Surgical treatment of invasive pulmonary fungal infections in immunocompromised pediatric patients: Aspergillus spp. and other emerging fungi.

PURPOSE: Invasive Pulmonary Fungal Infections (IPFIs) represent a diagnostic and therapeutic challenge. The exact role of surgery is not well defined. This study analyzes our experience with surgical treatment of IPFI in immunocompromised pediatric patients and, secondarily, compares IPFI caused by Aspergillus spp. with other fungal infections. METHODS: This is a retrospective review (2000-2019) of patients with IPFI surgically treated at our pediatric institution. Statistical analysis was used to compare data between Aspergillus spp. and non-Aspergillus IPFI. RESULTS: Twenty-five patients (64% female) underwent 29 lung resections. Median age at surgery was 7.19 years (1.63-19.14). The most frequent underlying condition (64%) was acute leukemia. Surgical indications included persistence or worsening of symptoms and pathological image findings (52%) or asymptomatic suspicious lesions in patients scheduled for intensive cytotoxic treatments or hematopoietic stem cell transplantation (48%). All patients underwent atypical lung resections, except one lobectomy. Aspergillus spp. was the most frequently isolated pathogen (68%). Follow-up was 4.07 years (0.07-18.07). Surgery-related mortality was 0%, but 4 patients died in the 100 days following surgery (2 due to disseminated fungal infection); the remaining 21 did not show signs of IPFI recurrence. Non-specific consolidations on CT scan were more frequent in non-Aspergillus IPFI (p < 0.05). CONCLUSION: Surgical treatment of IPFI should be considered as a part of the treatment in selected pediatric immunocompromised patients, and it may have both diagnostic and therapeutic advantages over non-surgical management. When there is clinical suspicion of IPFI but CT scan shows unspecific alterations, the possibility of a non-Aspergillus IPFI should be considered.

Pulmonary mucormycosis eroding the chest wall: challenges in the management.

Pulmonary mucormycosis is a rare, life-threatening fungal infection usually seen in immunocompromised patients. Mortality in such patients is high due to underlying immunosuppression and poor general condition of the patients. Invasion of the adjacent structures is known but, to the best of our knowledge, pulmonary mucormycosis presenting with a full thickness chest wall erosion has not been reported. We report such a case with chest wall destruction with superadded bacterial infection. The use of prosthetic materials for chest wall reconstruction was not possible due to the presence of infection. In addition, there were other intra-operative and post-operative challenges which we managed using a multidisciplinary approach. This report highlights the successful outcome of this complex situation using pre-operative optimisation, adequate surgical debridement and effective management of post-operative complications with patience and perseverance.

Successful Management of Pulmonary Mucormycosis Presenting as Round Pneumonia by Lung Resection in a Kidney Transplant Recipient.

Pulmonary mucormycosis is rare in kidney transplant recipients and has a high mortality rate. We report a case of pulmonary mucormycosis presenting as round pneumonia 1 year and 1 month after the transplant. The diagnosis was confirmed by a percutaneous lung biopsy. A complete resection of the lung mass, followed by intravenous liposomal amphotericin B therapy, saved the life of the patient. In conclusion, early and prompt diagnosis followed by complete resection of the lesion in pulmonary mucormycosis is lifesaving.

Outcomes after lung resection in renal transplant patients with pulmonary mucormycosis.

BACKGROUND: Pulmonary mucormycosis has been associated with high mortality (reported up to 100%) in renal transplant recipients. METHODS: This was a retrospective analysis of renal transplant patients with pulmonary mucormycosis between April 2014 and March 2020, who underwent surgical resection of the affected lung along with liposomal amphotericin therapy. Patients with lower respiratory illness features underwent chest X-ray, high-resolution computed tomography of the chest, and those with suspicious findings underwent analysis of bronchioloalveolar fluid and transbronchial lung biopsy. Patients with histological or microbiological evidence of mucormycosis were started on liposomal Amphotericin B. Tacrolimus and mycophenolate mofetil were stopped at the time of diagnosis. RESULT: Ten patients underwent combined management, while five patients were managed medically. At last follow up, seven out of ten patients (70%) who underwent combined management and two of the five patients (40%) who were managed medically, had a mean survival of 28.86 months (sd = 15.71, median = 25) and 14.17 months (sd = 12.21, median = 18), respectively, post-diagnosis of pulmonary mucormycosis. CONCLUSION: Surgical resection combined with antifungals in the perioperative period and decreased immunosuppression may improve the outcomes in renal transplant patients with pulmonary mucormycosis.

Intrathoracic transposition of the omentum.

Complex chest and lung infections with bronchial fistula are life-threatening situations with a mortality rate of up to 20%. If medical treatment fails, these patients require aggressive procedures to heal. Transposition of the omentum is a valuable, nonstandard option in these complex cases with aggressive infection involving the pleural space, with or without a bronchial fistula, when medical treatment is unsuccessful. We present a 29-year-old female patient diagnosed with primary immunodeficiency and invasive fungal infection with involvement of the left upper lobe and mediastinal and vertebral bodies treated with a lobectomy and intrathoracic transposition of the omentum.

Pulmonary mucormycosis with diaphragm and liver involvement in a patient with haematopoietic stem cell transplant.

Pulmonary mucormycosis is a rare but life-threatening fungal infection. We report a post-haematopoietic stem cell transplant patient with pulmonary mucormycosis that extended to the diaphragm and subphrenic space. He underwent lung and diaphragm resection, debridement of liver capsule and diaphragm reconstruction using a pedicled latissimus dorsi flap. Following surgery, the patient remained well and has resumed his regular daily activities.

Surgical resection for persistent localized pulmonary fungal infection prior to allogeneic hematopoietic stem cell transplantation: Analysis of six cases.

OBJECTIVE: Although invasive fungal disease (IFD) is an important complication in allogeneic hematopoietic stem cell transplantation (HSCT), the clinical significance of surgery, including the role of surgical resection for persistent pulmonary fungal disease prior to allogeneic HSCT in the current era with a variety of available antifungal agents, is controversial. We investigated the role of surgical resection. METHODS: We retrospectively investigated six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT between April 2007 and June 2016 at our medical center. RESULTS: We present six patients who underwent surgical resection of suspected pulmonary fungal disease prior to allogeneic HSCT. In our case series, three of four patients who were given a presurgical diagnosis of possible IFD were given a proven diagnosis after surgery, including two cases of invasive aspergillosis (IA) and one case of mucormycosis. All surgeries were performed by video-assisted thoracic surgery (VATS) for lobectomy without major complications. Recurrence of IFD was not observed after allogeneic HSCT in any of the six patients. CONCLUSION: Our experience indicated that surgical resection of persistent localized pulmonary lesions of IFD before allogeneic HSCT was helpful for obtaining a definitive diagnosis and might be useful for reducing recurrence after HSCT.

Concomitant lung adenocarcinoma and pulmonary cryptococcosis confirmed by pathologic examinations.

To describe the characteristics of concomitant lung cancer and pulmonary cryptococcosis (PC) cases.A total of 8 patients with lung cancer and coexisting PC, who were admitted to Fuzhou Pulmonary Hospital of Fujian from 1st January 2009 to 31st December 2015 and whose diagnoses were confirmed by pathological examinations, were studied.One patient had a history of diabetes mellitus and 1 had a history of treated with surgery. The lesions in 7 cases manifested as nodular shadows; only 1 case showed the lesion of the 2 diseases mergedmixed together, and it manifested as a large flake-like infiltrated shadow in the same lobe. The histological type in all of the patients was lung adenocarcinoma. Lung cancer stage was advanced (III-IV) in 25.0% of the cases. The 5 patients who received surgery and drug treatment are presently healthy following resection. Recurrence and metastasis of lung cancer following surgery occurred in 2 patients in whom the tumor was controlled again after anti-tumor treatment. One patient with advanced lung cancer and PC was treated with antifungal therapy in combination with antineoplastic chemotherapy, but she failed to improve and died 10 months after symptom onset during the follow-up period.PC coexisting with pulmonary carcinoma is rare. PC can manifest as pulmonary nodules and mimic malignant lesions, so it must be considered during a differential diagnosis of pulmonary nodules, especially in immunosuppressed patients.

Scedosporium spp lung infection in immunocompetent patients: A systematic review and MOOSE-compliant meta-analysis.

Scedosporium genus as a significant emerging opportunist causes a broad spectrum of disease in not only immunosuppressed but also immunocompetent patients. The lung is one of the most commonly encountered sites of Scedosporium infection. Due to its very high levels of antifungal resistance, surgery has been recommended as an important part in the treatment of pulmonary Scedosporium spp infection, even in immunocompetent cases. However, whether lung surgery could help to reduce the risk of death in immunocompetent patients is not clear.We retrospectively retrieved the records of pulmonary infections with Scedosporium species in immunocompetent patients through a comprehensive literature search. The association of surgery on all-cause mortality was explored using binary logistic regression (BLR). Receiver operating characteristic (ROC) curve analysis was carried out to evaluate the capability of the model.The comprehensive searching strategy yielded 33 case reports and 3 case series in total, with 40 individual patients being included. The overall mortality was 12.50%. The fatality rate was 9.09% (2/22) in cases with surgery and 16.67% (3/18) in cases without surgery (odds ratio, 0.50; 95% confidence interval, 0.07-3.38; P = .48). Consistently, BLR analysis identified no statistical association between surgery and reduced mortality (odds ratio, 1.19; 95% confidence interval, 0.09-15.64; P = .89), after adjusting for age, gender, and antifungal chemotherapy. The area under the ROC curve was 0.88.For immunocompetent patients with pulmonary Scedosporium spp infection, surgical therapy may not be associated with reduced mortality. Surgical excision could be considered but is not imperative in this group of patients.

A case report of pulmonary Botrytis sp. infection in an apparently healthy individual.

BACKGROUND: Botrytis species are well known fungal pathogens of various plants but have not been reported as human pathogens, except as allergenic precipitants of asthma and hypersensitivity pneumonitis. CASE PRESENTATION: The asymptomatic patient was referred because of a nodule revealed by chest X-ray. Computed tomography (CT) showed a cavitary nodule in the right upper lobe of the lung. He underwent wedge resection of the nodule, which revealed necrotizing granulomas and a fungus ball containing Y-shaped filamentous fungi, which was confirmed histopathologically. Culture of the specimen yielded white to grayish cotton-like colonies with black sclerotia. We performed multilocus gene sequence analyses including three single-copy nuclear DNA genes encoding glyceraldehyde-3-phosphate dehydrogenase, heat-shock protein 60, and DNA-dependent RNA polymerase subunit II. The analyses revealed that the isolate was most similar to Botrytis elliptica. To date, the pulmonary Botrytis sp. infection has not recurred after lung resection and the patient did not require any additional medication. CONCLUSIONS: We report the first case of an immunocompetent patient with pulmonary Botrytis sp. infection, which has not recurred after lung resection without any additional medication. Precise evaluation is necessary for the diagnosis of pulmonary Botrytis infection because it is indistinguishable from other filamentous fungi both radiologically and by histopathology. The etiology and pathophysiology of pulmonary Botrytis infection remains unclear. Further accumulation and analysis of Botrytis cases is warranted.

Cut it out! Thoracic surgeon's approach to pulmonary mucormycosis and the role of surgical resection in survival.

BACKGROUND: Mucormycosis portends a poor prognosis with mortality rates ranging from 50% to 70% in pulmonary mucormycosis (PM) and up to 95% in disseminated disease. However, detailed outcomes data have been lacking. It remains unknown how to identify patients who would benefit from surgical resection. OBJECTIVES: We present our experience with patients undergoing surgical resection for PM, including an analysis of factors affecting postoperative survival. We also describe a thoracic surgeon's approach through illustrative cases. PATIENTS/METHODS: We conducted a single-centre retrospective study of all adult patients with PM who received antifungal therapy and underwent surgical resection or who received antifungal therapy alone at Stanford between January 2004 and June 2018. RESULTS: Twelve patients received antifungal therapy and underwent surgical resection and 13 patients received antifungal therapy alone. From infection onset to death (or right-censoring if still alive), patients who underwent surgical resection had a median survival of 406 days (mean, 561.3; range, 22-2510), and patients who received antifungal therapy alone had a median survival of 28 days (mean, 66.7; range, 8-447). In patients who underwent surgical resection, median postoperative survival time was 154 days (range, 11-2495), in-hospital mortality was 16.7%, and 1-year mortality was 50.0%. Age, primary disease, ASA status, extrapulmonary dissemination, laterality, multilobar involvement, number of lesions, largest lesion size, platelet count, surgical approach, type of resection or extent of resection were not significantly associated with postoperative survival. CONCLUSIONS: Surgical resection significantly increases survival and should be strongly considered for selected patients with PM.

Pulmonary Scedosporium apiospermum Infection with Pulmonary Tumorlet in an Immunocompetent Patient.

Scedosporium apiospermum is an opportunistic fungus that can cause various types of infections, including localized infections and life-threatening disseminated infections, particularly in immunocompromised patients. Treatment is especially challenging due to its multidrug resistance. We herein report the case of a 73-year-old woman who was non-immunocompromised but developed S. apiospermum lung infection and a pulmonary tumorlet. To our knowledge, this is the first report of the coexistence of pulmonary S. apiospermum infection and tumorlet. The lung lesion was successfully treated by surgical excision without any antifungal agents, and no recurrence of the tumorlet or S. apiospermum infection has occurred.

Thoracoabdominal Resection of Mucormycosis Lesions in a Leukemic Patient.

Mucormycosis is a rare fungal infection that poses a severe threat to immunocompromised patients. In the case presented herein, a 56-year-old leukemic patient, who was treated with amphotericin B and posaconazole, was scheduled for surgical resection of mucormycosis lesions that had spread to the thorax and abdomen. Surgery was aggressive and the resection involved the left lateral thoracoabdominal wall, 2 ribs, the left diaphragm, and the spleen. The patient tolerated the procedure well and the leukemia went into remission. Aggressive surgery can benefit immunocompromised patients with mucormycosis.

Surgical Treatment of Multifocal Pulmonary Mucormycosis.

Mucormycosis is a devastating opportunistic fungal infection to which the immunosuppressed are particularly vulnerable. We report the case of a 60-year-old man who was found to have multifocal pulmonary mucormycosis 10 weeks after concomitant heart and kidney transplantation. Despite appropriate antifungal therapy, the infection progressed rapidly and soon involved critical pulmonary vasculature. He successfully underwent staged operative resection of his pulmonary mucormycosis without recurrence of infection. Although surgical debridement of pulmonary mucormycosis is typically reserved for localized disease, this case demonstrates that surgical intervention should be considered as an adjunct to antifungal therapy in multifocal disease.

Successful Treatment of Pulmonary Mucormycosis Caused by Cunninghamella bertholletiae with High-Dose Liposomal Amphotericin B (10 mg/kg/day) Followed by a Lobectomy in Cord Blood Transplant Recipients.

Infection caused by Cunninghamella bertholletiae carries one of the highest mortality rates among mucormycosis, and there are no reported cases that survived from the infection in allogeneic hematopoietic stem cell transplantation recipients occurring before neutrophil engraftment. Here, we present two cases of pulmonary mucormycosis caused by C. bertholletiae occurring before neutrophil engraftment after cord blood transplantation. Both were successfully treated with high-dose liposomal amphotericin B (10 mg/kg/day) combined with micafungin, which was then followed by neutrophil recovery, reduction in immunosuppressive agents, and a subsequent lobectomy. The intensive antifungal therapy immediately administered upon suspicion of mucormycosis greatly suppressed the infection in its early stage and was well tolerated despite its prolonged administration and simultaneous use of nephrotoxic agents after transplantation. Although the synergic effect of micafungin remains unclear, these cases highlight the importance of prompt administration of high-dose lipid polyene when suspecting mucormycosis in highly immunocompromised patients, which enables subsequent diagnostic and therapeutic interventions, resulting in a favorable outcome.

Pulmonary Mucormycosis Treated With Lobectomy.

A 57 year old man was referred from an outside facility for an unresolving pneumonia. Imaging of the chest demonstrated a right lung mass with a consolidation in the middle lobe, pleural effusion, and mediastinal lymphadenopathy. Cytologic examination of cultures from the bronchoscopy and thoracentesis did not yield a definitive diagnosis. Video-assisted thoracoscopic surgery (VATS) was performed because of a retained hemothorax and a suggestive lesion. Biopsy specimens obtained during VATS were consistent with mucormycosis. The patient underwent a middle lobectomy and pleurectomy without any adverse event. When bronchoscopy and thoracentesis cannot provide a diagnosis, thoracoscopic pleural biopsy can be the next step in the diagnosis of mucormycosis.

The Effective Treatment of Lung Infection Due to Scedosporium prolificans with Voriconazole and Surgery.

Scedosporium prolificans is a fungus that has demonstrated resistance against most currently available antifungal agents and which causes a rapidly disseminating and potentially fatal infection. A 68-year-old woman presented with a fever and consolidation in the lung field. Her symptoms and inflammatory reaction did not improve despite treatment with tazobactam/piperacillin, meropenem, and micafungin. Scedosporium prolificans was detected from the patient's bronchial lavage fluid, and we initiated treatment with voriconazole. Voriconazole was effective in shrinking the consolidation and suppressing the inflammatory reaction. The residual lesion was surgically resected because of the risk of systemic dissemination. The patient is currently alive without relapse or dissemination.

Phanerochaete sordida as a cause of pulmonary nodule in an immunocompromised patient: a case report.

BACKGROUND: Phanerochaete sordida is a species of wood rotting fungus, which can degrade lignin, cellulose and hemicellulose contained in wood and other hard-to-biodegrade organic substances. However, to date, there have been no other reports demonstrating that P. sordida can infect humans. CASE PRESENTATION: A 66-year-old Japanese man presented for a mass increasing in size on his left thigh. He had been suffering from rheumatoid arthritis for 18 years and chronic obstructive pulmonary disease for 20 years, for which he was being treated with 5 mg/day prednisolone and 8 mg/week methotrexate. The mass resection was performed two months later, and was diagnosed as malignant fibrous histiocytosis. However, a computed tomography examination for tumor recurrence after surgery showed a newly emergent pulmonary nodule. We therefore decided to resect the nodule by thoracoscopic procedure. Histopathological examination of the excised specimen showed that the lesion was a granuloma, with necrotic tissue and clumping of Aspergillus-like hyphae. Therefore, the nodule was diagnosed as a fungal infection and tissue specimens were cultured microbiologically. However, fungal growth was not observed. We consequently performed genetic analysis using a broad-range polymerase chain reaction. The 28S rRNA sequence demonstrated 100% homology with P. sordida using the NCBI BLAST program against the GenBank DNA databases. CONCLUSIONS: Using broad-range polymerase chain reaction, we identified P. sordida as the causative agent of a pulmonary nodule. These findings indicate that P. sordida may be an additional opportunistic causative organism of pulmonary infection in immunocompromised patients.

Surgical Resection during Chemotherapy of Pulmonary Cryptococcoma in a Patient with Cryptococcal Meningitis.

We herein report the case of a 72-year-old-man with pulmonary cryptococcoma along with cryptococcal meningitis who underwent surgery for pulmonary lesions while receiving chemotherapy. We noted two major clinical issues. First, the presence of pulmonary cryptococcoma had a detrimental influence on the cryptococcal meningitis. Second, resolution of the pulmonary cryptococcoma through antifungal therapy had a beneficial influence on the recovery from cryptococcal meningitis. As observed in the current case with pulmonary and meningeal cryptococcosis, surgery for pulmonary cryptococcoma with continuous antifungal treatment should be considered for cases where the symptoms respond poorly to antifungal therapy and radiographic abnormalities persist.

[Clinical comparative analysis for pulmonary histoplasmosis and progressive disseminated histoplasmosis].

OBJECTIVE: To compare clinical features, diagnosis and therapeutic effect between pulmonary histoplasmosis and progressive disseminated histoplasmosis.
 Methods: A retrospective analysis for 12 cases of hospitalized patients with histoplasmosis, who was admitted in Xiangya Hospital, Central South University during the time from February 2009 to October 2015, was carried out. Four cases of pulmonary histoplasmosis and 8 cases of progressive disseminated histoplasmosis were included. The differences of clinical features, imaging tests, means for diagnosis and prognosis were analyzed between the two types of histoplasmosis.
 Results: The clinical manifestations of pulmonary histoplasmosis were mild, such as dry cough. However, the main clinical symptoms of progressive disseminated histoplasmosis were severe, including recurrence of high fever, superficial lymph node enlargement over the whole body, hepatosplenomegaly, accompanied by cough, abdominal pain, joint pain, skin changes, etc.Laboratory examination showed pancytopenia, abnormal liver function and abnormal coagulation function. One pulmonary case received the operation of left lower lung lobectomy, 3 cases of pulmonary histoplasmosis and 6 cases of progressive disseminated histoplasmosis patients were given deoxycholate amphotericin B, itraconazole, voriconazole or fluconazole for antifungal therapy. One disseminated case discharged from the hospital without treatment after diagnosis of histoplasmosis, and 1 disseminated case combined with severe pneumonia and active tuberculosis died ultimately.
 Conclusion: As a rare fungal infection, histoplasmosis is easily to be misdiagnosed. The diagnostic criteria depends on etiology through bone marrow smear and tissues biopsy. Liposomeal amphotericin B, deoxycholate amphotericin B and itraconazole are recommended to treat infection for histoplasma capsulatum.