Progression of portal hypertension after atezolizumab plus bevacizumab for hepatocellular carcinoma-report a case and literature review.

BACKGROUND: Atezolizumab/bevacizumab combination therapy became the first-line therapy for advanced hepatocellular carcinoma (HCC). Gastroesophageal varices should be monitored and managed before treatment. The progression of portal hypertension during bevacizumab-containing therapy is unclear. METHOD: A case of new development of esophageal varices, ascites, and hepatic hydrothorax during atezolizumab/bevacizumab therapy at National Taiwan University Hospital was reported, and relevant literature was reviewed. RESULTS: We presented an 83-year-old male with resolved hepatitis B without cirrhosis. He had BCLC stage C HCC and received tri-weekly atezolizumab/bevacizumab therapy for 34 cycles with sustained partial response. Progressive ascites, esophageal varices, and hepatic hydrothorax developed, though his portal vein was patent and the tumor was under control. Five similar cases of HCC (BCLC B/C: n = 3/2) had been reported previously. Among them, three had cirrhosis with pre-existing small esophageal varices before treatment. After the administration of 1-15 cycles of atezolizumab/bevacizumab therapy, one patient had a progression of varices, and the other four developed variceal bleeding. The association between atezolizumab/bevacizumab and portal hypertension was possible, which might relate to the VEGF pathway and immune-related adverse events with progressive hepatic fibrosis. CONCLUSION: Atezolizumab/bevacizumab treatment might exacerbate portal hypertension. Careful monitoring and management should be considered during treatment.

Complications of ultrasound guided very small-bore chest drains for pleural effusions of different etiology.

Background: Small-bore chest drains are now the most common drains for treating pleural effusion (PE), but knowledge on complications is limited especially in malignant PE and empyema. We aimed to evaluate rate of complications of ultrasound guided small bore chest drains [6-10 French (F)] by PE etiology. Methods: Retrospective cohort study of 484 chest drains inserted in 330 adults in a Swedish department 2018-2020. Rate of complications (blockage, dislocation, infection, or misplacement) and repeat intervention (new drain within 2 weeks or surgery) was analyzed by effusion type (organ failure, parapneumonic, malignant, empyema, other, unknown), age, sex, seniority of radiologist, and bore size using multivariable logistic regression. Results: Most inserted drains (73.3%) were 6 F. The rate of repeat intervention was substantially higher in malignant PE [25.5%; adjusted odds ratio (aOR) 3.3; 95% confidence interval (CI): 1.6-6.8] and empyema (56.4%; aOR 11.9; 95% CI: 4.8-29.4) compared to other aetiologies (range, 9.5-17.8%). Surgery as complication occurred in empyema in 23.0% of cases (aOR 10.6; 95% CI: 1.4-79.4). The rate of repeat intervention in simple PE (parapneumonic or due to organ failure) was low (range, 9.5-12.5%). Conclusions: A single small-bore chest drain (6-10 F) was successful in the vast majority of simple PEs, but had high complication rates in empyema with frequent need of additional drains or surgery. These findings support use of larger drains and early consultation with a thoracic surgeon in empyema.

Hepatic hydrothorax.

Hepatic hydrothorax (HH) refers to the presence of a pleural effusion that develops in the context of underlying liver cirrhosis and portal hypertension. It carries a high risk of morbidity and mortality, with a median survival of 8-12 months. Diagnosis is usually confirmed by pleural aspiration, demonstrating typical features of a transudative effusion in the absence of co-existent cardio-pulmonary or renal pathology. The clinical presentation is quite variable, with some patients remaining relatively asymptomatic in the presence of small or incidental effusions, while others present with frank respiratory failure requiring pleural intervention. The development of spontaneous bacterial empyema (SBEM) is a significant and not infrequent complication, requiring prompt recognition and treatment. While the mainstay of management is focused on optimising fluid balance through dietary salt restriction and diuretic therapy, liver transplantation remains the definitive treatment option. As such, it is crucial to adopt a multi-disciplinary approach-involving pulmonologists, hepatologists, dieticians, and palliative care physicians-in order to optimise care for this often complex group of patients. This review will discuss the basic pathophysiology of HH, its clinical presentation and diagnosis, as well as the approach to management of HH in clinical practice, focussing on both interventional and non-interventional treatment modalities.

Chromosomal abnormalities associated with fetal pleural effusion (I): General overview.

Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of chromosomal abnormalities associated with fetal pleural effusion which is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

Syndromic and single gene disorders associated with fetal pleural effusion (I): Noonan syndrome, RASopathy and congenital lymphatic anomalies.

Fetal pleural effusion has been reported to be associated with chromosomal abnormalities, genetic syndromes, obstructive uropathy, lymphatic vessel abnormalities such as Noonan syndrome, RASopathy and congenital lymphatic anomalies, thoracic cavity defects, Rh or ABO incompatibility, non-immune hydrops fetalis, infections, congenital cardiac anomalies, metabolic diseases and hematologic diseases such as α-thalassemia. This review provides an overview of syndromic and single gene disorders associated with fetal pleural effusion that is useful for genetic counseling and fetal therapy at prenatal diagnosis of fetal pleural effusion.

Diagnosis and Management of Hepatic Hydrothorax.

Hepatic hydrothorax is a pleural effusion (typically ≥500 mL) that develops in patients with cirrhosis and/or portal hypertension in the absence of other causes. In most cases, hepatic hydrothorax is seen in patients with ascites. However, ascites is not always found at diagnosis and is not clinically detected in 20% of patients with hepatic hydrothorax. Some patients have no symptoms and incidental findings on radiologic examination lead to the diagnosis of the condition. In the majority of cases, the patients present with symptoms such as dyspnea at rest, cough, nausea, and pleuritic chest pain. The diagnosis of hepatic hydrothorax is based on clinical manifestations, radiological features, and thoracocentesis to exclude other etiologies such as infection (parapneumonic effusion, tuberculosis), malignancy (lymphoma, adenocarcinoma) and chylothorax. The management strategy involves a stepwise approach of one or more of the following: Reducing ascitic fluid production, preventing fluid transfer to the pleural space, fluid drainage from the pleural cavity, pleurodesis (obliteration of the pleural cavity), and liver transplantation. The complications of hepatic hydrothorax are associated with significant morbidity and mortality. The complication that causes the highest morbidity and mortality is spontaneous bacterial empyema (also called spontaneous bacterial pleuritis).

Atypical Psuedo-Demons-Meigs Syndrome Presenting As Acute Dyspnoea With Pseudomembranous Colitis.

Demons-Meigs syndrome is a rare clinical presentation of benign ovarian mass with hydrothorax and ascites. As ascites can be present in any ovarian mass, hydrothorax is a salient feature of the syndrome. The syndrome is subtyped as atypical in the absence of ascites from the triad. Nevertheless, it is labeled as pseudo-Demons-Meigs syndrome if the ovarian tumor is neoplastic rather than benign. The management of Demons-Meigs syndrome is complex and could be misleading due to pleural effusion and ascites, so an understanding of the syndrome is important. This case report is unique as it has two rare findings of neoplastic tumor and absence of ascites. Furthermore, this case is distinct as both ovaries are involved in malignant granulosa theca cell tumor with right-sided pleural effusion without ascites.

A case of refractory hepatic hydrothorax due to pleuroperitoneal communication successfully controlled by diaphragmatic plication and subsequent peritoneovenous shunting.

In general, control of hepatic hydrothorax is difficult, and patients have a poor prognosis. A case in which hepatic hydrothorax was well controlled for a long time after diaphragm plication and subsequent Denver shunt placement is reported. A 70-year-old man with decompensated liver cirrhosis presented with progressive exertional dyspnea. 5 years before admission, hepatic ascites associated with portal hypertension appeared, and a left pleural effusion subsequently developed. The pleural effusion was not controlled by salt restriction and diuretics. Based on the clinical findings, the existence of pleuroperitoneal communication was strongly suspected, and surgical diaphragmatic plication was performed. After the treatment, the pleural effusion did not accumulate, but ascites increased significantly, and conservative therapy was ineffective. For the treatment of massive ascites, a peritoneovenous shunt (Denver shunt®) was placed. Although more than 2 years have passed, the thoracoabdominal effusions have not accumulated, and the patient has been asymptomatic. The present case suggests that multidisciplinary treatment may improve the prognosis of patients with refractory thoracoabdominal effusions.

[Pulmonary Complications in Patients with Liver Cirrhosis].

Portal hypertension is a clinical syndrome defined by an increased portal venous pressure. The most frequent cause of portal hypertension is liver cirrhosis, and many of the complications of cirrhosis, such as ascites and gastroesophageal variceal bleeding, are related to portal hypertension. Portal hypertension is a pathological condition caused by the accumulation of blood flow in the portal system. This blood flow retention reduces the effective circulation volume. To compensate for these changes, neurotransmitter hormone changes and metabolic abnormalities occur, which cause complications in organs other than the liver. A hepatic hydrothorax is fluid accumulation in the pleural space resulting from increased portal pressure. Hepatopulmonary syndrome and portopulmonary hypertension are the pulmonary complications in cirrhosis by deforming the vascular structure. Symptoms, such as dyspnea and hypoxia, affect the survival and the quality of life of patients. These lung complications are usually underestimated in the management of cirrhosis. This review briefly introduces the type of lung complications of cirrhosis.

Clinical Features of Severe Ovarian Hyperstimulation Syndrome with Hydrothorax.

PROBLEM: Does the presence of hydrothorax suggest that severe ovarian hyperstimulation syndrome (OHSS) is associated with more severe conditions and worse pregnancy outcomes? METHOD OF STUDY: The clinical data for 868 hospital patients with severe OHSS following IVF-ET at Peking University Third Hospital between 1 January 2016 and 21 July 2021 were retrospectively analysed. The patients were divided into two groups, the ascites alone group (n = 417) and the ascites combined with hydrothorax group (n = 451), to investigate the clinical features and pregnancy outcomes of patients with severe ovarian hyperstimulation syndrome (OHSS) combined with hydrothorax plus ascites. RESULTS: The clinical data for 868 hospital patients with severe OHSS following IVF-ET were included. A total of 51.96% of patients with severe OHSS had hydrothorax plus ascites, mainly bilateral and moderate hydrothorax. Most cases with hydrothorax could be monitored and observed, and only 2.66% of the cases required thoracentesis and pleural drainage. Clinically, the time to visit due to worsening symptoms was longer; the hospital stay was shorter; and the OHSS-related laboratory tests, such as white blood cells (WBC), haematocrit (HCT), and ovarian diameter, were less severe in the ascites combined with hydrothorax group than in the ascites alone group. For live-birth outcomes of IVF-ET, the presence and the volume of hydrothorax were not independent risk factors, while the late onset of OHSS (odds ratio [OR]: 0.857 95% confidence interval [CI]: 0.795, 0.925) and a history of foetal reduction (OR: 13.796 95% CI: 1.808, 105.288) were independent protective factors for live birth. CONCLUSIONS: Patients with severe OHSS combined with hydrothorax plus ascites have less severe clinical manifestations and laboratory tests than those with ascites alone. The presence and the volume of hydrothorax are unrelated to live-birth outcomes following in vitro fertilization and embryo transfer (IVF-ET).

Pulmonary Assessment of the Liver Transplant Recipient.

Respiratory symptoms and hypoxemia can complicate chronic liver disease and portal hypertension. Various pulmonary disorders affecting the pleura, lung parenchyma, and pulmonary vasculature are seen in end-stage liver disease, complicating liver transplantation (LT). Approximately 8% of cirrhotic patients in an intensive care unit develop severe pulmonary problems. These disorders affect waiting list mortality and posttransplant outcomes. A thorough history, physical examination, and appropriate laboratory tests help diagnose and assess the severity to risk stratify pulmonary diseases before LT. Hepatopulmonary syndrome (HPS), portopulmonary hypertension (POPH), and hepatic hydrothorax (HH) are respiratory consequences specific to cirrhosis and portal hypertension. HPS is seen in 5-30% of cirrhosis cases and is characterized by impaired oxygenation due to intrapulmonary vascular dilatations and arteriovenous shunts. Severe HPS is an indication of LT. The majority of patients with HPS resolve their hypoxemia after LT. When pulmonary arterial hypertension occurs in patients with portal hypertension, it is called POPH. All other causes of pulmonary arterial hypertension should be ruled out before labeling as POPH. Since severe POPH (mean pulmonary artery pressure [mPAP] >50 mm Hg) is a relative contraindication for LT, it is crucial to screen for POPH before LT. Those with moderate POPH (mPAP >35 mm Hg), who improve with medical therapy, will benefit from LT. A transudative pleural effusion called hepatic hydrothorax (HH) is seen in 5-10% of people with cirrhosis. Refractory cases of HH benefit from LT. In recent years, increasing clinical expertise and advances in the medical field have resulted in better outcomes in patients with moderate to severe pulmonary disorders, who undergo LT.

Case report: Acute dyspnea secondary to urinothorax following ureteroscopy.

A 63-year-old female presented with a tension urinothorax after pyeloscopy, lithotripsy, and percutaneous nephrolithotomy that manifested as dyspnea and abdominal pain. CT Thorax demonstrated a large right pleural effusion with middle and lower lobe collapse with leftward shift concerning for tension hydrothorax. Analysis of the effusion after pigtail catheter demonstrated an exudative effusion with resultant resolution of the effusion after a 5-day hospital course. This case illustrates a uniquely rare complication of percutaneous urologic intervention. We highlight this case to stress the importance of considering urinothorax as a cause for dyspnea and abdominal pain after renal and ureteric interventions.

International survey among hepatologists and pulmonologists on the hepatic hydrothorax: plea for recommendations.

BACKGROUND: The Hepatic hydrothorax is a pleural effusion related to portal hypertension; its diagnosis and therapeutic management may be difficult. The aims of this article are which follows: To gather the practices of hepatogastroenterologists or pulmonologists practitioners regarding the diagnosis and management of the hepatic hydrothorax. METHODS: Practitioners from 13 French- speaking countries were invited to answer an online questionnaire on the hepatic hydrothorax diagnosis and its management. RESULTS: Five hundred twenty-eight practitioners (80% from France) responded to this survey. 75% were hepatogastroenterologists, 20% pulmonologists and the remaining 5% belonged to other specialities. The Hepatic hydrothorax can be located on the left lung for 64% of the responders (66% hepatogastroenterologists vs 57% pulmonologists; p = 0.25); The Hepatic hydrothorax can exist in the absence of clinical ascites for 91% of the responders (93% hepatogastroenterologists vs 88% pulmonologists; p = 0.27). An Ultrasound pleural scanning was systematically performed before a puncture for 43% of the responders (36% hepatogastroenterologists vs 70% pulmonologists; p < 0.001). A chest X-ray was performed before a puncture for 73% of the respondeurs (79% hepatogastroenterologists vs 54% pulmonologists; p < 0.001). In case of a spontaneous bacterial empyema, an albumin infusion was used by 73% hepatogastroenterologists and 20% pulmonologists (p < 0.001). A drain was used by 37% of the responders (37% hepatogastroenterologists vs 31% pulmonologists; p = 0.26).An Indwelling pleural catheter was used by 50% pulmonologists and 22% hepatogastroenterologists (p < 0.01). TIPS was recommended by 78% of the responders (85% hepatogastroenterologists vs 52% pulmonologists; p < 0.001) and a liver transplantation, by 76% of the responders (86% hepatogastroenterologists vs 44% pulmonologists; p < 0.001). CONCLUSIONS: The results of this large study provide important data on practices of French speaking hepatogastroenterologists and pulmonologists; it appears that recommendations are warranted.

Meigs Syndrome and Elevated CA-125: Case Report and Literature Review of an Unusual Presentation Mimicking Ovarian Cancer.

Background and Objectives: Meigs syndrome is represented by a benign adnexal tumor, ascites, and hydrothorax. Even though the ovarian mass is often characterized by a fibroma-like origin, cancer antigen-125 (CA-125) serum levels could be elevated as in the development of ovarian cancer. Here, we present the case of a patient with Meigs syndrome and increased CA-125. Materials and Methods: We performed systematic research for articles including similar cases in PubMed, EMBASE, and Scopus in February 2023, adopting the string of idioms: "Meigs syndrome AND Cancer antigen 125", and following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Results: Eligible records were 25. Hydrothorax was right-sided in 10 cases over 25; left-sided in two patients over 25. Concerning ascites, two patients showed more than 6 L of ascitic fluid, whereas three patients had 6 L or less. CA-125 elevation ranged from 149 IU/mL to 3803 IU/mL. Adnexal mass histotypes were: struma ovarii (12 cases), thecomas (two cases), fibrothecomas (five cases), fibromas (five cases), and one sclerosing stromal tumor (SST). Conclusions: In postmenopausal women with elevated CA-125 serum levels and an adnexal mass suspicious for malignancy at ultrasound (US), ascites and pleural effusion, surgery, and histopathological examination are necessary. MS is a diagnostic option, with an excellent prognosis after exeresis of the mass.

Brucella pleuritis misdiagnosed as tuberculous pleuritis: a case report.

Pleurisy and pleural effusion caused by Brucella infection are rare. However, clinicians lack an understanding of these possibilities, and the underlying disorder is easy to misdiagnose. We report a 52-year-old male farmer who was admitted to hospital with a fever, chest pain, and shortness of breath. Closed chest drainage was performed by thoracocentesis, and the concentration of adenosine deaminase (ADA) in the pleural fluid was >45 U/L. Mononuclear cells in the pleural fluid accounted for 90% of the cells, and pathology indicated a large number of lymphocytes. The clinical diagnosis was tuberculosis with tuberculous pleurisy. However, subsequent pleural fluid culture results did not support tuberculous pleurisy. The results of pleural fluid culture indicated Brucella, and the results of Brucella tiger red plate agglutination indicated a titer of 1:400 (+++). The final diagnosis was brucellosis with pneumonia and pleurisy. After 12 weeks of oral treatment, the patient underwent follow-up chest radiographs. Radiography indicated complete resolution of the hydrothorax and pneumonia, and the patient reported no discomfort. The short-term curative effect was excellent. Pleurisy associated with brucellosis should be considered a differential for pleurisy in regions where brucellosis is endemic, to minimize the risk of misdiagnosis.

Updates on Infectious and Other Complications in Peritoneal Dialysis: Core Curriculum 2023.

The last few years have seen several developments in the field of peritoneal dialysis (PD), including successful use of acute PD, increasing emphasis on home dialysis utilization, and improved understanding of models of peritoneal solute transfer. This installment of AJKD's Core Curriculum in Nephrology emphasizes the latest data available for prevention and management of infectious and noninfectious complications of PD. Through case vignettes, appropriate strategies for diagnosis and care of patients with PD peritonitis are reviewed as well as noninfectious complications evident in clinical practice including complications from increased intra-abdominal pressure, namely pericatheter and abdominal leaks, hernia formation, and complications from pleuroperitoneal communication (hydrothorax). Although rates of incisional hernias and pericatheter leaks have decreased with improved peritoneal dialysis catheter insertion techniques, these mechanical complications continue to be common occurrences and are reviewed via pertinent clinical vignettes which aim to address and discuss common implications of these scenarios. Finally, this Core Curriculum article covers a practical overview of peritoneal dialysis catheter dysfunction.

Clinical features of fetal hydrothorax associated with mucopolysaccharidosis-VII.

Mucopolysaccharidosis (MPS)-VII, called Sly disease, is a lysosomal storage disorder that can cause fetal hydrops, including fetal hydrothorax (FHT). We describe two fetal cases that received thoracoamniotic shunting for FHT, which was later found to be associated with MPS-VII by exome sequencing. Bilateral FHT accompanied by skin edema and ascites was found before 20 weeks of gestation in both cases. One fetus died in utero at 35 weeks of gestation, and the other survived with preterm delivery at 30 weeks of gestation. Both cases inherited compound pathogenic variants of GUSB from parents. Comparison with previously reported primary FHT cases revealed distinct clinical features in MPS-VII-associated FHT: early gestational age at diagnosis (<26 weeks), bilateral effusion, skin edema with ascites, and poor survival. A genetic analysis would be considered for FHT cases, with consideration of shunting when they show early-onset bilateral effusions with skin edema and ascites.

Risk factors for hepatic hydrothorax in patients with cirrhosis: a clinical retrospective study.

Aims and background: Hepatic hydrothorax, which presents as an unexplained pleural effusion, is one of the important complications in patients with end-stage cirrhosis. It has a significant correlation with prognosis and mortality. The aim of this clinical study was to detect the risk factors for hepatic hydrothorax in patients with cirrhosis and to better understand potentially life-threatening complications. Methods: Retrospectively, 978 cirrhotic patients who were hospitalized at the Shandong Public Health Clinical Center from 2013 to 2021 were involved in this study. They were divided into the observation group and the control group based on the presence of hepatic hydrothorax. The epidemiological, clinical, laboratory, and radiological characteristics of the patients were collected and analyzed. ROC curves were used to evaluate the forecasting ability of the candidate model. Furthermore, 487 cases in the experimental group were divided into left, right, and bilateral groups, and the data were analyzed. Results: The patients in the observation group had a higher proportion of upper gastrointestinal bleeding (UGIB), a history of spleen surgery, and a higher model for end-stage liver disease (MELD) scores compared with the control group. The width of the portal vein (PVW) (P = 0.022), prothrombin activity (PTA) (P = 0.012), D-dimer (P = 0.010), immunoglobulin G (IgG) (P = 0.007), high-density lipoprotein cholesterol (HDL) (P = 0.022), and the MELD score were significantly associated with the occurrence of the hepatic hydrothorax. The AUC of the candidate model was 0.805 (P < 0.001, 95% CI = 0.758-0.851). Portal vein thrombosis was more common in bilateral pleural effusion compared with the left and right sides (P = 0.018). Conclusion: The occurrence of hepatic hydrothorax has a close relationship with lower HDL, PTA, and higher PVW, D-dimer, IgG, and MELD scores. Portal vein thrombosis is more common in cirrhotic patients with bilateral pleural effusion compared to those with unilateral pleural effusion.

Tension hydrothorax in a patient with a history of pulmonary tuberculosis.

A tension hydrothorax is a massive pleural effusion that leads to hemodynamic instability. Here we present a case of tension hydrothorax secondary to poorly differentiated carcinoma. A 74-year-old male smoker presented after a one-week history of dyspnea and unintentional weight loss. Physical exam demonstrated tachycardia, tachypnea, and decreased breath sounds diffusely over the right lung. Imaging revealed a massive pleural effusion causing mass effect on the mediastinum with tension physiology. Chest tube placement revealed an exudative effusion with negative cultures and cytology. Pleural biopsy revealed atypical epithelioid cells consistent with poorly differentiated carcinoma.