Biosynthesized nanoparticles: a novel approach for cancer therapeutics.

Nanotechnology has become one of the most rapid, innovative, and adaptable sciences in modern science and cancer therapy. Traditional chemotherapy has limits owing to its non-specific nature and adverse side effects on healthy cells, and it remains a serious worldwide health issue. Because of their capacity to specifically target cancer cells and deliver therapeutic chemicals directly to them, nanoparticles have emerged as a viable strategy for cancer therapies. Nanomaterials disclose novel properties based on size, distribution, and shape. Biosynthesized or biogenic nanoparticles are a novel technique with anti-cancer capabilities, such as triggering apoptosis in cancer cells and slowing tumour growth. They may be configured to deliver medications or other therapies to specific cancer cells or tumour markers. Despite their potential, biosynthesized nanoparticles confront development obstacles such as a lack of standardisation in their synthesis and characterization, the possibility of toxicity, and their efficiency against various forms of cancer. The effectiveness and safety of biosynthesized nanoparticles must be further investigated, as well as the types of cancer they are most successful against. This review discusses the promise of biosynthesized nanoparticles as a novel approach for cancer therapeutics, as well as their mode of action and present barriers to their development.

Etiological spectrum of isolated ileo-cecal ulcers in patients with gastrointestinal symptoms.

Background: Isolated ileo-cecal region (ICR) ulcers may represent underlying Crohn's disease (CD), intestinal tuberculosis (ITB), bacterial infections (including typhoid), amoebiasis, eosinophilic enteritis, drug-induced sequelae, or neoplasm. Overlapping morphological and microscopic characteristics of many of these diseases make it challenging to unequivocally confirm a diagnosis. Aims: The aim of the study was to investigate the etiology and clinical outcomes of isolated ileo-cecal ulcers discovered during an ileocolonoscopy in patients with gastrointestinal symptoms. Methods: Patients with isolated ileo-cecal ulcers and symptoms within the age range of 10 - 80 years were included in the study (N = 100). Patients not giving consent (assent in case of a minor), with a prior diagnosis of tuberculosis or inflammatory bowel disease, with incomplete colonoscopy and associated colonic lesions other than ICR were excluded from the study. Demographics, clinical information, and relevant biochemical and serological tests were recorded. During the colonoscopy, multiple biopsies were taken from the ileo-cecal ulcers for histopathological examination. Repeat ileocolonoscopy was performed as needed in consenting patients. Results: The mean age and mean duration of symptoms were 36.0 ± 15.6 years and 18.8 ± 21.6 months, respectively. The majority of the patients presented with abdominal pain (59%), followed by diarrhea (47%), weight loss (20%), gastrointestinal bleeding (15%), and fever (11%). A history of taking nonsteroidal anti-inflammatory drugs was present in only 5% of the patients. Mean hemoglobin, C-reactive protein, and albumin levels were 11.6 ± 2.8 g/dL, 6.9 ± 9.5 mg/L, and 3.7 ± 0.8 g/dL, respectively. Based on clinical, colonoscopic, and histopathological findings, initial treatment was symptomatic/antibiotics in 55%, anti-tubercular treatment in 21%, 5-aminosalicylic acid/steroids for CD in 13%, oral budesonide in 10% of patients, and one patient was referred for management of malignancy. Final diagnoses after 8 - 24 weeks of follow-up were non-specific ileitis/colitis (45%), CD (20%), ITB (18%), infective (7%), eosinophilic ileitis/colitis (6%), non-steroidal anti-inflammatory drug-induced (2%), and amoebic and malignant in 1% of patients each. Conclusions: The majority of patients with ileo-cecal ulcers have specific etiologies. Non-specific ulcers at the ICR can be managed symptomatically; however, close follow-up is necessary as sometimes the ulcers may harbor an underlying specific disease. Relevance for Patients: Isolated ileo-cecal ulcers are common findings during colonoscopy in both symptomatic and asymptomatic patients. The majority of these ulcers harbor underlying significant diseases that can cause morbidity and mortality if left undiagnosed and untreated. Reaching a specific diagnosis in such cases is not straightforward, and patients are often subjected to repeat examinations.

Thromboembolism is associated with poor prognosis and high mortality in patients with inflammatory bowel disease: A case-control study.

BACKGROUND: The information on the risk of thromboembolism (TE) in inflammatory bowel disease (IBD) and its predictors are lacking, especially from developing countries. The present study evaluated the prevalence, predictors, and prognosis of TE in IBD. METHODS: This case-control study included 35 patients with IBD (ulcerative colitis [UC, n = 25]; Crohn's disease [CD], n = 10) and history of TE, from a cohort of 3597 patients (UC n = 2752, CD n = 845) under follow-up from 2005 to 2018. Details on demographics, extraintestinal manifestations (EIMs), patient status, type and outcomes of TE, treatment details, and disease course were compared with IBD patients without TE (age, gender, and duration of follow-up matched) in the ratio of 1:4. RESULTS: Prevalence of TE in IBD was 0.9% (UC-0.89%, CD-1.2%). Among TE patients (mean age: 34.9 ± 13.1 years, 48.6% males), median duration from diagnosis to TE was 12 (inter-quartile range [IQR]: 3-36) months, 37% had other EIMs, 94.1% had moderate/severe disease at time of TE, 62.8% had steroid-dependent/refractory disease, and 5 patients (14.2%) died because of disease-related complications. Lower limb was the commonest site (57.1%), 14.3% had pulmonary TE, and 31.4% had involvement of multiple sites. Phenotypically, more patients with TE (among UC) had steroid-dependent disease (60% vs. 25%, p = 0.001), pancolitis (76% vs. 36%, p = 0.002), chronic continuous disease course (44% vs. 19%, p = 0.009), and acute severe colitis (48% vs. 18%, p = 0.002), of which the latter three were also independent predictors of TE. CONCLUSION: Approximately 1% of patients with IBD develop thromboembolism relatively early during their disease course, and TE is associated with severe disease and higher disease-related complications including mortality.

Hypercalcemia - An enigmatic cause of acute pancreatitis.

Background: Acute pancreatitis (AP) continues to be one of the common abdominal emergencies encountered in tertiary care hospitals. The majority of AP is caused by gall stones and alcohol. Hypercalcemia though uncommon has been reported to cause AP, recurrent AP, and chronic pancreatitis (CP). Aim: The aim of this study was to describe hypercalcemia-induced AP in different settings. Materials and Methods: In total 100 patients with AP, admitted from January 2021 to December 2021 at our center, etiologies were biliary (36%), alcohol (19%), idiopathic (21%), alcohol plus Biliary (5%), post-endoscopic retrograde cholangiopancreaticography (7%), drug-induced (6%), hypercalcemia (3%), and dengue infection (3%). Overall mortality was 11%. Results: In three patients with hypercalcemia-induced pancreatitis, causes of hypercalcemia were multiple myeloma, parathyroid adenoma leading to hyperparathyroidism, and hypervitaminosis D in association with hyperthyroidism. Conclusion: Hypercalcemia-induced AP is not a rare phenomenon and should be actively investigated to prevent further attacks of AP and progression to CP. Relevance for Patients: Hypercalcemia is a potentially treatable cause of AP and its identification will not only help to treat and prevent further episodes of pancreatitis but also to manage underlying diseases leading to hypercalcemia.

Clinical profile of patients presenting with dysphagia - an experience from a tertiary care center in North India.

BACKGROUND AND AIM: Dysphagia can lead to substantial morbidity and mortality, especially in the elderly. It has both benign and malignant causes. Despite having a varied etiology, there have been few studies in India. Therefore, a study was undertaken to evaluate the clinical profile and various etiologies of dysphagia. METHODS: A prospective study was conducted on 220 patients with a complaint of dysphagia. Detailed history and examination, endoscopy and biopsies, and barium swallow were performed. Computed tomography and magnetic resonance imaging were performed wherever required. Patients who had an oropharyngeal or neurological cause of dysphagia were excluded. RESULTS: The mean age of patients was 57.2 years, with the male: female ratio being 1.7:1. Of the patients, 35% (78 patients) had malignant etiology, with a mean age of 65.2 years, and 65% (142 patients) had a benign etiology, with a mean age of 51 years. Among the patients with malignancy, 56 had squamous cell carcinoma of esophagus (71.7%), 20 had adenocarcinoma of esophagus (25.7%), and 2 had gastric cardia adenocarcinoma (2.6%). Malignancy was most commonly located in distal esophagus (48 patients), and among the cases, 18 had involvement of the gastroesophageal junction. The most common benign cause was esophagitis secondary to reflux in 25.5% (56 patients), followed by esophageal ulcer in 5.9%, achalasia in 5%, corrosive stricture in 4.5%, and peptic stricture in 3.6%. CONCLUSION: Dysphagia has diverse etiology, and a majority can be diagnosed by endoscopy and barium swallow. Malignancy is an important cause of dysphagia in elderly. Esophageal squamous cell carcinoma remains the most common malignancy, but the incidence of gastroesophageal junctional adenocarcinoma is increasing.

Prognostic and Therapeutic Potentials of OncomiRs Modulating mTOR Pathways in Virus-Associated Hepatocellular Carcinoma.

BACKGROUND: Dysregulated oncomiRs are attributed to hepatocellular carcinoma (HCC) through targeting mTOR signaling pathway responsible for cell growth and proliferation. The potential of these oncomiRs as biomarker for tumor response or as target for therapy needs to be evaluated. AIM: Tumor response assessment by OncomiR changes following locoregional therapy (LRT) and targeting of these oncomiRs modulating pathway. METHODS: All consecutive viral-HCC patients of BCLC stage-A/B undergoing LRT were included. OncomiRs (miR-21, -221, and -16) change in circulation and AFP-ratio at 1-month post-LRT to baseline was estimated to differentiate various categories of response as per mRECIST criteria. OncomiR modulating mTOR pathway was studied by generating miR-21 and miR-221 overexpressing Huh7 stable cell lines. RESULTS: Post-LRT tumor response was assessed in 90 viral-HCC patients (CR, 40%; PR, 31%, and PD, 29%). Significant increase of miRNA-21 and -221 expression was observed in PD (p = 0.040, 0.047) and PR patients (miR-21, p = 0.045). Fold changes of miR-21 can differentiate response in group (CR from PR+PD) at AUROC 0.718 (95% CI, 0.572-0.799) and CR from PD at AUROC 0.734 (95% CI, 0.595-0.873). Overexpression of miR-21 in hepatoma cell line had shown increased phosphorylation p70S6K, the downstream regulator of cell proliferation in mTOR pathway. Upregulation of AKT, mTOR, and RPS6KB1 genes were found significant (P < 0.005) and anti-miR-21 specifically reduced mTOR gene (P = 0.02) expression. CONCLUSIONS: The miR-21 fold change correlates well with imaging in predicting tumor response. Overexpression of miR-21 has a role in HCC through mTOR pathway activation and can be targeted.

Colonic Crohn's Disease Is Associated with Less Aggressive Disease Course Than Ileal or Ileocolonic Disease.

BACKGROUND: The literature on disease characteristics of colonic Crohn's disease (CD) is sparse, especially from Asia, where the burden of inflammatory bowel disease is on the rise. The present study aims to describe the disease characteristics of colonic CD, and compare it with that of ileal/ileocolonic disease. METHODS: This retrospective study included adult patients of CD (diagnosed by standard criteria, follow-up duration > 6 months) on follow-up between August 2004 and January 2016. The disease location was classified by Montreal classification. The data were recorded on demographic characteristics, smoking status, disease phenotype, disease course, treatment received, hospitalization and surgeries. RESULTS: Of 406 CD patients, 123 had colonic [mean age (at onset) 30.4 ± 13.2 years, 59.3% males] and 265 had ileal/ileocolonic disease [mean age (at onset) 32.9 ± 13.8 years, 61.5% males] while 18 patients had isolated upper GI disease. The frequency of inflammatory behavior (B1 phenotype; 61.8 vs. 46.4%, p = 0.003), perianal disease (23.6 vs. 4.5%, p < 0.001), and extra-intestinal manifestation (42.3 vs. 30.2%, p = 0.019) was higher in colonic than ileal/ileocolonic CD. Though not statistically significant, requirement of atleast one course of steroid was lower in colonic CD (72.7 vs. 84.2%, p = 0.098). Although there was no difference in the frequency of hospitalization (30.1 vs. 27.1%, p = 0.45), the overall requirement for surgery was significantly lower in colonic CD (17.1 vs. 26.1%, p = 0.032) and patients with colonic disease had a lower cumulative probability of first surgery in the first 10 years of follow-up [Hazard ratio 0.556 (95% CI 0.313-0.985), p = 0.045]. CONCLUSION: Colonic CD was associated with less aggressive disease behavior and lower requirement of surgery as compared to ileal/ileocolonic CD.

Effect of oral tobacco use and smoking on outcomes of Crohn's disease in India.

BACKGROUND AND AIM: Smoking has been linked with adverse outcomes in Crohn's disease (CD); however, it is not known whether oral tobacco (OT) use affects disease outcomes in these patients. The study aimed to assess the association between smoking or OT and outcomes in CD. METHODS: Retrospective analysis was performed on prospectively maintained records of CD patients from 2004 to 2016. The parameters assessed included disease characteristics at baseline (location, behavior, age at onset, perianal disease, and extraintestinal manifestations), course pattern, and outcomes (surgery, hospitalizations, immunomodulator or biologics use, and steroid requirement). RESULTS: A total of 426 patients were included (mean age: 39.9 years; 59.9% men; median follow up: 71 months). Forty patients were ever-OT users, and 59 were ever-smokers, ever-use being defined as daily use for at least 2 years. OT use was associated with male sex and smoking. Both OT use and smoking had no effect on baseline characteristics, but upper gastrointestinal disease was less common in ever-smokers. Both OT use and smoking did not have any effect on surgery, immunomodulator, and biologic use. Similarly, no association was found between these outcomes and duration, daily, and cumulative exposure to tobacco. Current but not former tobacco use in both smoked (adjusted odds ratio = 2.59 [1.22-5.49]) and OT (adjusted odds ratio = 2.97 [1.03-8.6]) forms increased risk of hospitalizations. CONCLUSION: Oral tobacco use and smoking had no significant detrimental effect on disease phenotype or medical and surgical requirements in CD in Indian patients, affirming other non-Caucasian studies that found lack of effect of smoking. However, current tobacco use in any form was associated with hospitalization during follow up.

Combination of increased visceral fat and long segment involvement: Development and validation of an updated imaging marker for differentiating Crohn's disease from intestinal tuberculosis.

BACKGROUND AND AIM: Computed tomographic (CT) features (long segment, ileocaecal area involvement, and lymph nodes > 1 cm) have demonstrated good specificity but poor sensitivity, while visceral to subcutaneous fat ratio on CT (VF/SC > 0.63) has moderate sensitivity and specificity in differentiating Crohn's disease (CD) and intestinal tuberculosis (ITB). This study aims to develop and validate an updated model incorporating CT features and VF/SC to improve the diagnostic accuracy of imaging in differentiating CD/ITB. METHODS: Computed tomographic features and VF/SC were documented in two cohorts (development [n = 59, follow-up: January 2012 to November 2014] and validation [n = 69, follow-up: December 2014 to December 2015]) of CD/ITB patients diagnosed by standard criteria. Patients with normal CT were excluded. Features significantly different between CD/ITB were incorporated into a model. RESULTS: In both the cohorts, necrotic lymph nodes were exclusive for ITB (23.1% vs 0% and 43.3% vs 0%), while long segment involvement (57.6% vs 7.7%, P < 0.001, and 52.6% vs 16.1%, P < 0.001) and VF/SC ratio > 0.63 (72.7% vs 19.2%, P < 0.001, and 81.6% vs 25.8%, P < 0.001) were significantly more common in CD. A risk score of 2, based upon long segment involvement and VF/SC ratio > 0.63, had an excellent specificity of 100% and 100% and sensitivity of 54% and 50% for CD in development and validation cohorts, respectively. Based upon these features, in 43% patients with the diagnostic dilemma of CD/ITB, a definite diagnosis based only on imaging could be made. CONCLUSION: Necrotic lymph nodes are exclusive for ITB, and the combination of long segment involvement and VF/SC ratio > 0.63 is exclusive for CD, and these features can make a definite diagnosis in 43% patients with a CD/ITB dilemma.

Body Composition in Crohn's Disease and Ulcerative Colitis: Correlation with Disease Severity and Duration.

BACKGROUND: Results on body composition in Crohn's disease (CD) and ulcerative colitis (UC) have been heterogeneous and are lacking from Asia. Present study assessed body composition in CD/UC and correlated it with disease severity/duration. METHODS: Patients of CD/UC following between Dec 2014 and Dec 2015 who consented for bioimpedance analysis for body fat measurement were included. Lean mass and fat-free mass index (FFMI) were calculated with standard formulae. Visceral fat area (VFA), subcutaneous fat area (SCA), and visceral to subcutaneous fat ratio (VF/SC) were evaluated in CD patients on abdominal CT. RESULTS: Lean mass in CD (n = 44, mean age: 41.2 ± 15.8 years, 73% males) was significantly lower than UC (n = 53, mean age: 33.2 ± 11.2 years, 68% males; 44.2 ± 7.8 versus 48.3 ± 8.4 Kg, p = 0.01). In both UC/CD, disease severity was associated with nonsignificant decline in BMI (UC: 22.1 ± 4.9 versus 20.2 ± 3.2 versus 19.9 ± 3.2 kg/m2, p = 0.23; CD: 22.1 ± 4.2 versus 19.9 ± 2.3 versus 19.7 ± 4.2 kg/m2, p = 0.18) and fat mass (UC: 10.9 ± 8.9 versus 8.1 ± 5.9 versus 5.7 ± 3.6 kg, p = 0.14; CD: 11.2 ± 7 versus 7.9 ± 4.4 versus 7.2 ± 5.9 kg, p = 0.16), and disease duration was associated with significant decline in FFMI (p < 0.05). In CD, disease severity was associated with nonsignificant decline in SCA and increase in VF/SC. CONCLUSIONS: CD patients have lower lean mass than UC. Body fat decreases with increasing disease severity and fat-free mass decreases with increasing disease duration in both UC/CD.

Tubercular Intestinal Strictures Show a Poor Response to Anti-Tuberculous Therapy.

BACKGROUND: The literature on resolution of intestinal strictures in patients with intestinal tuberculosis (ITB) after anti-tuberculous therapy (ATT) is sparse and ambivalent. We aimed to assess the frequency of stricture resolution after ATT and its predictors. METHODS: This ambispective cohort study included consecutive ITB patients with strictures who received ATT for ≥6 months and were on regular follow-up between January 2004 and December 2015. Resolution of stricture was assessed at the end of ATT by endoscopy/radiology. RESULTS: Of 286 patients, 128 had strictures, and 106 were finally included (63 males, median age 35 years). The stricture location was distal ileum/ileocecal in 52 (49.1%), colon in 37 (34.9%), ileocolonic in 4 (3.8%), proximal small bowel in 10 (9.4%), and gastroduodenal in 4 (3.8%) patients. Although all patients demonstrated mucosal healing (indicating resolution of active infection), stricture resolution occurred only in 25/106 (23.6%) patients. Symptoms pertaining to stricture (pain abdomen/recurrent SAIO) were present in 104/106 (98%) patients, and after a median of 6 (6-9) months of ATT, these symptoms resolved only in half, 88% (22/25) in patients with stricture resolution and 38% (30/79) in patients with persistent strictures. Colonic strictures had the least resolution (5.4%) followed by proximal small intestinal (20%) and distal ileal/ileocecal (36.5%). Although not statistically significant, stricture resolution was less frequent in patients with multiple strictures, longer strictures (>3 cm), and strictures in which scope was not negotiable prior to ATT. CONCLUSION: Only one-fourth of ITB patients with strictures show resolution of stricture following ATT. The resolution of strictures is dependent on disease location, and majority of them exhibit symptoms pertaining to stricture even after ATT.

Long-term follow-up reveals high incidence of colorectal cancer in Indian patients with inflammatory bowel disease.

BACKGROUND: As the magnitude of sporadic colorectal cancer (CRC) in India is low, magnitude of CRC in ulcerative colitis (UC) is also considered low. As a result, screening for CRC in UC although advocated may not be followed everywhere. We report our data of UC-related CRC from a low-incidence area of sporadic CRC. METHODS: A total of 1012 patients with left-sided colitis/pancolitis having more than one full-length colonoscopy performed at least a year after the onset of symptoms were included in retrospective analysis of prospectively maintained case records. In addition, 136 patients with duration of disease >10 years underwent surveillance white-light colonoscopy prospectively during the study period. RESULTS: A total of 1012 individuals were finally included (6542 person-years of follow-up, 68.5% males, disease duration: 6.4 ± 6.8 years). Twenty (1.97%) patients developed CRC. Two (10%) patients developed CRC during the first decade, 10/20 (50%) during the second and 8/20 (40%) after the second decade of disease. The cumulative risk of developing CRC was 1.5%, 7.2% and 23.6% in the first, second and third decade, respectively. Of 136 high-risk UC cases, five (3.6%) had CRC on screening colonoscopy. Disease duration and increasing age of onset were associated with higher risk of CRC. CONCLUSIONS: Cumulative risk of CRC in Indian UC patients is as high as 23.6% at 30 years. The risk of CRC increases with increasing age of onset and increasing duration of disease. A low risk of sporadic CRC does not confer a low risk of UC-related CRC, and regular screening is warranted.

Impact of dietary beliefs and practices on patients with inflammatory bowel disease: An observational study from India.

BACKGROUND AND AIM: Patients with inflammatory bowel disease (IBD) are at a risk of nutritional deficits because of poor dietary beliefs and practices. There are no data on this aspect from Asia, which is experiencing a rise in IBD incidence. We aimed to establish dietary beliefs and practices in patients of IBD from India. METHODS: Patients with ulcerative colitis (UC) and Crohn's disease (CD) followed up between November 2016 and March 2017 were included. A questionnaire extracted information on the patients' sociodemographic, nutritional and disease profile, smoking and drinking habits, dietary beliefs and practices, current dietary preferences, intake and avoidance, dietary changes made after diagnosis of IBD, dietary changes made during relapse, frequency of consumption of major food groups, and the attitudes toward dietary advice. RESULTS: A total of 316 patients (218 UC and 98 CD; mean age: 38.5 ± 12.2 years) were included. Forty-four percent patients perceived food as a risk factor for IBD, 52% felt dietary habits to have a more important role than medicines in disease control, 77% reported certain foods improve symptoms during relapse, 86% had modified their diet since the diagnosis of IBD (UC > CD, P = 0.04), 90% imposed food restrictions, and <50% had received dietary counseling. About 40% of patients could not meet their dietary requirements and 66% had decreased their dietary intake since diagnosis, which further decreased during relapse (85%). CONCLUSION: Dietary beliefs and practices play a central role in perception of disease in IBD patients. A large majority of them make dietary changes which can lead to undernutrition. Proper dietary counseling is required in these patients to prevent malnutrition.

Role of random biopsies in surveillance of dysplasia in ulcerative colitis patients with high risk of colorectal cancer.

BACKGROUND/AIMS: Recent data suggest that the incidence of ulcerative colitis (UC) related colorectal cancer (CRC) in India is similar to that of West. The optimum method for surveillance is still a debate. Surveillance with random biopsies has been the standard of care, but is a tedious process. We therefore undertook this study to assess the yield of random biopsy in dysplasia surveillance. METHODS: Between March 2014 and July 2015, patients of UC attending the Inflammatory Bowel Disease clinic at the All India Institute of Medical Sciences with high risk factors for CRC like duration of disease >15 years and pancolitis, family history of CRC, primary sclerosing cholangitis underwent surveillance colonoscopy for dysplasia. Four quadrant random biopsies at 10 cm intervals were taken (33 biopsies). Two pathologists examined specimens for dysplasia, and the yield of dysplasia was calculated. RESULTS: Twenty-eight patients were included. Twenty-six of these had pancolitis with a duration of disease greater than 15 years, and two patients had associated primary sclerosing cholangis. No patient had a family history of CRC. The mean age at onset of disease was 28.89±8.73 years and the duration of disease was 19.00±8.78 years. Eighteen patients (64.28%) were males. A total of 924 biopsies were taken. None of the biopsies revealed any evidence of dysplasia, and 7/924 (0.7%) were indefinite for dysplasia. CONCLUSIONS: Random biopsy for surveillance in longstanding extensive colitis has a low yield for dysplasia and does not suffice for screening. Newer techniques such as chromoendoscopy-guided biopsies need greater adoption.