Triose-phosphate isomerase is a novel target of miR-22 and miR-28, with implications in tumorigenesis.

Aerobic glycolysis is the hallmark of many cancer cells that results in a high rate of adenosine triphosphate (ATP) production and, more importantly, biosynthetic intermediates, which are required by the fast-growing tumor cells. The molecular mechanism responsible for the increased glycolytic influx of tumor cells is still not fully understood. In the present study, we have attempted to address the above question by exploring the role of the glycolytic enzyme, triose-phosphate isomerase (TPI), in the cancer cells. The western blot analysis of the 30 human colorectal cancer samples depicted higher post-transcriptional expression of TPI in the tumor tissue relative to the normal tissue. In addition, we identified two novel microRNAs, miR-22 and miR-28, that target the TPI messenger RNA (mRNA) and regulate its expression. miR-22 and the miR-28 showed significant inverse expression status viz-a-viz the expression of the TPI. The specificity of the miR-22/28 regulation of the TPI mRNA was confirmed by various biochemical and mutagenic assays. Moreover, the hypoxia conditions resulted in an increased expression of the TPI protein, with a concomitant decrease in miR-22/28. The physiological significance of the TPI and miR-22/28 interaction for the glycolytic influx was confirmed by the l-lactate production in the HCT-116+/+ cells. Overall, our data demonstrate the novel microRNA mediated post-transcriptional regulation of the TPI glycolytic enzyme, which may be one of the possible reasons for the increased glycolytic capacity of the tumor cells.

A Study of Predictors of Failure of Nonoperative Management of Ileocolic Intussusception in Children.

Background: Surgery remains the mainstay in treating intussusception in developing nations. A correspondingly high bowel resection rate exists despite a shift to nonoperative reduction in high-income countries. We aimed to study the clinical profile of the patients with intussusception presenting to our hospital and to assess the clinical and radiological predictors of success or failure of nonoperative management of intussusception. Materials and methods: This prospective study was conducted in the Department of Pediatric Surgery over a period of 3 years and included a total of 118 patients who presenting to our emergency division with features suggestive of intussusception and were managed accordingly either with hydrostatic reduction or by surgical intervention. Results: We observed that the majority of the patients were males (65.5%). The mean age was 13.54 months. Intermittent pain was the most common symptom. Both pain and vomiting did not affect the outcome. Lab parameters like raised total leukocyte counts (TLC), C-reactive protein (CRP) and lactate levels were significantly associated with failure of hydrostatic reduction. Patients with air fluid levels on X-ray were more likely to end up in surgery. Ultrasound findings of bowel wall edema, aperistaltic gut loops and a pathological lead point was associated with failure of hydrostatic reduction as well. The overall success rate of hydrostatic reduction was 85.5%. Conclusion: Hydrostatic reduction of intussusception is a safe and effective method of management of intussusception whenever indicated. Factors that might reduce the chance of its success include continuous pain, irritability, tenderness, deranged lab parameters like TLC, CRP and lactate levels, air fluid levels on X-ray, bowel wall edema, aperistalsis and the presence of a lead point. How to cite this article: Shah JY, Banday I, Hamdani HZ, et al. A Study of Predictors of Failure of Nonoperative Management of Ileocolic Intussusception in Children. Euroasian J Hepato-Gastroenterol 2024;14(1):81-85.

Pellet gunfire injuries among agitated mobs in Kashmir.

BACKGROUND: Pellet gunfire injuries inflicted while controlling agitated mobs has been studied. METHODS: A total of 198 patients admitted to the Accident and Emergency Department with pellet gun injuries were studied in terms of anatomic site, severity and type of injury, treatment, and outcomes. RESULTS: 72.7% of patients were aged 16-25 years. The most common sites of injury were the extremities (47.9%), abdomen (36.3%) and chest (31.3%). 59.5% of patients were found to have minor injuries. Of the 80 patients admitted to the hospital for their injuries, 43 (53.7%) required an operative procedure. Six deaths (3.03%) were observed. CONCLUSION: While the pellet wound itself may seem trivial, if not appreciated for the potential for tissue disruption and injuries to the head, chest, and abdomen, there can be catastrophic results. Patients should be evaluated and managed in the same way as those sustaining bullet injuries.:

Unilateral absence of external oblique musculo-aponeurotic complex during routine inguinal hernia repair.

INTRODUCTION: The isolated absence of the external oblique musculo-aponeurotic complex in adults is an extremely rare anomaly. This complex is an important contributor to the strength of the inguinal canal. The present case report describes the unilateral absence of the external oblique muscle in a patient. CASE PRESENTATION: A 40-year-old male patient presented with a history of intermittent lower abdominal pain for 5 years which had increased over the past 6 months. Abdominal examination revealed unilateral reducible, incomplete, left sided direct inguinal hernia. CLINICAL DISCUSSION: Elective unilateral Lichtenstein's mesh hernioplasty was planned for the patient. Intraoperatively, there was no evidence of the external oblique aponeurosis and the spermatic cord was noted deep to the thickened membranous fascial layer. The inguinal ligament was thin and atrophic and was attached to the pubic tubercle medially and anterior superior iliac spine laterally. There was no evidence of any superior aponeurotic connection to the inguinal ligament. A postoperative ultrasound examination of the abdomen confirmed the unilateral absence of the external oblique musculo-aponeurotic complex. CONCLUSION: The possibility of such an anomaly should be considered in patients without other risk factors for hernia.

Predictors of pathological complete response following neoadjuvant chemoradiotherapy for rectal cancer.

Background: Neoadjuvant chemoradiotherapy (NACRT) is an established treatment option for locally advanced rectal cancer (LARC). Patients achieving pathological complete response (pCR) following NACRT have better oncological outcomes and may be subjected to wait and watch policy as well. The aim of this study was to identify predictors of pCR in LARC following NACRT. Materials and Methods: A retrospective analysis of a prospectively maintained colorectal cancer database from January 2018 to December 2019 was undertaken. A total of 129 patients of LARC who were subjected to conventional long course NACRT, followed by surgery were included in the study. Pathological response to NACRT was assessed using Mandard grading system and response was categorized as pCR or not-pCR. Correlation between various clinico pathological parameters and pCR was determined using univariate and multivariate logistic regression analysis. Results: Mean age of patients was 53.79 ± 1.303 years. Complete pathological response (Mandard Gr 1) was achieved in 24/129 (18.6%) patients. Age of patients more than 60 years (P = 0.011; odds ratio [OR] 3.194, 95% confidence interval [CI] 1.274-8.011), interval between last dose of NACRT and surgery >8 weeks (P = 0.004; OR 4.833, 95% CI 1.874-12.467), well-differentiated tumors (P < 0.0001; OR 32.00, 95% CI 10.14-100.97) and node-negative disease (P = 0.003; OR 111.0, 95% CI 2.51-48.03) proved to be strong predictors of pCR. Conclusion: Older age, longer interval between NACRT and surgery, node-negative disease and favorable tumor grade help in achieving better pCR rates. Awareness of these variables can be valuable in counseling patients regarding prognosis and treatment options.

Fistulectomy and incontinence: do we really need to worry?

Background: Anal fistula is often considered to be a dilemma because of the need to maintain a fine balance between postoperative incontinence and recurrence. We tried to find whether apprehension of causing incontinence should stop us from performing fistulectomy. The aim of this study was to determine whether fistulectomy was associated with increased rate of fecal incontinence and recurrence, compared to other procedures used for the treatment of anal fistula. Methods: It was a prospective, single center, observational study. All patients with anal fistula operated at a tertiary care teaching institute over a period of two years were included in the study. Recurrence rates and fecal incontinence were compared between patients subjected to fistulectomy and other procedures for treatment of fistula in ano. Results: A total of 124 patients with anal fistula were included. 92.8% patients were ≤ 60 years of age with high male preponderance (89.5%). Perineal discharge was the commonest complaint (95.96%). Intersphincteric (47.58%) followed by transphincteric fistulas (45.16%) accounted for the majority of fistulas. Fistulectomy was the most common procedure, performed in 90 (72.58%) patients. Incontinence occurred in 8/90 (8.88%) from the fistulectomy group and 2/34 (5.9%) patients in other surgery group, p=0.726. Recurrence occurred in 8/90 (8.88%) from the fistulectomy group and 8/34 (23.5%) patients from other surgery group, p=0.038. Overall rates of incontinence and recurrence were 8.1% and 12.9% respectively. Conclusion: Fistulectomy, as compared to other procedures, results in less chances of recurrence without compromising continence.

TEAD4 nuclear localization and regulation by miR-4269 and miR-1343-3p in colorectal carcinoma.

BACKGROUND AND AIMS: TEAD4 transcription factor belonging to TEAD-family, is a key downstream element of the Hippo Signalling pathway and is very important for YAPinduced tumor progression. YAP-TEAD interaction is required to promote tumor progression and metastasis in various cancers. This study aims to investigate the role of TEAD4 in CRC progression and to compare the TEAD4 expression with different clinicopathological parameters of the study population. We also aim to explore the expression pattern of miR-4269 and miR-1343-3p and their functional role in TEAD4 mediated CRC progression. Furthermore, we intend to evaluate the prognostic significance of TEAD4, miR-4269, and miR-1343-3p in colorectal carcinoma. METHODS: Real-time PCR, Immunohistochemical Staining, and Western Blotting were performed on 71 human CRC tissue specimens and their adjacent normal tissues to evaluate the TEAD4 expression and the results were statistically analyzed against the clinicopathological variables of patient data and also with survival data using STATA software. miRNA expression was analyzed by quantitative real-time PCR. RESULTS: TEAD4 expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with TNM stage, Duke Stage, tumor grade, invasion depth, node status, necrosis of tumor tissue, lymphovascular and perineural invasion. As per the cox-regression model and classification tree analysis, TNM stage and perineural invasion were important predictors for TEAD4 expression and prognosis of CRC patients. Survival analysis indicated that TEAD4 overexpression was associated with poorer overall and disease-free survival. miR-4269 and miR-1343-3p were downregulated in CRC tumors and showed a negative correlation with TEAD4. The nuclear overexpressed TEAD4 and downregulated miR-4269 and miR-1343-3p evaluated for the first time in CRC, are believed to serve as important prognostic markers in CRC. CONCLUSION: Expression of TEAD4 was increased in CRC and was negatively regulated by miR-4269 and miR-1343-3p. The overexpression of TEAD4 is linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus TEAD4 may be a possible prognostic marker in CRC.

Role of sonic hedgehog ligand in gastric cancer therapeutics.

Purpose: The abnormal activation of the sonic hedgehog (SHH) signaling pathway is responsible for the progression of several types of cancers including Gastric Cancer (GC). SHH has been associated with the activation of different signaling pathways. Therefore, in this study, we investigated messenger RNA (mRNA) and protein expression of SHH in gastric malignancies and possible correlation with various clinicopathological parameters. Materials and Methods: A total of 53 surgically resected tumors and adjacent histologically normal tissues from GC patients were investigated in study subjects. A quantitative real-time polymerase chain reaction and immunohistochemistry methods were used for expression analysis of SHH. Results: At mRNA level, SHH was overexpressed in 60% (27/45) of GC cases as compared to their adjacent normal tissues. SHH immunohistochemical analysis revealed abundant cytoplasmic localization and overexpression in 43.39% (23/53) of GC tissues. SHH overexpression was not associated with any of the clinicopathological parameters. Conclusion: Our results showed that SHH is dysregulated in GC and might be considered as a biomarker for GC progression and can be used as a target in cancer therapeutics.

Connective tissue growth factor expression hints at aggressive nature of colorectal cancer.

BACKGROUND: Connective tissue growth factor (CTGF) is a mediator of transforming growth factor-beta signaling and plays a key role in connective tissue remodeling, inflammatory processes and fibrosis in various illnesses including cancer. AIM: To investigate the role of CTGF in colorectal cancer (CRC) progression and to compare the CTGF expression with different clinicopathological parameters. METHODS: Real-time polymerase chain reaction, immunohistochemistry and Western blotting was performed to evaluate the CTGF expression and the results were statistically analyzed against the clinicopathological variables of patient data using STATA software version 16. RESULTS: CTGF expression levels in tumor specimens were significantly higher than their paired normal specimens. The higher protein expression levels showed a significant association with smoking, staging, tumor grade, invasion depth, necrosis of tumor tissue, and both lymphovascular and perineural invasion. As per the cox regression model and classification tree analysis, tumor-node-metastasis stage and perineural invasion were important predictors for CTGF expression and prognosis of CRC patients. Survival analysis indicated that CTGF overexpression was associated with poorer overall and disease-free survival. CONCLUSION: Expression of CTGF was increased in CRC and was linked with poor overall and disease-free survival of CRC patients. These findings support prior observations and thus CTGF may be a possible prognostic marker in CRC.

Endometrial Stromal Sarcoma Recurrence in the Caecum.

Endometrial stromal sarcomas of uterus are quite rare. Most of the recurrences in these tumors are seen in the pelvis. However, extrapelvic recurrences and metastases to other parts are quite unusual. Here, we are reporting a rare case of caecal recurrence of endometrial stromal sarcoma. Case Report. A 52-year-old female presented to us with pain and lump in the right lower abdomen. The patient was earlier subjected to total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAHBSO) for low-grade endometrial stromal sarcoma. Postoperatively patient received radiotherapy but no hormone therapy. After 10 years of follow up patient presented with a polypoidal lesion in the caecum. Patient was evaluated fully and subjected to resection of this polypoidal lesion, which proved out to be high-grade endometrial stromal sarcoma. Conclusion. Recurrence of endometrial stromal sarcoma in the caecum is very rare. However, this entity needs to be kept in mind for differential diagnosis of a caecal mass. Recurrence in such cases may present quite late.

Ghost ileostomy release down: our initial experience

Background: Many publications describe the advantages of the creation of ghost ileostomy (GI) to prevent the need for formal covering ileostomy in more than 80% of carcinoma rectum patients. However, none of the papers describes exactly how to ultimately remove the GI in these 80% of patients in whom it doesn't need formal maturation. Aim: To describe and evaluate the ghost ileostomy release down (GIRD) technique in terms of feasibility, complications, hospital stay, procedure time etc. in patients with low anterior resection/ultra-low anterior resection (LAR/uLAR) with GI for carcinoma rectum. Method: The present was a prospective cohort study of patients with restorative colorectal resections with GI for carcinoma rectum, Postoperatively the patients were studied with respect to ease and feasibility of the release down of GI and its complications. The data was collected, analyzed and inference drawn. Results: A total of 26 patients needed the GIRD and were included in the final statistical analysis of the study. The procedure was done between 7th to 16th postoperative days (POD) and was successful in all patients without the need of any additional surgical procedure. None of the patients required any local anesthetic injection or any extra analgesics. The average time taken for procedure was 5-minutes and none of the patients had any significant difficulty in GI release. There were no immediate postprocedure complications. Conclusion: The GIRD technique is a simple, safe, and quick procedure done around the 10th POD that can easily be performed by the bedside of patient without the need of any anesthesia or additional analgesics. (AU)

Splenectomy in idiopathic hypersplenism.

The therapeutic effects of splenectomy in 15 patients with idiopathic hypersplenism were studied. The mean age was 43 years (range, 5-72 years). The male to female ratio was 1:1.14. The response to splenectomy was: in thrombocytopenia, complete response (CR) in 71%, partial response (PR) and no response (NR) in 14% each of patients; in anemia, CR in 83%, PR in 0%, and NR in 16% of patients; and in leukopenia, CR in 78% and PR and NR in 11% each of patients. However, the morbidity (27%) and mortality (20%) observed was quite high. Thus, we conclude that splenectomy is an excellent treatment to improve the hematological parameters in patients with idiopathic hypersplenism, but elderly patients and patients with multisystem disease should not have this surgery.

Role of covering Ileostomy in causation of anastomotic strictures in low anterior resections for rectum carcinoma / O papel da ileostomia de proteção como causa das estenoses anastomóticas nas ressecções anteriores de reto

Abstract Background Colorectal resection anastomosis is the commonest cause of rectal strictures. Anastomotic site ischemia, incomplete doughnuts from stapled anastomosis and pelvic infection, are some of the risk factors that play a role in the development of postoperative rectal strictures. However, the role of diverting stoma in the development of rectal strictures has not been studied extensively. Objectives To study the difference in the occurrence of anastomotic strictures (AS) in patients submitted to low anterior resection (LAR) with covering ileostomy (CI), and to LAR without CI for carcinoma rectum. Methods This was a prospective, comparative case control study carried out at a tertiary care referral center. Low anterior resection with covering ileostomy was performed in patients with rectum carcinoma in the study group, while LAR without covering ileostomy was performed in the control group. The study group had 29 patients, while the control group had 33 patients with rectum carcinoma. Results During themean follow-up period of 9.1months, 8 (28%) patients in the study group and 2 (6%) patients in the control group developed AS (p =0.019). Out of these 8 patients with AS in the study group, 50% had Grade-I AS, 25% had Grade-II AS, while 25% of the patients had Grade-III (severe) AS. However, both patients who developed AS in the control group had a mild type (Grade I) of AS. Conclusion Covering ileostomy increases the chances of AS formation after LAR for rectum carcinoma. Also, the SKIMS Clinical Grading of Rectal Strictures is a simple and

Resumo Introdução A anastomose de ressecção colorretal é a causa mais comum de estenoses retais. A isquemia do local da anastomose, donuts (anéis) incompletos de anastomose grampeada e infecção pélvica são alguns dos fatores de risco que desempenham um papel no desenvolvimento de estenoses retais pós-operatórias. No entanto, o papel do estoma de desvio no desenvolvimento de estenoses retais não foi estudado extensivamente. Objetivos Estudar a diferença na ocorrência de estenoses anastomóticas (EA) em pacientes submetidos à ressecção anterior baixa (LAR) com ileostomia de proteção e a LAR sem ileostomia de proteção para carcinoma de reto. Métodos Este foi um estudo prospectivo e comparativo de caso-controle realizado em um centro de referência de atenção terciária. A ressecção anterior baixa com ileostomia de proteção foi realizada em pacientes com carcinoma de reto no grupo de estudo, enquanto LAR sem ileostomia de proteção foi realizada no grupo controle. O grupo de estudo tinha 29 pacientes, enquanto o grupo controle tinha 33 pacientes com carcinoma de reto. Resultados Durante o período de acompanhamento médio de 9, 1 meses, 8 (28%) pacientes no grupo de estudo e 2 (6%) pacientes no grupo controle desenvolveram EA (p=0,019). Destes 8 pacientes com EA no grupo de estudo, 50% tinham EA de Grau I, 25% tinhamEA de Grau II, enquanto 25% dos pacientes tinham EA de Grau III (grave). No entanto, ambos os pacientes que desenvolveram EA no grupo de controle tinham um tipo leve (Grau I) de EA. Conclusão A ileostomia de proteção aumenta as chances de formação de AS após LAR para carcinoma de reto. Além disso, o SKIMS Clinical Grading of Rectal Strictures é uma ferramenta simples e útil disponível para cada cirurgião para graduar, classificar e monitorar as estenoses retais pós-operatórias.

Primary lymphoma of the spleen: an experience with seven patients.

Primary lymphoma of the spleen is a rare clinical entity. In our study, a group of 110 patients with various hematological disorders were subjected to splenectomy over a period of 20 years. We have been able to isolate 7 patients with primary lymphoma of the spleen. Main indications of splenectomy in these patients were anemia and leukopenia. There was no mortality, but morbidity was quite high (43%). We conclude that splenectomy may be a useful treatment in patients with cytopenias secondary to primary lymphoma of the spleen refractory to other types of therapy.

"PNR-Bleed" classification and Hemorrhoid Severity Score-a novel attempt at classifying the hemorrhoids / Classificação "PNR-Bleed" e escore de gravidade das hemorróidas - uma nova tentativa de classificação de hemorróidas

ABSTRACT Hemorrhoids are the most common anorectal disorders with a prevalence of 39% in general population. Hemorrhoids are generally classified on the basis of their location and degree of prolapse. Goligher's classification does not describe the number of hemorrhoidal columns involved and does not give much consideration to the amount of blood loss. To describe the hemorrhoidal disease more vividly, we devised the "PNR-Bleed" (or PNR-Booking) classification system. We tried to classify the hemorrhoids based on the four main characteristics of the hemorrhoidal disease i.e. the degree of hemorrhoidal Prolapse (P), Number (N) of the primary hemorrhoidal columns involved, Relation (R) of the hemorrhoidal tissue to dentate line and the amount of Bleeding (B) from it. All the four components in this classification system are graded into five grades ranging from 1 to 5. The peculiarity of this new classification system is that it allows more detailed documentation of the hemorrhoids in a particular patient and conveys more explicit meaning and information about the hemorrhoids for future references. Based on this 'PNR-Bleed' classification, we are introducing another concept of scoring the severity of hemorrhoids and referred it as the Hemorrhoid Severity Score (HSS). Hemorrhoid Severity Score (HSS) is the total score obtained by the sum of the numerical grades of all four characteristics of hemorrhoids in "PNR-Bleed" classification. This new "PNR-Bleed" system of classifying the hemorrhoids and calculation of HSS seems to be more comprehensive, detailed, more objective and easily reproducible.

RESUMO As hemorróidas são os distúrbios anorretais mais comuns, com uma prevalência de 39% na população em geral. As hemorróidas são geralmente classificadas com base em sua localização e grau de prolapso. A classificação de Goligher não descreve o número de colunas hemorroidais envolvidas e não dá muita importância à quantidade da perda de sangue. Para descrever a doença hemorroidária de maneira mais precisa, criamos o sistema de classificação "PNR-Bleed" (ou PNR-Booking). Tentamos classificar as hemorróidas com base nas quatro principais características da doença hemorroidária, isto é, o grau de prolapso da hemorroida (P), número (N) das colunas hemorroidais primárias envolvidas, a relação (R) do tecido hemorroidário para a linha denteada e a quantidade de sangramento (B) originando-se dele. Todos os quatro componentes deste sistema de classificação são classificados em cinco graus, variando de 1 a 5. A peculiaridade desse novo sistema de classificação é que ele permite uma documentação mais detalhada das hemorróidas em um paciente em particular e transmite o significado e informações mais explícitos sobre as hemorróidas. para referências futuras. Com base nessa classificação "PNR-Bleed", estamos introduzindo outro conceito para o escore da gravidade das hemorróidas e denominado HSS, de "Hemorrhoid Severity Score". O escore de gravidade da hemorroida (HSS) é o escore total obtido pela soma dos graus numéricos de todas as quatro características das hemorróidas na classificação "PNR-Bleed". Esse novo sistema "PNR-Bleed" de classificação de hemorróidas e cálculo do HSS parece ser mais abrangente, detalhado, mais objetivo e facilmente reproduzível.

Oriental cholangiohepatitis - is our surgery appropriate?

Oriental cholangiohepatitis, or recurrent pyogenic cholangitis is only noted in certain parts of the world, especially South East Asia. Due to increasing immigration the disease is now being seen in western countries also. Treating physicians may face difficulty in managing such cases due to lack of exposure. Furthermore management of such cases is not standardized because of lack of a universally accepted classification system. Here we review the disease and share our long experience with management of these patients.

Role of diversion ileostomy in low rectal cancer: a randomized controlled trial.

INTRODUCTION: Rectal cancer continues to be devastating malignancy worldwide. Sphincter preservation is the need of the hour. Distal anastomosis is more prone to leaks. Proximal diversion in form of ileostomy may be used to protect distal anastomosis. AIM: To compare two groups of low anterior resection with and without diversion ileostomy in rectal cancer patients. MATERIAL AND METHODS: A prospective, hospital based study of 78 rectal carcinoma patients were taken for the study. Inclusion criteria was operable rectal cancer 4-12 cm from anal verge. Patients were randomized into two groups. Group - A (34 patient) patients with low anterior resection with ileostomy (LAR with ileostomy); Group - B (44 patients) patients with low anterior resection without ileostomy (LAR without ileostomy). Quality of life was assessed by scoring done by self designed method. A total score of 0-20 given for various parameters. RESULTS: Skin excoriation was the commonest complication. Stomal retraction and stomal obstruction was seen in 1 patient each (3%). Hypokalemia was the commonest electrolyte imbalance present in ileostomy group. Anastomotic leak was present in 6% of Group A and 11% of Group B patients. Mean time of closure of ileostomy was 16 ± 4.3 weeks. CONCLUSION: LAR with ileostomy has certain advantages over LAR without ileostomy in terms of anastomotic leak, postoperative ileus, resumption of diet, wound infection, small bowel obstruction and in terms mortality and recurrence. However stoma related complications were main disadvantage in LAR with ileostomy.