Allograft infiltration and meningoencephalitis by SARS-CoV-2 in a pancreas-kidney transplant recipient.

Severe acute respiratory syndrome corona virus 2 (SARS-CoV-2) preferentially affects epithelia of the upper and lower respiratory tract. Thus, impairment of kidney function has been primarily attributed until now to secondary effects such as cytokine release or fluid balance disturbances. We provide evidence that SARS-CoV-2 can directly infiltrate a kidney allograft. A 69-year-old male, who underwent pancreas-kidney transplantation 13 years previously, presented to our hospital with coronavirus disease 2019 (COVID-19) pneumonia and impaired pancreas and kidney allograft function. Kidney biopsy was performed showing tubular damage and an interstitial mononuclear cell infiltrate. Reverse transcriptase polymerase chain reaction from the biopsy specimen was positive for SARS-CoV-2. In-situ hybridization revealed SARS-CoV-2 RNA in tubular cells and the interstitium. Subsequently, he had 2 convulsive seizures. Magnetic resonance tomography suggested meningoencephalitis, which was confirmed by SARS-CoV-2 RNA transcripts in the cerebrospinal fluid. The patient had COVID-19 pneumonia, meningoencephalitis, and nephritis. SARS-CoV-2 binds to its target cells through angiotensin-converting enzyme 2, which is expressed in a broad variety of tissues including the lung, brain, and kidney. SARS-CoV-2 thereby shares features with other human coronaviruses including SARS-CoV that were identified as pathogens beyond the respiratory tract as well. The present case should provide awareness that extrapulmonary symptoms in COVID-19 may be attributable to viral infiltration of diverse organs.

Interdisciplinary Comparison of PADUA and R.E.N.A.L. Scoring Systems for Prediction of Conversion to Nephrectomy in Patients with Renal Mass Scheduled for Nephron Sparing Surgery.

PURPOSE: We examined interdisciplinary variability using 2 established preoperative nephrometry scores to predict conversion to nephrectomy in patients with a renal mass who were scheduled for partial nephrectomy. MATERIALS AND METHODS: A total of 229 consecutive candidates for partial nephrectomy were included in this study at a single institution between January 2013 and May 2017. Patient, tumor and treatment characteristics were assessed. The PADUA (preoperative aspects and dimensions used for an anatomical) score and the R.E.N.A.L. (radius, exophytic/endophytic, nearness of tumor to collecting system or sinus, anterior/posterior, location relative to polar lines) score were independently calculated by board certified radiologists and urological residents using computerized tomography or magnetic resonance imaging. Statistical analyses were done with the κ statistic, ROC curves, and univariable and multivariable binary logistic regression analyses. RESULTS: Partial nephrectomy was performed in 198 of the 229 cases (86.5%) while 31 (13.5%) were converted to nephrectomy. The prevalent tumor stage was pT1a, noted in 94 of the 229 cases (41.1%), and the predominant histological entity was clear cell carcinoma, found in 128 (55.9%). Radiologist and urologist interdisciplinary comparison of the PADUA and R.E.N.A.L. scores revealed a κ of 0.40 and 0.56, respectively. ROC curve analyses demonstrated a higher AUC predicting conversion to nephrectomy using the PADUA score by the urologist and the radiologist (0.79 and 0.782) compared to that of the R.E.N.A.L. score (0.731 and 0.766, respectively). Using a cutoff of 10 or greater the PADUA score determined by the urologist had 81% sensitivity and 71% specificity, and it was independently associated with conversion to nephrectomy (OR 10.98, p<0.001). CONCLUSIONS: Our results indicate higher prediction of conversion to nephrectomy when using the PADUA score compared to the R.E.N.A.L. score. Calculation of the PADUA and the R.E.N.A.L. score by physicians without specialized radiological training is feasible and might achieve comparable results to predict conversion to nephrectomy compared to the gold standard provided by board certified radiologists. This information is helpful if nephrometry scores are not regularly included in the radiology report.

Pressurized intraperitoneal aerosol chemotherapy in women with recurrent ovarian cancer: A phase 2 study.

OBJECTIVE: Recurrent ovarian, fallopian or peritoneal cancer with peritoneal carcinomatosis (ROCPC) is resistant to systemic chemotherapy. We assessed the safety and activity of laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC) in women with this cancer. METHODS: In this open-label, single-arm phase 2 study, patients underwent 3 courses q 28-42 days of PIPAC with doxorubicin 1·5 mg/m(2) followed by cisplatin 7·5 mg/m(2). A pressure of 12 mm Hg and a temperature of 37 °C were applied for 30 min/course. The primary endpoint was the proportion of patients who had an objective tumor response (OTR) according to RECIST version 1.1 criteria. Analysis was by intention to treat. Secondary endpoints were tumor regression on histology, PC Index improvement on repeated video-laparoscopy, and quality of life measured with the EORTC QLQ-30 questionnaire. RESULTS: Sixty-four patients were enrolled. Laparoscopic non-access rate was 11/64 (17%). 53 patients were eligible for analyses. 33/53 (62%) patients had an OTR - three had a partial response and 30 patients had stable disease. Tumor regression on histology and PC Index improvement were observed in 26/34 (76%) and in 26/34 (76%) patients who underwent all 3 PIPACs. There were no treatment-related deaths. No grade 4 toxicity was observed. Grade 3 toxicities were trocar hernia (n=2), bowel obstruction (n=2), abdominal pain (n=2), hematoma (n=1), intraoperative bleeding (n=1), and cystitis with urosepsis (n=1). EORTC QLQ-30 global physical health scores, nausea/vomiting, appetite loss, diarrhea, and constipation improved during therapy. CONCLUSION: PIPAC is well tolerated and active in women with ROCPC and warrants further investigation in these patients.

Image quality of digital direct flat-panel mammography versus an analog screen-film technique using a phantom model.

OBJECTIVE: The objective of our study was to compare the detection and distinguishability of microcalcifications on mammograms obtained with a digital direct flat-panel detector versus an analog system using an anthropomorphic breast phantom. MATERIALS AND METHODS: Studies were performed with a digital mammography system (Selenia) and an analog mammography system (Mammomat 3). Sixty-five transparent films were used as test specimens. Randomly distributed round and heterogeneous silicate particles (diameter, 100-1,400 microm) and an anthropomorphic scatter body were applied to the films. All radiographs were taken at identical settings and exposures. Six radiologists rated the films and monitor-displayed images independently of each other in random order on a standardized electronic questionnaire. RESULTS: Interpretations based on monitor reading produced superior results over those based on digital image reading and analog film reading. In 41.1% (95% CI, 38.7-43.5%) of all the monitor readings, 20.2% (18.2-22.2%) of all digital images, and 19.6% (17.6-21.6%) of all analog films, the number of detectable microcalcifications agreed with the gold standard method. The diameter of visible microcalcifications was interpreted correctly in 35.6% (33.2-38.0%) of monitor readings, 19.0% (17.1-21.0%) of digital images, and 21.0% (18.9-23.0%) of analog films; and microcalcification shape was interpreted correctly in 53.8% (51.4-56.3%) of monitor readings, 28.2% (26.0-30.4%) of digital images, and 28.3% (26.0-30.5%) of analog films. Microcalcification number and size were underestimated more frequently than overestimated. Regardless of display medium, accuracy increased proportionately with the diameter of the simulated microcalcifications for all evaluation variables. CONCLUSION: Digital flat-panel mammography is superior to the analog screen-film method for the detection and morphologic characterization of microcalcifications larger than 200 microm in diameter when the display medium is a monitor.

Extracranial oral cavity metastasis from glioblastoma multiforme: A case report.

Glioblastoma multiforme is the most common primary malignant brain tumor. The clinical outcome following diagnosis remains extremely poor. The treatment of choice is wide surgical resection of the visible tumor, frequently followed by adjuvant combined radiochemotherapy (RCTx) with temozolomide as the chemotherapeutic agent. Extracranial metastases are extremely rare, with <200 cases of extracranial metastases from glioblastoma multiforme reported in the literature to date. We herein present a case of a patient suffering from a fast-growing metastasis to the oral cavity, completely filling the buccal cavity within 2 weeks, as the only manifestation of recurrent glioblastoma multiforme following initial surgical resection and adjuvant RCTx.

Electrostatic precipitation Pressurized IntraPeritoneal Aerosol Chemotherapy (ePIPAC): first in-human application.

Background: Pressurized IntraPeritoneal Aerosol Chemotherapy (PIPAC) is a drug delivery technique with superior pharmacological properties for treating peritoneal metastasis (PM). Adding electrostatic loading (ePIPAC) as an adjunct to aerosol and artificial hydrostatic pressure improved tissue uptake in a preclinical model. Methods: We report the first ePIPAC use in 3 patients with PM of hepatobiliary-pancreatic (HBP) origin. All 3 patients received concomitant palliative systemic chemotherapy that was discontinued in two patients. PIPAC with cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 was applied intraperitoneally at a pressure of 12 mmHg and a temperature of 37% °C for 30 min. Additionally, a voltage 7,500-9,500 V and a current≤10 µA were applied over a stainless steel brush electrode emitting a stream of electrons. Results: ePIPAC was technically feasible. No intraoperative complication was noted. The procedures were well tolerated with no adverse event CTCAE > 2. Patient 1 with PM of unknown origin (CUP with HBP phenotype) showed an objective histological and radiological response and survived 11 months. Patient 2 with ductal pancreatic cancer underwent secondary resection after ePIPAC with no residual PM; however, tumor recurred 5 months later. Patient 3 with adenocarcinoma of the gallbladder showed a radiological regression of liver infiltration and is alive after 22 months without histological evidence of PM. Conclusion: ePIPAC is technically feasible, is well tolerated and can induce tumor regression of PM in HBP cancers with and without concomitant systemic chemotherapy. These preliminary results justify prospective clinical studies with ePIPAC.

Development of a duodenal gallstone ileus with gastric outlet obstruction (Bouveret syndrome) four months after successful treatment of symptomatic gallstone disease with cholecystitis and cholangitis: a case report.

INTRODUCTION: Cases of gallstone ileus account for 1% to 4% of all instances of mechanical bowel obstruction. The majority of obstructing gallstones are located in the terminal ileum. Less than 10% of impacted gallstones are located in the duodenum. A gastric outlet obstruction secondary to a gallstone ileus is known as Bouveret syndrome. Gallstones usually enter the bowel through a biliary enteral fistula. Little is known about the formation of such fistulae in the course of gallstone disease. CASE PRESENTATION: We report the case of a 72-year-old Caucasian woman born in Germany with a gastric outlet obstruction due to a gallstone ileus (Bouveret syndrome), with a large gallstone impacted in the third part of the duodenum. Diagnostic investigations of our patient included plain abdominal films, gastroscopy and abdominal computed tomography, which showed a biliary enteric fistula between the gallbladder and the duodenal bulb. Our patient was successfully treated by laparotomy, duodenotomy, extraction of the stone, cholecystectomy, and resection of the fistula in a one-stage surgical approach. Histopathological examination showed chronic and acute cholecystitis, with perforated ulceration of the duodenal wall and acute purulent inflammation of the surrounding fatty tissue. Four months prior to developing a gallstone ileus our patient had been hospitalized for cholecystitis, a large gallstone in the gallbladder, cholangitis and a small obstructing gallstone in the common biliary duct. She had been treated with endoscopic retrograde cholangiopancreatography, endoscopic biliary sphincterotomy, balloon extraction of the common biliary duct gallstone, and intravenous antibiotics. At the time of her first presentation, abdominal ultrasound and endoscopic examination (including esophagogastroduodenoscopy and endoscopic retrograde cholangiopancreatography) had not shown any evidence of a biliary enteral fistula. In the four months preceding the gallstone ileus our patient had been asymptomatic. CONCLUSION: In patients known to have gallstone disease presenting with symptoms of ileus, the differential diagnosis of a gallstone ileus should be considered even in the absence of preceding symptoms related to the gallbladder disease. Gallstones large enough to cause intestinal obstruction usually enter the bowel by a biliary enteral fistula. During the formation of such a fistula, patients can be asymptomatic.

Tuberculous peritonitis in a German patient with primary biliary cirrhosis: a case report.

BACKGROUND: The number of cases of tuberculosis as a complication in people with immunodeficiency, people on immunosuppressive therapy and among the immigrant population is increasing in Germany. However, tuberculous peritonitis rarely occurs without these risks, particularly in Germans. The incidence of tuberculous peritonitis in Germany is very low; tuberculosis of the intestinal tract was found in approximately 0.8 % of tuberculosis cases in 2004. The diagnosis of tuberculous peritonitis is often delayed on account of non-specific clinical symptoms. The absence of specific biological markers, long incubation times for cultures and non-specific radiographic or ultrasonographic signs increase the morbidity associated with this treatable condition. CASE PRESENTATION: We report a case of tuberculous peritonitis in a 73-year-old female German patient. Her medical history revealed primary biliary cirrhosis (PBC) since 1992. On admission, she complained of abdominal pain, vomiting, ascites and peripheral edema. The patient has been in a seriously reduced general condition and had fever up to 39.6 degrees C. A few weeks earlier, the patient was in another hospital with the same complaint. Inflammatory parameters were elevated, but the procalcitonin level was normal. Blood culture was always negative, as was the tuberculin test. Ultrasonography of the abdomen showed massive ascites with multiple septa. The patient underwent a computed tomography (CT) scan of the abdomen which showed a thickened intestinal wall in the sigmoid colon and a pronounced enhancement of the peritoneum. Computed tomography scans of the lung showed only slight bilateral pleural effusion. Because of the anaesthetic and bleeding risk due to thrombocytopenia, laparoscopy was not immediately undertaken. The culture from ascites was positive for M.tuberculosis after three weeks. CONCLUSION: In primary biliary cirrhosis patients with non-specific clinical symptoms, such as vomiting, abdominal pain, ascites, weight loss, and fever, tuberculous peritonitis must be considered in the initial differential diagnosis, although these symptoms may be attributed to cirrhosis of the liver with spontaneous bacterial peritonitis. Ultrasonographic and CT scab findings are not specific for tuberculous peritonitis, but an awareness of the ultrasonographic features and the features of the CT scan may help in the diagnosis of tuberculous peritonitis and avoid clinical mismanagement.

Hypercalcemia after transplant nephrectomy in a hemodialysis patient: a case report.

INTRODUCTION: Hypercalcemia is a complication often seen in chronic hemodialysis patients. A rare cause of this condition is sarcoidosis. Its highly variable clinical presentation is challenging. Especially in patients suffering chronic kidney graft failure the nonspecific constitutional symptoms of sarcoidosis like fever, weight loss, arthralgia and fatigue may be easily misleading. CASE PRESENTATION: A 51 year old male developed hypercalcemia, arthralgia and B-symptoms after explantation of his kidney graft because of suspected acute rejection. The removed kidney showed vasculopathy and tubulointerstitial nephritis, which had not been overt in the biopsy taken half a year earlier. Despite explantation and withdrawal of the immunosuppression the patient's general condition deteriorated progressively. A rapid rise in serum calcium finally provoked us to check for sarcoidosis. CT scans of the lungs, broncho-alveolar-lavage and further lab tests confirmed the diagnosis. CONCLUSION: This case demonstrates that withdrawal of immunosuppressive drugs sometimes unmasks sarcoidosis. It should be considered as differential diagnosis even in hemodialysis patients, in whom other reasons for hypercalcemia are much more common.

Endovascular gamma irradiation of femoropopliteal de novo stenoses immediately after PTA: interim results of prospective randomized controlled trial.

PURPOSE: To report an interim analysis of whether centered endovascular irradiation with the iridium 192 ((192)Ir) source immediately after percutaneous transluminal angioplasty (PTA) of de novo femoropopliteal stenoses lowers the restenosis rate. MATERIALS AND METHODS: Thirty patients undergoing PTA to treat femoropopliteal stenoses were randomized for prophylaxis against restenosis with centered endovascular irradiation with a (192)Ir source (a dose of 14 Gy 2 mm deep to the vessel wall, irradiation group) or no irradiation (control group). Angiographic follow-up was available for 22 patients at 6 months (irradiation group, n = 10) and 12 patients at 12 months (irradiation group, n = 6). Duplex sonography, treadmill testing, and interviews were performed the day before and the day after PTA and after 1, 3, 6, 9, and 12 months. Results of angiography, duplex sonography, treadmill testing, and interviews were evaluated with a t test and multivariate analysis of variance (clinical characteristics, chi(2) test). RESULTS: Baseline characteristics were comparable in the two groups. Interim analysis of the 6-month follow-up data revealed a trend toward a significantly lower restenosis rate in the irradiation group. The change in the degree of stenosis compared with that after PTA was -14.7% +/- 20.8 (mean +/- SD) in the irradiation group versus 37.7% +/- 27.3 in the control group (P =.001) and became even more marked at 12 months (-9.5% +/- 34.5 vs 45.5% +/- 40.7 [P =.03], respectively). The follow-up results of treadmill testing and interviews showed a nonsignificant benefit for the irradiation group. One thromboembolic complication occurred during irradiation. No side effects were observed during follow-up. CONCLUSION: Endovascular irradiation with a centered (192)Ir source immediately after PTA of de novo femoropopliteal stenoses reduces the restenosis rate.