Tata Memorial Centre Evidence Based Management of Colorectal cancer.

ABSTRACT: This review article examines the evidence-based management of colorectal cancers, focusing on topics characterized by ongoing debates and evolving evidence. To contribute to the scientific discourse, we intentionally exclude subjects with established guidelines, concentrating instead on areas where the current understanding is dynamic. Our analysis encompasses a thorough exploration of critical themes, including the evidence surrounding complete mesocolic excision and D3 lymphadenectomy in colon cancers. Additionally, we delve into the evolving landscape of perioperative chemotherapy in both colon and rectal cancers, considering its nuanced role in the context of contemporary treatment strategies. Advancements in surgical techniques are a pivotal aspect of our discussion, with an emphasis on the utilization of minimally invasive approaches such as laparoscopy and robotic surgery in both colon and rectal cancers, including advanced rectal cases. Moving beyond conventional radical procedures, we scrutinize the feasibility and implications of endoscopic resections for small tumors, explore the paradigm of organ preservation in locally advanced rectal cancers, and assess the utility of total neoadjuvant therapy in the current treatment landscape. Our final segment reviews pivotal trials that have significantly influenced the management of colorectal liver and peritoneal metastasis.

Safety and efficacy of endoscopic retrograde cholangiopancreatography in pediatric pancreatic and biliary disorders.

INTRODUCTION: There is sparse data from India on indications, technical success, safety and outcomes of endoscopic retrograde cholangiopancreatography (ERCP) using standard adult duodenoscope in the pediatric population. METHODS: Retrospective analysis of prospectively maintained electronic endoscopy and clinical database was performed to identify pediatric patients (age ≤ 18 years) who underwent ERCP between January 2017 and December 2022. Demographics and procedural details including indications, cholangio-pancreatogram findings, endotherapy type performed, technical and clinical success and complications were noted. RESULTS: As many as 150 pediatric patients were included of whom 88 had pancreatic (mean age-13.7 years) and 62 had biliary disease (mean age- 14.9 years). Common pancreatic ERCP indications were chronic pancreatitis (n = 45 [51.1%]), pancreatic duct disruption fistula (n = 21 [23.9%]) and recurrent acute pancreatitis (n = 16 [18.2%]). Among biliary indications were choledocholithiasis (n = 29 [46.8%]), benign bile duct strictures (n = 13 [21%]), bile duct injury/leak and biliary stent removal (n = 7 [11.3%]) , choledochal cyst (n = 5  [8.1%]) and pancreatic mass causing biliary compression (n = 1 [1.6%]). Technical success in pancreatic and biliary ERCP was 94.3% and 95.2%, respectively, and clinical success was 84.1% and 93.5%, respectively. Most common complications following pancreatic ERCPs were acute pancreatitis (n = 9 [10.2%]) (mild = 5, moderate = 4) patients and post sphincterotomy bleed in one (1.1%). Among biliary ERCPs, post ERCP pancreatitis was seen in (n = 3 [4.8%]) (mild = 2, moderate = 1). CONCLUSION: ERCP can be safely and effectively performed in children using standard duodenoscope. Chronic pancreatitis, choledocholithiasis and pancreatic divisum are common pediatric ERCP indications.

IgG4-related disorders of the gastrointestinal tract: Experience from a tertiary care centre with systematic review of Indian literature.

INTRODUCTION: IgG4-related disease (IgG4-RD) is a rare disease entity in India. We aimed at studying the clinical profile of IgG4-RD of gastrointestinal tract (GIT) from our centre, while systematically reviewing data from India. METHODS: Retrospective review of IgG4-RD of GIT was done using electronic medical records between January 2013 and July 2022. Literature search was done for studies of IgG4-RD of the GIT reported from India from 2000 till January 2023. Case series, case reports of IgG4-RD of GIT and case reports describing GIT with multi-organ involvement were included in the review. Primary outcome measure was response to treatment. Secondary outcome measure was relapse after remission. RESULTS: Thirty-one patients were included with 71% (22/31) having autoimmune pancreatitis. The diagnosis was achieved on surgical specimen in 35% (11/31) patients. Steroid was given to 64% (20/31) patients with remission achieved in 70% (14/20) patients. Four patients exhibitted response to prolonged course of steroids with maintenance azathioprine. Relapse was seen in four (20%) patients who achieved remission. Of 731 articles screened, 48 studies (four case series and 44 case reports) were included in the literature review. Of 95 patients described, steroids were given to 65.2% (62/95), while surgery was done in 33.6% (32/95). Remission was seen in 96.6% (85/88) with relapse occurring in 11.4% (10/88) patients on follow-up. CONCLUSION: One-third patients of IgG4-RD of GIT are diagnosed after surgery. Response to steroids is good with relapse occurring in up to 12% patients.

Drug-Resistant Helicobacter pylori: Diagnosis and Evidence-Based Approach.

Helicobacter pylori (H. pylori) is the most common chronic bacterial infection, affecting approximately half of the world's population. H. pylori is a Class I carcinogen according to the World Health Organization, and the International Agency for Research on Cancer (IARC) has linked it to 90% of stomach cancer cases worldwide. The overall pattern points to a yearly reduction in eradication rates of H. pylori with the likelihood of success further decreasing after each unsuccessful therapeutic effort. Antimicrobial resistance in Helicobacter pylori is a major public health concern and is a predominant cause attributed to eradication failure. As a result, determining H. pylori's antibiotic susceptibility prior to the administration of eradication regimens becomes increasingly critical. Detecting H. pylori and its antimicrobial resistance has traditionally been accomplished by time-consuming culture and phenotypic drug susceptibility testing. The resistance of H. pylori to different antibiotics is caused by various molecular mechanisms, and advances in sequencing technology have greatly facilitated the testing of antibiotic susceptibility to H. pylori. This review will summarize H. pylori antibiotic resistance patterns, mechanisms, and clinical implications. We will also review the pros and cons of current antibiotic susceptibility testing methods. Along with a comparison of tailored susceptibility-guided regimens and empirical therapy based on the latest evidence, an evidence-based approach to such situations will be explored.

Reliability of Optical Coherence Tomography Angiography Retinal Blood Flow Analyses.

Purpose: Investigate the association between the optical coherence tomography angiography (OCTA) metrics derived from different analysis programs to understand the comparability of studies using these different approaches. Methods: Secondary analysis of a prospective observational study (March 2018-September 2021). Forty-four right eyes and 42 left eyes from 44 patients were included. Patients were either undergoing upper gastrointestinal surgery with a critical care stay planned or were already in the critical care unit with sepsis. OCTA scans were obtained in an ophthalmology department or critical care setting. Fourteen OCTA metrics were compared within and between the programs, and agreement was measured by Pearson's R coefficient and intraclass correlation coefficient. Results: Correlation was highest between all Heidelberg metrics and Fractalyse (all >0.84), and lowest between Matlab skeletonized or foveal avascular zone metrics and all other measures (e.g., skeletal fractal dimension and vessel density at -0.02). Agreement between eyes was moderate to excellent in all metrics (0.60-0.90). Conclusions: The significant variability between metrics and programs used for OCTA analysis demonstrates that they are not interchangeable and supports a recommendation for perfusion density metrics to be reported as standard. Translational Relevance: Agreement between different OCTA analyses is variable and not interchangeable. The high agreement between non-skeletonized vessel density metrics suggests that these should be routinely reported.

Endoscopic ultrasound guided biliary drainage in surgically altered anatomy: A comprehensive review of various approaches.

Endoscopic retrograde cholangiopancreatography (ERCP) is the preferred modality for drainage of the obstructed biliary tree. In patients with surgically altered anatomy, ERCP using standard techniques may not be feasible. Enteroscope assisted ERCP is usually employed with variable success rate. With advent of endoscopic ultrasound (EUS), biliary drainage procedures in patients with biliary obstruction and surgically altered anatomy is safe and effective. In this narrative review, we discuss role of EUS guided biliary drainage in patients with altered anatomy and the various approaches used in patients with benign and malignant biliary obstruction.

Anomalous Pancreatobiliary Ductal Union Presenting as Recurrent Acute and Chronic Pancreatitis in Children and Adolescents With Response to Endotherapy.

Introduction Anomalous pancreaticobiliary duct union (APBDU) is defined by the abnormal position of the junctional union of the common bile duct and the pancreatic duct, outside the duodenal wall above the influence of sphincter of Oddi, associated with choledochal cysts and biliary malignancies. APBDU may rarely present as recurrent acute pancreatitis (RAP) or chronic pancreatitis (CP). We aimed to study the prevalence of patients with APBDU presenting as RAP or CP and their response to endotherapy. Methods A retrospective audit of the prospectively maintained endoscopy database at our institute between January 2018 and November 2020 was conducted to identify cases of APBDU presenting as RAP or CP. Details of investigations, endoscopic retrograde cholangiopancreatography (ERCP) findings, and follow-up till six months were noted. Results We identified 26 cases of APBDU, of which five (19.2%) cases presented as RAP or CP. Of these five patients, two had RAP, while three presented with CP (median: 11 years; range: 4-25 years). Magnetic resonance cholangiopancreatography (MRCP) showed APBDU in three patients. One patient with RAP had a Komi type IIIB anomaly. Another patient with RAP had a rare anomaly with absent ventral PD, with the bile duct communicating and draining through the dorsal duct. Two patients with CP had a long common channel with Komi IIA anomaly. One patient with CP had IIIC2 anomaly. Pancreas divisum was noted in three patients, all of whom underwent minor-papilla sphincterotomy. Successful pancreatic stent placement was performed in all patients. Over one year of follow-up, patients with CP had a significant decrease in pain as measured by the visual analog scale. Those with RAP had no further episodes of pancreatitis. Conclusion APBDU is a rare cause of RAP and CP in young patients, occasionally missed on MRCP. RAP and CP caused by APBDU show good response to endotherapy.

Efficacy and Safety of Endoscopic Stenting for Crohn's Disease Related Strictures: A Systematic Review and Meta-analysis.

Background/Aims: Endoscopic stenting is an evolving treatment for symptomatic Crohn's strictures. Several case series and small studies have reported its efficacy. Future studies can be designed based on a systematic review of the evaluation of efficacy. Hence, this meta-analysis was conducted to assess the critical role of stents in the management of intestinal strictures associated with Crohn's disease (CD). Methods: A literature search of various databases from 2000 to February 2022 was conducted for studies evaluating the outcome of stents in patients with CD-related stricture. The outcomes assessed included technical and clinical success, adverse events, symptom recurrence, and the need for a surgical resection. Pooled event rates across studies were expressed with summative statistics. Results: Ten studies with 170 patients were included in the present analysis. The pooled event rates for technical success, clinical success, stent migration, and post-procedural pain were 98.2% (95% CI, 95.8-100), 71.3% (95% CI, 57.4-85.1), 32% (95% CI, 0.0-65.3) and 20.2% (95% CI, 4.1-36.2), respectively. The cumulative recurrence rate and need for surgery were 40.1% (95% CI, 20.3-59.9) and 8.6% (95% CI, 1.7-15.5), respectively. Subgroup analysis showed that partially-covered (PC) self-expanding metallic stent (SEMS) was significantly better than fully-covered SEMS with a lower stent migration rate and symptom recurrence rate. Conclusions: Overall efficacy of stents in the management of CD-related stricture remains moderate with a low complication rate. Among the stents, PC-SEMS may be associated with a more favorable outcome. Future studies will be needed to determine the long-term benefits of endoscopic stenting.

Outcomes and predictors of response to endotherapy in pancreatic ductal disruptions with refractory internal and high-output external fistulae.

Backgrounds/Aims: Endoscopic retrograde cholangiopancreatography (ERCP) remains the primary treatment for a subset of patients with pancreatic fistulae. The objective of this study was reporting outcomes of ERCP and predictors of resolution in patients with pancreatic fistulae refractory to conservative therapy. Methods: Retrospective review of patients who underwent ERCP and pancreatic stent placement for pancreatic fistula not responding to medical therapy was performed. Clinical features, laboratory parameters, radiological features and pancreatogram findings were noted. Clinical resolution of fistula was the primary outcome measure. Results: Sixty-eight patients underwent ERCP for high-output pancreatic fistula (Mean age 34.1 years, 91.1% males, 35/68 chronic pancreatitis, 52.9% alcohol etiology). Internal fistulae (pancreatic ascites, pleural effusion, or pericardial effusion) were seen in 55 (80.9%) patients and external fistula in 13 (19.1%) patients. Technical success for ERCP was 92.6% (63/68). Leak was seen in 98.4% (62/63). The most common leak site was body (69.8%). Multiple leak sites were seen in 23.1%. Pancreatic stricture was found in 36.5%. In 44 (69.4%) patients, stent was placed beyond the site of the leak. Resolution at six weeks was achieved in 76.4% (52/68). On univariate and multivariate analyses, placement of stent beyond site of leak was significantly associated with resolution of high-output fistulae (3/41 [7.3%] vs. 5/19 [26.3%], p = 0.03; odds ratio: 6.5, 95% confidence interval: 1.211-34.94). Conclusions: In our experience, ERCP was successful in 76% of patients with pancreatic fistulae refractory to conservative therapy. Stent placement beyond the site of leak was associated with higher resolution of fistulae.

Long-Term Outcomes of Endoscopic Management of Patients with Symptomatic Portal Cavernoma Cholangiopathy with No Shuntable Veins for Surgery or Failed Surgery.

Background and Aim: Shunt surgery is the definitive treatment for symptomatic patients with portal cavernoma cholangiopathy (PCC), but few patients are non-surgical candidates or fail to improve even after surgery. This study aims to analyze the long-term outcomes of endoscopic therapy in these patients. Methods: Retrospective review of a prospectively maintained database of all patients with symptomatic PCC managed with endoscopic retrograde cholangiography (ERC) followed by stent placement. Outcomes studied included number of biliary interventions, complications, resolution of stricture, development of decompensation and mortality. Results: Thirty-five patients (68.6% males, median age = 35 years) with a median follow-up duration of 46 months (12-112) were included in the analysis. Presentation was only jaundice in 51.4% cases while one-third (37.1%) of the patients presented with cholangitis. Patients underwent a total of 363 endoscopic sessions with a median of 9 procedures (3-29) per patient. Hemobilia was the most common complication of the procedure (6.06%). Ten (28.5%) patients required frequent stent exchanges. Patients who required frequent stent exchanges had higher number of cholangitis episodes and hospitalization. Secondary biliary cirrhosis developed in 4 (11.4%) patients and 2 (5.7%) patients had mortality. Of the 5 (14.3%) patients who were given a stent free trial, 3 patients required restenting due to redevelopment of symptoms. Conclusion: Patients with PCC without shuntable veins for surgery or those who failed to improve after surgery can be managed long-term with repeated endoscopic intervention with a slightly increased risk of non-fatal hemobilia.

Hepatocellular Carcinoma Evaluation and Management for Physicians: Joint Gastroenterology Research Society and Association of Physicians of India Guidelines.

Hepatocellular carcinoma (HCC) is the most common cause of, and accounts for almost 90% of all liver cancers. Data from India is limited especially due to cancer not being a reportable disease and in view of wide variation in diagnostic modalities. This document is a result of a consensus meeting comprising Hepatologists, Interventional Radiologists, Hepatobiliary surgeons, medical and surgical Oncologists nominated by the Association of Physicians of India and Gastroenterology Research Society of Mumbai. The following Clinical Practice Guidelines for practicing physicians is intended to act as an up to date protocol for clinical management of patients with hepatocellular carcinoma. The document comprises seven sections with statements and sub-statements with strength of evidence and recommendation.

Hepatic tuberculosis masquerading as malignancy.

BACKGROUND AND AIMS: Hepatic tuberculosis (HTB) is rare and mimics neoplastic liver lesions clinico-radiologically leading to misdiagnosis and even unnecessary surgery. METHODS AND MATERIAL: We analysed 43 cases of HTB diagnosed at a referral cancer centre over 10 years. Clinical details, investigations and treatment received were noted. RESULTS: The median age was 46 years with a female preponderance (58%). HTB was diagnosed incidentally in 28% cases during surveillance imaging for a previous cancer. Constitutional symptoms (31, 72%), abdominal pain (25, 58%), fever (12, 28%), hepatomegaly (22, 51%), elevated alkaline phosphatase (34, 79%), elevated aminotransferases (18, 42%) and hypoalbuminemia (19, 45%) were common features. All cases had negative HIV serology and normal tumor markers. Twenty-two (52.5%) had solitary liver lesion and lesions > 2 cm in 28 (65%). Ultrasound showed hypoechoic lesions in 31 of 33 cases. Computed tomography showed hypodense lesions (43,100%) with mild peripheral enhancement (32, 74%). Calcifications (5, 12%) and capsular retraction (8, 19%) was uncommon. MRI was performed in seven cases commonly showed T1 hypointense, T2 hyperintense lesions with restricted diffusion. Histopathology showed granulomatous inflammation (42, 97.5%), Langhan's giant cells (41, 95%) and caseation necrosis (35, 85%). Acid-fast stain and PCR positivity was uncommon. Extrahepatic organs were involved in 20 (46.5%). HTB mimicked cholangiocarcinoma (25, 58%), liver metastasis (11, 26%) and lymphoma (3, 7%). Six patients underwent liver resection with a presumptive diagnosis of cancer without a preoperative biopsy. All patients received antitubercular therapy, 37 had clinico-radiological response, there were 3 deaths and 3 patients were lost to follow-up. CONCLUSION: HTB is rare and can mimic a malignancy clinico-radiologically. Calcifications and pseudocapsule appearance on multiphase CT scan may help in differentiating HTB from hepatic malignancy. Tumor markers are normal while histopathology is generally diagnostic. A high index of suspicion is required to avoid unnecessary surgery as the patients respond well to ATT. TRIAL REGISTRATION: This is a retrospective and observational study hence clinical trial registration is not applicable.

Outcomes of Dilation of Recalcitrant Pancreatic Strictures Using a Wire-Guided Cystotome.

BACKGROUND/AIMS: Pancreatic strictures in chronic pancreatitis are treated using endoscopic retrograde cholangiopancreatography (ERCP) with plastic stent placement. The management of recalcitrant strictures remains a challenge, with the use of a Soehendra stent retriever or a needle knife described in case reports. Here, we discuss our experience with dilation of dominant pancreatic strictures with a 6-Fr cystotome. METHODS: A retrospective review of an endoscopy database was performed to search for patients with pancreatic strictures recalcitrant to conventional methods of dilation in which a cystotome was used. Technical success was defined as the successful dilation of the stricture with plastic stent placement. Functional success was defined as substantial pain relief or resolution of pancreatic fistulae. RESULTS: Ten patients (mean age, 30.8 years) underwent dilation of a dominant pancreatic stricture secondary to chronic pancreatitis, with a 6-Fr cystotome. Seven patients presented with pain. Three patients had pancreatic fistulae (two had pancreatic ascites and one had a pancreaticopleural fistula). The median stricture length was 10 mm (range, 5-25 mm). The head of the pancreas was the most common location of the stricture (60%). Technical and functional success was achieved in all patients. One patient had self-limiting bleeding, whereas another patient developed mild post-ERCP pancreatitis. CONCLUSION: The use of a 6-Fr cystotome (diathermy catheter) can be an alternative method for dilation of recalcitrant pancreatic strictures after the failure of conventional modalities.

Primary Amoebic Meningoencephalitis.

Primary amoebic meningoencephalitis due to free living amoeba, also called 'brain eating amoeba', Naegleria fowleri, was detected in retroviral disease patient of 40 years who has history of using well water. Patient was admitted with severe headache, fever intermittent, nausea, vomiting and slurring of speech. CT scan and MRI scan findings were normal. CSF examination showed increased protein, low sugar and predominant lymphocytes. CSF was negative for cryptococcal antigen but wet mount preparation showed highly motile free living amoeba Naegleria fowleri. Patient was put on Amphotericin B, Metronidazole, Rifampicin in addition to ART and ATT and other supportive medications. His headache was relieved and patient improved and was discharged on request. Earlier eight cases have been reported from India of which four cases survived the acute episode.