Glutamine addiction and therapeutic strategies in pancreatic cancer

Pancreatic cancer remains one of the most lethal diseases worldwide owing to its late diagnosis,early metastasis,and poor prognosis.Because current therapeutic options are limited,there is an urgent need to investigate novel targeted treatment strategies.Pancreatic cancer faces significant metabolic challenges,principally hypoxia and nutrient deprivation,due to specific microenvironmental constraints,including an extensive desmoplastic stromal reaction.Pancreatic cancer cells have been shown to rewire their metabolism and energy production networks to support rapid survival and proliferation.Increased glucose uptake and glycolytic pathway activity during this process have been extensively described.However,growing evidence suggests that pancreatic cancer cells are glutamine addicted.As a nitrogen source,glutamine directly(or indirectly via glutamate conversion)contributes to many anabolic processes in pancreatic cancer,including amino acids,nucleobases,and hexosamine biosynthesis.It also plays an important role in redox homeostasis,and when converted toα-ketoglutarate,glutamine serves as an energy and anaplerotic carbon source,replenishing the tricarboxylic acid cycle intermediates.The present study aims to provide a comprehensive overview of glutamine metabolic reprogramming in pancreatic cancer,focusing on potential therapeutic approaches targeting glutamine metabolism in pancreatic cancer.

Update on diagnosis and treatment of early signet-ring cell gastric carcinoma: A literature review

Gastric signet-ring cell gastric carcinoma(GSRC)is an unfavorable subtype of gastric cancer(GC)that presents with greater invasiveness and poorer prognosis in advanced stage than other types of GC.However,GSRC in early stage is often considered an indicator of less lymph node metastasis and more satisfying clinical outcome compared to poorly differentiated GC.Therefore,the detection and diagnosis of GSRC at early stage undoubtedly play a crucial role in the management of GSRC patients.In recent years,technological advancement in endoscopy including narrow-band imaging and magnifying endoscopy has significantly improved the accuracy and sensitivity of the diagnosis under endoscopy for GSRC patients.Researches have confirmed that early stage GSRC that meets the expanded criteria of endoscopic resection showed comparable outcomes to surgery after receiving endoscopic submucosal dissection(ESD),indicating that ESD could be considered standard treatment for GSRC after thorough selection and evaluation.This article summarizes the current knowledge and updates pertaining to the endoscopic diagnosis and treatment of early stage signet-ring cell gastric carcinoma.

Feasibility of endoscopic treatment and predictors of lymph node metastasis in early gastric cancer

BACKGROUND Endoscopic submucosal dissection (ESD) has been routinely performed in applicable early gastric cancer (EGC) patients as an alternative to conventional surgical operations that involve lymph node dissection. The indications for ESD have been recently expanded to include larger, ulcerated, and undifferentiated mucosal lesions, and differentiated lesions with slight submucosal invasion. The risk of lymph node metastasis (LNM) is the most important consideration when deciding on a treatment strategy for EGC. Despite the advantages over surgical procedures, lymph nodes cannot be removed by ESD. In addition, whether patients who meet the expanded indications for ESD can be managed safely remains controversial. AIM To determine whether the ESD indications are applicable to Chinese patients and to investigate the predictors of LNM in EGC. METHODS We retrospectively analyzed 12552 patients who underwent surgery for gastric cancer between June 2007 and December 2018 at the Affiliated Hospital of Qingdao University. A total of 1262 (10.1%) EGC patients were eligible for inclusion in this study. Data on the patients’ clinical, endoscopic, and histopathological characteristics were collected. The absolute and expanded indications for ESD were validated by regrouping the enrolled patients and determining the positive LNM results in each subgroup. Predictors of LNM in patients were evaluated by univariate and multivariate analyses. RESULTS LNM was observed in 182 (14.4%) patients. No LNM was detected in the patients who met the absolute indications (0/90). LNM occurred in 4/311 (1.3%) patients who met the expanded indications. According to univariate analysis, LNM was significantly associated with positive tumor marker status, medium (20-30 mm) and large (>30 mm) lesion sizes, excavated macroscopic-type tumors, ulcer presence, submucosal invasion (SM1 and SM2), poor differentiation, lymphovascular invasion (LVI), perineural invasion, and diffuse and mixed Lauren’s types. Multivariate analysis demonstrated SM1 invasion (odds ration [OR]= 2.285, P = 0.03), SM2 invasion (OR = 3.230, P < 0.001), LVI (OR = 15.702, P < 0.001), mucinous adenocarcinoma (OR = 2.823, P = 0.015), and large lesion size (OR = 1.900, P = 0.006) to be independent risk factors. CONCLUSION The absolute indications for ESD are reasonable, and the feasibility of expanding the indications for ESD requires further investigation. The predictors of LNM include invasion depth, LVI, mucinous adenocarcinoma, and lesion size.

Gastric pyloric gland adenoma resembling a submucosal tumor:A case report

BACKGROUND Pyloric gland adenoma(PGA)is a recently described and rare tumor.Submucosal tumor(SMT)-like PGA is more difficult to diagnose and differentiate from other submucosal lesions.CASE SUMMARY We present the case of a 69-year-old man with a 10 mm SMT-like elevated lesion with an opening in the upper part of the gastric body,referred to our hospital for further endoscopic treatment.Magnifying endoscopy with narrow-band imaging,endoscopic ultrasonography,and complete endoscopic submucosal dissection were performed on the patient.Histopathological findings revealed tightly packed tubular glands lined with cuboidal or columnar cells that had round-tooval nuclei containing occasional prominent nucleoli and an eosinophilic cytoplasm similar to that in non-neoplastic gastric pyloric glands.Additionally,immunohistochemical analysis showed positive staining for both mucin 5AC and mucin 6.Therefore,we arrived at the final diagnosis of gastric PGA.Although there was no apparent malignant component in this tumor,PGA has been considered a precancerous disease with a high risk of transformation into adenocarcinoma.CONCLUSION PGA should be considered when detecting gastric SMT-like lesions.Physicians and pathologists should focus on PGA due to its malignant potential.

Gastrointestinal amyloidosis in a patient with smoldering multiple myeloma:A case report

BACKGROUND Smoldering multiple myeloma(SMM)is an asymptomatic plasma cell proliferative disorder that can progress to multiple myeloma(MM).Amyloidosis(light chain)(AL)is the most common form of systemic amyloidosis.There are few reports of SMM coexisting with AL involving the digestive tract.CASE SUMMARY A 63-year-old woman presented with lower limb edema,abdominal distension,abdominal pain,and hematochezia.Gastroscopy showed gastric retention,gastric angler mucosal coarseness,hyperemia,and mild oozing of blood.Colonoscopy showed hyperemic and edematous mucosa of the distal ascending colon and sigmoid colon with the presence of multiple round and irregular ulcers,submucosal ecchymosis,and hematoma.Gastric and colonic tissue biopsy confirmed the diagnosis of AL by positive Congo red staining.MM was confirmed by bone marrow biopsy and immunohistochemistry.The patient had no hypercalcemia,renal dysfunction,anemia,bone lesions or biomarkers of malignancy defined as plasma cells>60%in bone marrow.Additionally,no elevated serum free light chain ratio,or presence of bone marrow lesions by magnetic resonance imaging(SLiM criteria)were detected.The patient was finally diagnosed with SMM coexisting with AL.She received chemotherapy and was discharged when the symptoms were relieved.She is doing well at nearly five years of follow up.CONCLUSION This case highlights that high index of suspicion is required to diagnose gastrointestinal AL.It should be suspected in elderly patients with endoscopic findings of granular-appearing mucosa,ecchymosis,and submucosal hematoma.Timely diagnosis and appropriate therapy can help to improve the prognosis of these patients.