Mistakes in utilising histopathology for the management of liver disease.

INTRODUCTION: Liver biopsy has become selective due to its invasiveness, potential adverse effects, patient acceptance and cost. Furthermore, the emergence of noninvasive tests (NITs) has challenged the necessity of liver biopsies in specific clinical situations. However, liver biopsy continues to play a crucial role in disease diagnosis, prognosis, and evaluating treatment compliance and response in selected patients. AREAS COVERED: In this narrative review, we discuss the errors and the shortcomings that can occur at various stages, from the initial patient selection for a liver biopsy to the final reporting phase, and strategies to address them. Clinicians and pathologists must take all necessary precautions to mitigate potential shortcomings that could compromise the value of liver biopsies. EXPERT OPINION: The increasing sophistication of NITs offers a safer, more convenient, and potentially more cost-effective approach to diagnosing chronic liver disease, especially for assessing the degree of liver fibrosis. As NITs continue to evolve, liver biopsy will likely transition to a more targeted role, ensuring optimal patient care in the ever-changing field of hepatology. However, liver biopsy will continue to have a pivotal role in assessing acute liver disease where the diagnostic yield of the liver biopsy still outweighs that of NITs.

Subclinical mucosal inflammation in diarrhea-predominant irritable bowel syndrome (IBS) in a tropical setting.

BACKGROUND AND AIMS: There is evidence for low-grade inflammation in the pathophysiology of post-infectious irritable bowel syndrome (IBS). We assessed the degree of subclinical intestinal mucosal inflammation in diarrhea-predominant IBS (IBS-D) in a tropical setting. MATERIAL AND METHODS: In a prospective study over 1 year, we investigated 49 patients with IBS-D (cases; median age 34 years (range 18-59); M:F 36:13), diagnosed on Rome III criteria. 14 individuals with a family history of colon cancer (median age 46.5 years (range 23-56); M:F 6:8) were selected as controls. Stools of cases and controls were tested for calprotectin. During colonoileoscopy, serial biopsies were obtained. Mucosal mast cells, neutrophils, eosinophils and lymphocytes/plasma cell infiltrate were quantified. Tissue expression of IL-8 and IL-10 was assessed in biopsies by semi-quantitative RT-PCR. RESULTS: A history suggestive of an episode of infectious diarrhea (ID) was present in 16/49 cases and 0/14 controls (p = 0.013). In cases, there were significantly more mucosal mast cells in the ileum and all segments of colon and significantly more eosinophils in the cecum. Tissue expression of IL-8 was significantly higher and IL-10 significantly lower in cases compared with controls (target/standard cDNA ratio, median (range) IL-8: 1.25 (0.75-2) vs. 0.85 (0.63-1.3), p < 0.0001, Mann-Whitney U test; IL-10: 0.33 (0-0.63) vs. 0.55 (0.5-0.7), p < 0.0001). There was a significant inverse correlation between IL-8 and IL-10 expression (Pearson correlation, (-) 0.509; p < 0.01). CONCLUSION: There was evidence of subclinical intestinal mucosal inflammation in patients with IBS-D. The finding of increased eosinophils is novel, and may be of special relevance to IBS-D in the tropics.

A rare presentation of an acute abdomen: an ileal diverticular perforation.

BACKGROUND: This case report highlights the value of prompt intervention of diagnostic laparoscopy in a patient suspects of having an acute abdomen due to an intestinal perforation, where there is a limitation of performing Contrast Enhanced Computed Tomography of abdomen. A previously healthy young adult presenting with an acute abdomen due to a spontaneous ileal perforation, without any associated risk factors is a rare clinical entity in a developing country. Therefore, entertaining an early diagnosis will possibly prevent a fatal consequence. CASE PRESENTATION: A male patient, 29 years old, recently diagnosed as a young hypertensive without any associated factors, currently on antihypertensive treatment, was admitted to our hospital presenting with an acute severe abdominal pain. During initial assessment, the patient was febrile (101 °F), ill looking, tachycardic (pulse rate 121 bpm) with rapid shallow breathing. Abdominal examination reviled diffuse guarding and rigidity, more severe on right iliac fossa. Following history and clinical examination probable clinical diagnosis was made as an acute appendicitis with perforation. However, ultrasonography was found to have normal appendix. Contrast Enhanced Computed Tomography was not performed as a subsequent investigation because of the impairment of renal functions of this patient. Though, non-contrast CT would have been ascertained more diagnostic yield, given the critically ill status of this patient we decided to perform urgent diagnostic laparoscopy. It reviled pus in several abdominal cavities and dense adhesions. Therefore, the procedure was converted to a laparotomy and found to have an ileal perforation with diffuse peritoneal contamination. Diseased ileal segment was resected and anastomosed. Followed by peritoneal lavage. CONCLUSION: Ileal perforation due to diverticular disease in a healthy young adult is rare. This case report highlights the importance of considering this clinical entity as a differential diagnosis, the value of early diagnostic laparoscopy, especially in clinical settings with limitations to CT scan, since late diagnosis can give rise to fatal outcome.

Overall Survival of Elderly Patients Having Surgery for Colorectal Cancer Is Comparable to Younger Patients: Results from a South Asian Population.

INTRODUCTION: There has been a continuous debate on whether elderly patients with colorectal cancer (CRC) fair worse. The aim of this study is to assess the thirty-day mortality (TDM) and overall survival (OS) of elderly patients undergoing surgery for CRC. METHOD: OS between two groups (≥70 versus <70 years) having surgery for CRC was analyzed. Demographics, tumour characteristics, and serological markers were considered as independent factors. Multivariable analysis was done using the Cox proportional hazard model. We also compared overall survival in the elderly versus those <60 and <50 years. RESULTS: 477 patients, 160 elderly (55% male; median age 75, range 70-89) and 317 younger patients (49% male; median age 55, range 16 to 69), were studied. Overall survival in CRC patients ≥70 is comparable to <70 (P = 0.45) and <60 years (P = 0.08). Poor OS was observed in the ≥70 versus <50 years (P = 0.03). TDM in the elderly was poor (P < 0.05). Postoperative cardiac complication was the only determinant affecting survival in the elderly (P = 0.01). CONCLUSION: OS in elderly CRC patients having surgery is not worse compared to <70 and <60 years although the TDM was higher. Postoperative cardiac complications significantly affected OS in those ≥70 compared to those <50 years. Chronological age alone should not negatively influence surgical decision-making in the elderly.

Intestinal tuberculosis masquerading as difficult to treat Crohn disease: a case report.

BACKGROUND: Crohn disease has low prevalence in Sri Lanka while compared to the West, while intestinal tuberculosis is common in the region. Since clinical, endoscopic and investigation features of Crohn disease overlap with intestinal tuberculosis, differentiating these two conditions becomes a dilemma for the clinician in the intestinal tuberculosis endemic setting. An 18-year old Sri Lankan Muslim female presented with chronic abdominal pain and weight loss. Colonoscopy revealed an ulcerated ileocaecal valve and a terminal ileal stricture. Biopsy confirmed Crohn disease with no supportive features to suggest intestinal tuberculosis. Despite treatment with adequate immunosuppression she failed to improve and underwent a limited right hemicolectomy and terminal ileal resection. Histology confirmed intestinal tuberculosis and she made full recover with 6 months of anti-tuberculosis treatment. CONCLUSION: This case illustrates the importance of reviewing the diagnosis to include intestinal tuberculosis in an endemic setting, when already diagnosed Crohn disease is treatment refractory.

Worsening cholestasis and possible cefuroxime-induced liver injury following "successful" therapeutic endoscopic retrograde cholangiopancreatography for a distal common bile duct stone: a case report.

BACKGROUND: Cefuroxime very rarely causes drug-induced liver injury. We present a case of a patient with paradoxical worsening of jaundice caused by cefuroxime-induced cholestasis following therapeutic endoscopic retrograde cholangiopancreatography for a distal common bile duct stone. CASE PRESENTATION: A 51-year-old, previously healthy Sri Lankan man presented to our hospital with obstructive jaundice caused by a distal common bile duct stone. Endoscopic retrograde cholangiopancreatography with stone extraction, common bile duct clearance, and stenting failed to improve the cholestasis, with paradoxical worsening of his jaundice. A liver biopsy revealed features of drug-induced intrahepatic cholestasis. Although his case was complicated by an episode of cholangitis, the patient made a complete recovery in 4 months with supportive treatment and withdrawal of the offending drug. CONCLUSIONS: This case highlights a very rare drug-induced liver injury caused by cefuroxime as well as our approach to treating a patient with paradoxical worsening of jaundice after therapeutic endoscopic retrograde cholangiopancreatography.

Total number of lymph nodes harvested is associated with better survival in stages II and III colorectal cancer.

BACKGROUND: Lymph node status is important in staging colorectal cancer (CRC). Presence of metastatic nodes differentiates stage III from stage II. The role of adjuvant therapy is still unclear in stage II CRC. Inadequate node sampling may result in inaccurate staging. METHOD: Records of 131 patients with stages II and III CRC who underwent curative resection, having five or more lymph nodes harvested from the specimen, were prospectively followed up and analyzed. The Kaplan-Meier method was used to analyze survival, based on groups of serially ascending values of lymph nodes harvested. Regression analysis was performed by Cox proportional hazards ratio model with right-censored CRC survival data at a 10 % significance level. The effect of nodal harvest on survival was adjusted for age, sex, preoperative carcinoembryonic antigen (CEA) level, neoadjuvant chemoradiation, pathological tumor stage, histological type, differentiation, margin positivity, angioinvasion, perineural invasion, and lymphovascular infiltration. RESULTS: The total population showed improved survival with 14 or more nodes harvested (p= 0.005). For both rectal (n= 83; p= 0.03) and colon cancers (n= 46; p= 0.08), most significant survival benefits were seen with over 14 nodes harvested, irrespective of the stage. With multiple regression analysis, advanced age (p= 0.003), male sex (p= 0.017), lymphovascular infiltration (p= 0.015), and preoperative CEA levels (p= 0.096) were found to be other significant factors. The lymph node effect remained significant (HR = 0.19, p= 0.004) after adjusting for the above factors. CONCLUSION: A lymph node harvest of 14 or more resulted in better survival outcome from CRC in this population. Staging of the disease could be accurate with increased nodal harvesting.

Distribution of human papillomavirus genotypes in archival cervical tissue from women with cervical cancer in urban Sri Lanka.

OBJECTIVE: To identify the contributions of various human papillomavirus (HPV) genotypes in tissue samples from women diagnosed with cervical cancer in Sri Lanka. METHODS: In a retrospective study, archival cervical tissues samples (n=108) obtained from Sri Lankan women diagnosed with histologically proven invasive squamous cell carcinoma between 2006 and 2007 were tested for HPV. Genotyping of HPV DNA was performed using an INNO-LiPA assay. RESULTS: Overall, 93% of tumor samples tested positive for HPV DNA. HPV types 16 and 18 accounted collectively for 83.4% of the positive samples. CONCLUSION: The findings suggest that the HPV genotypes responsible for causing cervical cancer in Sri Lanka are similar to those reported elsewhere worldwide. Consequently, women in Sri Lanka could benefit from currently available prophylactic HPV vaccines should they be implemented.

Neoadjuvant therapy for rectal cancer down-stages the tumor but reduces lymph node harvest significantly.

PURPOSE: The impact of neoadjuvant therapy (NAT) for rectal cancer on lymph node yield is not well known. This study evaluates the impact of NAT on tumor regression and lymph node harvest. METHODS: The subjects were 40 patients with rectal cancer; 20 receiving high-dose, long-course neoadjuvant therapy, and 20 age- and sex-matched controls who did not receive neoadjuvant therapy. Tumor regression (TRG) was graded from 1 to 5 as: TRG1, no residual tumor cells; TRG2, occasional residual tumor cells with marked fibrosis; TRG3, marked fibrosis with scattered tumor cells or groups; TRG4, abundant cancer cells with little fibrosis; TRG5, no tumor regression. We also evaluated the number of lymph nodes retrieved from excised specimens, the size of the largest node, and the extent of lymph node involvement by the tumor. RESULT: Tumor regression was seen in all patients; as TRG1 in 6 (30%), TRG2 in 2 (10%), TRG3 in 3 (15%), and TRG4 in 9 (45%). The median nodal harvest was 4 (range (0-12) in the NAT group vs 9 (range 1-19) in the control (P = 0.001). The median size of the largest lymph node was 5 mm (range 2-12 mm) in the NAT group vs 9 mm (range 4-15 mm) in the control group (P = 0.004). Tumor-positive nodes were identified in 4 of 17 of the NAT group patients and in 9 of the 20 controls (P = 0.308). CONCLUSION: Although NAT down-stages rectal cancer, it results in a significantly low yield of lymph nodes, which are also significantly smaller than those in nonirradiated controls. Therefore, surgeons and histopathologists must ensure adequate sampling and accurate staging is done for patients with irradiated rectal cancer.