An 88-Year-Old Woman With Pneumothorax and Black Pleural Effusion.

CASE PRESENTATION: An 88-year-old woman was admitted to our hospital with the sudden onset of dyspnea after eating. The patient had undergone nephrectomy for a left renal tumor 24 years previously. The patient had been prescribed ferrous citrate for iron-deficiency anemia. She complained of appetite loss a few days before admission but had no abdominal pain. CT scan showed no abnormalities in the lungs but a mass in the liver.

Early and late outcomes of congenital biliary dilatation in pediatric patients.

BACKGROUND: This study aimed to reveal the early and late postoperative complications and outcomes after surgery for congenital biliary dilatation (CBD) by reviewing cases over the past 40 years. METHODS: We retrospectively evaluated 59 patients with CBD who underwent radical surgery for complications and outcomes, based on medical records. Early complications were defined as those requiring treatment within 5 years of the initial operation. Late complications were defined as those treated more than 5 years later. RESULTS: The median age at the first surgery was 37 months. Regarding biliary reconstruction, 54 of the 59 patients (91.5%) underwent hepaticojejunostomy. Although three patients underwent cholecystoduodenostomy and one patient underwent hepaticoduodenostomy, all were converted to hepaticojejunostomy after a median of 12.5 years. One patient developed synchronous biliary carcinoma and underwent pancreaticoduodenectomy. Early complications occurred in seven patients with 10 events (surgical site infection, n = 3 bile leakage, n = 3; ileus, n = 3; bile duct obstruction, n = 1 and intussusception, n = 1). Late complications occurred in nine patients with 12 events (ileus, n = 3; anastomotic stricture, n = 3; hepatolithiasis, n = 3; asynchronous biliary carcinoma, n = 2; pancreatolithiasis, n = 1). Two of the three patients with hepatolithiasis underwent hepatectomy refractory to the endoscopic approach. Two patients developed asynchronous biliary carcinoma at 34 and 13 years after last operation; both ultimately died of the carcinoma. Only 35 patients (61.4%) underwent a follow-up examination. A total of 11 female patients (45.8%) eventually married, and all successfully gave birth. CONCLUSION: Although the long-term prognosis is excellent with complete cyst excision and hepaticojejunostomy, we emphasize the importance of long-term follow-up.

Malignancy After Living Donor Liver Transplantation.

OBJECTIVES: De novo malignancy (DNM) is a major cause of death in long-term recipients of liver transplantation (LT). We herein report our experience with DNM after living-donor LT (LDLT). PATIENTS AND METHODS: A total of 111 LDLT procedures were performed in our institute from 1999 to 2022. Among them, 70 adult (>13 years old) LDLT recipients who survived for more than 1 year were included in this study. RESULTS: During a median follow-up of 146 (range, 12-285) months, 7 out of 70 recipients developed 8 DNMs, including lung cancer in 4, post-transplant lymphoproliferative disease in 3, and skin cancer in 1. One patient developed metachronal skin cancer and post-transplant lymphoproliferative disease. The pre-LT smoking history rate in patients with DNM was higher than in patients without DNM (P = .004). The survival time after DNM was 6 (1-166) months. Only 2 patients underwent R0 resection. DNM did not recur during follow-up. Other patients who underwent R1 resection and/or chemotherapy and/or radiotherapy all died due to DNMs during the follow-up. The cumulative DNM incidence was 3.5% at 10 years and 18.4% at 20 years after LDLT. The cumulative survival rate in patients with DNM was significantly worse than that in patients without DNM after LDLT (P = .049). CONCLUSION: The survival rate of patients with DNM was lower than that of those without DNM. A pre-LT smoking history is a risk factor for DNM. R0 resection is effective for improving the prognosis of patients with DNM. Regular cancer screening is important for detecting DNM early after LDLT.

Sirolimus treatment for intractable lymphatic anomalies: an open-label, single-arm, multicenter, prospective trial.

Introduction: Intractable lymphatic anomalies (LAs) include cystic lymphatic malformation (LM; macrocystic, microcystic, or mixed), generalized lymphatic anomaly, and Gorham-Stout disease. LAs can present with severe symptoms and poor prognosis. Thus, prospective studies for treatments are warranted. We conducted a prospective clinical trial of sirolimus for intractable LAs. Methods: This was an open-label, single-arm, multicenter, prospective trial involving five institutions in Japan. All patients with LAs received oral sirolimus once daily, and the dose was adjusted to ensure that the trough concentration remained within 5-15 ng/mL. We prospectively assessed the drug response (response rate for radiological volumetric change in target lesion), performance state, change in respiratory function, visceral impairment (pleural effusion, ascites, bleeding, pain), laboratory examination data, quality of life (QOL), and safety at 12, 24, and 52 weeks of administration. Results: Eleven patients with LAs (9 generalized lymphatic anomaly, 1 cystic LM, 1 Gorham-Stout disease) were treated with sirolimus, of whom 6 (54.5%; 95% confidence interval: 23.4-83.3%) demonstrated a partial response on radiological examination at 52 weeks of administration. No patients achieved a complete response. At 12 and 24 weeks of administration, 8 patients (72.7%) already showed a partial response. However, patients with stable disease showed minor or no reduction after 12 weeks. Adverse events, such as stomatitis, acneiform dermatitis, diarrhea, and fever, were common with sirolimus. Sirolimus was safe and tolerable. Conclusion: Sirolimus can reduce the lymphatic tissue volume in LAs and may lead to improvements in clinical symptoms and QOL.

Pseudomonas fluorescens pneumonia.

Pseudomonas fluorescens (P. fluorescens) is not generally considered a bacterial pathogen in humans; however, multiple culture-based and culture-independent studies have identified it in the indigenous microbiota of multiple body sites. We herein report a rare case of pneumonia caused by P. fluorescens. A man in his 80 s with chronic obstructive pulmonary disease and diabetes mellitus was diagnosed with stage II rectal cancer. He underwent laparoscopic surgery, and on the 6th postoperative day, he developed a high fever. Chest computed tomography revealed infiltration in the left lower lung. Gram staining of the sputum showed Gram-negative rods phagocytosed by neutrophils, suggesting postoperative nosocomial pneumonia. The patient was started on tazobactam/piperacillin, and his pneumonia quickly improved. Later, only P. fluorescens was detected in a sputum culture. It was susceptible to common antipseudomonal agents. Gram staining of P. fluorescens appears to show a slightly thicker and larger morphology in comparison to Pseudomonas aeruginosa. Although there have been reports of opportunistic infections caused by P. fluorescens in immunosuppressed patients, including those with advanced cancer, most have been bloodstream infections, with very few reports of pneumonia alone. Clinicians should be aware that patients, who are not necessarily immunosuppressed, may develop pneumonia caused by P. fluorescens.

Desquamative Interstitial Pneumonia with Progressive Pulmonary Fibrosis.

A 70-year-old man who smoked was referred to our hospital because of progressive cough and dyspnea. Radiologic images showed ground-glass attenuation predominantly in the lower lung lobes. A surgical lung biopsy was performed, and a diagnosis of desquamative interstitial pneumonia (DIP) was made. The patient's symptoms improved with smoking cessation and steroid treatment, but the ground-glass attenuation did not completely resolve. At 10 years after the diagnosis, the fibrotic lesions deteriorated and treatment with nintedanib was subsequently initiated. Careful observation is needed in patients with DIP whose lung involvement does not completely improve with initial treatment.

Usefulness of NF2 hemizygous loss detected by fluorescence in situ hybridization in diagnosing pleural mesothelioma in tissue and cytology material: A multi-institutional study.

OBJECTIVES: BAP1, CDKN2A, and NF2 are the most frequently altered genes in pleural mesotheliomas (PM). Discriminating PM from benign mesothelial proliferation (BMP) is sometimes challenging; it is well established that BAP1 loss, determined by immunohistochemistry (IHC), and CDKN2A homozygous deletion (HD), determined by fluorescence in situ hybridization (FISH), are useful. However, data regarding the diagnostic utility of NF2 FISH in PM is limited. Thus, we performed a multi-institutional study examining the utility of NF2 alterations determined by FISH for diagnosing PM in combination with BAP1 loss and CDKN2A HD. MATERIALS AND METHODS: Multi-institutional PM cases, including 106 surgical and 107 cell block samples as well as 37 tissue cases of benign mesothelial proliferation (BMP) and 31 cell block cases with reactive mesothelial cells (RMC), were collected and analyzed using IHC for BAP1 and FISH for CDKN2A and NF2. RESULTS: In PM, NF2 FISH revealed hemizygous loss (HL) in 54.7% of tissue cases (TC) and 49.5% of cell block cases (CBC), with about 90% of HL being monosomy. CDKN2A HD or BAP1 loss were detected in 75.5%/65.4% TC or 63.6%/60% CBC, respectively. BMP or RMC showed no BAP1 loss, CDKN2A HD, or NF2 HL. For discriminating PM from BMP, a combination of BAP1 loss, CDKN2A HD, and NF2 HL yielded enhanced sensitivity of 98.1% TC/94.4% CBC. BAP1 loss, CDKN2A HD, or NF2 HL were observed in 69%, 70%, or 58% of epithelioid PM, but in 9%, 91%, or 27% of sarcomatoid PM, respectively. Histotype, histological gradings, and CDKN2A deletion status showed significant differences in overall survival, while BAP1 loss and NF2 HL did not. CONCLUSION: NF2 HL, consisting predominantly of monosomy, can be detected by FISH in both TC and CBC of PM, and is effective for distinguishing PM from BMP, especially when combined with BAP1 loss and CDKN2A HD.

Short stature as an initial presenting presentation of unicentric Castleman disease in a child: A case report with long-term follow-up and a literature review.

Short stature is a common clinical condition in paediatric outpatient clinics and is associated with various clinical conditions, ranging from normal variants to severe diseases. Short stature is known to be caused by chronic inflammatory conditions, in which over-produced inflammatory cytokines are reported to be involved in growth suppression. Castleman disease is a rare lymphoproliferative disorder known as a chronic inflammatory disease with overproduction of interleukin 6, which often causes systemic symptoms such as fever, fatigue, weight loss, and night sweats. Here, we report the case of a 10-year-old female diagnosed with unicentric Castleman disease, who presented with short stature as the sole clinical sign but lacked typical systemic symptoms of Castleman disease. An elevated serum C-reactive protein level led us to suspect a chronic inflammatory condition, and we found an intra-abdominal tumour that was histopathologically confirmed as Castleman disease. The tumour removal resulted in a steady catch-up in her height in the six years following the surgery. We also present a brief review of relevant literature on paediatric cases of Castleman disease associated with growth impairment. Clinicians should be aware that chronic inflammatory conditions can cause growth impairment, which may be a key clinical manifestation of such conditions.

A rare case of eosinophilic gastrointestinal disorders with short bowel syndrome after strangulated bowel obstruction.

BACKGROUND: Short bowel syndrome (SBS) is a rare yet costly disease with an incidence rate of 3 per million people. Herein, we report a rare case of eosinophilic gastrointestinal disorders (EGIDs) with SBS after strangulated bowel obstruction. CASE PRESENTATION: A 5-year-old male had a necrotic intestine of 340 cm resected due to strangulated bowel obstruction caused by an intestinal mesenteric hiatal hernia. The length of the residual intestine was 51 cm. Bloody stools appeared 19 days postoperatively. Colonoscopy showed diffuse redness of the colonic mucosa, and pathological findings showed moderate chronic inflammatory cellular infiltration. On blood examination, the eosinophil count was > 30%. EGIDs with short bowel syndrome (SBS) were suspected. Because his symptoms did not improve with initial nutrition therapy, he was transferred to our hospital 5 months after the operation. Prednisolone was administrated at an initial dose of 1.4 mg/kg/day, 6 days after his transfer. Bloody stools disappeared after prednisolone administration. Seven months after discharge, he had no bloody stool recurrence. CONCLUSION: The risk of developing secondary EGIDs in children with SBS should be considered, and postoperative management should include attention to abdominal symptoms and elevated eosinophil counts on blood examination.

Evaluation of Remdesivir for Mildly to Moderately Ill Patients with COVID-19: A Single-Arm, Single-Center, Retrospective Study.

Background and Objectives: Remdesivir (RDV) is the first antiviral agent approved in Japan for the treatment of coronavirus disease 2019 (COVID-19). The aim of our study was to assess the efficacy and safety of RDV treatment in mildly to moderately ill patients with COVID-19. Materials and Methods: A single-center, retrospective study was performed in Fukuoka University Chikushi Hospital. Patients admitted to our hospital from June to October 2021 for RDV treatment against COVID-19 were enrolled. The primary end point was clinical status on days 10 and 14, using a 6-point ordinal scale ranging from death (category 6) to discharge (category 1). Adverse events were assessed and graded using the Japanese version of Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: In total, 47 COVID-19 patients receiving RDV treatment were assessed during the study period. Thirty-four (72.3%) out of 47 patients required oxygen therapy. Out of these 34 patients, 30 (88.2%) showed a 2-point clinical improvement on day 14 after RDV was initiated. Serum alanine aminotransferase levels were elevated in three patients (6.4%) (CTCAE Grade 3) and neutropenia was detected in one patient (2.1%) out of the 47 patients. Conclusions: RDV may be highly effective, with good safety profiles, in patients with COVID-19 requiring oxygen therapy.

Challenges and limitation of MTAP immunohistochemistry in diagnosing desmoplastic mesothelioma/sarcomatoid pleural mesothelioma with desmoplastic features.

AIM: Genomic-based ancillary assays including immunohistochemistry (IHC) for BRCA-1 associated protein-1 (BAP1) and methylthioadenosine phosphorylase (MTAP), and fluorescence in situ hybridization (FISH) for CDKN2A are effective for differentiating pleural mesothelioma (PM) from reactive mesothelial proliferations. We previously reported a combination of MTAP and BAP1 IHC effectively distinguishes sarcomatoid PM from fibrous pleuritis (FP). Nevertheless, cases of sarcomatoid PM with desmoplastic features (desmoPM) are encountered where the IHC assessment is unclear. METHODS AND RESULTS: We evaluated assessment of MTAP IHC, BAP1 IHC, and CDKN2A FISH in 20 desmoPM compared to 24 FP. MTAP and BAP1 IHC could not be assessed in 11 (55 %) and 10 (50 %) cases, respectively, due to loss or faint immunoreactivity of internal positive control cells, while CDKN2A FISH could be evaluated in all cases. The sensitivities for MTAP loss, BAP1 loss, and CDKN2A homozygous deletion in desmoPM were 40 %, 10 %, and 100 %. A combination of MTAP loss and BAP1 loss yielded 45 % of sensitivity. CONCLUSIONS: MTAP IHC is a useful surrogate diagnostic marker in differentiating ordinary sarcomatoid PM from FP, but its effectiveness is limited in desmoPM. CDKN2A FISH is the most effective diagnostic assays with 100 % sensitivity and specificity in discriminating desmoPM from FP in the facilities where the FISH assay is available.

Update of pathological diagnosis of pleural mesothelioma using genomic-based morphological techniques, for both histological and cytological investigations.

As more than 80% of pleural mesothelioma (PM) cases start with pleural effusions, diagnosis with effusion smear cytology or pleural biopsy is important. For diagnosing PM, a three-step approach is used: (1) detecting atypical cells; (2) verifying their mesothelial origin using immunohistochemistry (IHC); and (3) discriminating PM from benign mesothelial proliferations (BMP). The third step is critical for diagnosing early lesions. In small biopsy or cytologic specimens in which tumor cell fat invasion cannot be assessed, genomic-based assays, including IHC-detected BAP1 loss and fluorescence in situ hybridization (FISH)-detected homozygous deletion (HD) of CDKN2A/p16, are effective for differentiation. Both BAP1 IHC and CDKN2A FISH can equally be applied to histologic and cytologic specimens, with 100% specificity in discriminating PM from BMP. We found that methylthioadenosine phosphorylase (MTAP) loss as detected by IHC could serve as a feasible alternative in tissue and cytologic preparations for CDKN2A FISH. However, a combination including FISH was still most effective: the addition of NF2 FISH to CDKN2A FISH and BAP1 IHC yielded a greater sensitivity of close to 100% in diagnosing PM tissues. Although IHC is more feasible than FISH, owing to remaining challenges in data interpretation, caution and familiarity are warranted when diagnosing PM.

The usefulness of OK-432 for the treatment of postoperative chylothorax in a low-birth-weight infant with trisomy 18.

Chylothorax is a rare but life-threatening condition in neonates. We herein report the successful use of OK-432 for a low-birth-weight infant with trisomy 18 who developed refractory chylothorax after thoracic surgery. Increasing the concentration of OK-432 seems useful in cases with a lot of pleural effusion.

Limited efficacy of nintedanib for idiopathic pleuroparenchymal fibroelastosis.

BACKGROUND: The antifibrotic agent nintedanib has been reported to effectively prevent the decline in forced vital capacity (FVC) in a broad range of interstitial lung diseases. However, the efficacy of nintedanib against idiopathic pleuroparenchymal fibroelastosis (iPPFE) remains unclear. METHODS: We retrospectively examined patients with idiopathic PPFE or idiopathic pulmonary fibrosis (IPF) who received nintedanib for more than 6 months. We evaluated annual changes in %FVC, radiological PPFE lesions, and body weight before and during nintedanib treatment. To investigate radiological PPFE lesions, we examined the fibrosis score, which was defined as the mean percentage of the high attenuation area in the whole lung parenchyma using three axial computed tomography images. RESULTS: Overall, 15 patients with iPPFE and 27 patients with IPF were included in the present study. In patients with IPF, the annual rate of decline in %FVC was significantly lower during nintedanib treatment than that before treatment (-2.01%/year [-7.64 to 3.21] versus -7.64%/year [-10.8 to -4.44], p = 0.031). Meanwhile, in patients with iPPFE, the annual rate of decline in %FVC during nintedanib treatment was higher than that before treatment (-18.0%/year [-21.6 to -12.7] versus -9.40%/year [-12.3 to -8.23], p = 0.109). In addition, nintedanib treatment failed to inhibit the annual rate of increase in fibrosis score in patients with iPPFE (6.53/year [1.18-15.3] during treatment versus 2.70/year [0.27-12.2] before treatment, p = 0.175). CONCLUSIONS: Nintedanib efficacy may be limited in patients with iPPFE.

Endometrial Cancer After Pancreas-After-Kidney Transplantation: A Case Report and Review of the Literature.

BACKGROUND: As the number of long-term survivors after organ transplantation increases, malignancy has become a problem as a late complication. We herein report a case of endometrial cancer during the follow-up of pancreas transplantation after kidney transplantation. CASE PRESENTATION: A 49-year-old woman was diagnosed with endometrial cancer. The patient had developed type 1 diabetes at 8 years old and started insulin treatment, and at 29 years old, she started hemodialysis for diabetic nephropathy. At 31 years old, she received living donor kidney transplantation and withdrew from dialysis. Hypoglycemia unawareness began to occur frequently from around 36 years old, and at 48 years old, the patient underwent deceased donor pancreas transplantation after kidney transplantation and achieved insulin independence. At 49 years old, she was diagnosed with endometrial cancer. Surgical treatment (total abdominal hysterectomy with left salpingo-oophorectomy) was performed. The pathologic diagnosis was confirmed as stage 1A uterine endometrioid carcinoma grade 1. The postoperative course was uneventful. She was discharged from our hospital on postoperative day 8. There has been no evidence of recurrence and/or metastasis of endometrial cancer for 16 months since the surgery. CONCLUSIONS: Carcinogenesis after pancreas transplantation may be a lethal late complication. It is important to carry out regular screening examinations with carcinogenesis in mind.

Usefulness of Living Donor Liver Transplantation for Patients After Undergoing the Kasai Operation for Biliary Atresia.

BACKGROUND: Living donor liver transplantation (LDLT) has been actively performed for patients with poor clearance of jaundice after the Kasai operation for biliary atresia (BA). The present study clarified the usefulness of LDLT for BA. MATERIALS AND METHODS: Between 2000 and 2020, 24 patients (late group) underwent radical surgery for BA in our institute. The overall survival rate, native liver survival rate, and proportion of LDLT in the late group were retrospectively compared with those of 47 patients treated before 1999 (early group). P values <.05 was considered statistically significant. RESULTS: The overall survival rates at 5, 10, and 15 years were 57%, 54%, and 49%, respectively, in the early group and 100%, 100%, and 100% in the late group (P < .001). The native liver survival rates at 5, 10, and 15 years were 57%, 52%, and 39%, respectively, in the early group and 57%, 49%, and 42% (P = .993) in the late group. In the early group, LDLT was performed in 7 of 47 patients (15%), and the overall survival rate after LDLT was 71%. In the late group, LDLT was performed in 11 of 24 patients (46%), and the overall survival rate after LDLT was 100%. CONCLUSIONS: The long-term outcomes after the Kasai operation for BA have improved in recent years. There were no marked differences in long-term native liver survival before and after 2000. LDLT was actively introduced for patients with poor clearance of jaundice after the Kasai operation, and the survival rate significantly improved.