Massive Invasion Research Articles

Lethal multiple colon necrosis and perforation due to fulminant amoebic colitis: a surgical case report and literature review

BackgroundAmoebiasis caused by the protozoan species Entamoeba histolytica rarely develops into fulminant amoebic colitis (FAC), but when it does, it shows an aggressive clinical course including colonic perforation, necrotizing colitis, and high mortality. Surgical treatment for FAC patients should be carried out urgently. However, even after surgery, the mortality rate can be 40–50%. Although FAC is one of the most unfavorable surgical diseases with a poor prognosis, there are a few reports on the perioperative diagnosis and management of FAC based on autopsy findings. We herein report the surgical case of a 64-year-old man who developed multiple colon necrosis and perforation due to FAC. A detailed autopsy revealed FAC as the cause of death. Additionally, we reviewed the existing literature on FAC patients who underwent surgery and followed their perioperative diagnosis and management.Case presentationA 64-year-old man presented with anorexia, diarrhea, and altered consciousness on arrival to our hospital. Computed tomography revealed a large mass in the upper right lobe of his lung, and the patient was admitted for close investigation. Bloody diarrhea, lower abdominal pain, and hypotension were observed soon after admission. Urgent abdominal contrast-enhanced computed tomography scan revealed extensive intestinal ischemia, intestinal pneumatosis, and free intra-abdominal gas. The preoperative diagnosis was bowel necrosis and perforation with intussusception of the small intestinal tumor. Emergency subtotal colectomy and enterectomy were performed soon after the contrast-enhanced computed tomography. He was taken to an intensive care unit after surgery. However, he could not recover from sepsis and died with disseminated intravascular coagulation and multiple organ failure on the 10th-day post-surgery. A histopathological examination of the resected colon showed transmural necrosis and massive amoebae invasion. He was diagnosed with FAC. An autopsy revealed that he had developed pulmonary large cell carcinoma with small intestinal metastasis. The death was caused by intestinal ischemia, necrosis and the perforation of the residual bowel caused by amoebae invasion.ConclusionsSince FAC is a lethal disease with a high mortality rate and antibiotic therapies except metronidazole are ineffective, preoperative serological testing and perioperative metronidazole therapy in FAC patients can dramatically improve their survival rates.

Successful Treatment of Massive Choroidal Invasion in Retinoblastoma with Intra-arterial Chemotherapy (Ophthalmic Artery Chemosurgery)

Retinoblastoma eyes with choroidal invasion may not have to be enucleated and may be successfully managed with OAC using Melphalan, Carboplatin and Topotecan without compromising patient survival.

Depressed Colorectal Cancer: A New Paradigm in Early Colorectal Cancer.

INTRODUCTION:In contrast to most colorectal carcinomas arising from pedunculated or sessile protruded adenomas, submucosal-invasive (pT1) colorectal carcinoma exhibiting a depressed surface (hereinafter, “depressed colorectal carcinoma,” identified by means of high-definition endoscopy) is considered to be derived from depressed precursors. We hypothesized that depressed colorectal neoplasms have unique clinicopathological features different that are different from those of protruded and flat colorectal neoplasms.METHODS:We classified 27,129 colorectal neoplasms (909 pT1 carcinomas and 26,220 adenomas) resected between 2001 and 2017 into depressed (211 carcinomas and 109 adenomas), flat (304 carcinomas and 11,246 adenomas), and protruded subtypes (394 carcinomas and 14,865 adenomas) and compared their clinicopathological features. As exploratory analyses of pT1 carcinomas, we conducted whole-exome sequencing for 19 depressed and 8 protruded subtypes and RNA sequencing for 8 depressed and 8 protruded subtypes.RESULTS:pT1 carcinomas were more common in depressed lesions (66%) than in protruded (2.6%) and flat lesions (2.6%) (P < 0.001). Compared with nondepressed pT1 carcinomas, depressed pT1 carcinomas were positively correlated with lymphovascular invasion, tumor budding, and massive submucosal invasion and inversely correlated with the presence of an adenoma component (all P < 0.001). Depressed adenomas were more likely to contain high-grade dysplasia than nondepressed adenomas (49% vs 11%, P < 0.001). A KRAS mutation was observed only in one of the 19 depressed pT1 carcinomas. Relative to protruded carcinomas, depressed carcinomas generally exhibited higher expression of genes related to angiogenesis and epithelial-mesenchymal transition.DISCUSSION:Depressed colorectal neoplasms may harbor a unique combination of malignant histopathological phenotypes and molecular features.

Depth and productivity as predictive parameters for the widespread invasion of Arctodiaptomus dorsalis (Marsh, 1907) (Copepoda: Calanoida) in tropical lakes in the Philippines

AbstractA massive invasion of the Neotropical calanoid copepod Arctodiaptomus dorsalis (Marsh, 1907) has been taking place in the Philippines since at least 1993. This copepod’s fecundity is known to depend on food concentration, increasing temperature appears to have detrimental effects on its hatching success and survivorship, but parameters that are truly predictive of the successful integration and propagation of this species in particular bodies of water have not yet been identified. We conducted a spatial analysis of morphometric features and reproductive capacity, the latter proxied by clutch size (CS), of different populations of A. dorsalis inhabiting 11 tropical lakes in the Philippines. Correlations between either morphometry or CS and selected water quality parameters were investigated based on collections and measurements made from December 2018 to April 2019. Means of morphometric measurements differed significantly (P &amp;lt; 0.001) among the populations of A. dorsalis in all lakes. Total length (TL) of adult males, TL of non-ovigerous adult females, and CS of ovigerous females all showed significant (P &amp;lt; 0.001) inverse correlations with lake depth, accounting for about 30% of the observed variability among lakes (r = –0.55, –0.55, and –0.58, respectively). Shallow lakes, which are more homogenous in terms of nutrient distribution throughout the water column, thus provide a more suitable habitat than deep lakes for A. dorsalis and provides a partial explanation of the widespread occurrence and abundance of the species in the shallower, more eutrophic lakes in the Philippines.

Rare and Massive Cardiac Invasion of Malignant Lymphoma.

Rare and Massive Cardiac Invasion of Malignant Lymphoma.

Combined association of massive choroidal and optic nerve invasion as a prognostic relevance in primary retinoblastoma: A 10-year study.

To determine the significance of both massive choroidal invasion and optic nerve invasion (retrolaminar [(RL]+cut end [CE]) as a criterion for classifying high metastatic potential retinoblastoma and their relationship with other known histopathological high-risk features. A retrospective review of 650 eyes diagnosed as retinoblastoma over a 10-year period. In our study, there is male predominance and a higher percentage of the poorly differentiated tumors. The age of most of the patients ranges from 1 month to 8years with a median age of 2years. There were 24% of eyes with massive choroidal invasion and 18% of eyes with optic nerve invasion up to the cut end. On performing Cox-proportional hazard analysis, it was found that massive choroidal invasion in association with optic nerve invasion up to the cut end was an independent prognostic parameter. On Kaplan-Meier analysis, overall survival had reduced in patients having both massive choroidal invasion and an optic nerve cut end invasion along with orbital invasion (P<.05). The presence of massive choroidal invasion in association with optic nerve cut end invasion (RL+CE) could be used as a better prognostic predictor in assessing retinoblastoma patients with high metastatic potential and need to be kept for longer follow up.

The Impact of Eye Size in Retinoblastoma

Background: The typical imaged findings of retinoblastoma are an intraocular tumor with intratumoral calcification. Normal eye size is a supported finding of retinoblastoma. In practice, more than just a few cases had an altered eye size. Objective: To evaluate the effect of eye size in retinoblastoma. Materials and Methods: The present study included 47 patients with 54 diseased eyes. Twenty-seven patients underwent enucleation with histopathological results. The axial lengths (AL) and equatorial diameters (ED) were measured in both diseased and normal eyes. The imaging characteristics, tumor volume, and histopathological findings were recorded and analyzed. Results: The results showed no statistically significant differences between AL, ED, and calculated eye volumes (EV) between diseased and normal eyes. Anterior chamber depths were statistically shallower in retinoblastoma eyes (p&lt;0.001). EV was weakly associated with tumor volumes. Large eye size was significantly related to choroidal invasion, massive choroidal invasion, scleral invasion, and optic nerve invasion in pathology (p=0.04, 0.03, 0.02, and 0.04, respectively). Conclusion: There were no statistically significant differences of eye size parameters in the eyes with retinoblastoma when compared to the normal eyes. Large eye size and large tumor volume are significantly related to invasive histopathological results. Keywords: Retinoblastoma, Intraocular tumor, Eye size, Tumor volume, Histopathology, Neoplasm invasion

High-risk features in primary versus secondary enucleated globes with advanced retinoblastoma: a retrospective histopathological study.

The management of bilateral advanced retinoblastoma (RB) cases is challenging with attempts to use neoadjuvant therapy salvaging of one of the globes. Our aim in this study was to demonstrate the effect of this primary therapy on the histopathological features and risk factors in secondary enucleated compared to primarily enucleated globes with groups D and E RB. We retrospectively reviewed all enucleated globes with advanced RB received in the pathology laboratories over a period of 5years. Patients were divided into two groups: one with primary enucleations and another with at least one secondary enucleated globe, and their demographic and clinical data were analyzed. The enucleated globes in the two groups were analyzed to compare the general histopathological features including tumor seeding, size, differentiation, growth pattern, mitotic figures, and focality. More importantly, high-risk features: choroidal invasion, optic nerve (ON) invasion, iris/anterior chamber invasion, ciliary body invasion, and scleral and extra-scleral extension, as well as the pathological classification of the tumor (pT) according to the American Joint Committee on Cancer 7th edition were also compared between the two groups. We had a total of 106 enucleated globes (78 primary and 28 secondary enucleations) from 99 patients with advanced RB (73 patients with primarily and 26 with secondarily enucleated globes). Demographic and clinical profiles of patients were similar in both, but the mean interval from presentation to enucleation was significantly longer in the secondary enucleations (P = 0.015). Rare/occasional mitotic figures were observed in secondary enucleations using multivariate analysis (P = 0.003). Primarily enucleated globes had higher risk of tumor seeding (P = 0.020), post-laminar/surgical margin ON invasion (P = 0.001), and massive choroidal invasion (P = 0.028). Half of the secondary enucleated globes had tumors confined to the globes without invasion (pT1) and statistically significant lower tumor classifications (pT1 or pT2a) compared to primary enucleations (P =0.001). However, 18% of the secondarily enucleated globes in 3 patients had unfavorable outcome with RB-related mortality after a period of 1-4years. Secondary enucleated globes with advanced RB show favorable histopathological findings mainly less mitosis. These eyes have significantly lower chance for harboring choroidal and ON invasion, thus mostly classified as pT1 or pT2a when compared to primarily enucleated globes. The decision for secondary enucleation was observed to be significantly delayed (8.0months ± 9.8). Prompt decision for needed enucleation based on the response to primary treatment and careful histopathological examination of enucleated globes are essential to prevent disease-related mortality.

Mo1635 CLASSIFICATION OF NUCLEAR MORPHOLOGY OF EC FINDINGS IN COLORECTAL ENDOCYTOSCOPY

Endocytoscopy (EC) is a next-generation endoscopy that allows diagnostic imaging at 520× magnification. In the EC classifications, lesions diagnosed as EC3a vary extensively from adenoma to carcinomas with massive submucosal invasion (SM-m), including some lesions that are unsuitable for endoscopic treatment. Therefore, to improve the accuracy of assessing the depth of invasion based on the EC classification, we investigated the presence or absence of 2 factors; high degree of nuclear enlargement (HNE) and multilayered nuclei (MNs), that are indicators of SM-m. Between May 2005 and August 2018, we retrospectively examined 866 lesions diagnosed as EC2 or EC3, according to the EC classification. We subclassified EC 3a into 2 grades (low or high grade) and defined low grade as not recognizing both HNE and MNs, and high grade as for any of the two factors. We examined the diagnostic accuracy of SM-m based on this EC3a subclassification. In addition, we compared the diagnostic ability of EC for SM-m with that of other modalities; narrow-band imaging (NBI) and pit pattern. The sensitivity, specificity, positive predictive value (PPV), negative predictive value NPV), accuracy, and positive likelihood ratio for the diagnostic accuracy of the EC3a subclassification were 89.3%, 91.2%, 80.6%, 92.3%, 90.6%, and 10.1, respectively (P < 0.001). Diagnostic performance for predicting SM-m or worse among EC, NBI and pit pattern is as follows: The sensitivity, specificity, PPV, NPV, and accuracy about EC were 95.1%, 96.5%, 94.9%, 96.7%, 96.0% respectively. On the other hand, those of NBI were 65.0%, 98.7%, 97.0%, 80.7%, 85.1%, and pit pattern were 88.8%, 96.0%, 93.7%, 92.7%, 93.1%, respectively. The sensitivity, specificity, NPV, and accuracy of EC were significantly higher than those of NBI .(P < 0.05) . Futhermore, the sensitivity, NPV, and accuracy of EC were significantly higher than those of pit pattern. (P < 0.05) From the EC findings, the presence of HNE, and MNs are important risk factors for SM-m or worse outcomes. Furthermore, the EC3a subclassification taking account of these findings could be effective for the diagnosis of SM-m or worse.

Total glossectomy in multimodal treatment of oropharyngeal cancer: immediate results

The study objective is to analyze the results of combined antitumor therapy, which included glossectomy, to treat locally advanced and recurrent oropharyngeal squamous cell cancer.Materials and methods. We performed a retrospective analysis of multimodal antitumor therapy of 19 patients, who were treated in the Nizhny Novgorod Regional Clinical Oncologic Dispensary within 2009–2019. All patients underwent segmental resection of the mandible due to massive tumor invasion into the periosteum. After total glossectomy the defect was filled using pectoralis musculocutaneous flap. Due to the wide local tumor spread, a neck dissection (n = 7) or radical cervical lymphadenectomy (n = 12) were performed. During preventive surgery, metastases that were not detected before surgery were revealed in 2 patients in 1 neck lymph node. Results. Eleven patients had local purulent-necrotic postoperative complications. It was noted that after surgery but without radiation therapy complications developed in fewer patients (n = 4) and were less severe: of I degree – in 3 patients, of III degree – in 1 patient. Radiation therapy before surgery resulted in more severe purulent-necrotic complications in 7 patients: of I degree – in 2 patients, of II degree – in 1, of III degree – in 4. Mortality rates: 30-day, 60-day and 90-day – 10.5 %, 21 % and 37 %, respectively. The causes of death were complications of gastrostomy: profuse bleeding from the stomach wall (n = 1), acute psychosis complicated by cerebral edema (n = 1), increased heart failure (n = 1), necrosis of the anterior abdominal wall and cachexia, developed after gastrostomy (n = 1), continued tumor growth between chemotherapy courses (n = 3). Twelve patients survived more than 90 days after surgery, 3 patients – more than 2 years. As most of the patients could not swallow, they were administered a nasogastric tube, since a simultaneous gastrostomy increases the duration of a traumatic operation and aggravates the postoperative period.Conclusion. Multicomponent surgery after radiation therapy results in more often local purulent-necrotic postoperative complications than if the surgery is performed before radiation therapy. High mortality in the first 90 days after surgery (n = 7) due to local cancer spread is generally determined by the severe condition of patients with advanced cancer and the concomitant diseases. However, rejection of gastrostomy in favor of nasogastric tube seems reasonable, since several deaths in the early postoperative period may be occurred due to complications associated with gastrostomy.

Blood Free-Circulating DNA Testing of Methylated RUNX3 Is Useful for Diagnosing Early Gastric Cancer.

The main modalities for gastric cancer screening are limited to upper gastrointestinal endoscopy and contrast radiography. The former is invasive, and the latter has high false-negative rates. Thus, alternative diagnostic strategies are required. One solution may be a liquid biopsy. Methylated RUNX3 is a well-known biomarker of gastric cancer but it is very difficult to detect with conventional bisulfite-based methylation assays when only a small amount of serum is available. We developed the combined restriction digital PCR (CORD) assay, a new methylation assay allowing for the counting of as little as one copy of a methylated gene in a small sample of DNA without necessitating DNA bisulfite treatment. We evaluated the sensitivity and specificity of the serum DNA testing of methylated RUNX3 by the CORD assay for the detection of early gastric cancer using 50 patients with early gastric cancer and 61 control individuals. The CORD assay had a sensitivity of 50.0% and a specificity of 80.3% for early gastric cancer. Methylated RUNX3 copies were significantly associated with tumor size, massive submucosal invasion, and lymph-vascular invasion. After the treatment, the median number of methylated RUNX3 copies was significantly decreased. The CORD assay may provide an alternative screening strategy to detect even early-stage gastric cancer.

Enucleated globes with advanced retinoblastoma: correlation of histopathological features and reclassification of tumors according to the 8th edition of the American Joint Committee on Cancer (AJCC).

We aim to study certain histopathological characteristics of the retinoblastoma (RB) tumors in globes with clinically advanced RB, which can be correlated with the high-risk features including: tumor differentiation, growth pattern and focality. We also aim to reclassify the tumor pathologically in the analyzed cases according to the American Joint Committee on Cancer (AJCC) 8th edition in an attempt to compare the validity of this newest classification. Retrospective study of patients diagnosed with clinical RB of groups D and E during the period: January 2013 to December 2017 at King Khaled Eye Specialist Hospital (KKESH) and King Abdulaziz University Hospital (KAUH). Charts were reviewed for demographic and basic clinical data. Histopathological features (tumor differentiation, growth pattern, focality, seeding, and presence of choroidal invasion (focal versus massive), level of optic nerve (ON) invasion, anterior chamber invasion, scleral and extra-scleral extension, and finally the documented pathological tumors (pT) classification based on the AJCC 7th edition were collected. We included 146 eyes with advanced retinoblastoma (groups D and E) from 104 patients. Gender distribution was almost equal with 54 males. Median age was 12months (range 1-96months), and a mean age was 17.1 ± 15.1months. No family history was found in the majority (94.2%). Clinically, the most common presenting symptoms: leukocoria (73.3%), squint (33.6%) and least commonly proptosis (2.7%). A total of 106 enucleation specimens were reviewed. Degree of RB differentiation was: well differentiated (18%), moderate (30%), poor (35%), and undifferentiated (17%). The most common high-risk features were ON invasion (68%) with the majority being prelaminar in nature, choroidal invasion (45%) with more than half being massive, iris/trabecular meshwork (TM)/Schlemm's canal invasion (8.5%), and then intra-scleral/extra-scleral extension (5%). Less tumor differentiation doubles the relative risk of massive choroidal invasion (with 95% CI) with a statistically significant P value (P = 0.030). Endophytic RB was associated with vitreous seeding, while exophytic tumors were associated with subretinal seeding (P = 0.001) each. Ten cases with combined ON invasion (pre-laminar) and focal choroidal invasion were reclassified pT2a in the AJCC 8th edition instead of pT2b in the older 7th edition. Our demographic and basic clinical data for advanced RB are comparable to other similar reports. The tumor growth pattern correlates well with the type of seeding observed in enucleated globes with RB. Less tumor differentiation is a relative risk of massive choroidal invasion. It is advocated to implement the AJCC 8th edition by ocular pathologists worldwide aiming to histopathologically classify the RB tumor in cases for selective adjuvant chemotherapy.

Clinical relevance of the comparative expression of immune checkpoint markers with the clinicopathological findings in patients with primary and chemoreduced retinoblastoma.

The goal of this study is to identify the pathological findings and expression of immune checkpoint marker (PD-1, PD-L1, and CTLA-4) in the tumor microenvironment of both primary and chemoreduced retinoblastoma and correlate them with clinicopathological parameters and patient outcome. Total of 262 prospective cases was included prospectively in which 144 cases underwent primary enucleation and 118 cases received chemotherapy/radiotherapy before enucleation (chemoreduced retinoblastoma). Immunohistochemistry, qRT-PCR and western blotting were performed to evaluate the expression pattern of immune checkpoint markers in primary and chemoreduced retinoblastoma. Tumor microenvironment were different for both primary and chemoreduced retinoblastoma. Expression of PD-1 was found in 29/144 (20.13%) and 48/118 (40.67%) in primary and chemoreduced retinoblastoma, respectively, whereas PD-L1 was expressed in 46/144 (31.94%) and 22/118 (18.64%) in cases of primary and chemoreduced retinoblastoma, respectively. Expression pattern of CTLA-4 protein was similar in both groups of retinoblastoma. On multivariate analysis, massive choroidal invasion, bilaterality and PD-L1 expression (p = 0.034) were found to be statistically significant factors in primary retinoblastoma, whereas PD-1 expression (p = 0.015) and foamy macrophages were significant factors in chemoreduced retinoblastoma. Overall survival was reduced in cases of PD-L1 (80.76%) expressed primary retinoblastoma, and PD-1 (63.28%) expressed chemoreduced retinoblastoma. This is the first of its kind study predicting a relevant role of the immune checkpoint markers in both groups of primary and chemoreduced retinoblastoma with prognostic significance. Differential expression of these markers in both group of retinoblastoma is a novel finding and might be an interesting and beneficial target for chemoresistant tumors.

Impact of Prunus serotina Ehrh. invasion on heathland vegetation: a case of study in North-Western Italy

Prunus serotina is one of the worst invasive alien plants throughout Europe, able to rapidly replace autochthonous vegetation and form monospecific stands both in open lands and forested areas. Invasion by shrubs and trees due to abandonment of traditional management practices, is one of the major threats to the conservation of “European dry heaths”, a priority habitat included in the Council Directive 92/43/EEC. The aim of this study was to assess the effects of P. serotina invasion on heathland vegetation in terms of species composition and cover, with special regards to the dominant Calluna vulgaris and Molinia arundinacea, in an area of North-Western Italy subjected to massive invasion by this alien species. We collected data on the plant cover along an invasion gradient in 10 linear transects running from P. serotina invaded stands towards non invaded ones. P. serotina differently affected the heathland vegetation. In particular, the cover of C. vulgaris and other typical heathland species such as Cytisus scoparius sharply decreased at P. serotina cover increasing. On the contrary, positive or no effect of P. serotina cover was found on M. arundinacea. Our results showed that shaded conditions created by the alien tree disfavored light demanding C. vulgaris and C. scoparius, enabling fast grower M. arundinacea to outcompete and replace them. This study emphasizes the urgency to develop management strategies to effectively control P. serotina spread in the area and to restore typical heathland species.

Modeling and implementation of 5G edge caching over satellite

SummaryThe fifth‐generation (5G) wireless networks have to deal with the high data rate and stringent latency requirements due to the massive invasion of connected devices and data‐hungry applications. Edge caching is a promising technique to overcome these challenges by prefetching the content closer to the end users at the edge node's local storage. In this paper, we analyze the performance of edge caching 5G networks with the aid of satellite communication systems. First, we investigate the satellite‐aided edge caching systems in two promising use cases: (a) in dense urban areas and (b) in sparsely populated regions, eg, rural areas. Second, we study the effectiveness of satellite systems via the proposed satellite‐aided caching algorithm, which can be used in three configurations: (a) mono‐beam satellite, (b) multi‐beam satellite, and (c) hybrid mode. Third, the proposed caching algorithm is evaluated by using both empirical Zipf‐distribution data and the more realistic Movielens dataset. Last but not least, the proposed caching scheme is implemented and tested by our developed demonstrators which allow real‐time analysis of the cache hit ratio and cost analysis.

Brain Invasion along Perivascular Spaces by Glioma Cells: Relationship with Blood-Brain Barrier.

The question whether perivascular glioma cells invading the brain far from the tumor bulk may disrupt the blood–brain barrier (BBB) represents a crucial issue because under this condition tumor cells would be no more protected from the reach of chemotherapeutic drugs. A recent in vivo study that used human xenolines, demonstrated that single glioma cells migrating away from the tumor bulk are sufficient to breach the BBB. Here, we used brain xenografts of patient-derived glioma stem-like cells (GSCs) to show by immunostaining that in spite of massive perivascular invasion, BBB integrity was preserved in the majority of vessels located outside the tumor bulk. Interestingly, the tumor cells that invaded the brain for the longest distances traveled along vessels with retained BBB integrity. In surgical specimens of malignant glioma, the area of brain invasion showed several vessels with preserved BBB that were surrounded by tumor cells. On transmission electron microscopy, the cell inter-junctions and basal lamina of the brain endothelium were preserved even in conditions in which the tumor cells lay adjacently to blood vessels. In conclusion, BBB integrity associates with extensive perivascular invasion of glioma cells.

Pathological complete response by advanced hepatocellular carcinoma with massive macrovascular invasion to hepatic arterial infusion chemotherapy: a case report

BackgroundAdvanced hepatocellular carcinoma (HCC) with macrovascular invasion has an extremely dismal prognosis. We report a rare case of multiple HCC with tumor thrombosis in the portal vein and inferior vena cava that was initially treated with hepatic arterial infusion chemotherapy (HAIC); later resection revealed pathological complete response.Case presentationA 75-year-old man presented with HCC in his right liver, with tumor thrombosis growing to the right portal vein and the inferior vena cava, and bilateral intrahepatic liver metastases. He underwent HAIC (5-fluorouracil [170 mg/m2] + cisplatin [7 mg/m2]) via an indwelling port. Although the tumor shrank and tumor marker levels decreased rapidly, we abandoned HAIC after one cycle because of cytopenia. We resumed HAIC 18 months later because of tumor progression, using biweekly 5-fluorouracil only [1000 mg] due to renal dysfunction. However, after 54 months, the HAIC indwelling port was occluded. The patient therefore underwent a right hepatectomy to resect the residual lesion. Histopathological findings showed complete necrosis with no viable tumor cells. The patient has been doing well without postoperative adjuvant therapy for more than 10 years after initially introducing HAIC and 6 years after the resection, without evidence of tumor recurrence.ConclusionsHAIC can be an effective alternative treatment for advanced HCC with macrovascular invasion.

Differential expression patterns of immune checkpoint markers in tumour-stromal microenvironment of primary and chemoreduced retinoblastoma

Abstract Background The goal of this study is to identify the pathological findings and expression of immune checkpoint marker (PD-1, PD-L1, and CTLA-4) in the tumor microenvironment of both primary and chemoreduced retinoblastoma and correlate with clinicopathological parameters and patient outcome. Methods Total of 262 prospective cases was included prospectively in which 144 cases underwent primary enucleation and 118 cases received chemotherapy/radiotherapy before enucleation (chemoreduced retinoblastoma). Immunohistochemistry, qRT-PCR and western blotting were performed to evaluate the expression pattern of immune checkpoint markers in primary and chemoreduced retinoblastoma. Results Tumor microenvironment was different for both primary and chemoreduced retinoblastoma. Expression of PD-1 was found in 29/144 (20.13%) and 48/118 (40.67%) in primary and chemoreduced retinoblastoma respectively, whereas PD-L1 was expressed in 46/144 (31.94%) and 22/118 (18.64%) in cases of primary and chemoreduced retinoblastoma respectively. Expression pattern of CTLA-4 protein was similar in both groups of retinoblastoma. On multivariate analysis, massive choroidal invasion, bilaterality and PD-L1 expression (p = 0.034) were found to be statistically significant factors in primary retinoblastoma whereas PD-1 expression (p = 0.015) and foamy macrophages were significant factors in chemoreduced retinoblastoma. Overall survival reduced in cases of PD-L1 (80.76%) expressed primary retinoblastoma, and PD-1 (63.28%) expressed chemoreduced retinoblastoma. Conclusion This is the first of its kind study predicting a relevant role of the immune checkpoint markers in primary and chemoreduced retinoblastoma with prognostic significance. Differential expression of these markers in both group of retinoblastoma is a novel finding and might be an interesting and beneficial target for chemoresistant tumors. Legal entity responsible for the study The authors. Funding Has not received any funding. Disclosure All authors have declared no conflicts of interest.

Gallbladder cancer accompanied by uncontrollable eosinophilia: report of a case.

A 48-year-old male was referred to our hospital for evaluation of motor speech disorders and difficulty in the movement of both the hands. The clinical diagnosis was Trousseau's syndrome due to advanced gallbladder cancer (cT3aN1M0). The patient received anticoagulation therapy and systemic chemotherapy (gemcitabine and cisplatin). Motor speech disorders and difficulty in movement of both hands were recovered. After 2 courses of chemotherapy, the primary tumor developed a massive hepatic invasion and the peripheral blood eosinophils increased gradually. The patient was admitted to our hospital for abdominal distension, fever, right upper quadrant pain, systemic edema, loss of appetite, and general malaise. The peripheral blood eosinophil count was markedly elevated to 45,900/μl (90.3%). The serum level of GM-CSF was high and there was no evidence of leukemia, allergic status and other diseases. The patient was diagnosed as paraneoplastic eosinophilia with advanced gallbladder cancer, which was suspected to produce GM-CSF. The patient received palliative support and died of disseminated intravascular coagulation 15days after admission. We herein reported a fatal case of gallbladder cancer suspected of producing GM-CSF.

Effect of bradykinin on rats with thromboangiitis obliterans through PI3K/Akt signaling pathway.

To explore the effect of bradykinin on rats with thromboangiitis obliterans (TAO) through the phosphatidylinositol 3-hydroxy kinase/protein kinase B (PI3K/Akt) signaling pathway. The female Wistar rats were injected with lauric acid via the femoral artery to establish the TAO model, and they were randomly divided into control group (healthy rats), model group (TAO rats) and bradykinin group (TAO rats injected with bradykinin B2 receptor-specific inhibitor). The control was set in each group before the operation. The level of serum bradykinin in each group was detected via enzyme-linked immunosorbent assay (ELISA), and the reactive oxygen species (ROS) level, Caspase-3 activity and PI3K/Akt protein concentration in vascular tissues were measured via ELISA, Western blotting, ROS assay, and Caspase-3 activity assay, respectively. Moreover, the specific therapeutic mechanism of bradykinin was analyzed. In control group, the intima of the lower extremity venous tissues was smooth, the extima had no evident changes, and there was no inflammatory cell invasion around the arteries and veins. In model group, there was massive inflammatory cell invasion into the lower extremity venous tissues. In bradykinin group, fibrosis and atrophy occurred in venous tissues, the extima was thickened without fibrosis, and there was phagocytosis of neutrophils and mononuclear macrophages around the arteries and veins, as well as massive inflammatory infiltration. The PI3K/Akt protein concentration in lower extremity venous tissues was the highest in control group and the lowest in bradykinin group, and there were statistically significant differences (p<0.01). At 24 h after administration of doxorubicin (DOX), the level of ROS in lower extremity venous tissues was higher in bradykinin group than that in model group (p<0.05), and it was also higher in model group than that in control group (p<0.05). Besides, the activity of Caspase-3 in lower extremity venous tissues was significantly increased in bradykinin group compared with that in model group and control group, while it was slightly higher in model group than that in control group (p<0.05). The low expression of bradykinin can promote TAO in rats by the mechanism that it inhibits the PI3K/Akt signaling pathway to raise the oxidative stress level, thereby aggravating TAO.