Carbonic anhydrases in normal gastrointestinal tract and gastrointestinal tumours

Carbonic anhydrases (CAs) catalyse the hydration of C02 to bicarbonate at physiological pH. This chemical interconversion is crucial since HCO3- is the substrate for several biosynthetic reactions. This review is focused on the distribution and role of CA isoenzymes in both normal and pathological gastrointestinal (GI) tract tissues. It has been known for many years that CAs are widely present in the GI tract and play important roles in several physiological functions such as production of saliva, gastric acid, bile, and pancreatic juice as well as in absorption of salt and water in intestine. New information suggests that these enzymes participate in several processes that were not envisioned earlier. Especially, the recent reports on plasma membrane-bound isoenzymes IX and XII have raised considerable interest since they were reported to participate in cancer invasion and spread. They are induced by tumour hypoxia and may also play a role in von Hippel-Lindau (VHL)-mediated carcinogenesis.

Impact of tumour rupture risk on the oncological rationale for the surgical treatment choice of gastrointestinal stromal tumours

Tumour rupture of gastrointestinal stromal tumours(GISTs)has been considered to be a remarkable risk factor because of its unfavourable impact on the oncological outcome.Although tumour rupture has not yet been included in the current tumor-node-metastasis classification of GISTs as a prognostic factor,it may change the natural history of a low-risk GIST to a high-risk GIST.Originally,tumour rupture was defined as the spillage or fracture of a tumour into a body cavity,but recently,new definitions have been proposed.These definitions distinguished from the prognostic point of view between the major defects of tumour integrity,which are considered tumour rupture,and the minor defects of tumour integrity,which are not considered tumour rupture.Moreover,it has been demonstrated that the risk of disease recurrence in R1 patients is largely modulated by the presence of tumour rupture.Therefore,after excluding tumour rupture,R1 may not be an unfavourable prognostic factor for GISTs.Additionally,after the standard adjuvant treatment of imatinib for GIST with rupture,a high recurrence rate persists.This review highlights the prognostic value of tumour rupture in GISTs and emphasizes the need to carefully take into account and minimize the risk of tumour rupture when choosing surgical strategies for GISTs.

Gastrointestinal stromal tumour of the rectum: Report of a case and review of literature

Gastrointestinal stromal tumour （GIST） is a rare tumour of the gastrointestinal tract which does not generally originate in the rectum. The authors describe a case of a 70-year-old man who underwent an anterior resection of the rectum for a low-risk GIST. The patient was not given adjuvant chemotherapy with imatinib and is still disease-free 30 mo after surgery. The authors conclude that although rectal GIST is extremely uncommon, it should be included in differential diagnosis when a tumour in the rectum is detected. Biopsy of the tumour is essential, since this makes it possible to reach a sure preoperative diagnosis based on the immunohistological features of the CDl17 and CD34. Although complete surgical resection with negative tumour margins is the principal curative procedure for primary and nonmetastatic tumours, further studies are still needed for the determination of the most effective treatment strategy for patients with rectal GIST.

Mucinous cyst exhibiting severe dysplasia in gastric heterotopic pancreas associated withe gastrointestinal stromal tumour

Heterotopic pancreatic tissue within the stomach is rare and dysplasia within heterotopic pancreatic tissue is very rare. We present the first report of a patient with concurrent occurrence of heterotopic pancreas in the stomach with a gastrointestinal stromal tumour.

Imaged guided surgery during arteriovenous malformation of gastrointestinal stromal tumor using hyperspectral and indocyanine green visualization techniques:A case report

BACKGROUND This case report demonstrates the simultaneous development of a gastrointestinal stromal tumour(GIST)with arteriovenous malformations(AVMs)within the jejunal mesentery.A 74-year-old male presented to the department of surgery at our institution with a one-month history of abdominal pain.Contrast-enhanced computed tomography revealed an AVM.During exploratory laparotomy,hyperspectral imaging(HSI)and indocyanine green(ICG)fluorescence were used to evaluate the extent of the tumour and determine the resection margins.Intraoperative imaging confirmed AVM,while histopathological evaluation showed an epithelioid,partially spindle cell GIST.CASE SUMMARY This is the first case reporting the use of HSI and ICG to image GIST intermingled with an AVM.The resection margins were planned using intraoperative analysis of additional optical data.Image-guided surgery enhances the clinician’s knowledge of tissue composition and facilitates tissue differentiation.CONCLUSION Since image-guided surgery is safe,this procedure should increase in popularity among the next generation of surgeons as it is associated with better postoperative outcomes.

Ampullary somatostatinomas and jejunal gastrointestinal stromal tumor in a patient with Von Recklinghausen's disease

Von Recklinghausen＇s disease is an autosomal dominant hereditary disease associated with a wide number of neoplasms. We report a case of a 47-year-old Caucasian male affected by Von Recklinghausen＇s disease who developed a malignant somatostatinoma of the papilla major and minor associated with jejunal gastrointestinal stromal tumour with uncertain behaviour. At laparotomy, multiple hepatic metastases were evident. Whipple pancreaticoduodenectomy, jejunal resection, extensive lymphadenectomy and multiple hepatic wedge resections were performed. The patient was alive without recurrence after 24 mo. This is the fourth case reported in the world literature of a patient with Von Recklinghausen＇s disease associated with periampuUary somatostatinomas and jejunal stromal tumor. In patients with Von Recklinghausen＇s disease who complain of gastrointestinal symptoms, a high suspicion index for periampullary endocrine tumours and/or gastrointestinal stromal tumour is required. An aggressive surgical approach seems to give long term survival also in metastatic patients.

Tunneled biopsy is an underutilised,simple,safe and efficient method for tissue acquisition from subepithelial tumours

BACKGROUND Tissue acquisition from subepithelial lesions is often attempted by endoscopic ultrasound(EUS)-sampling as conventional endoscopic biopsy usually fails to reach deeper layers of the gastrointestinal wall.AIM To investigate the utilisation,safety and diagnostic yield of an intensified“biteon-bite”tunnel biopsy technique.METHODS In this retrospective cohort study,all patients presenting with subepithelial masses in the upper gastrointestinal tract from March 2013 to July 2019 were included.Data were analysed for size and location of the subepithelial mass,use of intensified tunnel biopsy protocol(more than 10 double bite-on-bite biopsies)or superficial conventional biopsies,histology and imaging results,occurrence of readmission and adverse events after endoscopy.RESULTS Two hundred and twenty-nine patients with subepithelial lesions were included.Superficial conventional biopsies were taken in 117 patients and were diagnostic only in one lipoma(0.9%).Tunnel biopsies taken in 112/229(48.9%)patients were significantly more likely to provide histological diagnosis(53.6%;P<0.001).For lesions≥10mm the diagnostic yield of tunnel biopsies further increased to 41/67(61.2%).No immediate or delayed complications were reported.Only 8 of the 51 endoscopists(15.7%)regularly attempted tunnel biopsies.CONCLUSION Tunnel biopsy is a simple,safe and efficient but underutilised diagnostic modality for tissue acquisition in subepithelial masses.It should be routinely attempted at the initial endoscopy.

Effect of preoperative immunonutrition and other nutrition models on cellular immune parameters

AIM:To evaluate the effects of preoperative immunonutrition and other nutrition models on the cellular immunity parameters of patients with gastrointestinal tumors before surgical intervention.In addition,effects on postoperative complications were examined. METHODS:Patients with gastrointestinal tumors were randomized into 3 groups.The immunonutrition group received a combination of arginine,fatty acids and nucleotides.The second and third group received normal nutrition and standard enteral nutrition,respectively.Nutrition protocols were administered for 7 d prior to the operation.Nutritional parameters,in particular prealbumin levels and lymphocyte subpopulations(CD4+,CD8+,CD16+/56+,and CD69 cells)were evaluated before and after the nutrition protocols.Groups were compared in terms of postoperative complications and duration of hospital stay. RESULTS:Of the 42 patients who completed thestudy,16 received immunonutrition,13 received normal nutrition and 13 received standard enteral nutrition. prealbumin values were low in every group,but this parameter was improved after the nutritional protocol only in the immunonutrition group(13.64±8.83 vs 15.98±8.66,P=0.037).Groups were similar in terms of CD4+,CD16+/56,and CD69+prior to the nutritional protocol;whereas CD8+was higher in the standard nutrition group compared to the immunonutrition group.After nutritional protocols,none of the groups had an increase in their lymphocyte subpopulations.Also,groups did not differ in terms of postoperative complications and postoperative durations of hospital stay. CONCLUSION:Preoperative immunonutrition provided a significant increase in prealbumin levels,while it did not significantly alter T lymphocyte subpopulation counts,the rate of postoperative complications and the duration of hospital stay.

Histopathological landscape of rare oesophageal neoplasms

The landscape of neoplastic pathology of the oesophagus is dominated by malignancies of epithelial origin,in particular by oesophageal adenocarcinoma and oesophageal squamous cell carcinoma.However,several other histopathological variants can be distinguished,some associated with peculiar histopathological profiles and prognostic behaviours and frequently underrecognized in clinical practice.The aim of this review is to provide a comprehensive characterization of the main morphological and clinical features of these rare variants of oesophageal neoplastic lesions.

Contrast-enhanced harmonic endoscopic ultrasound imaging: Basic principles, present situation and future perspectives

Over the last decade, the development of stabilised microbubble contrast agents and improvements in available ultrasonic equipment, such as harmonic imaging, have enabled us to display microbubble enhancements on a greyscale with optimal contrast and spatial resolution. Recent technological advances made contrast harmonic technology available for endoscopic ultrasound(EUS) for the first time in 2008. Thus, the evaluation of microcirculation is now feasible with EUS, prompting the evolution of contrast-enhanced EUS from vascular imaging to images of the perfused tissue. Although the relevant experience is still preliminary, several reports have highlighted contrast-enhanced harmonic EUS(CHEUS) as a promising noninvasive method to visualise and characterise lesions and to differentiate benign from malignant focal lesions. Even if histology remains the gold standard, the combination of CH-EUS and EUS fine needle aspiration(EUS-FNA) can not only render EUS more accurate but may also assist physicians inmaking decisions when EUS-FNA is inconclusive,increasing the yield of EUS-FNA by guiding the puncture with simultaneous imaging of the vascularity.The development of CH-EUS has also opened up exciting possibilities in other research areas,including monitoring responses to anticancer chemotherapy or to ethanolinduced pancreatic tissue ablation,anticancer therapies based on ultrasound-triggered drug and gene delivery,and therapeutic adjuvants by contrast ultrasound-induced apoptosis.Contrast harmonic imaging is gaining popularity because of its efficacy,simplicity and noninvasive nature,and many expectations are currently resting on this technique.If its potential is confirmed in the near future,contrast harmonic imaging will become a standard practice in EUS.

A ruptured recurrent small bowel gastrointestinal stromal tumour causing hemoperitoneum

Hemoperitoneum is a rare and potentially life-threatening complication of GIST. We reported a 54- year-old man who developed disseminated intra-abdominal recurrence from a previously resected gastrointestinal stromal tumour （GIST） of the small bowel, and the patient presented with hemoperitoneum. Emergent debulking surgery was performed. A high dose imatinib was prescribed. Despite the presence of residual disease, the patient was well clinically 8 months after the operation. Even though, there is no evidence to support the routine use of debulking surgery in the management of GIST. In our patient, disease progression after second line targeted therapy and the absence of alternative treatment options for spontaneous rupture and hemoperitoneum prompted us to treat the patient aggressively. Resection of the ruptured GIST was carried out for control of bleeding and to prevent recurrent bleeding in this patient with good surgical risks. During the treatment decision-making, the patient＇s general condition, the risk of surgery and the extent of dissemination were taken into consideration. In this patient who presented with spontaneous rupture of a small intestinal GIST, the novel use of targeted therapy and aggressive surgical treatment produced reasonably good survival outcome.

Genetic characteristics of a patient with multiple primary cancers:A case report

BACKGROUND Two or multiple primary malignant neoplasms(MPMNs)rarely occur in the same patient.It has been reported that MPMNs are easily misdiagnosed as the recurrence or metastasis of malignancies in clinical practice,affecting the choice of treatment for the patients,thereby resulting in the delay of optimal diagnosis.Next generation sequencing(NGS)can be used to distinguish between multiple primary lung cancers and intrapulmonary metastasis,and may distinguish the origin of tumours in different sites of the body.CASE SUMMARY We report the case of 66-year-old woman who suffered from different malignant neoplasms in the rectum and esophageal and gastrointestinal tract.The first neoplasm rectal adenocarcinoma was diagnosed and removed in 2016.The second and third lesions were diagnosed with esophageal squamous-cell carcinoma(ESCC)and gastrointestinal stromal tumour(GIST),respectively,in 2019.Nextgeneration whole exome sequencing was performed on the tissue specimens of rectal carcinoma,esophageal cancer,GIST,and white blood cells to investigate the relationship between malignancies at different timeframe and determine whether the ESCC and GIST evolved from the rectal adenocarcinoma.Mutations including v-Ki-ras2-Kirsten rat sarcoma viral oncogene homolog,adenomatosis polyposis coli,and mothers against decapentaplegic homolog 4 were detected in rectal adenocarcinoma sample,mast/stem cell growth factor receptor was detected in GIST tissue,and lysine methyltransferase 2D was detected in ESCC specimen.Overall,ESCC and GIST were not genetically evolved from rectal adenocarcinoma,and this patient did not have a trunk driven clone.CONCLUSION NGS is an effective tool to study clonal evolution of tumours and distinguish between MPMNs and intrapulmonary metastasis.

Excitation-emission matrices （EEMs） of colorectal tumors- tool for spectroscopic diagnostics of gastrointestinal neoplasia

The autofluorescence spectroscopy of biologi- cal tissues is a powerful tool for non-invasive detection of tissue pathologies and evaluation of any biochemical and morphological changes arising during the lesions＇ growth. To obtain a full picture of the whole set of endogenous fluorophores appearing in the gastrointestinal （GI） tumors investigated, the technique of excitation-emission matrix （EEM） development was applied in a broad spectral region, covering the ultraviolet and visible spectral ranges. We could thus address a set of diagnostically-important chromophores and their alterations during tumor develop- ment, namely, collagen, elastin, nicotinamide adenine dinucleotide （NADH）, flavins, porphyrins, while hemo- globin＇s absorption influence on the spectra obtained could be evaluated as well. Comparisons are presented between EEM data of normal mucosae, benign polyps and malignant carcinoma, and the origins are determined of the fluorescence signals forming these matrices.