Esophageal leiomyomatosis – an unusual cause of pseudoachalasia

Esophageal leiomyomatosis is a rare hamartomatous disorder with varied presentation. In the literature, it is described mostly in children, and is associated with Alport’s syndrome. A case of leiomyomatosis that presented as achalasia not associated with Alport’s syndrome is described in a 35-year-old woman with a 16-year history of dysphagia. Barium swallow showed a smooth narrowing at the lower end of the esophagus with a longer than usual stricture length. Endoscopy showed a dilated esophagus with a submucosal nodule in the region of the cardia. A computed tomography scan revealed circumferential thickening of the esophagus involving the gastroesophageal junction, with fat planes maintained with the adjacent structure. Endoscopic ultrasound demonstrated a lesion arising from the muscularis propria. The manometry findings were suggestive of achalasia. She underwent transhiatal esophagectomy with gastric pull-up

Differentiation between benign and malignant hilar obstructions using laboratory and radiological investigations: A prospective study

Background: Preoperative determination of the aetiology of bile duct strictures at the hilum is difficult. We evaluated the diagnostic accuracy of laboratory parameters and imaging modalities in differentiating between benign and malignant causes of hilar biliary obstruction. Patients and methods: Fifty-eight patients (26 men) with a history of obstructive jaundice and liver function tests (LFTs) and ultrasound suggestive of biliary obstruction at the hilum were studied. They were evaluated by tumour marker assay (CA19-9), CT and MRI/MRCP. A single experienced radiologist, blinded to the results of other tests, evaluated the imaging. The final diagnosis was made either from histology of the resected specimen, operative findings or image-guided biopsy in inoperable patients. A receiver operator characteristic (ROC) curve was constructed for each laboratory parameter to determine optimal diagnostic cut-off to predict malignant biliary stricture (MBS). Results: In all, 34 patients had a benign and 24 had malignant aetiology. The mean age of benign patients was 38 years compared with 54 years for MBS. Forty-seven patients were treated with surgery while 11 had ERCP/PTC and stenting. The ROC curve showed that preoperative bilirubin level >8.4 mg/dl (sensitivity 83.3%, specificity 70%), alkaline phosphatase level >478 IU (sensitivity 63%, specificity 49%) and CA19-9 levels >100 U/L (sensitivity 45.8%, specificity 88.2%) for predicting MBS. The sensitivity, specificity and diagnostic accuracy of MRI/MRCP (87.5%, 85.3%, 82.7%, respectively) was marginally superior to CT (79.2%, 79.4%, 79.3%, respectively). Conclusions: Patients with a bilirubin level of >8.4 mg% and CA19-9 level >100 U/L were more likely to have malignant aetiology. MRI/MRCP was a better imaging modality than CT

Early recurrence after laparoscopic radical cholecystectomy in a patient with gallbladder cancer

Laparoscopic radical cholecystectomy for gallbladder cancer (GBC) has been performed at various oncology centres reporting its technical feasibility. Considering GBC an aggressive malignancy, laparoscopic radical cholecystectomy should be dealt with caution. We recently encountered a case of carcinoma gallbladder who underwent laparoscopic radical cholecystectomy elsewhere and presented with early recurrence. The patient's records were evaluated and he underwent re-resection. Hereby, we discuss the factors that could lead to early recurrence after laparoscopic radical cholecystectomy and measures that can be taken to prevent it

Ligand decorated biodegradable nanomedicine in the treatment of cancer

Cancer is one of the major global health problems, responsible for the second-highest number of deaths. The genetic and epigenetic changes in the oncogenes or tumor suppressor genes alter the regulatory pathways leading to its onset and progression. Conventional methods are used in appropriate combinations for the treatment. Surgery effectively treats localized tumors; however, it fails to treat metastatic tumors, leading to a spread in other organs, causing a high recurrence rate and death. Among the different strategies, the nanocarriers-based approach is highly sought for, but its nonspecific delivery can cause a profound side effect on healthy cells. Targeted nanomedicine has the advantage of targeting cancer cells specifically by interacting with the receptors overexpressed on their surface, overcoming its non-specificity to target healthy cells. Nanocarriers prepared from biodegradable and biocompatible materials are decorated with different ligands by encapsulating therapeutic or diagnostic agents or both to target cancer cells overexpressing the receptors. Scientists are now utilizing a theranostic approach to simultaneously evaluate nanocarrier bio-distribution and its effect on the treatment regime. Herein, we have summarized the recent 5-year efforts in the development of the ligands decorated biodegradable nanocarriers, as a targeted nanomedicine approach, which has been highly promising in the treatment of cancer

Hypoxia-driven oncometabolite L-2HG maintains stemness-differentiation balance and facilitates immune evasion in pancreatic cancer

In pancreatic cancer, the robust fibroinflammatory stroma contributes to immune suppression and renders tumors hypoxic, altering intra-tumoral metabolic pathways and leading to poor survival. One metabolic enzyme activated during hypoxia is lactate dehydrogenase A (LDHA). As a result of its promiscuous activity under hypoxia, LDHA produces L-2 hydroxyglutarate, an epigenetic modifier, that regulates the tumor transcriptome. However, the role of L-2HG in remodeling the pancreatic tumor microenvironment is not known. Here we used mass spectrometry to detect L-2HG in serum samples from pancreatic cancer patients, comprising tumor cells as well as stromal cells. Both hypoxic pancreatic tumors as well as serum from pancreatic cancer patients accumulated L-2HG as a result of promiscuous activity of LDHA. This abnormally accumulated L-2HG led to H3 hypermethylation and altered gene expression, which regulated a critical balance between stemness and differentiation in pancreatic tumors. Secreted L-2HG inhibited T cell proliferation and migration, suppressing anti-tumor immunity. In a syngeneic orthotopic model of pancreatic cancer, inhibition of LDHA with GSK2837808A decreased L-2HG, induced tumor regression, and sensitized tumors to anti-PD1 therapy. In conclusion, hypoxia-mediated promiscuous activity of LDHA produces L-2HG in pancreatic tumor cells, regulating the stemness-differentiation balance and contributing to immune evasion. Targeting LDHA can be developed as a potential therapy to sensitize pancreatic tumors to checkpoint inhibitor therapy