa biopsy during plastic surgery were used as controls for the immunohistochemical evaluation (Group C).All women in groups A and B underwent evaluation of nasal stuffiness score, mucociliary transport time, rhinoscopy, and active anterior rhinomanometry at the beginning of the study and after, VIP, SP, and 6 months of HT. Nasal biopsies and evaluation of local concentrations of E2, ERalpha NPY were performed in groups A and B before and after 6 months of HT and in group C. RESULTS: Both intranasal and transdermal HT improve nasal symptomatology and nasal mucosa appearance and reduce mean mucociliary transport time. The effectiveness of intranasally administered therapy at improving nasal function is significantly better than transdermal therapy. In comparison with premenopausal controls, untreated postmenopausal women of group A and B showed significantly decreased immunopositivity for E2, ERalpha, and SP. HT induced a significant increase in E2, ERalpha, VIP, and SP and a decrease in NPY immunopositivity. Intranasal therapy was associated with a significantly higher immunopositivity for VIP and SP. CONCLUSIONS: HT improves nasal function and symptomatology in postmenopausal women with paradoxical nasal stuffiness, modulating nasal mucosa function through an action on cholinergic, adrenergic, and sensory peptides. Intranasally administered HT is more effective at improving nasal function than transdermal HT.     

Grass pollen immunotherapy for hayfever is associated with increases in local nasal but not peripheral Th1:Th2 cytokine ratios

Grass pollen immunotherapy is the only treatment for hayfever that is both effective and confers long-term benefit. Immunotherapy may act by altering the local nasal mucosal T helper type 2 (Th2) to type 1 (Th1) cytokine balance either by down-regulation and/or immune deviation of T-lymphocyte responses. There is controversy as to whether these changes are detectable in peripheral blood. We therefore examined both local nasal and peripheral T-cell responses to allergen exposure in the same subjects before and after immunotherapy. In a double-blind trial of grass pollen immunotherapy, nasal biopsies were obtained at baseline and during the peak pollen season following 2 years of immunotherapy. Placebo-treated patients showed a seasonal increase in CD3(+) T cells (P = 0.02) and in interleukin-5 (IL-5) mRNA(+) cells (P = 0.03) and no change in interferon-gamma (IFN-gamma ) mRNA(+) cells (P = 0.2) in the nasal mucosa. In contrast, in the immunotherapy-treated group, there were no changes in the number of CD3(+) T cells (P = 0.3) and IL-5 mRNA+ cells (P = 0.2) but a significant increase in the number of IFN-gamma mRNA(+) cells (P = 0.03). Furthermore, clinical improvement in the immunotherapy-treated group was accompanied by a seasonal increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa (P = 0.03). In contrast, there were no significant changes in peripheral T-cell proliferative responses or cytokine production for IFN-gamma or IL-5 in response to grass pollen either within or between the two treatment groups. We conclude that successful grass pollen immunotherapy was associated with an increase in the ratio of IFN-gamma to IL-5 mRNA(+) cells in the nasal mucosa, whereas these changes were not reflected by alterations in peripheral blood T-cell proliferative responses or cytokine production before/after treatment.     

内镜下改良切口个性化三线减张鼻中隔成形的疗效分析

目的 探讨鼻内窥镜下鼻中隔成形术术式的改良及手术疗效。方法 采用随机抽样法将2014年1月~2017年7月100例鼻中隔偏曲手术患者,随机分为改良组与对照组,每组50例,改良组采用鼻内镜下改良切口鼻中隔成形术新方法,对照组采用传统鼻中隔黏膜下矫正术手术方法,针对两组患者术后的鼻中隔病变、症状消失率、伤口出血、肿胀,疼痛、愈合情况及术后并发症进行回顾对比分析。结果 观察组手术时间、术中出血量、并发症、治疗效果优于对照组,比较差异均有统计学意义(P＜0.05);随访6个月,观察组无鼻中隔穿孔、鼻腔粘连等并发症发生,鼻塞、头痛等症状改善,改良组患者有效率（96.00%）高于对照组（84.00%）,差异有统计学意义（P<0.05）,整体治疗满意度高。结论 采用鼻内窥镜下改良切口个性化鼻中隔成形术改变了以往传统的手术方式,具有出血少、粘膜张力小、视野广、愈合好、微创、并发症少、疗效确切,更符合鼻腔生理功能,值得临床推广应用。     

藻酸钙棉条在鼻腔手术中的应用

为了探讨藻酸钙棉条在鼻腔术后填塞的效果 ,随机分组采用藻酸钙棉条 (实验组 )和碘仿纱条 (对照组 )填塞术后鼻腔 ,观察记录病人头痛和术腔粘膜恢复情况。表明 :(1)实验组病人头痛及鼻腔胀痛发生率明显降低 ,与对照组差异显著 (p<0 .0 0 0 5 )。 (2 )实验组术腔粘膜恢复情况优于对照组 (p <0 .0 5 )。藻酸钙棉条填塞术后鼻腔 ,病人头痛少 ,创面恢复快。     

神经内镜引导下经鼻蝶窦入路切除垂体瘤的临床研究

目的：观察神经内镜下经单鼻孔蝶窦入路手术切除垂体瘤的临床疗效及安全性。方法：选取我院197例经单鼻孔蝶窦入路手术的垂体瘤患者,其中神经内镜下治疗的患者为105例(神经内镜组),显微镜下治疗的患者为92例(显微镜组)。比较两组手术时间、术中出血量、1年后随访复发率、术后住院时间与术后并发症、肿瘤全切率、内分泌激素下降情况。结果：神经内镜组术中出血量、手术时间、术后住院时间、1年后随访复发率、术后并发症(尿崩症、低钾血症、视力障碍、颅内血肿、鼻腔出血)发生率均低于显微镜组;肿瘤全切率、内分泌激素下降率均高于显微镜组,差异具有统计学意义(P<0.05)。结论：神经内镜辅助下行经鼻蝶窦入路垂体瘤切除术效果显著,具有手术时间短、术中出血量少、术后住院时间短,且并发症发生率低,安全性更强,值得在临床中推广。     

The effect of transplantation of nasal mucosal epithelial cell sheets after middle ear surgery in a rabbit model

Postoperative regeneration of the middle ear mucosa and pneumatization of the middle ear cavity are of great importance after middle ear surgery. This study developed a new method to transplant autologous nasal mucosal epithelial cell sheets into the damaged middle ear cavity. The aim of this study was to evaluate postoperative healing after the transplantation of the cell sheets. Rabbit nasal mucosal epithelial cell sheets were fabricated on a temperature-responsive culture dish, and transplanted into the damaged middle ear of rabbit, which was surgically created. The healing of middle ears was evaluated by histology and X-ray computed tomography after transplantation. Functional evaluation was performed by measuring the maximum middle ear total pressure reflecting a trans-mucosal gas exchange function. Two control groups were used: the normal control group and the mucosa-eliminated control group. Transplantation of cell sheets suppressed the bone hyperplasia and the narrowing of pneumatic space in the middle ear cavity compared with the mucosa-eliminated control group. The mucosal gas exchange function was also better in the cell sheet-transplanted group. Nasal mucosal epithelial cell sheet was confirmed to be useful as an effective graft material after middle ear surgery and hopefully become a novel therapy in the future.     

黄连解毒汤对变应性鼻炎大鼠TLR4/NF-κB信号通路及黏膜杯状细胞的影响

目的:探究黄连解毒汤对变应性鼻炎大鼠黏膜杯状细胞及Toll样受体4(TLR4)/核因子κB(NF-κB)信号通路的影响.方法:卵白蛋白制备变应性鼻炎大鼠模型,模型制作成功后分为:模型组,黄连解毒汤低、中、高剂量组,以及阳性对照组.黄连解毒汤低、中、高剂量组分别按5、10和20 g/kg生药量灌胃,阳性对照组给予丙酸氟替...     

表皮生长因子在鼻窦炎患者鼻内镜手术后对术腔上皮化的影响

目的 观察对鼻窦炎患者进行鼻内镜手术后运用表皮生长因子对术腔上皮化的影响.方法 回顾性分析2013年11月至2015年11月期间于我院耳鼻喉科进行鼻内镜手术治疗的110名鼻窦炎患者的病历资料,将术后采用布地奈德混悬液常规治疗的60例患者设为对照组,常规治疗基础上加用重组人表皮生长因子治疗的50例患者设为观察组.分别比较治疗后两组患者临床治疗疗效、上皮化率、鼻腔粘膜Lund-Kennedy评分以及临床症状VAS评分.结果 观察组患者治疗总有效率为94.00%,显著高于对照组80.00%(P<0.05),差异具有统计学意义;观察组患者术后30d、3个月鼻腔粘膜Lund-Kennedy以及临床症状VAS评分显著低于对照组(P<0.05),术后14d、6个月差异无统计学意义(P>0.05);观察组患者术后1个月、术后3个月上皮化率显著高于对照组(P<0.05),术后6个月差异无统计学意义(P>0.05).结论在鼻窦炎患者鼻内镜手术后采用糖皮质激素喷雾剂的治疗基础上加用重组人表皮生长因子能有效缓解鼻窦炎症状,缩短上皮化时间,有着很高的临床价值.     

The role of chemical mediators and mucosal hyperreactivity in nasal hypersecretion in nasal allergy

This study was designed to elucidate, first, the degree of participation of direct effects of histamine on the nasal glands and the nasal vasculature in clinical manifestation of hyperrhinorrhea in nasal allergy and, second, the existence of hyperreactivity of the nasal glands to acetylcholine in nasal allergy. The study demonstrates that histamine released by degranulation of basophilic cells in the nasal mucosa causes nasal hypersecretion mostly by way of the reflexive pathway. Approximately 4% of the amount of nasal secretion induced by an antigen challenge in subjects with house-dust nasal allergy was due to a leakage of plasma. There were almost no direct effects of histamine on the nasal glands. Nasal secretion induced by nasal challenge with acetylcholine after vidian neurectomy comes from the nasal glands by its direct effects on the nasal glands, the amount of which indicates degree of reactivity of the nasal glands to acetylcholine independent of hypersensitivity of the mucosal sensory system. The nasal glands of vidian neurectomized subjects having nasal allergy reacted more excessively to extrinsic acetylcholine than nasal glands of subjects of the control group. This verifies the existence of hyperreactivity in the nasal glands to acetylcholine in nasal allergy. The nasal glands of nasal allergy patients may respond more excessively to a given amount of acetylcholine released from parasympathetic terminals.     

Desloratadine therapy for symptoms associated with perennial allergic rhinitis.

BACKGROUND: Perennial allergic rhinitis (PAR) has a substantial negative social and economic impact. Recent studies emphasize the potential seriousness of PAR and the need for improved treatment of this condition. OBJECTIVE: To confirm the efficacy and safety of the H1-antihistamine desloratadine in reducing the symptoms of PAR in a randomized, double-blind, placebo-controlled trial. METHODS: Patients with PAR (N = 1,179) from 67 US/international centers received desloratadine, 5 mg once daily, or identical placebo tablets. The primary efficacy measure was the change from baseline to week 4 in average morning and evening reflective total symptom scores (TSSs). Secondary end points included changes from baseline in total nasal and nonnasal symptom scores and peak nasal inspiratory flow (PNIF) rates. RESULTS: Desloratadine was significantly more effective than placebo in reducing morning and evening reflective TSSs for each week and during weeks 1 through 4 (P = .001). Mean changes in TSSs during the 4-week study were -3.9 (26.6% reduction) and -3.2 (22.3% reduction) for the desloratadine and placebo groups, respectively (P = .001, desloratadine vs placebo). With desloratadine therapy, significant improvements were also seen in secondary efficacy end points compared with placebo use (total nasal and nonnasal symptom scores: P < or = .04). Improvements in mean morning PNIF were significantly greater in the desloratadine-treated group than in the placebo group (P = .03). CONCLUSIONS: These results confirm and extend previous findings that desloratadine is safe and is associated with a statistically significant reduction in nasal and nonnasal symptoms in patients with PAR. Objective nasal airflow, evaluated by PNIF, was statistically significantly improved after desloratadine treatment.     

Intranasal capsaicin reduces nasal hyperreactivity in idiopathic rhinitis: a double-blind randomized application regimen study

BACKGROUND: In a recent study, we showed that intranasal capsaicin spray gives a significant and long-term reduction of symptoms in nonallergic noninfectious perennial rhinitis patients. However, in daily practice, the studied application regimen proved to be impractical because of the large number of visits required in a short period of time. In the present study, we conducted a double-blind double-dummy parallel groups trial to determine whether a more practical capsaicin application schedule is equally effective. METHODS: Thirty patients were randomized into two different treatment regimens: one group received capsaicin five times on the first day at 1-h intervals. This was followed by a placebo dummy once every second or third day for a total of five treatments 2 weeks after the capsaicin application (group A). The other group (B) received the placebo dummy five times on the first day followed by capsaicin once every second or third day for a total of five treatments 2 weeks after the placebo application. RESULTS: The visual analogue scale scores for overall nasal symptoms, rhinorrhea and nasal blockage showed significant decrease after the start of treatment in both groups, with a significantly steeper decrease in group A. A significant reduction in cold dry air dose responsiveness was also found up to 9 months after therapy in both groups, reflecting a decrease in nasal hyperreactivity. No significant changes in safety data (smell, blood pressure, heart rate) were found. CONCLUSIONS: We conclude that intranasal capsaicin seems safe to use and that five treatments of capsaicin on a single day is at least as effective as five treatments of capsaicin in 2 weeks.     

Amyloid in localised deposits and plasmacytomas of the respiratory tract.

Clinical and histological features of 25 cases with amyloid deposits in the respiratory tract are described. The false cord is the commonest single site of such "primary" amyloid involvement. Evidence of extensive involvement and replacement of seromucinous glands by amyloid was seen in each case. Fourteen cases of plasmacytoma with "secondary" amyloid deposits are also described. The nose and nasopharynx were principally involved as with respiratory tract plasmacytomas in general but a similar association of the amyloid with seromucinous glands was also seen. Electron microscopy showed early involvement of the basal lamina of the duct of a seromucinous gland by amyloid in one case. Possible reasons for the association of amyloid precursors in respiratory tract amyloid with seromucinous glands are given.     

Intra-nasal beclomethasone dipropionate and intra-nasal sodium cromoglycate: a comparative trial

Ten patients with either seasonal allergic or perennial rhinitis were treated with intra-nasal beclomethasone dipropionate B.P. (Beconase) and nine comparable patients were treated with sodium cromoglycate B.P. (Rynacrom). The beclomethasone dipropionate was administered as 50 μg per puff into each nostril three times a day and the sodium cromoglycate as one capsule insufflated into each nostril four times a day. Treatments were allocated on a randomized basis and each patient received a course of treatment lasting 2 weeks during the summer of 1973 when the pollen counts were high. Utilizing patient daily symptom diary cards, physician's assessment and by examination of the nasal mucosa prior to and at the end of treatment, it was concluded that both intra-nasal beclomethasone dipropionate and intra-nasal sodium cromoglycate effect a reduction in the symptoms associated with rhinitis. No side effects of importance were noted, nor were there any adverse changes observed in the state of the nasal mucosa.     

Pulmonary vascular disease and hypertension after valve surgery for mitral stenosis

The reduction of pulmonary hypertension that occurs within 24 hours of valve replacement for mitral stenosis is well documented, but patients who die after surgery have not been adequately studied. Clinical and autopsy data for 16 patients who died following mitral valve replacement were reviewed. The emphasis was on preoperative and postoperative pulmonary arterial pressure and pulmonary vascular disease, including arterial, venous, and capillary changes. Morphologic features were graded and summed to obtain an additive histologic assessment (AHA). Patients were divided into three groups: 1) those who had uneventful operations and early postoperative periods but died prior to discharge; 2) those who had postoperative difficulty, with identifiable acute anatomic causes of death; and 3) those who had postoperative difficulty, with no apparent acute anatomic cause of death. In group 1 (n = 4) the preoperative pulmonary arterial pressure was 43 +/- 17 mm Hg, and AHA ranged from 0 to 4; in group 2 (n = 5) the preoperative pulmonary arterial pressure was 60 +/- 15 mm Hg, but AHA ranged only from 2 to 5. In group 3 (n = 7) the preoperative pulmonary arterial pressure was 59 +/- 12 mm Hg; AHA ranged from 6 to 9, significantly higher than that of the other groups (P less than 0.005). Three patients from group 3 had elevated pulmonary arterial pressure (60, 52, and 50 mm Hg three, six, and 15 days after surgery, respectively). Two additional patients had right heart failure with normally contracting left ventricles terminally. It is concluded that some patients with mitral stenosis who die after surgery with persistently elevated pulmonary arterial pressure have sufficiently severe pulmonary vascular disease to account for their persistent pulmonary hypertension and death.