Undifferentiated Adenocarcinoma Research Articles

Targeted-gene sequencing of an undifferentiated gallbladder carcinoma: a case report

BackgroundUndifferentiated carcinomas of the gallbladder are extremely rare. Most undifferentiated carcinomas are accompanied by adjacent foci of other conventional carcinomas, and a transition zone is shared between them. However, genetic alterations of undifferentiated gallbladder carcinoma and the similarities or differences between the undifferentiated carcinoma and the foci conventional carcinoma are unknown.Case presentationHerein, we report a case of undifferentiated gallbladder carcinoma with osteoclast-like giant cells with invasion into the liver, duodenum, and stomach in a 56-year-old man. The tumor was microscopically formed from the tubular adenocarcinoma (< 5% of the entire tumor), the undifferentiated carcinoma, and a transition zone between them. Four somatic mutations (TP53, TERT, ARID2, and CDH1), three amplifications (CCND1, FGF19, and MET), and a tumor mutation burden (TMB) of 3.45 muts/Mb were detected in the undifferentiated component using targeted gene sequencing, whereas 102 somatic mutations (including TP53, TERT, ARID2, and CDH1), one amplification (CCND1), and a higher TMB of 87.07 muts/Mb were detected in the tubular component. This patient died of tumor recurrence 2 months after the surgery.ConclusionsThe undifferentiated gallbladder carcinoma had its unique molecular alterations. The similarities in the genetic alterations of the undifferentiated carcinoma and adenocarcinoma provide evidence of a common origin at the genetic level. The occurrence of an undifferentiated carcinoma may be due to heterogeneity-associated branched evolution from the tubular adenocarcinoma.

Retrospective investigation of patients receiving additional surgery after endoscopic non-curative resection for early colorectal cancer

Objective: To investigate the clinical application of additional surgery after non-curative endoscopic resection for early colorectal cancer. Methods: A retrospectively descriptive cohort study was conducted. Inclusion criteria: (1) pathologically confirmed primary colorectal adenocarcinoma;(2) receiving additional surgery after endoscopic resection; (3) semi-elective operation. Exclusion criteria: familial adenomatous polyposis, appendiceal neoplasms, anal canal neoplasms, neuroendocrine tumors, and surgery because of perforation or bleeding after endoscopic resection. Indications of additional surgery: (1) pathologically positive lateral or basal resection margin; (2) submucosal invasion depth ≥ 1000 μm; (3) lymphovascular invasion; (4) poorly differentiated, undifferentiated or mucinous adenocarcinoma; (5) more than grade G2 in tumor budding; (6) incomplete resection or piecemeal specimen with margin impossible to evaluate; (7) patient's consent due to undetermined pathology. According to the above criteria, clinical data of 92 patients at the Colorectal Surgery Department, the First Affiliated Hospital of Nanjing Medical University between January 2013 and December 2018 were collected. Demographic data, pathological examinations, operative methods and outcomes were analyzed. Results: There were 61 (66.3%) male and 31 female (33.7%) patients with an average age of (58.2±10.7) years. The average BMI was (23.8±3.5) kg/m(2). The lesions located in the right-sided colon, left-sided colon and rectum in 19, 37 and 36 patients respectively. Sixteen patients received endoscopic snare resection, 45 received endoscopic mucosal resection and 31 received endoscopic submucosal dissection. Reasons for additional surgery included endoscopic specimen with pathologically positive margin (n=22, 23.9%), submucosal invasion depth ≥ 1000 μm (n=9, 9.8%), lymphovascular invasion (n=4, 4.3%), poorly differentiated, undifferentiated or mucinous adenocarcinoma (n=5, 5.4%), piecemeal resection (n=13, 14.1%), undetermined pathology (n=52, 56.5%). The median duration from endoscopic resection to additional surgery was 16 days. Thirty-four patients (37.0%) received preoperative endoscopic localization with carbon nanoparticles suspension injection and 5 (5.4%) were marked with titanium clip. Seventy-four patients (80.4%) received laparoscopic surgery, 17 (18.5%) received open surgery, while 1 patient (1.1%) was converted to open surgery due to missing titanium clip. Three patients (3.3%) were treated with transanal excision, 2 (2.2%) with bowel resection, and 87 (94.6%) with radical excision. After additional surgery, histopathological examination of surgical specimens revealed the presence of residual tumor in 5 patients (5.4%), lymph node metastasis in 8 (8.7%), lymphovascular invasion in 1 (1.1%) and tumor deposit in 1 (1.1%). Twelve patients (13.0%) developed postoperative complications, including 4 mid-low rectal cancer patients (4.3%) with anastomostic leakage or bleeding. After surgery, according to the TNM staging system, 83 patients (90.2%) were classified as TNM stage 0-I, 9 (9.8%) as TNM stage II-IV. One patient of stage IV with liver metastasis underwent concomitant hepatectomy. One patient of stage II received regular follow-up after operation. Seven cases of stage III and 1 of stage IV received postoperative chemotherapy. Eighty-five patients (92.4%) were followed up with a median time of 12.8 (IQR: 8.1, 24.3) months. No recurrence or metastasis was observed. Conclusions: Surgery is an effective salvage measure for non-curative endoscopic resection of early colorectal cancer. Since surgery may have complications, indications of the additional surgery should be considered carefully. Preoperative endoscopic localization should be performed in order to ensure the safety and efficacy of surgery.

Lung adenocarcinoma as a cause of spontaneous pneumothorax in a cat

A 15-year-old indoor/outdoor female, neutered, domestic European short haired cat was presented to our clinic with a history of neck-elongation and wheezing during inspiration/expiration. The first signs of respiratory disease occurred two weeks before the clinical presentation. After taking of clinical history, clinical examination and basic laboratory tests (complete blood count, blood smear, snap Feline Immunodeficiency Virus / Feline Leukemia Virus Combo test), a lung x-ray was performed showing the presence of left lung atelectasis and pneumothorax. The primary causes of lung atelectasis were not determined. Given that the general condition of the cat was very bad, she was put in an oxygen cage, thoracocentesis was performed, but the animal?s condition did not improve, and 24 hours after clinical presentation, the cat died. Autopsy revealed the presence of a tumor mass on the caudal lobe of the right lung, tumor formation in the area of trachea bifurcation and changes in the liver in the form of four round structures of different sizes. Histopathologically, the existence of primary undifferentiated lung adenocarcinoma with metastases on the liver and trachea was determined.

Risk factors for stage underestimation in patients with clinical T1N0 gastric cancer.

Limited gastrectomy has been generally performed in clinical T1N0 gastric cancer. The aim of this study was to identify risk factors for stage underestimation in clinical T1N0 gastric cancer. This study reviewed the medical records of 566 patients who underwent gastrectomy for clinical T1N0 gastric cancer. The tumor stage was underestimated in 122 (21.6%) patients. The relapse-free survival rate was significantly lower in the patients with pathological stage II (P = 0.021) and III (P < 0.001) disease than in those with pathological stage IA disease. In the multivariate analysis, a location in the upper third of the stomach, tumor size of ≥ 30mm, undifferentiated adenocarcinoma and clinical tumor depth of SM were identified as independent risk factors for pathological stages II and III. The rate of pathological stages II and III was 0% in the patients with no risk factors, 3% in those with 1 risk factor, 10.5% in those with 2 risk factors, 19.8% in those with 3 risk factors and 50% in those with 4 risk factors. Location, tumor size, undifferentiated adenocarcinoma and clinical tumor depth were independent risk factors for pathological stages II and III in clinical T1N0 gastric cancer.

Expression of Integrin-linked Kinase in Gastric Cancer and Its Relationship with Clinicopathological Characteristics

Objective: To explore the value of integrin-linked kinase (ILK) in the diagnosis of gastric cancer, its mechanism of action in the pathogenesis and its influence on tumor metastasis. Methods: Collect 100 cases of gastric cancer diagnosed pathologically, detect the positive expression of ILK, and analyze its biological characteristics. Results: The positive rate of ILK in gastric cancer tissue (57.0%) is significantly higher than that in the control group (12%), and the positive rate of ILK gradually increased with the progress of superficial gastritis, chronic atrophic gastritis with atypical hyperplasia and gastric cancer. The differences between the four groups are statistically significant. There is a significant difference in the positive rate of ILK among well-differentiated, moderately-differentiated, poorly-differentiated and undifferentiated adenocarcinomas (P<0.001). The positive rate (25%) of ILK in the uninvaded serosal layer (T1+T2) is significantly lower than the positive rate (75.0%) in the invaded serosal layer (T3+T4). There is a significant difference in the positive rate of ILK in stage I, II, III and IV (P<0.001). In the localized type (I+II), the positive rate of ILK (24.39%) is significantly lower than that of the invasive type (III+IV) (79.66%). The positive rate of ILK in patients without lymph node metastasis (30.23%) is significantly lower than that of patients with lymph node metastasis (77.19%). Conclusion: The positive rate of ILK in gastric cancer tissue is significantly higher than that in adjacent tissues. The higher the positive rate, the worse the prognosis. ILK is an independent risk factor affecting the prognosis of patients.

Impact of the ESM-1 Gene Expression on Outcomes in Stage II/III Gastric Cancer Patients Who Received Adjuvant S-1 Chemotherapy.

Endothelial cell-specific molecule-1 (ESM-1) is a soluble proteoglycan which has important role in various biological events. We investigated the impact of the ESM-1 expression in cancer tissues on outcomes in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy. The ESM-1 mRNA expression in cancerous tissues and adjacent normal mucosa from 253 patients was measured. The associations between the ESM-1 gene expression and the survival and clinicopathological features were investigated. A significant association was observed between high ESM-1 expression and undifferentiated adenocarcinoma. The overall survival curve was significantly lower in patients with high ESM-1 expression than in those with low expression (p=0.005). High ESM-1 expression was a significant independent prognosticator (HR=2.291, p=0.007). ESM-1 gene expression in cancerous tissues is an important prognosticator in stage II/III gastric cancer patients who received adjuvant S-1 chemotherapy.

Assessment of lymphatic flow based on the sentinel node concept in early gastric adenocarcinoma that satisfies expanded endoscopic resection criteria.

Even though indications for endoscopic resection (ER) in early gastric cancer are determined based on the potential risk of lymph node metastasis, the criteria for ER remain controversial. Sentinel node (SN) mapping for early gastric cancer can help determine regional lymphatic flow patterns. The aim of this study was to assess lymphatic flow according to the SN concept in patients with early gastric cancer, especially those who satisfy the expanded criteria for ER. We retrospectively enrolled 301 patients diagnosed with pT1 adenocarcinoma who had undergone gastrectomy with SN mapping and had no lymphovascular invasion. Patients were categorized into six groups based on oncological assessment. We analyzed lymphatic flow, including the number of identified SN and SN basin, and the rate of SN metastasis in each group. Of the 301 patients, 128 (42.5%) met the criteria for ER, with 18 in the absolute group and 110 in the expanded group; 173 (57.5%) were assigned to the surgical group. SN metastasis rate tended to be higher in surgical group patients than in ER criteria patients. In the expanded criteria group, the sub-group of patients with intramucosal, undifferentiated adenocarcinoma measuring 20mm or less had a significantly greater number of identified SNs (p = 0.013) and SN basins (p = 0.032). Furthermore, SN metastasis was observed only in this group. Patients with intramucosal, nonulcerated, undifferentiated adenocarcinoma measuring 20mm or less could develop a lymphatic network. For these patients, careful follow-up is required after ER.

A switch of N-glycosylation of proteome and secretome during differentiation of intestinal epithelial cells

The maintenance of homeostasis of the intestinal epithelium depends on the complex process of epithelial cells differentiation, which repeatedly continues throughout the entire life. Many studies suggest, that cellular differentiation is regulated by glycosylation, or at least that changes of the latter are the hallmark of the process. The detailed description and understanding of this relationship are important in the context of gastrointestinal tract disease, including cancer. Here we employ a broadly used in vitro model of intestinal cell differentiation to track the glycosylation changes in details. We analyzed the glycoproteome- and glycosecretome-derived N-glycomes of undifferentiated Caco-2 adenocarcinoma cells and Caco-2-derived enterocyte-like cells. We used HILIC-HPLC and MALDI-ToF-MS approach together with exoglycosidases digestions to describe qualitative and quantitative N-glycosylation changes upon differentiation. Derived glycan traits analysis revealed, that differentiation results in substantial upregulation of sialylation of glycoproteome and increment of fucosylation within glycosecretome. This was also clearly visible when we analyzed the abundances of individual glycan species. Moreover, we observed the characteristic shift within oligomannose N-glycans, suggesting the augmentation of mannose trimming, resulting in downregulation of H8N2 and upregulation of H5N2 glycan. This was supported by elevated expression of Golgi alpha-mannosidases (especially MAN1C1). We hypothesize, that intensified mannose trimming at the initial steps of N-glycosylation pathway during differentiation, together with the remodeling of the expression of key glycosyltransferases leads to increased diversity of N-glycans and enhanced fucosylation and sialylation of complex structures. Finally, we propose H4N5F1 glycan as a potential biomarker of intestinal epithelial cell differentiation.

Distribución Topográfica de Metástasis de Origen Desconocido

Introducción: La metástasis de origen desconocido es una entidad clínica relativamente común, que representa del 5% de todos los cánceres invasivos. La búsqueda del origen primario puede resultar desafiante por un patrón atípico metastásico, no obstante el adenocarcinoma y carcinomas indiferenciados representan un 75% siendo el adenocarcinoma el más complicado de determinar su sitio primario ya que sus características citológicas/histológicas generalmente no son específicas. Por esta razón surge la necesidad identificar el origen primario de las lesiones metastásica de origen desconocido en pacientes con y sin antecedentes oncológicos personales, el sexo y edad de mayor prevalencia.&#x0D; Métodos: Investigación observacional descriptiva, retrospectiva tomándose como universo de 100 pacientes con diagnóstico histopatológico de Carcinoma/Adenocarcinoma metastásico en el departamento de Anatomía patológica del ION – SOLCA en el periodo 2013-2015, con y sin antecedentes oncológicos personales.&#x0D; Resultados: Se obtuvo una muestra de 91 pacientes, donde la localización metastásica más frecuente fue en los ganglios cervicales (27%), seguida del hígado (13%), hueso y epiplón (9%). Además, en 69 de ellos pudo ser posible la identificación del origen primario de la lesión metastásica.&#x0D; Conclusiones: La topografía metastásica de neoplasia primaria desconocida tales como los ganglios cervicales y el hígado son los lugares de notable predominio, siendo el ganglio cervical el lugar de biopsia por excelencia debido a su mayor accesibilidad. La metástasis de origen desconocido a pesar de ser más frecuente en el sexo femenino, tiene una gran incidencia en el grupo etario entre 61-70 años.

The impact of histological type on the accuracy of preoperative N staging in patients with gastric cancer

BackgroundThe low accuracy of preoperative diagnosis of lymph node metastasis in gastric cancer (GC) complicates decisions on patient indication for neoadjuvant chemotherapy.MethodsWe investigated the use of preoperative clinical diagnosis of lymph node involvement (cN) in GC patients compared with postoperative pathological diagnosis.ResultsIn a series of 265 patients enrolled at the University of Yamanashi Hospital, the overall sensitivity was 44.4% and specificity was 93.4% of CT for detecting lymph node metastasis. The positive and negative predictive values were 80.0% and 73.8%, respectively. The negative predictive value was lower for undifferentiated adenocarcinoma than that for differentiated adenocarcinoma (64.9% vs. 78.7%, p = 0.034). In cT2 ≤ and cN2 ≤ GC, overdiagnosis of lymph node metastasis was significantly more frequent in patients with differentiated (50.0%) than in undifferentiated (13.3%) adenocarcinoma (p = 0.046).ConclusionsDiagnostic accuracy of lymph node involvement depended on histological type and cT-stage. Thus, considering preoperative histological type in GC, it may be useful to decide treatment plan.

Abstract SY20-01: Linking epigenetics, metabolism, and cancer: Lessons from SIRT6

Abstract In recent years, chromatin regulators have emerged as key modulators in cancer. These factors could work as both tumor suppressors and oncogenes, providing plasticity to cancer cells as they adapt to overcome the host responses. In recent years, we discovered that the mammalian histone deacetylase SIRT6 is a key chromatin factor, modulating expression of metabolic, developmental, and ribosomal protein genes. In recent studies, we identified a loss of function mutation in SIRT6 behind a human syndrome of perinatal lethality. In the context of cancer, we found SIRT6 to act as a robust tumor suppressor, by modulating glucose metabolism. As Otto Warburg described decades ago, cancer cells exhibit glycolytic metabolism, where pyruvate, instead of contributing to ATP production in the mitochondria, is converted to lactate even under normoxia conditions. We found SIRT6 as the first chromatin factor in charge of suppressing the Warburg effect in colon cancer. At the cellular level, SIRT6 inactivation leads to increased cellular glucose uptake, higher lactate production and decreased mitochondrial activity. Our results indicate that SIRT6 directly regulates expression of several key glycolytic and ribosomal genes, co-repressing Hif1a and Myc, respectively, and acting as a histone H3 lysine9 (H3K9) and lysine 56 (H3K56) deacetylase to specifically inhibit transcriptional elongation in these genes. Strikingly, we determined in new studies that such glycolytic switch provides an advantage even at the early initiating cancer stem cells stage, in what we identified as the cell-of-origin for the Warburg effect. In addition, we found SIRT6 to act as a robust tumor suppressor in the context of pancreatic cancer. However, in this case, SIRT6 did not influence metabolism, but rather silenced expression of the developmental gene Lin28b, in this way protecting against aggressive undifferentiated pancreatic adenocarcinoma. Our studies highlight the important role epigenetic factors, such as SIRT6, play in protecting against tumor progression by providing “epigenetic plasticity”, inhibiting adaptive responses in transformed cells.

Undifferentiated endometrial adenocarcinoma: Treatment and characteristics of a rare disease

Undifferentiated endometrial adenocarcinoma: Treatment and characteristics of a rare disease

Protein Hydrolysates from Fenugreek (Trigonella foenum graecum) as Nutraceutical Molecules in Colon Cancer Treatment.

The application of plant extracts for therapeutic purposes has been used in traditional medicine since the plants are a source of a great variety of chemical compounds that possess biological activity. Actually, the effect of these extracts on diseases such as cancer is being widely studied. Colorectal adenocarcinoma is one of the main causes of cancer related to death and the second most prevalent carcinoma in Western countries. The aim of this work is to study the possible effect of two fenugreek (Trigonella foenum graecum) protein hydrolysates on treatment and progression of colorectal cancer. Fenugreek proteins from seeds were hydrolysed by using two enzymes separately, which are named Purafect and Esperase, and were then tested on differentiated and undifferentiated human colonic adenocarcinoma Caco2/TC7 cells. Both hydrolysates did not affect the growth of differentiated cells, while they caused a decrease in undifferentiated cell proliferation by early apoptosis and cell cycle arrest in phase G1. This was triggered by a mitochondrial membrane permeabilization, cytochrome C release to cytoplasm, and caspase-3 activation. In addition, the hydrolysates of fenugreek proteins displayed antioxidant activity since they reduce the intracellular levels of ROS. These findings suggest that fenugreek protein hydrolysates could be used as nutraceutical molecules in colorectal cancer treatment.

Possibility of limited gastrectomy for early gastric cancer located in the upper third of the stomach, based on the distribution of sentinel node basins.

Several recent studies have evaluated the feasibility of the sentinel node (SN) concept for gastric cancer. The aim of our study was to investigate limited gastrectomy with SN basin dissection in SN navigation surgery (SNNS) for patients with early-gastric cancer located in the upper-third of the stomach. 147 patients received SNNS for early-gastric cancer at our institution. Of these, 26 patients diagnosed with early-gastric cancer < 4cm in size and located in the upper-third of the stomach were retrospectively analyzed for the distribution of SN and SN basins. In three of the 26 patients, lymph node metastasis was limited to the left gastric artery (LGA) basin. The breakdown of the basins were as follows: A single LGA basin, 19 cases; a non-single LGA basin, seven cases. A non-single LGA basin was significantly associated with the clinicopathological factors, such as tumor spread to the middle-third of the stomach, tumor location at the center of the greater curvature, and undifferentiated adenocarcinoma, compared to the single LGA basin group. Our data revealed that the distribution of the SN basins in early-gastric cancer measuring less than 4cm in size and located in the upper-third of the stomach was significantly correlated with tumor spread, tumor location, and the pathological findings.

Multicenter prospective study on the histological diagnosis of gastric cancer by narrow band imaging-magnified endoscopy with and without acetic acid.

Background and study aims The usefulness of endoscopy for diagnosing histological type remains unclear. This study aimed to examine the diagnostic accuracy of white light endoscopy (WLE), magnified endoscopy with narrow band imaging (NBI-ME), and NBI-ME with acetic acid enhancement (NBI-AA) for histological type of gastric cancer. Patients and methods Patients with depressed-type gastric cancers resected by endoscopic submucosal dissection were prospectively enrolled, and 221 cases were analyzed. Histological type was diagnosed by WLE, followed by NBI-ME and NBI-AA. Histological type was classified into differentiated adenocarcinoma and undifferentiated adenocarcinoma. Histological type was diagnosed based on lesion color in WLE, surface patterns (pit, villi, and unclear) and vascular irregularities in NBI-ME, and surface patterns in NBI-AA. Results Histological types of target areas were differentiated adenocarcinoma and undifferentiated adenocarcinoma in 206 and 15 cases, respectively. Diagnostic accuracy of WLE, NBI-ME, and NBI-AA for the histological type was 96.4 % (213/221), 96.8 % (214/221), and 95.5 % (211/221), respectively. No significant differences were observed among modalities. Positive predictive value based on endoscopic findings in NBI-ME was 98.0 % (149/152) for the villi pattern, 100 % (19/19) for the irregular pit pattern, 100 % (9/9) for the unclear surface pattern with a vascular network, 90.3 % (28/31) for the unclear surface pattern with mild vascular irregularity, and 88.9 % (8/9) for the unclear surface pattern with severe vascular irregularity. Conclusions NBI-ME and NBI-AA did not show any advantages over WLE for diagnostic accuracy. Villi pattern, irregular pit pattern, and vascular network may be useful for identifying differentiated adenocarcinoma.

Effect of ethyl acetate extract of usnea longissima on esophagogastric adenocarcinoma in rats1.

Purpose To investigate the effects of the EtOAc extract of U. longissima which is uninvestigated previously on esophagogastric cancer induced in rats with N-methyl-N-nitro-N-nitrosoguanidin (MNNG). Methods The anticancer activity of EtOAc extract of U. longissima was examined in the esophagogastric adenocarcinoma models induced in rats with MNNG. EtOAc extract of U. longissima, 50 and 100 mg/kg oral doses were administered once daily for six months. MNNG induced differentiated and undifferentiated type adenocarcinomas in the esophageal and gastric tissues of rats. Results EtOAc extract of U. longissima obtained from U. longissima prevented gastric and esophageal cancerogenesis induced in rats with MNNG. EtOAc extract of U. longissima did not have a lethal effect at doses of 500, 1000 and 2000 mg/kg. The prominent anticarcinogenic activity of EtOAc extract of U. longissima 50 and 100 mg/kg suggests that it is not toxic and it is selective to the cancer tissue. Conclusion This information may shed light on clinical implementation of EtOAc extract of U. longissima in future.

Mixed Histology Is a Risk Factor for Lymph Node Metastasis in Early Gastric Cancer

BackgroundThe risk factors of lymph node (LN) metastasis are important factors to consider in endoscopic submucosal dissection in early gastric cancer (EGC). The aim of the study was to identify the correlation between mixed histology and LN metastasis in EGC. MethodsA total of 1645 patients who underwent curative radical gastrectomy for EGC were divided into three groups (pure differentiated [pure D], mixed, and pure undifferentiated [pure UD]) according to histologic type. They were subsequently analyzed retrospectively for LN metastasis. The patients who had mixed histology between differentiated and undifferentiated tubular adenocarcinoma were defined as mixed group. ResultsThe pure UD group was significantly younger than the other groups. Tumor size was larger in the mixed group. LN metastasis occurred more frequently in the mixed group and the pure UD group than in the pure D group (pure D, mixed, and pure UD, 7.7%, 23.2%, and 10.8%, respectively; P < 0.001). A logistic regression analysis revealed that the independent risk factors for LN metastasis were large tumor size (odd ratio [OR], 1.308), submucosal invasion (OR, 3.565), lymphovascular invasion (OR, 9.755), and histologic types of mixed (OR, 2.360) and pure UD (OR, 1.657). ConclusionsMixed histology is an important risk factor for LN metastasis in EGC. Thus, radical gastrectomy should be considered in the cases of mixed-type histology after endoscopic resection.

ROS1-rearranged high-PD-L1-expressing lung adenocarcinoma manifesting as mediastinal tumor: A case report.

ROS proto-oncogene 1 receptor tyrosine kinase (ROS1)-rearranged lung cancer is rare and comprises only 1% of lung adenocarcinoma cases. It has recently been reported to have good response to crizotinib, a tyrosine kinase inhibitor of anaplastic lymphoma kinase. Driver oncogene mutations with approved therapies seldom coexist with a high expression of Programmed death-ligand 1 (PD-L1). The present case report describes a rare case of ROS1 rearrangement with high-PD-L1-expressing occult lung adenocarcinoma. A 32-year-old woman presented with chest pain and a prolonged cough. Chest computed tomography (CT) revealed a 57×36-mm tumor in the mediastinum, with no tumors detected in other regions. Positron emission tomography (PET)-CT showed a strong fluorodeoxyglucose accumulation in the tumor (SUVmax 13.2). Mediastinal tumor resection was completely resected using a video-assisted thoracic surgery approach. Pathological examination showed the tumor cells were positive for thyroid transcription factor 1, Napsin-A, ROS1, and PD-L1 (tumor proportion score >99%). ROS1 rearrangement was confirmed by fluorescence in situ hybridization. The mediastinal tumor was diagnosed as mediastinal lymph node metastasis of ROS1-rearranged PD-L1 high-expression undifferentiated lung adenocarcinoma (pathological stage 3, TxN2M0). Two months after the operation, the CT scan showed multiple mediastinum lymph nodes metastases with rapid tumor growth. The patient achieved a complete response after three cycles of S-1 plus cisplatin with concurrent radiotherapy 60 Gy/30 Fr.

Metastatic Gastric Adenocarcinoma Diagnosed Following Spontaneous Bacterial Peritonitis: A Rare Complication of Malignant Ascites

Spontaneous bacterial peritonitis (SBP) complicating malignant ascites without evidence of liver disease or portal hypertension is a rare clinical presentation. We report a case of non-cirrhotic SBP leading to a new diagnosis of metastatic gastric cancer. A 51-year-old male presented with a one-month history of diffuse abdominal pain, early satiety, nausea and non-bloody, non-bilious emesis. On exam, the patient's abdomen was notably distended and diffusely tender to palpation. Admission laboratory data were significant for a mild leukocytosis of 12,700 WBC/mm3 with a neutrophilic predominance of 83% and mild anemia of 13.1 g/dl. Liver function tests showed a serum total bilirubin of 0.5 mg/dl, aspartate aminotransferase of 28 U/L, alanine aminotransferase of 16 U/L, protein of 6.7 g/dl, and albumin of 3.8 g/dl. Computed tomography of the abdomen and pelvis revealed new large volume abdominal ascites without radiological evidence of cirrhosis, portal vein thrombosis, or portal hypertension. A diagnostic paracentesis revealed 2843 WBC/ mm3, 40% neutrophils, 25% lymphocytes, fluid protein of 4.8 g/dl, and fluid albumin of 2.9 g/dl with a serum ascites albumin gradient (SAAG) of 0.9 g/dl. The patient was started on ceftriaxone for five days. Fluid culture remained negative, but repeat fluid studies showed 1475 WBC/mm3 with 25% neutrophils indicating ceftriaxone treated SBP. Upper endoscopy revealed a 10 mm, oozing, cratered gastric ulceration with surrounding congested mucosa. Biopsies later confirmed undifferentiated gastric adenocarcinoma. In addition, ascitic fluid cytology was positive for metastatic signet ring cells. SBP is an established diagnosis that has been known to complicate at least 8-10% of the cirrhotic patient population. However, spontaneous infection of ascites fluid in malignancy has not been well-described in the literature. Other cases of SBP complicating malignant ascites reported were in patients with hepatic involvement of their primary malignancies. One other case of SBP complicating gastric cancer without liver disease has been reported in the literature; this patient had hematemesis with severe anemia thought to result in bowel ischemia and bacterial gut translocation. Our patient did not report a history of gastrointestinal bleed and had a stable hemoglobin on presentation. In conclusion, this patient's diagnostic course represents a unique presentation of a rare complication of malignant ascites in gastric cancer.2681_A Figure 1. Computed tomography of abdomen revealing diffuse abdominal ascites2681_B Figure 2. Upper endoscopy revealing ulceration with surrounding congested mucosa of the greater curvature of the gastric body

A retrospective comparative analysis between endoscopic treatment and surgical treatment for early gastric cancer accorded with expanded indications of endoscopic submucosal dissection

Objective To compare the efficacy of endoscopic treatment with surgical treatment for early gastric cancer accorded with expanded indications of endoscopic submucosal dissection (ESD). Methods A total of 165 patients (167 lesions) with early gastric cancer underwent ESD (ESD group, 77 cases) or surgery (surgery group, 88 cases) from January 2011 to December 2016. The lesions fulfilled expanded indications of ESD, and were pathologically identified as differentiated or undifferentiated adenocarcinoma. Chi-square test, continuity-adjusted Chi square test, and Fisher exact test were used to analyze the incidence of lesion residual, local recurrence, metachronous recurrence, short-term complications and long-term complications. The 3-year overall survival rate and 3-year disease-free survival rate of the two groups were analyzed by Kaplan-Meier method. Results There were no differences on the incidence of lesion residual (P=0.473), local recurrence (P=1.000) and metachronous recurrence (P=1.000) between the ESD group and the surgery group. The 3-year overall survival rate (100.0% VS 98.3%, P=0.343) and the 3-year disease-free survival rate (98.1% VS 96.7%, P=0.655) were not significantly different between the two groups. There was no significant difference on the incidence of short-term complications between the two groups [7.8% (6/77) VS 5.7% (5/88), χ2=0.294, P=0.588]. The incidence of long-term complications in the ESD group was lower than that in the surgery group [0 (0/77) VS 8.0% (7/88), continuity-adjusted χ2=4.588, P=0.032]. Conclusion For patients with early gastric cancer fulfilled expanded indications of ESD, ESD has a lower incidence of long-term complications with similar efficacy compared to surgery. Key words: Retrospective studies; Stomach neoplasms; Surgical procedures; Endoscopic submucosal dissection