Gastrointestinal Neoplasia Research Articles

Surgical Management of Colonic Adenocarcinoma in a Rat (Rattus norvegicus)

A 9-month-old female Dumbo rat (Rattus norvegicus) was evaluated for a 24-hour history of obstipation. A general physical examination revealed a large irregular abdominal mass, extending caudally from mid-abdomen to the pelvis. The mass had a firm central region with a compressible periphery. Radiographic imaging confirmed severe intestinal distention, but failed to delineate a discrete mass. Following 3 days of unsuccessful medical therapy for possible colonic impaction, surgical intervention was elected. A colocolic resection and anastomosis was completed to remove 7cm of the colon, including the 5cm mass and 1cm of grossly normal appearing colon proximal and distal to the mass. Histology confirmed colonic adenocarcinoma. The rat lived for 2 years, following colonic resection and anastomosis, uncomplicated by gastrointestinal neoplasia or metastatic disease and was euthanized due to unrelated quality of life issues. Necropsy revealed no evidence of colonic tumor recurrence or metastatic disease.

Feasibility of a Newly Developed Thumb Control Device for Simultaneous Manipulation of the Endoscope and Treatment Devices in Endoscopic Submucosal Dissection: A Clinical Feasibility Study

Background/Aim: We developed a new device for the simultaneous manipulation of an endoscope and treatment devices, which we named the Smart Shooter®. The aim of this study was to validate the feasibility of using the Smart Shooter® in endoscopic submucosal dissection (ESD). Methods: This pilot feasibility study conducted between March and June 2014 involved 20 consecutive patients who underwent ESD for superficial gastrointestinal neoplasia. The primary endpoint was a serious adverse event during the ESD procedure. The secondary endpoints were completion rate of ESD using the Smart Shooter® and a mechanical problem with the Smart Shooter® during ESD. Results: A total of 20 patients underwent ESD for 23 lesions: 5 pharyngeal, 8 esophageal, 7 gastric, and 3 colonic lesions. There were no serious adverse events or mechanical problems during ESD. The completion rate of ESD using the Smart Shooter® was 82.6% (19/23). Conclusion: ESD using the Smart Shooter® appears to be technically feasible. Clinical trial registration: UMIN 000013710.

Deletion of IQGAP1 promotes Helicobacter pylori-induced gastric dysplasia in mice and acquisition of cancer stem cell properties in vitro.

Helicobacter pylori infection is responsible for gastric carcinogenesis but host factors are also implicated. IQGAP1, a scaffolding protein of the adherens junctions interacting with E-cadherin, regulates cellular plasticity and proliferation. In mice, IQGAP1 deficiency leads to gastric hyperplasia. The aim of this study was to elucidate the consequences of IQGAP1 deletion on H. pylori-induced gastric carcinogenesis.Transgenic mice deleted for iqgap1 and WT littermates were infected with Helicobacter sp., and histopathological analyses of the gastric mucosa were performed. IQGAP1 and E-cadherin expression was evaluated in gastric tissues and in gastric epithelial cell lines in response to H. pylori infection. The consequences of IQGAP1 deletion on gastric epithelial cell behaviour and on the acquisition of cancer stem cell (CSC)-like properties were evaluated. After one year of infection, iqgap1+/- mice developed more preneoplastic lesions and up to 8 times more gastro-intestinal neoplasia (GIN) than WT littermates. H. pylori infection induced IQGAP1 and E-cadherin delocalization from cell-cell junctions. In vitro, knock-down of IQGAP1 favoured the acquisition of a mesenchymal phenotype and CSC-like properties induced by H. pylori infection.Our results indicate that alterations in IQGAP1 signalling promote the emergence of CSCs and gastric adenocarcinoma development in the context of an H. pylori infection.

Prediction of Poor Response to Modified Neuroleptanalgesia with Midazolam for Endoscopic Submucosal Dissection for Esophageal Squamous Cell Carcinoma

Background/Aims: Modified neuroleptanalgesia (m-NLA) with midazolam is often used for sedation and analgesia during endoscopic submucosal dissection (ESD) for gastrointestinal neoplasia. However, interruption due to poor response to midazolam is often experienced during ESD for esophageal squamous cell carcinoma (ESCC) because most patients with ESCC have a history of heavy alcohol intake. We examined the incidence and risk factors for poor response to m-NLA with midazolam and pethidine hydrochloride. Methods: This retrospective cross-sectional study was conducted at a single institution. Between April 2007 and July 2013, 151 patients with superficial ESCC who underwent ESD under sedation using m-NLA with midazolam and pethidine hydrochloride were enrolled. Poor response to sedation was defined as the use of a second drug when Ramsay Sedation Score 1-2. Results: Poor response to sedation occurred in 66.2% patients. Most cases of poor response were controlled by using additional flunitrazepam. Multivariate logistic regression analysis showed that cumulative alcohol intake and major specimen size were independent risk factors for poor response to sedation (OR 3.63, 95% CI 1.20-10.99, and OR 3.23, 95% CI 1.26-8.25). Conclusion: Our study indicated that cumulative alcohol intake and major specimen size were associated with poor response to m-NLA with midazolam and pethidine hydrochloride.

Chronic Vomiting in Cats: Etiology and Diagnostic Testing.

Chronic vomiting in cats is a common presenting problem seen in veterinary practice today. The initial step when presented with a vomiting patient is to differentiate between vomiting and regurgitation or dysphagia. There are numerous causes for chronic vomiting in cats, and therefore a detailed and comprehensive patient history and a systematic diagnostic approach are key steps in determining the cause for vomiting and the most appropriate treatment plan. Common causes for chronic vomiting in cats may include inflammatory bowel disease, food allergy, gastrointestinal motility disorders, neoplasia, and extra-gastrointestinal diseases, such as renal disease, hepatobiliary disease, and hyperthyroidism.

Association Between Nutritional Status, Inflammatory Condition, and Prognostic Indexes with Postoperative Complications and Clinical Outcome of Patients with Gastrointestinal Neoplasia

ABSTRACTThe aim of this study is to describe and relate nutritional and inflammatory status and prognostic indexes with postoperative complications and clinical outcome of patients with gastrointestinal malignancies. Twenty-nine patients were evaluated; nutritional assessment was carried out by subjective and objective parameters; albumin, pre-albumin, C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP) were determined. To assess prognosis, the Glasgow scale, the Prognostic Inflammatory Nutritional Index (PINI), and CRP/albumin ratio were used; the clinical outcomes considered were hospital discharge and death. A high Subjective Global Assessment (SGA) score was associated with the occurrence of postoperative complications: 73% of the patients with postoperative complications had the highest SGA score, but only 6% of those without postoperative complications had the highest SGA score (P < 0.001). Greater occurrence of death was observed in patients with a high SGA score, low serum albumin, increased CRP, PINI > 1, and Glasgow score 2. There was a positive correlation between weight loss percentage with serum CRP levels (P = 0.002), CRP/albumin (P = 0.002), PINI (P = 0.002), and Glasgow score (P = 0.000). This study provides evidence that the assessment of the nutritional status and the use of prognostic indexes are good tools for predicting postoperative complications and clinical outcome in patients with gastrointestinal neoplasia.

Serum cobalamin concentrations and small intestinal ultrasound changes in 75 cats with clinical signs of gastrointestinal disease: a retrospective study.

Objectives The aim of the study was to evaluate ultrasonographic changes in the small intestine of cats with clinical signs of gastrointestinal disease and low or low-normal serum cobalamin concentrations. Methods Records for client-owned cats presenting to the small animal hospital with signs of gastrointestinal disease and in which serum cobalamin concentrations were measured from 2000-2013 were reviewed. Inclusion criteria were cobalamin concentrations <500 ng/l, abdominal ultrasound within 1 month of cobalamin testing and definitive diagnosis. Results Of 751 serum cobalamin measurements, hypocobalaminemia or low-normal cobalamin was identified in 270 cats, abdominal ultrasound was performed in 207 of those cats and a diagnosis was available for 75 of them. Small intestinal ultrasound changes were detected in 49/75 (65%) cats. Abnormalities included thickening, loss of wall layer definition, echogenicity alterations and discrete masses. Serum cobalamin concentrations <500 ng/l were observed with diagnoses of inflammatory disease, neoplasia, infectious disease and normal histopathology. Cobalamin concentration was significantly lower in cats with lymphoma or inflammatory bowel disease compared with other gastrointestinal neoplasia ( P = 0.031). No difference was found between cobalamin concentration and the presence of ultrasound abnormalities, specific ultrasound changes or albumin concentration. Conclusions and relevance One-third of symptomatic cats with hypocobalaminemia or low-normal cobalamin concentrations may have an ultrasonographically normal small intestine. For the majority of cats in this study, histopathologic abnormalities were observed in the small intestine, regardless of ultrasound changes. These findings suggest gastrointestinal disease should not be excluded based on low-normal cobalamin concentrations, even with a concurrent normal ultrasound examination. Additional studies are needed in cats with low-normal serum cobalamin concentrations, as a definitive diagnosis was not pursued consistently in those cats. However, data from this study suggest that careful monitoring, histopathologic evaluation and future cobalamin supplementation may be warranted.

Long Term Outcome of Routine Image-enhanced Endoscopy in Newly Diagnosed Head and Neck Cancer: a Prospective Study of 145 Patients.

Synchronous second primary tumors (SPTs), especially esophageal squamous cell neoplasia (ESCN), in patients with head and neck squamous cell carcinoma (HNSCC) are not uncommon. Image-enhanced endoscopy (IEE) screening may identify SPTs while there is no evidence to support its benefit. We prospectively recruited an adult cohort with newly-diagnosed HNSCC for IEE screening of upper gastrointestinal (UGI) tract neoplasia. 145 HNSCC patients were recruited. 22 (15.2%) patients had synchronous UGI tract neoplasia, including 20 ESCNs and 2 gastric adenocarcinoma. At a median follow-up of 2.72 (±1.73) years, the 3-year overall survival (OS) rate was 0.71. HNSCC patients with synchronous ESCN/UGI tract neoplasia had poorer prognosis than those without (multivariate analysis, hazard ratio [HR] 2.75/2.79, 95% confidence interval [CI] 1.11~6.82/1.15~6.80, p = 0.03/0.02). HNSCC patients with advanced (stage III&IV) ESCN had worst survivals (p < 0.001). Among those with synchronous ESCNs, hypopharyngeal cancers were associated with poorer prognosis when compared with oral cancers (HR 2.36, 95% CI 1.08~5.15, p = 0.03). IEE screening for UGI SPTs in HNSCC patients could be used for risk stratification and prognosis prediction. HNSCC patients with advanced ESCN had the worst prognosis. Further studies are needed to demonstrate the survival benefits from IEE screening.

Endoscopic strategies in minimal invasive therapy

Due to higher detection rates of early gastrointestinal neoplasia endoscopic resection of early GI cancers or precancerous lesions is increasing. Endoscopic piece-meal resection (EMR) remains the standard technique for the endoscopic resection of large sessile colorectal adenomas. Cap-assisted EMR techniques show excellent long-term results in the endoscopic therapy of neoplastic Barrett's esophagus. For the endoscopic resection of early gastrointestinal cancers of more than 2 cm endoscopic submucosal dissection (ESD) is the method of choice. The value of endoscopic full thickness resection in the therapy of GI tumors remains to be seen.

Sa2035 Fiber-Optic Raman Spectroscopy for Label-Free In Vivo Molecular Diagnostics of Gastrointestinal Neoplasia at Endoscopy

Sa2035 Fiber-Optic Raman Spectroscopy for Label-Free In Vivo Molecular Diagnostics of Gastrointestinal Neoplasia at Endoscopy

Gastrointestinal Findings in the Largest Series of Patients With Hereditary Biallelic Mismatch Repair Deficiency Syndrome: Report from the International Consortium.

Hereditary biallelic mismatch repair deficiency (BMMRD) is caused by biallelic mutations in the mismatch repair (MMR) genes and manifests features of neurofibromatosis type 1, gastrointestinal (GI) polyposis, and GI, brain, and hematological cancers. This is the first study to characterize the GI phenotype in BMMRD using both retrospective and prospective surveillance data. The International BMMRD Consortium was created to collect information on BMMRD families referred from around the world. All patients had germline biallelic MMR mutations or lack of MMR protein staining in normal and tumor tissue. GI screening data were obtained through medical records with annual updates. Thirty-five individuals from seven countries were identified with BMMRD. GI data were available on 24 of 33 individuals (73%) of screening age, totaling 53 person-years. The youngest age of colonic adenomas was 7, and small bowel adenoma was 11. Eight patients had 19 colorectal adenocarcinomas (CRC; median age 16.7 years, range 8-25), and 11 of 18 (61%) CRC were distal to the splenic flexure. Eleven patients had 15 colorectal surgeries (median 14 years, range 9-25). Four patients had five small bowel adenocarcinomas (SBC; median 18 years, range 11-33). Two CRC and two SBC were detected during surveillance within 6-11 months and 9-16 months, respectively, of last consecutive endoscopy. No patient undergoing surveillance died of a GI malignancy. Familial clustering of GI cancer was observed. The prevalence and penetrance of GI neoplasia in children with BMMRD is high, with rapid development of carcinoma. Colorectal and small bowel surveillance should commence at ages 3-5 and 8 years, respectively.

Retrospective evaluation of recurrent secondary septic peritonitis in dogs (2000-2011): 41 cases.

To describe the clinical characteristics of recurrent septic peritonitis in dogs. Multicenter retrospective observational study. Client-owned dogs with recurrent septic peritonitis. Three university emergency and referral hospitals. None. Medical records from 3 veterinary university teaching hospitals were reviewed and data were collected using a standardized data collection sheet for all cases of septic peritonitis during the study period (2000-2011). Forty one dogs met the inclusion criteria for recurrent peritonitis. All dogs underwent relaparotomy. The original cause of septic peritonitis in these cases included previous surgery for gastrointestinal foreign body removal (n = 26), gastrointestinal neoplasia (n = 3), gastric or duodenal ulceration (n = 3), biliary tract leakage (n = 2), and single instance for each of the following: penetrating foreign body, hernia strangulation, intussusception, mesenteric volvulus, infection of the laparotomy incision, prostatic abscess, and trauma. Eighteen animals survived to discharge. There was no difference detected between survivors and nonsurvivors with recurrent peritonitis in terms of inciting cause, serum albumin concentration, surgical management, or provision of appropriate initial antimicrobials. The survival rate for dogs having recurrent peritonitis was 43.9% (18/41 dogs). This retrospective study did not identify any significant prognostic indicators for dogs with recurrent peritonitis and that the mortality rate for dogs having more than one surgery for septic peritonitis is similar to that reported for a single surgery for septic peritonitis.

Streptococcus bovis infectious endocarditis and occult gastrointestinal neoplasia: experience with 25 consecutive patients treated surgically.

To assess the prevalence of gastrointestinal neoplasia in patients with Streptococcus bovis infectious endocarditis we performed a retrospective cohort analysis of all episodes of S. bovis infectious endocarditis treated at our institution between January 2000 through December 2014. Twenty-five patients were identified for this purpose. 12/25 patients received colonoscopy and 1/25 of the patients was assessed with CT colonography. Of the 13 who underwent colonic assessment, 11 were diagnosed with colonic neoplasms at different stages of development. In the absence of any strong contraindication, gastroenteroscopic evaluation in all patients diagnosed with S. bovis infectious endocarditis should be pursued.

Lgr5-expressing stem cells are not the cells of origin of pyloric neuroendocrine carcinomas in mice.

In intestinal and pyloric epithelia, leucine-rich repeat-containing G protein-coupled receptor 5 (Lgr5)-expressing cells represent long-lived adult stem cells that give rise to all epithelial cell types, including endocrine cells. Ablation of the Apc gene in Lgr5-expressing cells leads to intestinal and pyloric adenomas. To assess whether all epithelial tumours of the gastrointestinal tract are derived from LGR5-positive stem cells, we crossed Lgr5-EGFP-IRES-creER(T2) mice, which express EGFP and Cre recombinase driven by the Lgr5 promoter, with CEA424-SV40-TAg mice, which develop pyloric neuroendocrine carcinomas of epithelial origin. In 19 day-old mice, single SV40 T antigen (TAg)-positive cells were identified preferentially at the the bases of pyloric glands, close to the stem cell compartment. However, contrary to previous publications describing subpopulations of LGR5-positive cells in gastrointestinal neoplasia, we could not detect Lgr5-EGFP-positive tumour cells in malignant lesions. The lack of expression of the Wnt target gene Lgr5 is probably not caused by suppression of Wnt signalling by TAg, since β-catenin-mediated Wnt signalling, as measured by the TOPflash assay, was not inhibited. To determine the cellular origin of CEA424-SV40-TAg tumours, we performed tracing experiments using Lgr5-EGFP-IRES-creERT2:CEA424-SV40-TAg:ROSA26-tdRFP mice. Following tamoxifen induction, it was possible to efficiently trace the progeny of Lgr5-expressing cells in gastrointestinal tissue via red fluorescent protein (RFP) expression. No RFP-positive tumour cells were detected, even when RFP gene activation occurred in 7 day-old mice well before the appearance of TAg-positive tumour cells. Hence, we conclude that Lgr5-expressing stem cells probably do not constitute the cells of origin in CEA424-SV40-TAg mice. Consequently, not all epithelial tumours in the pyloric region are initiated by transformation of LGR5-positive stem cells. Thus, additional long-lived LGR5-negative stem cells or progenitor cells with a low turnover rate might exist in the pyloric region, which could give rise to tumours.

Differences in the pathological diagnosis of colorectal neoplasia between the East and the West: Present status and future perspectives from Japan

It is well known that there are discrepancies in the diagnosis of gastrointestinal neoplasia between Western and Japanese pathologists. In the West, colorectal cancer (CRC) is defined by invasion through the muscularis mucosa into the submucosa, especially depending on the presence of desmoplasia. In Japan, however, CRC is defined based on a combination of nuclear and architectural abnormalities, regardless of invasion status. As a result, intramucosal carcinoma is diagnosed as high-grade dysplasia and even intramucosal carcinoma with poorly differentiated component is classified as 'Tis' in the West. It is logical and reasonable that the term 'T1' is used to currently describe intramucosal carcinoma. Use of the term 'high-grade dysplasia' for intramucosal CRC is outdated. In order to determine appropriate clinical treatment of CRC, the various risk factors of metastasis should be fully evaluated. With improved contributions and communication between pathologists and clinicians, overtreatment and inadequate follow up can be avoided. The discrepancies in the diagnosis of CRC between Western and Japanese pathologists may be addressed by an increase in East-West exchange. In addition, in the future, molecular analysis may also be useful for establishment of standardized diagnostic criteria of CRC.

MALNUTRITION IN PATIENTS WITH GASTROINTESTINAL CANCER: EFFECTIVENESS OF DIFFERENT DIAGNOSTIC METHODS.

to estimate the effectiveness of methods for identifying the risk and/or presence of malnutrition in individuals with gastrointestinal neoplasia. participated 143 patients with gastrointestinal cancer, cared for in the Oncology Clinic Infirmary of "Hospital Amaral Carvalho" (Jaú-SP). Excluded from the study were patients hospitalized in the intensive care unit, in a terminal state or those who had members amputated; those who had received blood transfusions during the last month; significant clinical bleeding; received endovenous albumin and uncontrolled infection. The nutritional status was classified according to the ratio between Real Weight and Habitual Weight, Body Mass Index, Nutritional Risk Index and Percent Adequacy. As the gold standard method the Scored Patient-Generated Subjective Global Assessment was used. The effectiveness of the methods for detecting the risk for or presence of malnutrition was evaluated. A ROC curve was constructed and its area (AUROC) was estimated. The areas were compared using z statistics. For each method the best cut-off point was established. of the patients, 74.1% presented an advanced stage of the disease, and 83.2% were undergoing chemotherapy treatment. All the methods showed adequate discriminatory capacity for detecting the risk of malnutrition and presence of malnutrition. The BMI was significantly better for detecting malnutrition than for the risk of malnutrition. The RW/HW was significantly better for detecting the risk of malnutrition than the other methods. The cut-off points were slightly lower than those recommended for the normative population for the methods RW/HW, NRI and Score %. For the BMI the cut-off point was higher than the recommended for the normative population. the methods for evaluating nutritional status showed adequate discriminatory capacity for the risk of malnutrition and presence of malnutrition in patients with gastrointestinal cancer.

Is there a need to shield ulcers after endoscopic submucosal dissection in the gastrointestinal tract?

Is there a need to shield ulcers after endoscopic submucosal dissection in the gastrointestinal tract?

Use of confocal laser endomicroscopy to assess the adequacy of endoscopic treatment of gastrointestinal neoplasia: a systematic review and meta-analysis.

Evaluation of the adequacy of endoscopic mucosal resection (EMR) of gastrointestinal lesions remains challenging by use of conventional endoscopy. Confocal laser endomicroscopy (CLE) is a novel imaging technique, designed to provide in vivo histology, and facilitate diagnosis with real-time intervention. We undertook a systematic review of the available literature, exploring the role of CLE in assuring completeness of EMR of gastrointestinal lesions. The number of pertinent studies is very limited, including only 1 randomized controlled study and 2 prospective comparative case series. Per-lesion meta-analysis showed that the sensitivity of CLE for detection of residual neoplasia was 91% (95% confidence interval, 82.5%-96%) with specificity of 69% (95% confidence interval, 61%-77%), with significant heterogeneity noted in all outcomes. In conclusion, the evidence underpinning the usefulness of CLE in ensuring adequate EMR of gastrointestinal neoplasia is currently very weak, with limited promising results related to gastric and colorectal polyp resections.

Could preoperative and postoperative optimal nutrition support modulate the inflammatory response and clinical outcome of severe malnourished surgical patients with gastrointestinal neoplasia?

Our aim was to assess whether perioperative and postoperative optimal 7-day nutrition support could modulate the inflammatory status and clinical outcome of severe malnourished patients with surgery for gastrointestinal neoplasia.

A Case of an Ileal Inflammatory Fibroid Polyp Causing Intestinal Intussusception

Inflammatory fibroid polyp (IFP) usually appears as a solitary benign lesion, rarely located in the ileum. The clinical presentation varies according to its location, frequently they are mistaken as gastrointestinal (GI) neoplasia. Intussusception and obstruction are the most frequent initial symptoms when the polyp is located in the small intestine. A thirty nine years old man presented with upper abdominal pain. Though he prescribed anti biotic medicine, his intermittent pain continued. He presented to hospital two days later, and abdominal ultrasound (US) detected intestinal intussusception. Abdominal computed tomography (CT) and oral ileal barium study also revealed ileal mass. So he had partial ilectomy on the seventh hospital day. Pathology showed it IFP in small intestine. Intussusception secondary to IFPs of the small intestine is difficult to diagnose without recognition of its clinical and pathological characteristics. Abdominal US is useful in confirming an anatomical abnormality, histological examination establishes the final diagnosis of IFPs. Abdominal US detected an intussusception with a mass lesion at its lead point.