Quantitative monitoring of circulating tumor DNA in patients with advanced pancreatic cancer undergoing chemotherapy.

According to cancer genome sequences, more than 90% of cases of pancreatic ductal adenocarcinoma (PDAC) harbor active KRAS mutations. Digital PCR (dPCR) enables accurate detection and quantification of rare mutations. We assessed the dynamics of circulating tumor DNA (ct-DNA) in patients with advanced PDAC undergoing chemotherapy using dPCR. KRAS G12/13 mutation was assayed by dPCR in 47 paired tissue- and ct-DNA samples. The 21 patients were subjected to quantitative ct-DNA monitoring at 4 to 8-week intervals during chemotherapy. KRAS mutation was detected in 45 of those 47 patients using tissue DNA. In the KRAS mutation-negative cases, next-generation sequencing revealed KRAS Q61K and NRAS Q61R mutations. KRAS mutation was detected in 23/45 cases using ct-DNA (liver or lung metastasis, 18/19; mutation allele frequency [MAF], 0.1%-31.7%; peritoneal metastasis, 3/9 [0.1%], locally advanced, 2/17 [0.1%-0.2%]). In the ct-DNA monitoring, the MAF value changed in concordance with the disease state. In the 6 locally advanced cases, KRAS mutation appeared concurrently with liver metastasis. Among the 6 cases with liver metastasis, KRAS mutation disappeared during the duration of stable disease or a partial response, and reappeared at the time of progressive disease. The median progression-free survival was longer in cases in which KRAS mutation disappeared after an initial course of chemotherapy than in those in which it was continuously detected (248.5 vs 50 days, P < .001). Therefore, ct-DNA monitoring enables continuous assessment of disease state and could have prognostic utility during chemotherapy.

Utility of the New Early Warning Score (NEWS) in combination with the neutrophil-lymphocyte ratio for the prediction of prognosis in older patients with pneumonia.

OBJECTIVE: Predictors of prognosis are necessary for use in routine clinical practice for older patients with pneumonia, given the ageing of the population. Recently, the National Early Warning Score (NEWS), a comprehensive predictor of severity that consists solely of physiological indicators, has been proposed to predict the prognosis of pneumonia. The neutrophil/lymphocyte ratio (NLR) is a simple index of inflammation that may also be predictive of pneumonia. In the present study, we aimed to determine whether NEWS or a combination of NEWS and NLR predicts mortality in older patients with pneumonia. DESIGN: A retrospective cohort study. SETTING: A general hospital in Japan. PARTICIPANTS: We collected data from patients aged ≥65 years with pneumonia who were admitted between 2018 and 2020 (n=282; age=85.3 (7.9)). Data regarding vital signs, demographics and the length of hospital stay, in addition to the NEWS and NLR, were extracted from the participants' electronic medical records. INTERVENTION: The utility of the combination of NEWS and NLR was assessed using NEWS×NLR and NEWS+NLR. MAIN OUTCOME MEASURES: Their predictive ability for 30-day mortality as the primary outcome was assessed using receiver operating characteristic (ROC) curve analysis. RESULTS: According to the NEWS classification, 80 (28.3%), 64 (22.7%) and 138 (48.9%) of the participants were at low, medium and high risk of mortality, respectively. The 30-day mortality for the entire cohort was 9.2% (n=26), and the mortality rate increased with the NEWS classification: low, 1.3%; medium, 7.8%; and high, 14.5%. The NLRs were 6.0 (4.2-9.8), 6.8 (4.8-10.4) and 14.6 (9.4-22.2), respectively (p<0.001). The areas under the ROC curves for 30-day mortality were 0.73 for the NEWS score, 0.84 for NEWS×NLR and 0.83 for NEWS+NLR, indicating that the combinations represent superior predictors of mortality to the NEWS alone. NEWS×NLR and NEWS+NLR tended to have better sensitivity, accuracy, positive predictive value and negative predictive value than NEWS alone (p=0.06). CONCLUSIONS: A combination of the NEWS and NLR (NEWS×NLR or NEWS+NLR) may be superior to the NEWS alone for the prediction of 30-day mortality in older patients with pneumonia. However, further validation of these combinations for use in the prediction of prognosis is required.

Hemoperitoneum due to a ruptured right gastroepiploic artery following non-interventional endoscopic ultrasonography: a case report.

Endoscopic ultrasonography has become a routine procedure in clinical practice and is widely accepted as a safe procedure. Previous studies have reported that severe bleeding rarely occurs even when performing fine-needle aspiration biopsy. Severe hemorrhage following non-interventional endoscopic ultrasonography has never been reported. We herein report a case of hemorrhagic shock due to hemoperitoneum caused by a ruptured right gastroepiploic artery consequent to a diagnostic endoscopic ultrasonography. The patient was administered two antithrombotic agents. An extensive diagnostic workup contributed to the correct diagnosis, which led to a successful treatment by transcatheter arterial embolization. Endoscopists should be aware of this rare, but potentially fatal, adverse event of endoscopic ultrasonography.

Reversible cerebral vasoconstriction syndrome associated with tetrodotoxin poisoning: A case report.

An 81-year-old woman with a history of hypertension and Alzheimer's disease presented to the emergency department because of impaired consciousness. Physical examination revealed acute progressive generalized flaccid paralysis, hypertension, respiratory failure, and pupillary dilation. Although the patient did not complain of headache, head magnetic resonance angiography and magnetic resonance imaging showed multifocal segmental cerebral vasospasm and cerebral infarction in the left occipital lobe. Her family reported that although she did not have a license to cook pufferfish, she was in the habit of eating pufferfish. We subsequently detected tetrodotoxin in the patient's urine, and she was diagnosed with tetrodotoxin poisoning. As the symptoms of tetrodotoxin intoxication improved, head magnetic resonance angiography showed the disappearance of the multifocal segmental cerebral vasospasm. The patient's clinical course and imaging findings were consistent with reversible cerebral vasoconstriction syndrome (RCVS). Sympathetic overactivity after tetrodotoxin intoxication possibly caused the development of RCVS, and RCVS could not be ruled out even in the absence of the typical thunderclap headache. Magnetic resonance angiography is a useful modality when performing repeated examinations.

Biliary stent removal through a transgastric fistula created with endoscopic ultrasound-guided hepaticogastrostomy.

Therapeutic endoscopic ultrasound has become widespread as an effective procedure for biliary drainage; however, it is rarely used to remove foreign bodies such as a biliary stent. A 57-year-old man was referred to our hospital for a benign biliary stricture in the left hepatic duct after hepatectomy. Initially, a 7-Fr plastic stent was placed in the left hepatic duct with the distal end set above the papilla, and it was replaced with an 8.5-Fr stent as the stricture remained after 3 months. Endoscopic retrograde cholangiopancreatography was performed to retrieve the plastic stent 3 months later; however, the stent could not be moved because the proximal flap was caught in the stricture. Attempts using various devices failed to retrieve the stent; thus, endoscopic ultrasound-guided hepaticogastrostomy was performed to create a route for stent retrieval. Eventually, the plastic stent was successfully retrieved with biopsy forceps through a fully covered self-expandable metallic stent located in a transgastric fistula. We propose our new method involving endoscopic ultrasound-guided hepaticogastrostomy for endoscopic stent retrieval that fails via the transpapillary route.

Development of Acute Inflammatory Demyelinating Polyneuropathy 11 Days after Spinal Surgery: A Case Report and Literature Review.

Guillain-Barré syndrome (GBS) usually has a good prognosis; however, patients may develop sequelae without prompt treatment. We herein describe an 81-year-old woman who developed acute-onset excruciating thigh pain and weakness in her lower extremities after spinal surgery. We diagnosed acute inflammatory demyelinating polyradiculoneuropathy by a nerve conduction study, which showed findings of demyelination without cerebrospinal fluid analysis because of a spinal prosthesis. Although anti-GM1 and anti-GalNAc-GD1a antibodies were positive, the patient was clinically diagnosed with acute inflammatory demyelinating polyradiculoneuropathy (a subtype of GBS), not acute motor axonal neuropathy. She recovered well with immunoglobulin therapy. A literature review of 18 cases revealed that unexplained weakness, areflexia, and numbness of the extremities after spinal surgery, a shorter time from spinal surgery to symptom onset to general GBS, abnormal nerve conduction study results, normal spinal imaging findings, and the development of atypical symptoms such as cranial and autonomic nerve syndrome and respiratory failure are useful for diagnosing GBS when cerebrospinal fluid examination cannot be performed after spinal surgery.

Clinical outcome of a highly flexible duodenal stent for gastric outlet obstruction: A multicenter prospective study.

BACKGROUND AND AIM: Endoscopic duodenal stenting for patients with malignant gastric outlet obstruction (GOO) has been widespread; however, clinical trials evaluating the structures of duodenal stents are lacking. Thus, we aimed to investigate the clinical outcomes of a highly flexible duodenal stent for GOO patients. METHODS: A prospective study of duodenal stenting for GOO patients from five hospitals between August 2017 and August 2018 was performed. WallFlex Duodenal Soft were used in all procedures. The primary endpoint was clinical success, defined as an improvement in the GOO scoring system. RESULTS: The study enrolled 31 patients (12 women, 19 men) with GOO, with a median age of 70 (range 52-90) years. Primary diseases were pancreatic cancer, gastric cancer, biliary tract cancer, and others in 14, 10, 3, and 4 patients, respectively. The technical success rate was 97%, and the clinical success rate was 87%. Simultaneous biliary drainage was performed in 19% of patients. Adverse events occurred in three patients. Chemotherapy was given in 41% of clinically successful cases, and the median overall survival time after stent placement was 82 days (range, 30-341 days), and. Stent dysfunction occurred in 30% of clinically successful cases (stent ingrowth in seven and stent overgrowth in one patient). The median time to stent dysfunction was 157 days (range, 11-183 days). Six patients were treated with additional stent placement after dysfunction. CONCLUSION: Placement of a highly flexible duodenal stent is an effective and safe treatment for patients with GOO (UMIN-CTR 000028783).

Older-age onset of Kimura's disease.

A 60-year-old man was admitted to our hospital with bilateral post auricular masses, first noticed 1 year earlier. Blood tests showed eosinophilia and high immunoglobulin E (IgE) levels, and cervical computed tomography showed 10-mm soft tissue masses with scattered lymphadenopathy. The tumors showed intermediate and high signal intensity on T1- and T2-weighted cervical magnetic resonance imaging, respectively. After mass resection, the tumors were diagnosed as Kimura's disease (KD). Generally, KD affects young men; however, even in older patients, KD should be included as a differential diagnosis for head and neck tumors in patients with eosinophilia and high IgE.

A Multicenter Retrospective Study of Gemcitabine Plus Nab-Paclitaxel for Elderly Patients With Advanced Pancreatic Cancer.

OBJECTIVES: This study aimed to assess the lesser known therapeutic benefit, particularly safety and effectiveness of gemcitabine plus nab-paclitaxel (GnP) treatment in elderly patients with advanced pancreatic cancer. METHODS: We retrospectively enrolled advanced pancreatic cancer patients aged ≥75 years who received GnP as first-line treatment between December 2014 and December 2016. We assessed survival, adverse events, and early treatment discontinuation. RESULTS: The cohort comprised 116 patients (median age, 77 [range, 75-84] years). The overall survival and progression-free survival were 21.8 and 12.1 months in patients with locally advanced cancer and 13.3 and 5.9 months, in patients with metastasis, respectively. The response and disease control rates were 31% and 81%, respectively. Within the first 2 months of treatment, grade 4 hematological and grade 3-4 nonhematological toxicities occurred in 10 and 23 patients, respectively. Early discontinuation due to adverse events occurred in 12 patients; the associated risk factors were age ≥80 years (odds ratio, 9.43) and serum albumin level <3.5 g/dL (odds ratio, 5.12). CONCLUSIONS: In selected patients aged ≥75 years, GnP showed acceptable toxicities and effectiveness. However, patients aged ≥80 years and those with serum albumin levels <3.5 g/dL should be carefully assessed for treatment eligibility.

Magnetic resonance imaging and symptoms in patients with neurosarcoidosis and central diabetes insipidus.

INTRODUCTION: In the clinical setting, the diagnosis of neurosarcoidosis in patients with central diabetes insipidus (CDI) is typically based both on symptoms (i.e. polydipsia or polyuria) and brain magnetic resonance imaging (MRI) findings (e.g. pituitary abnormality). However, inconsistent changes in the patient's symptoms and brain MRI findings may occur during the clinical course of the disease. This review was performed to summarise the relationship between symptoms and brain MRI findings in previously reported cases of neurosarcoidosis with CDI. MATERIAL AND METHODS: Case studies of patients diagnosed with neurosarcoidosis with CDI were collected via a PubMed search of studies published through 30 June 2018. RESULTS: Thirteen eligible studies were reviewed (20 patients; 12 men, 8 women; mean age 33 years). Polydipsia or polyuria was the first symptom in 13 patients. The mean duration from disease onset to diagnosis was 3.4 months. Brain MRIs showed abnormal findings in the hypothalamus and pituitary for 17 patients. Immunosuppressive drugs were used in 17 patients. For 14 patients, MRI findings improved, while symptoms did not. CONCLUSION: Patients with both neurosarcoidosis and CDI symptoms often do not improve, despite the fact that brain MRI findings often improve following treatment. More studies involving detailed pathological analyses and longer follow-up periods are necessary.

Differential diagnosis of gallbladder polypoid lesions using contrast-enhanced ultrasound.

PURPOSE: The purpose of the study is to evaluate the utility of contrast-enhanced ultrasound (CEUS) for the differential diagnosis of gallbladder polypoid lesions (GPLs). METHODS: Thirty-six patients with GPLs (17 with gallbladder cancer, 19 with benign polyps) who underwent CEUS were enrolled in the study. The mean age of patients was 65.7 ± 12.6 years. Perflubutane-based contrast agent and high-mechanical index mode, which can eliminate the background B-mode and provide precise visualization of tumor vessels, were used for CEUS, and two blinded readers evaluated the images, retrospectively. RESULTS: Patient age and size of malignant GPLs (72.4 ± 9.4 years and 23.4 ± 7.5 mm) were significantly greater than those for benign lesions (59.6 ± 12.3 years and 12.4 ± 2.9 mm) (P < 0.01, respectively), and the receiver operating characteristic analysis showed the cut-off value as over 65 years and 16 mm. Univariate analysis showed that heterogeneity in B-mode (80% [12/15]), sessile shape (76% [13/17]), dilated vessel (71% [12/17]), irregular vessel (82% [14/17]), and heterogeneous enhancement (59% [10/17]) on CEUS were significantly correlated with malignant GPLs (P < 0.01, respectively). On CEUS, the diagnostic criterion for malignant GPLs was defined as having one or more of the above four features because of the highest accuracy. Sensitivity, specificity, and accuracy for malignant GBLs were 88%, 68%, and 78% for patient age; 76%, 89%, and 83% for size of GPLs; 80%, 68%, and 74% for B-mode; and 94%, 89%, and 92% for CEUS, respectively. CONCLUSIONS: CEUS is useful for the differential diagnosis of malignant and benign GPLs.

Superior Mesenteric Artery Vasculitis in Behçet's Disease: A Case Report and Literature Review.

A 55-year-old male presented with abdominal pain that had begun about 5 days ago. Physical examination revealed oral aphtha, genital aphthosis, and pseudofolliculitis, and the patient was diagnosed with incomplete Behçet's disease (BD). Contrast-enhanced computed tomography (CECT) showed dilation of the superior mesenteric artery and mesenteric infiltration of inflammation, indicating vasculo-BD. The symptoms were improved by 3-day of intravenous methylprednisolone pulse therapy followed by oral prednisolone. A literature review suggested that vasculo-BD should be included as a differential diagnosis in cases with unexplained abdominal pain, arterial dilation, and mesenteric invasion, and CECT examination and steroid therapy should be considered.

Predictive value of ERCC1, ERCC2, ERCC4, and glutathione S-Transferase Pi expression for the efficacy and safety of FOLFIRINOX in patients with unresectable pancreatic cancer.

The platinum-based chemotherapy regimen FOLFIRINOX (leucovorin, fluorouracil, irinotecan, and oxaliplatin) is currently used as a standard treatment for patients with unresectable pancreatic cancer. FOLFIRINOX is associated with severe toxicities, including neutropenia, febrile neutropenia, and anorexia; however, there are currently no reliable biomarkers to predict its efficacy and safety. Several studies of patients with various cancers have shown that tumor expression of excision repair cross-complementing (ERCC) proteins and glutathione S-transferase Pi (GSTPi) correlates with the response to platinum-based chemotherapies. Therefore, in this study, we examined the associations between expression of ERCC proteins and GSTPi and the safety and efficacy of FOLFIRINOX in 34 patients with unresectable pancreatic cancer. ERCC1, ERCC2, ERCC4, and GSTPi expression were examined by immunohistochemical staining of tumor specimens and the results were correlated with overall survival, progression-free survival, response rate, disease control rate, and the frequency of grade 3-4 neutropenia and non-hematologic toxicities. We found that ERCC1, ERCC2, ERCC4, and GSTPi were expressed in tumor samples from 64%, 24%, 18%, and 64% of patients, respectively. Notably, there were no statistically significant associations between the expression pattern of any of the proteins and either the clinical outcomes or the frequency of grade 3-4 neutropenia or grade 3-4 anorexia. Collectively, these data indicate that tumor expression of ERCC1, ERCC2, ERCC4, and GSTPi does not predict the safety or efficacy of FOLFIRINOX in patients with pancreatic cancer.