Corrigendum to "Correlation of Clinicopathological Profile, Prognostic Factors, and Survival Outcomes with Baseline Alfa-Fetoprotein Levels in Patients with Hepatocellular Carcinoma: A Biomarker that is Bruised but Not Broken" [J Clin Exp Hepatol 12 (2022) 841-852].

[This corrects the article DOI: 10.1016/j.jceh.2021.11.006.].

Correlation of Clinicopathological Profile, Prognostic Factors, and Survival Outcomes with Baseline Alfa-Fetoprotein Levels in Patients With Hepatocellular Carcinoma: A Biomarker that is Bruised but Not Broken.

Background and aims: The role of Alfa-fetoprotein (AFP) in the management of hepatocellular carcinoma (HCC) is still debated, with differences in recommendations between international guidelines. We analyzed the relationship of the clinicopathological profile, prognostic features, and survival outcomes with baseline serum AFP levels in patients with HCC. Methods: Retrospective analysis of a prospectively accrued dataset of consecutive HCC patients was done. Results: 508 treatment naive patients were included in the analysis. AFP at presentation was normal (<10 ng/ml) in 18% patients. Patients with very high AFP (>400 ng/ml) had poor hepatic reserves (higher mean serum bilirubin, AST, ALT, INR, and lower mean albumin) and advanced disease at presentation (higher incidence of extrahepatic metastasis, and less proportion of patients with well-differentiated tumors). AFP >400 ng/ml was an independent predictor for presence of portal vein tumor thrombosis (PVTT) (OR, 4.08; 95% CI, 2.34-7.12; P < 0.001), higher tumor size (OR, 2.19; 95% CI, 1.36-3.54, P = 0.001) and advanced BCLC stage (OR, 4.19; 95% CI, 2.51-7.03; P < 0.001). Two-third of patients with small HCC (MTD <3 cm) and more than half with early-stage HCC (BCLC stage 0/A) had elevated AFP levels. No significant relationship was seen between overall survival (OS) and baseline AFP in patients who underwent surgery, but median OS in patients subjected to nonsurgical therapies was 19.4,10.5 and 5.7 months in patients having AFP <10 ng/ml, 10-400 ng/ml and >400 ng/ml respectively (P = 0.003). AFP >400 ng/ml was an independent predictor of survival in patients receiving any form of therapy (HR = 2.23; 95% CI = 1.19-4.18, P = 0.012). Conclusion: AFP as a biomarker still has a significant role to play in the management of HCC patients and is here to stay till the search for an ideal biomarker in HCC is over.

Laparoscopic ovarian transposition in teenage and young women with locally advanced rectal cancer: Respite amidst cancer chaos.

AIM: Ovarian transposition is an established surgical technique to salvage ovaries in premenopausal women requiring pelvic radiation. The success rate of ovarian transposition varies widely depending on the route, technique of surgery, type of cancer and treatment. Here, we aimed to analyse the effectiveness of laparoscopic ovarian transposition (LOT) in teenage and young women prior to pelvic radiation in locally advanced rectal cancers (LARC). METHODS: Patients who underwent LOT for rectal cancers were retrieved from a prospectively maintained database from June 2013-September 2019. Disease characteristics, return of menstrual function and oncological outcomes were analysed. RESULTS: A total of 46 women with a mean age of 25.2 years who underwent LOT at the cancer centre were included in the study. Seventy percent were nulliparous. All patients were fit for discharge by 24 h. Mean time to start radiation was 19.6 days (range 3-47 days). Median follow-up of patients was 42 months. A total of 41 patients were assessable for ovarian function, 65.5% had resumption of menses. Median ovarian survival was 79 months and 5-year ovarian survival was 54%. Median overall survival from rectal cancer was 51 months. CONCLUSION: Laparoscopic ovarian transposition is a safe and effective technique of ovarian protection from the gonadotoxic effects of pelvic radiation in LARC. It does not delay primary treatment and does not compromise oncological outcomes. Long-term follow-up is required to evaluate fertility and quality of life.

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.

A study of the clinical profile, predictors, prognostic features, and survival of patients with hepatocellular carcinoma having macroscopic portal vein tumor thrombosis.

BACKGROUND: Macroscopic portal vein tumor thrombosis (PVTT) is considered a negative prognostic factor in hepatocellular carcinoma (HCC) patients. There is divergent opinion regarding management of these patients worldwide. We aimed to evaluate the clinical profile, predictors, prognostic features, and survival of patients of HCC with PVTT. METHODS: Treatment-naïve HCC patients with and without PVTT were analyzed retrospectively using a prospectively accrued dataset. Patients with PVTT were further divided as per treatment groups for survival analysis. RESULTS: Of 508 patients, 46.1% had radiological evidence of PVTT at presentation. On logistic regression, serum albumin (odds ratio [OR]=0.65, 95% confidence interval [CI]= 0.44-0.96; p= 0.031); international normalized ratio (OR = 3.78,95% CI = 1.42-10.00; p=0.008); alpha-feto protein >400 ng/mL (OR=3.58, 95%CI = 2.00-6.40; p <0.001); size of largest tumor nodule >5 cm (OR =6.37, 95%CI =2.03-19.99; p =0.002); and male gender (OR =1.84, 95%CI = 1.01-3.33; p = 0.045) were independent predictors for PVTT. Patients with PVTT amenable to aggressive therapies had significantly better median overall survival (in months) as compared to those receiving sorafenib or best supportive care only (13.1, 3.9, and 1.8 respectively, p<0.0001). Treatment modality received (p<0.001) and extrahepatic metastasis (p=0.006) were independent predictors of mortality in these patients. CONCLUSION: Size of largest tumor nodule >5 cm and alpha-fetoprotein >400 ng/mL are strongly associated with the presence of PVTT in patients with HCC. A multidisciplinary approach may identify a subgroup of patients who can be offered aggressive therapies like surgery and/or locoregional therapy with significant survival benefit.

The Role of Gallstones in Gallbladder Cancer in India: A Mendelian Randomization Study.

BACKGROUND: Past history of gallstones is associated with increased risk of gallbladder cancer in observational studies. We conducted complementary observational and Mendelian randomization (MR) analyses to determine whether history of gallstones is causally related to development of gallbladder cancer in an Indian population. METHODS: To investigate associations between history of gallstones and gallbladder cancer, we used questionnaire and imaging data from a gallbladder cancer case-control study conducted at Tata Memorial Hospital, Mumbai, Maharashtra, India (cases = 1,170; controls = 2,525). We then used 26 genetic variants identified in a genome-wide association study of 27,174 gallstone cases and 736,838 controls of European ancestry in an MR approach to assess causality. The association of these genetic variants with both gallstones and gallbladder cancer was examined in the gallbladder cancer case-control study. Various complementary MR approaches were used to evaluate the robustness of our results in the presence of pleiotropy and heterogeneity, and to consider the suitability of the selected SNPs as genetic instruments for gallstones in an Indian population. RESULTS: We found a strong observational association between gallstones and gallbladder cancer using self-reported history of gallstones [OR = 4.5; 95% confidence interval (CI) = 3.5-5.8] and with objective measures of gallstone presence using imaging techniques (OR = 2.0; 95% CI = 1.5-2.7). We found consistent causal estimates across all MR techniques, with ORs for gallbladder cancer in the range of 1.3-1.6. CONCLUSIONS: Our findings indicate a causal relationship between history of gallstones and increased risk of gallbladder cancer, albeit of a smaller magnitude than those found in observational analysis. IMPACT: Our findings emphasize the importance of gallstone treatment for preventing gallbladder cancer in high-risk individuals.

Laparoscopic Versus Open Approach for Intersphincteric Resection-Results from a Tertiary Cancer Center in India.

The study aims to compare open intersphincteric resection (OISR) with laparoscopic intersphincteric resection (LISR) in terms of short-term oncological and clinical outcomes. This is a retrospective review of a prospectively maintained database including all the patients of rectal cancer who underwent intersphincteric resection (ISR) at Tata Memorial Centre between 1st July 2013 and 30th November 2015. Short-term oncological parameters evaluated included circumferential resection margin involvement (CRM), distal resection margin involvement, and number of nodes harvested. Perioperative outcomes included blood loss, length of hospital stay and 30-day postoperative morbidity and mortality. Chi-square test was used to compare the results between the two groups. Thirty nine cases of OISR and 34 cases of LISR were included in the study. Median BMI was higher in LISR group; otherwise, the two groups were comparable in all aspects. There were no conversions in LISR group. CRM involvement was seen in four patients (10%) in the conventional group compared to none in the LISR group. Median hospital stay was comparable between the two groups. Laparoscopic ISR is safe and can be performed with low conversion rate in selected group of patients.

Colorectal Cancer in India: An Audit from a Tertiary Center in a Low Prevalence Area.

Colorectal cancer (CRC) is a common cancer worldwide with a low reported incidence in India. There is significant geographical variation in the incidence rates, and the presentation may also vary. There are few studies evaluating the clinical profile of CRC in Indian patients. We analyzed a prospective database maintained at the Tata Memorial Hospital, a referral cancer center in Mumbai, of consecutive patients with CRC between August 2013 and August 2014. We captured details regarding the demography, symptoms, pathology, stage, and treatment plan. The aim was to assess the demographic and clinical details of patients with CRC in India and compare it with those of the reported literature. Eight hundred new patients with CRC were seen in the colorectal clinic in one year. The mean age was 47.2 years. Sixty-five percent were males. Patients were symptomatic for an average period of 4 months prior to presentation. The commonest symptoms were rectal bleeding (57%), pain (44%), and altered bowel habits (26%). Thirteen percent of the patients had signet ring tumors. The median CEA (carcinoembryonic antigen) level was 5.8 ng/mL. Most patients had localized or locally advanced disease. Twenty-eight percent of the patients had metastatic disease with liver being the commonest site of metastases (14%) followed by peritoneum and lung. More than half of the patients received treatment with a curative intent. Colorectal cancer in India differs from that described in the Western countries. We had more young patients, higher proportion of signet ring carcinomas, and more patients presenting with an advanced stage. Inadequate access to healthcare and socioeconomic factors may play a role in some of these differences.

Ovarian Metastases of Colorectal Origin: Treatment Patterns and Factors Affecting Outcomes.

The purpose of this study is to evaluate the patterns of treatment and factors affecting outcomes in ovarian metastases of colorectal origins treated at our institution and to assess the response of ovarian metastases to chemotherapy. Survival in R0 and R+ resections and patients receiving only chemotherapy is also analyzed. This is a retrospective study of 25 patients registered between January 2012 and December 2015. Patient's age, disease status, mode of presentation, disease spread, mode of treatment, response to chemotherapy, completeness of resection, histology, and outcomes were considered as variables for analysis. There were 21 synchronous presentations and 4 metachronous presentations. In synchronous presentations, only 2 had extra-abdominal disease. Of these patients, 15 underwent surgeries of various extents. The remaining 6 patients were treated with chemotherarpy initially. Only one of them could come up to surgery later. In R0 resections, disease recurred between 1 and 9 months (median 3.5 months). The recurrence was in peritoneum and ovaries. In operated cases, 12 of 15 patients received chemotherapy and 9 patients progressed on first line chemotherapy. In all 4 metachronous patients, the disease was in the peritoneum. No one underwent surgery for the recurrence due to the extensive nature of the disease. All received chemotherapy. Sixty-six percent ovarian metastases showed progression on chemotherapy. There was no significant difference in the median survival between patients treated with surgery plus chemotherapy (23 months) vs. those treated with chemotherapy alone (28 months). Age and presence of disease at other sites did not affect the outcomes. Non-signet ring cell histologies showed better outcomes compared to signet ring cell histology (p = 0.02). Synchronous presentation, R0 resections, and responsive disease showed better survival, however it was clinically not significant. Treatment of ovarian metastases of colorectal origins is varied but has consistently poor outcome. Non-signet histology was the only prognostic factor which showed better outcome. Survival was not different between patients treated with surgery+chemotherapy and chemotherapy alone but majority of ovarian metastases progressed on chemotherapy. Considering the poor response to chemotherapy and peritoneum being the most common site of disease, both in primary and recurrent setting, R0 resection should always be attempted after selecting the correct patients using PET scan, laparoscopy and standard exploratory protocols. Treatment should be tailored upon patient's status and disease burden with an aim to do complete cytoreduction whenever possible. CRS+HIPEC (cytoreductive surgery + hyperthermic intraperitoneal chemotherapy) can be considered on case to case basis as even R0 resections tend to recur.

Selective extra levator versus conventional abdomino perineal resection: experience from a tertiary-care center.

BACKGROUND: To compare extra levator abdomino perineal resection (ELAPER) with conventional abdominoperineal resection (APER) in terms of short-term oncological and clinical outcomes. METHODS: This is a retrospective review of a prospectively maintained database including all the patients of rectal cancer who underwent APER at Tata Memorial Center between July 1, 2013, and January 31, 2015. Short-term oncological parameters evaluated included circumferential resection margin involvement (CRM), tumor site perforation, and number of nodes harvested. Peri operative outcomes included blood loss, length of hospital stay, postoperative perineal wound complications, and 30-day mortality. The χ(2)-test was used to compare the results between the two groups. RESULTS: Forty-two cases of ELAPER and 78 cases of conventional APER were included in the study. Levator involvement was significantly higher in the ELAPER compared with the conventional group; otherwise, the two groups were comparable in all the aspects. CRM involvement was seen in seven patients (8.9%) in the conventional group compared with three patients (7.14%) in the ELAPER group. Median hospital stay was significantly longer with ELAPER. The univariate analysis of the factors influencing CRM positivity did not show any significance. CONCLUSIONS: ELAPER should be the preferred approach for low rectal tumors with involvement of levators. For those cases in which levators are not involved, as shown in preoperative magnetic resonance imaging (MRI), the current evidence is insufficient to recommend ELAPER over conventional APER. This stresses the importance of preoperative MRI in determining the best approach for an individual patient.

Clinical Outcome in Definitive Concurrent Chemoradiation With Weekly Paclitaxel and Carboplatin for Locally Advanced Esophageal and Junctional Cancer.

There are little data on the efficacy and safety of taxane/platinum with definitive radiotherapy (RT) for esophageal/GEJ cancer. This article is a retrospective analysis of patients who received weekly paclitaxel 50 mg/m(2) and carboplatin AUC 2 with radical definitive RT for locally advanced esophageal/GEJ cancer. Between February 2011 and July 2014, 179 patients were included. The median age was 54 years. Ninety-two percent of patients had squamous histology. Mean RT dose was 58.7 Gy in 32 fractions over 53 days, with mean of six chemotherapy cycles. Fifty-six percent of patients developed ≥grade 3 acute toxicities, commonly febrile neutropenia (12%) and infection (11%); ≥grade 3 laboratory abnormalities included hyponatremia (38%), leukopenia (49%), neutropenia (27%), and anemia (16%). Twelve percent of patients developed ≥grade 3 chronic toxicity. Fatal toxicities included six during CRT, eight within 30 days of completing CRT, and three chronic. Radiologic response was 49% (CR 5.6%, PR 43%). Follow-up endoscopy showed remission in 53% and residual disease in 14%. At a median follow-up of 28 months, median PFS was 11 months (95% CI: 8-13.9), median OS was 19 months (95% CI: 15.4-22.6), and estimated 1-year, 2-year, and 3-year survivals were 70%, 47%, and 39%, respectively. Weekly paclitaxel-carboplatin concurrently with definitive RT is efficacious with manageable toxicity. [The trial was registered with the Clinical Trials Registry-India (CTRI), registration number: CTRI/2014/07/004776.].

Multimodality therapy of rectal gastrointestinal stromal tumors in the era of imatinib-an Indian series.

BACKGROUND: Primary objective was to determine if sphincter preservation is possible with the use of neoadjuvant imatinib in cases of rectal gastrointestinal stromal tumor (GIST). Secondary objectives were to determine clinicopathological characteristics and intermediate term oncological outcomes of the cases of rectal GIST. METHODS: This is a retrospective review of 13 cases of GIST of the rectum diagnosed between January 1, 2010 and June 30, 2015 at Tata Memorial Centre, Mumbai, India. Clinical parameters that were assessed were duration of the neoadjuvant imatinib therapy, type of surgery performed as well as perioperative morbidity. Pathological parameters that were assessed included the size of the tumor, completeness of resection, mitotic count and mutational analysis. RESULTS: Of the 13 patients included, 11 were nonmetastatic at the time of presentation. All the patients received neoadjuvant imatinib in view of locally advanced nature of the tumors. Median distance from anal verge was 2 cm. Median duration of imatinib was 9 months. Of the 9 patients who underwent surgery, three had sphincter preserving surgery (33%) whereas the rest had abdomino-perineal resection. Two patients had perineal wound infections. All the operated patients received adjuvant imatinib therapy for 3 years. Median follow up period was 34 months. One patient developed distant metastasis; otherwise rest had no local or distant recurrence. CONCLUSIONS: In cases of rectal GIST, sphincter preservation may not be possible in spite of neoadjuvant therapy with imatinib.

Serum ferritin and the risk of hepatocellular carcinoma in chronic liver disease of viral etiology: a case-control study.

BACKGROUND: The worldwide incidence rates of hepatocellular carcinoma (HCC) vary widely. Some countries like India have a low incidence despite having a large burden of chronic hepatitis B (HBV) and C virus (HCV) infection. We hypothesized that long-term iron deficiency could attenuate the hepatic inflammation and lead to a lower incidence of HCC in India than expected. METHODS: We evaluated the association of serum ferritin levels and HCC in Indian patients with HBV- or HCV-related chronic liver disease (CLD) using a case-control study design. We enrolled 141 patients with HCC (cases) and 240 patients having chronic HBV or HCV infection-related CLD (controls). Study participants were grouped on the basis of ferritin values into low-normal, high-normal, and high subgroups. RESULTS: Mean ferritin values were higher in cases as compared to controls (425.8 vs. 135.6 ng/mL, p = 0.000). A significant dose-response effect for serum ferritin levels and HCC was seen with an odds ratio (95 % confidence interval) of 3.0 (1.6-5.9, p = 0.001) for subjects with high-normal ferritin levels and 8.2 (4.1-16.5, p = 0.000) for subjects with high ferritin levels in a multivariate model. Other significant independent risk factors in the multivariate model included older age, male gender, alcohol and tobacco use, elevated alanine aminotransferase, higher family income, and coffee drinking. CONCLUSION: We found an independent association between serum ferritin levels and HCC in patients with CLD of viral etiology. Further prospective studies are needed to confirm the hypothesis that iron deficiency protects against HCC in CLD.