Evaluation of pembrolizumab plus cisplatin and fluorouracil in radical treatment for patients with T4b esophageal squamous cell carcinoma.

BACKGROUND: Pembrolizumab plus cisplatin and 5-fluorouracil administered as first-line therapy for advanced esophageal cancer patients has shown a better objective response and survival than conventional chemotherapy with less severe hematological adverse events. The safety and efficacy of this regimen were evaluated in patients with T4b esophageal squamous cell carcinoma (ESCC). METHODS: Eight consecutive patients with T4b ESCC received this regimen according to KEYNOTE-590 as induction, and they were evaluated after 1-3 courses. The programmed death-ligand 1 (PD-L1) combined positive score (CPS) was also evaluated before chemotherapy. Efficacy for the primary lesion was evaluated by our original formula for the tumor reduction rate. RESULTS: The numbers of patients with partial response (PR), stable disease, and progressive disease (PD) were 5, 1, and 2, respectively. The tumor reduction rate ranged from 69 to 87% in PR patients, and all PR patients had relief from T4b. Two patients underwent conversion surgery with R0 resection. PD-L1 CPS was over 90 in 2 PR patients, but under 10 in 2 other PR patients. PD-L1 CPS was under 10 in PD patients. One patient had hyperprogression, resulting in an esophago-pulmonary fistula. Greater than grade 3 adverse events were bleeding gastric ulcer in one patient (12.5%), neutropenia without G-CSF in 3 patients (37.5%), and hypopotassemia in 1 patient (12.5%). No patient had febrile neutropenia. CONCLUSIONS: Marked tumor reduction was confirmed in 62.5% of patients with pembrolizumab plus cisplatin and 5-fluorouracil with less adverse events. This regimen could be administered as induction chemotherapy for patients with T4b ESCC.

Pembrolizumab plus cisplatin and fluorouracil as induction chemotherapy followed by definitive chemoradiotherapy for patients with cT4 and/or supraclavicular lymph node metastasis (M1Lym) of esophageal squamous cell carcinoma.

Definitive chemoradiotherapy (DCRT) is administered as standard treatment for patients with cT4 and/or M1Lym esophageal squamous cell carcinoma (ESCC); however, its long-term result is inadequate. Although several studies have reported that conversion surgery can improve the survival of these patients, none have identified significantly better long-term survival than that achieved by DCRT. Thus, enhancing DCRT seems important to improve the survival of these patients. A strategy of shrinking tumor volume before DCRT and providing consolidation chemotherapy for systemic control is expected to improve the survival of these patients. Pembrolizumab plus cisplatin and fluorouracil has demonstrated good local control and significant improvement in the survival of patients with advanced esophageal cancer. Based on these results, the following strategy is proposed: This protocol should be applied as induction for these patients; then, DCRT should be provided depending on the initial response; and finally, adjuvant chemotherapy with an immune checkpoint inhibitor should be given to all responders.

Transarterial Embolization of Neovascularity for Refractory Nighttime Shoulder Pain: A Multicenter, Open-Label, Feasibility Trial.

PURPOSE: To assess the feasibility of transarterial embolization (TAE) for recalcitrant nighttime shoulder pain in a multicentric study. MATERIALS AND METHODS: This prospective, open-label, feasibility trial included 100 patients treated at 5 institutions. TAE was performed in 76 patients with adhesive capsulitis (AC) and 24 patients with symptomatic rotator cuff tears (sRCTs). The ipsilateral radial artery was punctured, and imipenem/cilastatin sodium was infused as an embolic agent. Adverse events, 10 point pain numerical rating scale (NRS), range of motion (ROM) of the shoulder joint, and quality of life (via the EuroQol-5D [EQ-5D]) were evaluated. RESULTS: All patients exhibited neovascularity on baseline angiography, and all TAE procedures were performed successfully. No patient experienced a major adverse event. The mean nighttime pain NRS scores at baseline and 1, 3, and 6 months after TAE were 6.4 ± 2.2, 3.4 ± 2.6, 2.3 ± 2.5, and 1.6 ± 2.2, respectively (for all, P < .001). The mean ROM of anterior elevation at baseline and 1, 3, and 6 months after TAE were 97° ± 29°, 119° ± 28°, 135° ± 27°, and 151° ± 17°, respectively (for all, P < .001). The mean EQ-5D scores at baseline and 1, 3, and 6 months after TAE were 0.63 ± 0.17, 0.73 ± 0.16, 0.80 ± 0.17, and 0.84 ± 0.17, respectively (for all, P < .001). There was no significant difference in the clinical success rate between the AC and sRCT groups. CONCLUSIONS: TAE for nighttime shoulder pain caused by AC and sRCTs was feasible with sufficient safety and efficacy.

Accuracy of preoperative staging of gastric stump cancer.

BACKGROUND: In this study, the accuracy of preoperative staging for gastric stump cancer, which has not been thoroughly investigated since the condition is rare, was investigated using computed tomography and gastroscopic imaging. METHODS: Between February 1994 and April 2018, 49 patients with gastric stump cancer, following subtotal or total gastrectomy, were reviewed retrospectively. Preoperative diagnoses of clinical T and clinical N categories were compared with post-operative pathological diagnoses (pT and pN categories). Positive predictive values, accuracy, sensitivity and specificity were also evaluated. RESULTS: The overall accuracy of T staging was 40.8%. The positive predictive value for cT3/T4 was 96.3%, whereas the positive predictive value for cT1/T2 was 72.7%. The overall accuracy for N staging was 61.2%. The positive predictive value of lymph node positive patients was 73.3%. The positive predictive value and sensitivity of over stage II were 96.6% and 84.8%, respectively. CONCLUSIONS: The accuracy of preoperative diagnosis using both computed tomography and gastroscopy imaging may be feasible for T3/T4 advanced gastric stump cancer, whereas diagnosing T1/2 gastric stump cancer must be carefully considered due to high misdiagnosis rates, relating to depth.

New Class of Radially Adjustable Stentrievers for Acute Ischemic Stroke: Primary Results of the Multicenter TIGER Trial.

[Figure: see text].

Embolic Characteristics of Imipenem-Cilastatin Particles in Vitro and in Vivo: Implications for Transarterial Embolization in Joint Arthropathies.

PURPOSE: To elucidate in vitro and in vivo characteristics and embolic properties of imipenem-cilastatin (IPM-CS) compared with hydrogel microspheres. MATERIALS AND METHODS: Particle size distribution was microscopically evaluated with 3 samples of 50 mg IPM-CS suspensions in each of 6 conditions by a mixture of contrast volume: 500 or 1000 µL and vortex mixing time: 5, 10, or 30 s. Time-dependent changes up to 3 h post-mixing were also evaluated. Fifteen male Sprague-Dawley rats (460.2 ± 5.0 g) underwent unilateral renal artery embolization using IPM-CS (n = 11) or hydrogel microspheres (n = 4). Follow-up angiography 48 h after embolization and histological evaluation, including acute tubular necrosis (ATN) and inflammation, were scored using a 5-point scale (from 0 = normal to 4 = severe). RESULTS: Over 91% of IPM-CS particles were <40 µm under all in vitro conditions. With the increased contrast volume, the average particle size also increased (mean ± standard deviation: 11.6 ± 13.9 vs 16.7 ± 18.2 µm for 500 and 1000 µL iodinated contrast, P < .001); however, the impact of the mixing/elapsed time were limited. At 48 h after embolization, all cases in the IPM-CS groups (11/11) showed major to complete recanalization versus no recanalization with hydrogel microspheres (0/4) (P < .001). The following are the median ATN and inflammation grades in the cortex (ventral/dorsal) and medulla (ventral/dorsal) in both groups: IPM-CS, ATN in cortex (2/4) and medulla (1/1), inflammation in cortex (0/0) and medulla (0/0); hydrogel microspheres, ATN in cortex (4/4) and medulla (3/2), inflammation in cortex (1/1) and medulla (1/1). CONCLUSIONS: IPM-CS suspension generated particles that were predominantly smaller than 40 µm and with unique short-term embolic effects, leaving predominantly peripheral ischemic changes.

Transtail Artery Access in Rats: A New Technique for Repeatable Selective Angiography.

Transtail artery approach successfully enables selective arterial catheterization and angiography in the rat. This technique is effective and repeatable. In addition to its utility in imaging, it may also have a wide range of applications in transcatheter therapy and experimental cerebral stroke models.

Transarterial Delivery of a Biodegradable Single-Agent Theranostic Nanoprobe for Liver Tumor Imaging and Combinatorial Phototherapy.

PURPOSE: To assess selective accumulation of biodegradable nanoparticles within hepatic tumors after transarterial delivery for in vivo localization and combinatorial phototherapy. MATERIALS AND METHODS: A VX2 hepatic tumor model was used in New Zealand white rabbits. Transarterial delivery of silicon naphthalocyanine biodegradable nanoparticles was performed using a microcatheter via the proper hepatic artery. Tumors were exposed via laparotomy, and nanoparticles were observed by near-infrared (NIR) fluorescence imaging. For phototherapy, a handheld NIR laser (785 nm) at 0.6 W/cm2 was used to expose tumor or background liver, and tissue temperatures were assessed with a fiberoptic temperature probe. Intratumoral reactive oxygen species formation was assessed using a fluorophore (2',7'-dichlorodihydrofluorescein diacetate). RESULTS: Nanoparticles selectively accumulated within viable tumor by NIR fluorescence. Necrotic portions of tumor did not accumulate nanoparticles, consistent with a vascular distribution. NIR-dependent heat generation was observed with nanoparticle-containing tumors, but not in background liver. No heat was generated in the absence of NIR laser light. Reactive oxygen species were formed in nanoparticle-containing tumors exposed to NIR laser light, but not in background liver treated with NIR laser or in tumors in the absence of NIR light. CONCLUSIONS: Biodegradable nanoparticle delivery to liver tumors from a transarterial approach enabled selective in vivo tumor imaging and combinatorial phototherapy.

VIDEO: Technique to Restrict the Gore Viatorr Stent-Graft for TIPS Reduction.

OBJECTIVE: The Viatorr stent-graft (W. L. Gore and Associates), specifically made for transjugular intrahepatic portosystemic shunt (TIPS) creation, has significantly improved TIPS patency compared with bare metal stents. Post-TIPS hepatic encephalopathy (HE), however, remains relatively common after TIPS creation. We describe a technique to secondarily restrict a Viatorr stent-graft to treat post-TIPS refractory HE and maintain use of the Viatorr device. CONCLUSION: We show a simple technique to modify the Viatorr stent-graft for TIPS reduction.

Clinical Significance of Area of Psoas Major Muscle on Computed Tomography after Gastrectomy in Gastric Cancer Patients.

BACKGROUND: The measurement of a single abdominal image on computed tomography (CT) can provide an estimate of the total body skeletal muscle. We evaluate the change of the area of the psoas major muscle (PMMA) in a CT which was performed routinely after gastrectomy in gastric cancer. METHODS: A total of 119 gastric cancer patients who underwent gastrectomy were enrolled for the study. A CT image at the top of the iliac crest level was obtained at the following times: 3 postoperative months (POM), 6 POM, 1 postoperative year (POY), 2 POY, 3 POY, and 5 POY. We analyzed the change rate of PMMA after gastrectomy and before or after recurrence. RESULTS: PMMA change after gastrectomy was approximately between -8 and -10% over the 5-year observation period. PMMA in the R2 (macroscopic residual tumor)/recurrence group was lower than that in the no recurrence group, and a significant difference was observed at 2 POY (-21.7 ± 3.6% vs. -7.9 ± 2.3%, p < 0.01). PMMA after freshly diagnosed recurrence had decreased significantly by 14.1 ± 1.8% (p < 0.01). CONCLUSIONS: Evaluation of PMMA change by CT after gastrectomy could assist in the diagnosis of the progression of cancer state in gastric cancer patients.

Baseline Tumor Lipiodol Uptake after Transarterial Chemoembolization for Hepatocellular Carcinoma: Identification of a Threshold Value Predicting Tumor Recurrence.

BACKGROUND: The aim of the study was to evaluate the association between baseline Lipiodol uptake in hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE) with early tumor recurrence, and to identify a threshold baseline uptake value predicting tumor response. PATIENTS AND METHODS: A single-institution retrospective database of HCC treated with Lipiodol-TACE was reviewed. Forty-six tumors in 30 patients treated with a Lipiodol-chemotherapy emulsion and no additional particle embolization were included. Baseline Lipiodol uptake was measured as the mean Hounsfield units (HU) on a CT within one week after TACE. Washout rate was calculated dividing the difference in HU between the baseline CT and follow-up CT by time (HU/month). Cox proportional hazard models were used to correlate baseline Lipiodol uptake and other variables with tumor response. A receiver operating characteristic (ROC) curve was used to identify the optimal threshold for baseline Lipiodol uptake predicting tumor response. RESULTS: During the follow-up period (mean 5.6 months), 19 (41.3%) tumors recurred (mean time to recurrence = 3.6 months). In a multivariate model, low baseline Lipiodol uptake and higher washout rate were significant predictors of early tumor recurrence (P = 0.001 and < 0.0001, respectively). On ROC analysis, a threshold Lipiodol uptake of 270.2 HU was significantly associated with tumor response (95% sensitivity, 93% specificity). CONCLUSIONS: Baseline Lipiodol uptake and washout rate on follow-up were independent predictors of early tumor recurrence. A threshold value of baseline Lipiodol uptake > 270.2 HU was highly sensitive and specific for tumor response. These findings may prove useful for determining subsequent treatment strategies after Lipiodol TACE.

Embolization of Arteriovenous Malformations: Effect of Flow Control and Composition of n-Butyl-2 Cyanoacrylate and Iodized Oil Mixtures with and without Ethanol in an in Vitro Model.

Purpose To elucidate the effect of flow control (ie, balloon occlusion) and the composition of various mixtures of n-butyl-2 cyanoacrylate (NBCA) and iodized oil, with and without the addition of ethanol, for the treatment of arteriovenous malformations in an in vitro model. Materials and Methods A simulation circuit device that featured an artificial nidus was filled with heparinized swine blood obtained during exsanguination from another Institutional Animal Care and Use Committee-approved protocol and was constructed to generate pulsatile flow. Mixtures of NBCA and iodized oil (NL) at a 1:1 ratio (NL 1:1); NL and ethanol (NLE) at a 1:1:3 ratio (NLE 1:1:3) with or without flow control; and NL at 1:3, 1:5, and 1:10 ratios without flow control were injected six times each for a total of 42 trials. Embolization was classified as complete filling, proximal occlusion, pass through, or distal overpenetration after occlusion balloon deflation, and the trial results were compared. The results of the embolization test were evaluated by using the Fisher exact probability test to compare optimal and suboptimal embolization groups. Results NLE 1:1:3 with flow control completely filled the nidus in all six trials. NL 1:1 delivered with flow control achieved complete nidus filling in three of six injections, as did the NL 1:5 ratio trial without flow control. Complete embolization with NLE 1:1:3 with flow control was more feasible to achieve complete nidus filling than was NL 1:1 with flow control or NL 1:5 without flow control, although there was no statically significant difference (all, P = .09). None of the other mixtures produced complete embolization. Conclusion NLE 1:1:3 showed consistent and reproducible complete embolization with flow control and was stable after balloon deflation, making it an acceptable material for embolization in an in vitro arteriovenous malformation model. Further study should be performed before the NLE 1:1:3 mixture is used in routine clinical practice. (©) RSNA, 2015.

Practical Tantalum Coating of Microspheres for Experimental Visualization under Fluoroscopy and CT.

The present report describes a simple technique for tantalum coating of microspheres for visualization by fluoroscopy and computed tomography (CT). Spherical microspheres were soaked with Ta powder under different conditions and microscopically evaluated for Ta-coating quality by assessing bound and unbound Ta. For 100-300-µm Embosphere particles, soaking with 0.05 mL Ta powder for 30 minutes and centrifugation at 500 rpm produced optimal coating. Optimized microspheres were injected in swine renal arteries and assessed by fluoroscopy and micro-CT for the opacification of segmental, arcuate, and interlobular arteries. This practical method can be used for experimental studies with commonly available microspheres.

Development of Conventional Transarterial Chemoembolization for Hepatocellular Carcinomas in Japan: Historical, Strategic, and Technical Review.

OBJECTIVE: This article reviews the development of transarterial chemoembolization (TACE) in Japan, particularly ethiodized oil-based conventional TACE, from historical, strategic, and technical points of view. We also present the current status of standardized conventional TACE. CONCLUSION: Conventional TACE has been developed toward a more-selective and hemodynamic-conscious method, along with technical innovation and knowledge accumulation. Standardization of this method is necessary for further scientific evaluation.

Phase I clinical study of multiple epitope peptide vaccine combined with chemoradiation therapy in esophageal cancer patients.

BACKGROUND: Chemoradiation therapy (CRT) has been widely used for unresectable esophageal squamous cell carcinoma (ESCC) patients. However, many patients develop local recurrence after CRT. In this study, we hypothesized that the immunotherapy by peptide vaccine may be effective for the eradication of minimal residual cancer cells after CRT. This study was conducted as a phase I clinical trial of multiple-peptide vaccine therapy combined with CRT on patients with unresectable ESCC. PATIENTS AND METHODS: HLA-A*2402 positive 11 unresectable chemo-naïve ESCC patients were treated by HLA-A*2402-restricted multi-peptide vaccine combined with CRT. The peptide vaccine included the 5 peptides as follows; TTK protein kinase (TTK), up-regulated lung cancer 10 (URLC10), insulin-like growth factor-II mRNA binding protein 3 (KOC1), vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). CRT consisted of radiotherapy (60 Gy) with concurrent cisplatin (40 mg/m²) and 5-fluorouracil (400 mg/m²). Peptide vaccines mixed with incomplete Freund's adjuvant were injected subcutaneously once a week on at least 8 occasions combined with CRT. RESULTS: Vaccination with CRT therapy was well-tolerated, and no severe adverse effects were observed. In the case of grade 3 toxicities, leucopenia, neutropenia, anemia and thrombocutopenia occurred in 54.5%, 27.3%, 27.3% and 9.1% of patients, respectively. Grade 1 local skin reactions in the injection sites of vaccination were observed in 81.8% of patients. The expressions of HLA class I, URLC10, TTK, KOC1, VEGFR1 and VEGFR2 antigens were observed in the tumor tissues of all patients. All patients showed peptide-specific cytotoxic T lymphocytes responses in at least one of the 5 kinds of peptide antigens during the vaccination. Six cases of complete response (CR) and 5 cases of progressive disease (PD) were observed after the 8th vaccination. The 4 CR patients who continued the peptide vaccination experienced long consistent CR for 2.0, 2.9 4.5 and 4.6 years. CONCLUSIONS: A combination therapy of multi-peptide vaccine with CRT can successfully be performed with satisfactory levels of safety, and application of this combination therapy may be an effective treatment for patients with unresectable ESCC. TRIAL REGISTRATION: ClinicalTrial.gov, number NCT00632333.

Recurrent laryngeal nerve monitoring during thoracoscopic esophagectomy.

INTRODUCTION: There have been several reports on the feasibility and curability of thoracoscopic esophagectomy, which may reduce injury to the thoracic cage and decrease the invasiveness of surgery. Although the recurrent laryngeal nerve (RLN) is identified and kept intact during operations, RLN palsy sometimes occurs. Currently, surgical aides, including intraoperative neurological monitoring, are being utilized to avoid RLN injury during thyroid surgery. This system is utilized during thoracoscopic esophagectomy in the prone position. PATIENTS AND METHODS: Seven consecutive patients (six men, one woman; age range 62-74 years; mean 68 years) were included. Patients underwent general anesthesia and were intubated using the NIM TriVantage™ electromyography (EMG) tube. One-lung ventilation was performed with an endobronchial blocker. Thoracoscopic esophagectomy was performed in the prone position. The nerve stimulator was calibrated to 0.5 mA, and after the RLN was visually identified it was subsequently stimulated, which also confirmed normal machine functioning. In some situations, in the absence of a response, stimuli were increased to 1.0 mA and then 2.0 mA. RESULTS: Intraoperatively, all seven patients had their nerve signals monitored. In one case, a nerve signal disappeared after complete lymph node dissection along the left RLN. This system could identify the site of injury, and the thoracoscopic magnified view allowed the disrupted point to be located precisely. When we checked VTR after surgery, the source of injury was one point tension of the nerve pulled by fiber during lymph node dissection. CONCLUSIONS: Intraoperative RLN monitoring during thoracoscopic esophagectomy in the prone position, with one-lung ventilation performed using the TriVantage™ EMG tube and a bronchial blocker, is technically feasible, easy, and reliable.

Acute posterior fossa epidural hematoma in a newborn infant with Menkes disease.

Epidural hematoma (EDH) in newborn infants is rare compared with other types of intracranial hemorrhages. Furthermore, posterior fossa EDH is extremely rare. We present a case of posterior fossa EDH in an infant with Menkes disease with accessory bones in the occiput. A male infant with a condition diagnosed with Menkes disease by prenatal testing was born at 39 weeks via vacuum extraction. The patient presented with a mild tremor at 2 days after delivery. A brain computed tomography (CT) scan showed an acute EDH in the posterior fossa, extending into the occipitoparietal area. Three-dimensional CT and bone window CT scan revealed several accessory bones, diastasis of 1 accessory suture, a communicated fracture, and a linear fracture in the occipital bone. Furthermore, a bone fragment from a communicated fracture displaced toward the inside. The patient was treated conservatively for EDH because of his good general condition. The hematoma gradually resolved, and his tremor did not recur. We suggest the following mechanism of posterior fossa EDH development in our patient: (1) external force was applied to the occiput inside the birth canal during delivery, resulting in diastasis; (2) a communicated fracture occurred, and a bone fragment displaced toward the inside (linear fracture was caused indirectly by the force); (3) a transverse sinus was injured by the fragment; and (4) EDH developed in both the posterior fossa and supratentorial region. Copper deficiency can also cause fragility of connective tissues, vessels, and bones.

Safety and short-term outcomes of robotic-assisted transabdominal preperitoneal repair for inguinal hernia in pioneering hospitals in Japan: A nationwide retrospective cohort study.

INTRODUCTION: We aimed to evaluate the safety and short-term outcomes of robotic-assisted transabdominal preperitoneal repair for inguinal hernia in 12 pioneering hospitals in Japan. METHODS: Clinical data of patients who underwent robotic-assisted transabdominal preperitoneal repair between September 1, 2016, and December 31, 2021 were collected. Primary outcome measures were intra-operative adverse events and post-operative complications, whereas secondary outcomes were surgical outcomes, including chronic pain, recurrence, and learning curve. RESULTS: In total, 307 patients were included. One case of inferior epigastric arterial injury was reported; no cases of bowel or bladder injury were reported. Thirty-five seromas were observed, including four (1.3%) cases that required aspiration. The median operative time of a unilateral case was 108 minutes (interquartile range: 89.8-125.5), and post-operative pain was rated 1 (interquartile range: 0-2) on the numerical rating scale. In complicated cases, such as recurrent inguinal hernias and robotic-assisted radical prostatectomy-associated hernias, dissection and suture were safely achieved, and no complications were observed, except for non-symptomatic seroma. All patients underwent robotic procedures, and there was no chronic post-operative inguinal pain, although one case of hernia recurrence was reported. Regarding the learning curve, plateau performance was achieved after 7-10 cases in terms of operative time (P < .001). CONCLUSION: Robotic-assisted transabdominal preperitoneal repair can be safely introduced in Japan. Regardless of the involvement of many surgeons, the mastery of robotic techniques was achieved relatively quickly. The advantage of robotic technology such as wristed instruments may expand the application of minimally invasive hernia repair for complicated cases.

Treatment of ureteroarterial fistula with an endoureteral stent graft.

A patient with a history of total cystectomy for bladder cancer, cutaneous ureterostomy, irradiation, and long-term indwelling urinary catheters presented with an aortoureteral fistula (UAF), which was treated with an endoureteral stent graft. The described ureteral approach using stent grafts may be considered for the management of UAFs when more traditional approaches are unavailable.