A Case of Organizing Pneumonia Resembling Lung Cancer.

BACKGROUND: Organizing pneumonia (OP) is a pathologic diagnosis with clinical and imaging manifestations that often resemble other diseases, such as infections and cancers, which can lead to delays in diagnosis and inappropriate management of the underlying disease. In this article, we present a case of organized pneumonia that resembles lung cancer. METHODS: We report a case of initial suspicion of pulmonary malignancy, treated with anti-inflammatory medication and then reviewed with CT suggesting no improvement, and finally confirmed to be OP by pathological biopsy taken via transbronchoscopy. A joint literature analysis was performed to raise clinicians' awareness of the diagnosis and treatment of OP. RESULTS: Initially, because of the atypical auxiliary findings, we thought that the disease turned out to be a lung tumor, which was eventually confirmed as OP by pathological diagnosis. CONCLUSIONS: The diagnosis and treatment of OP requires a combination of clinical information and radiological expertise, as well as biopsy to obtain histopathological evidence. That is, clinical-imaging-pathological tripartite cooperation and comprehensive analysis.

CEA Negative Initial Diagnosis of HP Infection Finally Confirmed by Bronchoscopic Biopsy as Lung Adenocarcinoma.

BACKGROUND: Carcinoembryonic antigen (CEA) is a polysaccharide complex that is found in the human respiratory system. It is of significant use in disease surveillance of lung cancer; however, serum CEA can occasionally only offer little assistance. We present a case of recurring infection initially diagnosed as carcinoembryonic antigen-negative in a patient with a history of hypersensitivity pneumonitis infection, which finally led to the diagnosis of lung adenocarcinoma following percutaneous lung puncture. METHODS: Appropriate laboratory tests, chest CT, bronchoscopy, percutaneous lung puncture, and pathologic examination were performed to explore the cause of the disease. RESULTS: Because CEA was negative and a chest CT showed interstitial changes in both lungs with numerous hyperdense shadows, coupled with the patient's history of hypersensitivity pneumonitis, we initially believed that the infection was relapsing. However, a percutaneous lung puncture eventually revealed that the patient had lung adenocarcinoma. CONCLUSIONS: Vigilance needs to be increased in clinical work for patients with interstitial lung disease, low tumor markers such as CEA, and imaging suggestive of inflammatory progression, which in fact turns into lung cancer. When the treatment is ineffective after standardized application of hormone and anti-infection, lung tissue should be obtained for pathological examination in time to obtain pathological evidence.

Development and validation of a nomogram to predict postsurgical intra-abdominal infection in blunt abdominal trauma patients: A multicenter retrospective study.

BACKGROUND: Intra-abdominal infection is a common complication of blunt abdominal trauma. Early detection and intervention can reduce the incidence of intra-abdominal infection and improve patients' prognoses. This study aims to construct a clinical model predicting postsurgical intra-abdominal infection after blunt abdominal trauma. METHODS: This study is a retrospective analysis of 553 patients with blunt abdominal trauma from the Department of General Surgery of 7 medical centers (2011-2021). A 7:3 ratio was used to assign patients to the derivation and validation cohorts. Patients were divided into 2 groups based on whether intra-abdominal infection occurred after blunt abdominal trauma. Multivariate logistic regression and least absolute shrinkage and selection operator regression were used to select variables to establish a nomogram. The nomogram was evaluated, and the validity of the model was further evaluated by the validation cohort. RESULTS: A total of 113 were diagnosed with intra-abdominal infection (20.4%). Age, prehospital time, C-reactive protein, injury severity score, operation duration, intestinal injury, neutrophils, and antibiotic use were independent risk factors for intra-abdominal infection in blunt abdominal trauma patients (P < .05). The area under the receiver operating curve (area under the curve) of derivation cohort and validation cohort was 0.852 (95% confidence interval, 0.784-0.912) and 0.814 (95% confidence interval, 0.751-0.902). The P value for the Hosmer-Lemeshow test was .135 and .891 in the 2 cohorts. The calibration curve demonstrated that the nomogram had a high consistency between prediction and practical observation. The decision curve analysis also showed that the nomogram had a better potential for clinical application. To facilitate clinical application, we have developed an online at https://nomogramcgz.shinyapps.io/IAIrisk/. CONCLUSION: The nomogram is helpful in predicting the risk of postoperative intra-abdominal infection in patients with blunt abdominal trauma and provides guidance for clinical decision-making and treatment.

Accidental Detection of Tuberculous Empyema at Health Check-Up.

BACKGROUND: Patients with tuberculous empyema (TE) can have a serious impact on lung function as their disease progresses, and, if left untreated, can cause damage to other parts of the body such as the thorax and spine, causing pain and inconvenience to the patient. Early diagnosis and the search for appropriate treatment are key to improving the survival rate of the disease. METHODS: We report a case of a young patient with an unexpected finding of right pleural effusion on physical examination, who was eventually diagnosed with TE using next-generation sequencing of pleural tissue. We analyzed the literature to improve clinicians' understanding of TE and how to properly diagnose and treat the disease. RESULTS: Laboratory results of the pleural effusion suggested a possible Mycobacterium tuberculosis infection, but pathogen-related tests were negative, and the diagnosis was eventually successfully confirmed by thoracoscopic pleural biopsy. CONCLUSIONS: The diagnosis of TE should be considered in young patients with pleural thickening of the empyema. Adenosine deaminase may provide diagnostic direction in patients with unexplained thorax abscess. Pleural biopsy, although an invasive procedure, is an essential diagnostic tool in some cases.

Positive Herpesvirus IgG Antibodies in Lung Cancer Patients Finally Proved as Drug-induced Pemphigus.

BACKGROUND: Herpesvirus IgG antibody positivity can be a lifelong burden of disease replication and reinfection or recent viruses can be reactivated and play an important role in the diagnosis and monitoring of herpesvirus [1]. However, sometimes serum IgG antibody positivity is of limited help in determining the onset of disease. We reported a case of herpesvirus IgG antibody positive in a patient with lung cancer who was initially misdiagnosed as herpes simplex and later confirmed drug-induced pemphigus (DIP) by histological and immunofluorescence studies. METHODS: Appropriate laboratory tests, enzyme-linked immunosorbent assay (ELISA), immunofluorescence and histological tests were performed for diagnosis. RESULTS: In lung cancer patients who were positive for herpesvirus IgG antibodies, were initially misdiagnosed as herpes simplex and eventually confirmed by histological and immunofluorescence examinations as DIP. CONCLUSIONS: Positive herpesvirus IgG antibody is not a specific manifestation of herpesvirus infection. For patients with unexplained skin blisters, we should improve histological examinations as soon as possible to clarify the type of lesion.

Left Lung High-Density Shadow Combined with Elevated NSE Ultimately Confirmed as Pulmonary Aspergillosis.

BACKGROUND: Detection of serum neuron specific enolase (NSE) has high sensitivity and specificity in the diagnosis of lung cancer, especially small cell lung cancer, but sometimes serum NSE provides limited help. We report a case of high-density shadow of the left lung and elevated serum NSE which mimicked lung cancer. It was ultimately confirmed to be pulmonary aspergillosis (PA) by bronchoscopic alveolar lavage fluid (BALF) and next-generation sequencing (NGS). METHODS: Appropriate laboratory tests, chest computed tomography (CT) scan, bronchoscopic alveolar lavage fluid, and next-generation sequencing were used to explore latent causes. RESULTS: NSE level was elevated, chest CT scan showed high-density shadow of the left lung, bronchoscopy showed flesh-colored new organisms in the lower lobe of the left lung, BALF and NGS revealed the presence of Aspergillus. CONCLUSIONS: Elevated NSE is not a typical manifestation of lung cancer, and we should perform BALF and NGS early to determine whether there is infection with special pathogenic bacteria.

Elevated CEA Misdiagnosed as Lung Cancer Ultimately Confirmed Pulmonary Cryptococcosis.

BACKGROUND: Carcinoembryonic antigen (CEA) is a polysaccharide complex present in the human respiratory system, which can reflect the presence of tumors in the human body and has important value in the monitoring of lung cancer [1], but sometimes serum CEA provides limited help. We reported a case of multiple consolidation of the lungs with elevated serum CEA, initially misdiagnosed as lung cancer and eventually confirmed by bronchoscopic lung biopsy as pulmonary cryptococcosis (PC). METHODS: Appropriate laboratory examination, chest computed tomography (CT) scan, and bronchoscopy lung biopsy were used to explore the latent etiology. RESULTS: CEA level was elevated, chest CT scan showed multiple consolidation of the lungs, serum cryptococcal antigen was positive, and pathological findings on bronchoscopic lung biopsy confirmed pulmonary cryptococcosis. CONCLUSIONS: Elevated CEA is not typical of lung cancer. We should also consider the possibility of specific pathogenic infection. Bronchoscopic lung biopsy is the gold standard should be performed as soon as possible to identify the lesion.

Acute Eosinophilic Pneumonia Masquerading as a Lung Abscess.

BACKGROUND: Acute Eosinophilic Pneumonia (AEP) is a rare form of non-infectious pneumonia that is easily missed and misdiagnosed because of its atypical clinical symptoms and misleading laboratory and imaging studies. METHODS: By reporting a case of an initial diagnosis of lung abscess, which was treated with antibiotics and then CT suggesting that the lesion continued to worsen, it was eventually confirmed to be AEP by lung biopsy, A joint literature analysis was conducted to improve clinicians' understanding of the diagnosis and treatment of AEP. RESULTS: Initially, because of the atypical ancillary findings, we thought the disease was a lung abscess, which was eventually confirmed by pathology as AEP. CONCLUSIONS: The presence of AEP needs to be considered when various laboratory findings point to infectious dis-ease, but anti-infection is not effective. Diagnosis can be confirmed by bronchoalveolar lavage and lung tissue biopsy. Prompt treatment can provide rapid relief and reduce the risk of patient death.

Pulmonary Tuberculosis with Elevated CEA and Positive PET-CT.

BACKGROUND: Pulmonary tuberculosis presenting as solitary pulmonary nodules in imaging is sometimes difficult to differentiate from lung cancer and is more likely to be misdiagnosed when accompanied by elevated CEA and positive PET-CT findings. METHODS: By reporting a case of misdiagnosed lung cancer, which was confirmed to be pulmonary tuberculosis by lung biopsy, a joint literature analysis was performed to raise clinicians' awareness of isolated nodules in the lung. RESULTS: With a series of ancillary tests, we initially considered the nodule to be malignant, and the lung biopsy pathology eventually confirmed pulmonary tuberculosis. CONCLUSIONS: When chest imaging suggests the presence of malignant features in solitary pulmonary nodules, invasive procedures can be performed appropriately to clarify the nature of the lesion. The diagnosis cannot be made blindly to ensure that no incorrect diagnosis is made nor wrong treatment given.

[Short-term outcomes and long-term quality of life after undergoing radical proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis for Siewert type II and III adenocarcinoma of the esophagogastric junction: A propensity score matching analysis].

Objective: To evaluate the effects on short-term clinical outcomes and long-term quality of life of laparoscopic-assisted radical proximal gastrectomy with esophageal gastric tube anastomosis versus total gastrectomy with Roux-en-Y anastomosis for adenocarcinoma of the esophagogastric junction. Methods: This was a propensity score matching, retrospective, cohort study. Clinicopathological data of 184 patients with adenocarcinoma of the esophagogastric junction admitted to two medical centers in China from January 2016 to January 2021 were collected (147 in the First Affiliated Hospital of Xiamen University and 37 in the Affiliated Hospital of Qinghai University). All patients had undergone laparoscopic-assisted radical gastrectomy. They were divided into two groups based on the extent of tumor resection and technique used for digestive tract reconstruction. A proximal gastrectomy with reconstruction by esophageal gastric tube anastomosis group comprised 82 patients and a total gastrectomy with reconstruction by Roux-en-Y anastomosis group comprised 102 patients. These groups differed significantly in the following baseline characteristics: age, preoperative hemoglobin, preoperative albumin, tumor length, tumor differentiation, and tumor TNM stage (all P<0.05). To eliminate potential bias caused by unequal distribution between the two groups, 1∶1 matching was performed by the nearest neighbor matching method. The 13 matched variables comprised sex, age, height, body mass, body mass index, preoperative glucose, preoperative hemoglobin, preoperative total protein, preoperative albumin, neoadjuvant radiotherapy, tumor length, degree of differentiation, and pathological TNM stage. Postoperative complications, postoperative nutritional status, incidence of reflux esophagitis 1 year after surgery, and quality of life were compared between the two groups. Results: After propensity score matching, 60 patients each were enrolled in the proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis groups. The baseline characteristics were comparable between these groups (all P>0.05). There were no significant differences between the two groups in operative time, intraoperative bleeding, time to semifluid diet, postoperative hospital days, tumor length, and total hospital costs (P>0.05). Patients in the proximal gastrectomy with esophageal gastric tube anastomosis group had earlier postoperative gastric tube and abdominal drainage tube removal time than those in the total gastrectomy with Roux-en-Y anastomosis group (t=-2.183, P=0.023 and t=-4.073, P<0.001, respectively). In contrast, significantly fewer lymph nodes were cleared and significantly fewer lymph nodes were positive in the proximal gastrectomy with esophageal gastric tube anastomosis group than in the total gastrectomy with Roux-en-Y anastomosis group (t=-5.754, P<0.001 and t=-2.575, P=0.031, respectively). The incidence of early postoperative complications was 43.3% (26/60) in the total gastrectomy with Roux-en-Y anastomosis group; this is not significantly higher than the 26.7% (16/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=3.663，P=0.056). The incidences of pulmonary infection (31.7%, 19/60) and pleural effusion (30.0%, 18/60) were significantly higher in the total gastrectomy with Roux-en-Y anastomosis group than in the proximal gastrectomy with esophageal gastric tube anastomosis group (13.3%, 8/60 and 8.3%, 5/60, respectively); these differences are significant (χ2=8.711, P=0.003 and χ2=11.368, P=0.001, respectively). All early complications were successfully treated before discharge. The incidence of long-term postoperative complications was 20.0% (12/60) in the total gastrectomy with Roux-en-Y anastomosis group and 35.0% (21/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this difference is not significant (χ2=3.386，P=0.066). The incidence of reflux esophagitis was 23.3% (14/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group; this is significantly higher than the 1.7% (1/60) in the total gastrectomy with Roux-en-Y anastomosis group (χ2=12.876, P<0.001). Body mass index had decreased significantly in both groups 1 year after surgery compared with preoperatively; however, the difference between the two groups was not significant (P>0.05). The differences in hemoglobin and albumin concentrations between 1 year postoperatively and preoperatively were not significant (both P>0.05). Quality of life was assessed using the Visick grade. Visick grade I dominated in both groups. The percentage of patients with Visick II and III in the total gastrectomy with Roux-en-Y anastomosis group was 11.7% (7/60), which is significantly lower than the 33.3% (20/60) in the proximal gastrectomy with esophageal gastric tube anastomosis group (χ2=8.076, P=0.004). No patients in either group had a grade IV quality of life. Conclusions: Both proximal gastrectomy with esophageal gastric tube anastomosis and total gastrectomy with Roux-en-Y anastomosis laparoscopic-assisted radical surgery for adenocarcinoma of the esophagogastric junction are safe and feasible. However, both procedures have their own advantages and disadvantages in terms of postoperative complications. The incidence of reflux esophagitis is higher after proximal gastrectomy with esophageal gastric tube anastomosis, whereas the long-term quality of life is lower than that of patients after total gastrectomy with Roux-en-Y anastomosis.

Development and assessment of a community-based screening tool for mental health disorders among people who inject drugs.

INTRODUCTION: The prevalence of mental health disorders among people who use drugs is high and well documented. This hard-to-reach population faces a very low awareness and access to mental health care, especially in developing countries. The objectives of this study were to design and assess a quick screening tool (QST) that community-based organisations (CBO) could routinely apply to a Vietnamese population of people who inject drugs (PWID), in order to refer them appropriately to mental health specialists. METHODS: We devised a tool that included nine questions covering anxiety, depression, suicide risk and psychotic symptomatology. Its use required no specific background and 2 h training. Specificity and sensitivity of the QST were assessed in a population of 418 PWID recruited via respondent driven sampling, using the Mini International Neuropsychiatric Interview questionnaire plus clinical evaluation as a reference standard. Acceptability was assessed using a self-administered anonymous questionnaire submitted to all CBO members who used the QST. RESULTS: CBO members considered the QST easy to use, relevant and helpful to deal with mental health issues. Area under the curve for detection of any symptom using the QST was 0.770. The maximum sensitivity and specificity were reached with a cut-off of 2 [sensitivity was 71.1% (95% confidence interval 62.4, 78.8), specificity was 75.9% (70.5, 80.7)]. DISCUSSION AND CONCLUSIONS: The QST appeared to be both efficient and well accepted. Given the burden of mental health problems among hard-to-reach PWID in developing countries, community-based screenings such as this one could be a particularly appropriate response.

[Uniportal thoracoscopic decortication for stage â ¢ tuberculous empyema of 158 cases].

Objective: To examine the safety and feasibility of uniportal video-assisted thoracoscopic (VATS) decortication in patients presenting with stage Ⅲ tuberculous empyema. Methods: From August 2017 to July 2020, 158 patients of stage Ⅲ tuberculous empyema underwent uniportal VATS decortication with partial rib resection and customized periosteal stripper in Department of Thoracic Surgery, Shanghai Pulmonary Hospital. There were 127 males and 31 females, aged (M(IQR)) 32(28) years (range:14 to 78 years). Follow-up was performed in the outpatient clinic or via social communication applications, at monthly thereafter. If there was no air leak and chest tube drainage was less than 50 ml/day, a chest CT was performed. If the lung was fully re-expanded, chest tubes were removed. All patients received a follow-up chest CT 3 to 6 months following their initial operations which was compared to their preoperative imaging. Results: There was one conversion to open thoracotomy. The operative time was 2.75 (2.50) hours (range: 1.5 to 7.0 hours), and median blood loss was 100 (500) ml (range: 50 to 2 000 ml). There were no perioperative mortalities. There were no major complications except 1 case of redo-VATS for hemostasis due to excessive drainage and 1 case of incision infection, The incidence of prolonged air leaks (>5 days) was 80.3%(126/157). The postoperative hospital stay was 5.00 (2.25) days (range: 2 to 15 days). All patients were discharged with 2 chest tubes, and the median duration drainage was 21.00 (22.50) days (range: 3 to 77 days). Follow-up was completed in all patients over a duration of 20 (14) months (range: 12 to 44 months). At follow-up, 149 patients(94.9%) recovered to grade Ⅰ level, 7 patients to grade Ⅱ level, and 1 patient to grade Ⅲ level. Conclusion: Uniportal VATS decortication involving partial rib resection and a customized periosteal stripper is safe and effective for patients with stage Ⅲ tuberculous empyema.

Successful removal of a trapped epidural catheter facilitated by using a nickel/titanium alloy (nitinol) suture as a guidewire.

Epidural catheters are often used in the provision of surgical anaesthesia and analgesia. These catheters need to be removed after a certain period, but difficulties may be encountered during this process. We present a case of difficult epidural catheter removal in an elderly woman who had undergone surgery for reduction and internal fixation of a comminuted intertrochanteric fracture at the left femur under combined spinal epidural anaesthesia. Anaesthesia was satisfactory during the operation; however, initial attempts to remove the catheter at the end of the procedure was met with significant resistance. Normal saline (5 ml) was injected through the catheter without difficulty, suggesting that the catheter was likely trapped and compressed but not obstructed. A nickel/titanium memory alloy suture was used as a guidewire to remove the catheter without damaging it. This case was analysed subsequently, and the management of future problematic removals is discussed herein. This article aims to raise awareness of, and to explore techniques for managing difficult epidural catheter removal.

[Perirectal fascial anatomy and pelvic autonomic nerve preservation during the transanal total mesorectal excision].

The difficulty of transanal total mesorectal excision (TME) is to find the correct dissection plane of perirectal space. As a complex new surgical procedure, the fascial anatomic landmarks of transanal approach operation are more likely to be ignored. It is often found that dissection plane is false after the secondary injury occurs during the operation, which results in the damage of pelvic autonomic nerves. Meanwhile, the mesorectum is easily damaged if the dissection plane is too close to the rectum. Thus, the safety of oncologic outcomes could be limited by difficulty achieving adequate TME quality. The promotion and development of the theory of perirectal fascial anatomy provides a new thought for researchers to design a precise approach for transanal endoscopic surgery. Transanal total mesorectal excision based on fascial anatomy offers a solution to identify the transanal anatomic landmarks precisely and achieves pelvic autonomic nerve preservation. In this paper, the authors focus on the surgical experience of transanal total mesorectal excision based on the theory of perirectal fascial anatomy, and discuss the feature of perirectal fascial anatomy dissection and technique of pelvic autonomic nerve preservation during transanal approach operation.

Biomarker analyses in the phase III ASCENT study of sacituzumab govitecan versus chemotherapy in patients with metastatic triple-negative breast cancer.

BACKGROUND: The pivotal phase III ASCENT trial demonstrated improved survival outcomes associated with sacituzumab govitecan (SG), an anti-trophoblast cell-surface antigen 2 (anti-Trop-2) antibody-drug conjugate linked with the topoisomerase-inhibitor SN-38, over single-agent chemotherapy treatment of physician's choice (TPC) in previously treated metastatic triple-negative breast cancer (mTNBC). This prespecified, exploratory biomarker analysis from the ASCENT trial evaluates the association between tumor Trop-2 expression and germline BRCA1/2 mutation status with clinical outcomes. PATIENTS AND METHODS: Patients with mTNBC refractory to or progressing after two or more prior chemotherapies, with one or more in the metastatic setting, were randomized to receive SG (10 mg/kg intravenously days 1 and 8, every 21 days) or TPC (capecitabine, eribulin, vinorelbine, or gemcitabine) until disease progression/unacceptable toxicity. Biopsy or surgical specimens were collected at study entry to determine Trop-2 expression level using a validated immunohistochemistry assay and histochemical scoring. Germline BRCA1/2 mutation status was collected at baseline. RESULTS: Of 468 assessable patients, 290 had Trop-2 expression data [64% (n = 151 SG) versus 60% (n = 139 TPC)] and 292 had known BRCA1/2 mutation status [63% (n = 149 SG) versus 61% (n = 143 TPC)]. Median progression-free survival in SG- versus TPC-treated patients was 6.9, 5.6, and 2.7 months versus 2.5, 2.2, and 1.6 months for high, medium, and low Trop-2 expression, respectively. Median overall survival (14.2, 14.9, and 9.3 months versus 6.9, 6.9, and 7.6 months) and objective response rates (44%, 38%, and 22% versus 1%, 11%, and 6%) were numerically higher with SG versus TPC in patients with high, medium, and low Trop-2 expression, respectively. Efficacy outcomes were numerically higher with SG versus TPC in patients with and without germline BRCA1/2 mutations. CONCLUSIONS: SG benefits patients with previously treated mTNBC expressing high/medium Trop-2 compared with standard-of-care chemotherapy and regardless of germline BRCA1/2 mutation status. The small number of patients with low Trop-2 expression precludes definitive conclusions on the benefit of SG in this subgroup.

Sacituzumab govitecan, a Trop-2-directed antibody-drug conjugate, for patients with epithelial cancer: final safety and efficacy results from the phase I/II IMMU-132-01 basket trial.

BACKGROUND: Sacituzumab govitecan (SG), a trophoblast cell surface antigen-2 (Trop-2)-directed antibody-drug conjugate, has demonstrated antitumor efficacy and acceptable tolerability in a phase I/II multicenter trial (NCT01631552) in patients with advanced epithelial cancers. This report summarizes the safety data from the overall safety population (OSP) and efficacy data, including additional disease cohorts not published previously. PATIENTS AND METHODS: Patients with refractory metastatic epithelial cancers received intravenous SG (8, 10, 12, or 18 mg/kg) on days 1 and 8 of 21-day cycles until disease progression or unacceptable toxicity. Endpoints for the OSP included safety and pharmacokinetic parameters with investigator-evaluated objective response rate (ORR per RECIST 1.1), duration of response, clinical benefit rate, progression-free survival, and overall survival evaluated for cohorts (n > 10 patients) of small-cell lung, colorectal, esophageal, endometrial, pancreatic ductal adenocarcinoma, and castrate-resistant prostate cancer. RESULTS: In the OSP (n = 495, median age 61 years, 68% female; UGT1A1∗28 homozygous, n = 46; 9.3%), 41 (8.3%) permanently discontinued treatment due to adverse events (AEs). Most common treatment-related AEs were nausea (62.6%), diarrhea (56.2%), fatigue (48.3%), alopecia (40.4%), and neutropenia (57.8%). Most common treatment-related serious AEs (n = 75; 15.2%) were febrile neutropenia (4.0%) and diarrhea (2.8%). Grade ≥3 neutropenia and febrile neutropenia occurred in 42.4% and 5.3% of patients, respectively. Neutropenia (all grades) was numerically more frequent in UGT1A1∗28 homozygotes (28/46; 60.9%) than heterozygotes (69/180; 38.3%) or UGT1A1∗1 wild type (59/177; 33.3%). There was one treatment-related death due to an AE of aspiration pneumonia. Partial responses were seen in endometrial cancer (4/18, 22.2% ORR) and small-cell lung cancer (11/62, 17.7% ORR), and one castrate-resistant prostate cancer patient had a complete response (n = 1/11; 9.1% ORR). CONCLUSIONS: SG demonstrated a toxicity profile consistent with previous published reports. Efficacy was seen in several cancer cohorts, which validates Trop-2 as a broad target in solid tumors.

Sacituzumab govitecan in previously treated hormone receptor-positive/HER2-negative metastatic breast cancer: final results from a phase I/II, single-arm, basket trial.

BACKGROUND: Trophoblast cell-surface antigen-2 (Trop-2) is expressed in epithelial cancers, including hormone receptor-positive (HR+) metastatic breast cancer (mBC). Sacituzumab govitecan (SG; Trodelvy®) is an antibody-drug conjugate composed of a humanized anti-Trop-2 monoclonal antibody coupled to SN-38 at a high drug-to-antibody ratio via a unique hydrolyzable linker that delivers SN-38 intracellularly and in the tumor microenvironment. SG was granted accelerated FDA approval for metastatic triple-negative BC treatment in April 2020. PATIENTS AND METHODS: We analyzed a prespecified subpopulation of patients with HR+/human epidermal growth factor receptor 2-negative (HER2-) HR+/HER2- mBC from the phase I/II, single-arm trial (NCT01631552), who received intravenous SG (10 mg/kg) and whose disease progressed on endocrine-based therapy and at least one prior chemotherapy for mBC. End points included objective response rate (ORR; RECIST version 1.1) assessed locally, duration of response (DOR), clinical benefit rate, progression-free survival (PFS), overall survival (OS), and safety. RESULTS: Fifty-four women were enrolled between 13 February 2015 and 1 June 2017. Median (range) age was 54 (33-79) years and all received at least two prior lines of therapy for mBC. At data cut-off (1 March 2019), 12 patients were still alive. Key grade ≥3 treatment-related toxicities included neutropenia (50.0%), anemia (11.1%), and diarrhea (7.4%). Two patients discontinued treatment due to treatment-related adverse events. No treatment-related deaths occurred. At a median follow-up of 11.5 months, the ORR was 31.5% [95% confidence interval (CI), 19.5%-45.6%; 17 partial responses]; median DOR was 8.7 months (95% CI 3.7-12.7), median PFS was 5.5 months (95% CI 3.6-7.6), and median OS was 12 months (95% CI 9.0-18.2). CONCLUSIONS: SG shows encouraging activity in patients with pretreated HR+/HER2- mBC and a predictable, manageable safety profile. Further evaluation in a randomized phase III trial (TROPiCS-02) is ongoing (NCT03901339). TRIAL REGISTRATION: ClinicalTrials.gov NCT01631552; https://clinicaltrials.gov/ct2/show/NCT01631552.

The Dynamic Life of Virus Capsids.

Protein-shelled viruses have been thought as "tin cans" that merely carry the genomic cargo from cell to cell. However, through the years, it has become clear that viruses such as rhinoviruses and caliciviruses are active and dynamic structures waiting for the right environmental cues to deliver their genomic payload to the host cell. In the case of human rhinoviruses, the capsid has empty cavities that decrease the energy required to cause conformational changes, resulting in the capsids "breathing", waiting for the moment when the receptor binds for it to release its genome. Most strikingly, the buried N-termini of VP1 and VP4 are transiently exposed during this process. A more recent example of a "living" protein capsid is mouse norovirus (MNV). This family of viruses have a large protruding (P) domain that is loosely attached to the shell via a single-polypeptide tether. Small molecules found in the gut, such as bile salts, cause the P domains to rotate and collapse onto the shell surface. Concomitantly, bile alters the conformation of the P domain itself from one that binds antibodies to one that recognizes receptors. In this way, MNV appears to use capsid flexibility to present one face to the immune system and a completely different one to attack the host tissue. Therefore, it appears that even protein-shelled viruses have developed an impressive array of tricks to dodge our immune system and efficiently attack the host.