Prognostic Significance of EMVI in Rectal Cancer in a Tertiary Cancer Hospital in India.

Background Presence of extramural venous invasion (EMVI) is a poor prognostic factor for rectal cancer as per literature. However, India-specific data are lacking. Aim The aim of the study is to determine the prognostic significance of EMVI in locally advanced rectal cancer on baseline MRI. Materials and Methods We retrospectively reviewed 117 MRIs of operable non-metastatic locally advanced rectal cancers in a tertiary cancer institute. Three dedicated oncoradiologists determined presence or absence of EMVI, and its length and thickness, in consensus. These patients were treated as per standard institutional protocols and followed up for a median period of 37 months (range: 2-71 months). Kaplan-Meier curves (95% CI) were used to determine disease-free survival (DFS), distant-metastases free survival (DMFS), and overall survival (OS). Univariate analysis was performed by comparing groups with log-rank test. Results EMVI positive cases were 34/114 (29%). More EMVI-positive cases developed distant metastasis compared with EMVI-negative cases (14/34-41% vs. 22/83-26%). The difference, however, was not statistically significant ( p = 0.146). After excluding signet-ring cell cancers ( n = 14), EMVI showed significant correlation with DMFS ( p = 0.046), but not with DFS or OS. The median thickness and length of EMVI was 6 and 14 mm, respectively in patients who developed distant metastasis, as compared with 5 and 11 mm in those who did not, although this difference was not statistically significant. Conclusion EMVI is a predictor of distant metastasis in locally advanced non-metastatic, non-signet ring cell rectal cancers. EMVI can be considered another high-risk feature to predict distant metastasis.

ERBB2 and KRAS alterations mediate response to EGFR inhibitors in early stage gallbladder cancer.

The uncommonness of gallbladder cancer in the developed world has contributed to the generally poor understanding of the disease. Our integrated analysis of whole exome sequencing, copy number alterations, immunohistochemical, and phospho-proteome array profiling indicates ERBB2 alterations in 40% early-stage rare gallbladder tumors, among an ethnically distinct population not studied before, that occurs through overexpression in 24% (n = 25) and recurrent mutations in 14% tumors (n = 44); along with co-occurring KRAS mutation in 7% tumors (n = 44). We demonstrate that ERBB2 heterodimerizes with EGFR to constitutively activate the ErbB signaling pathway in gallbladder cells. Consistent with this, treatment with ERBB2-specific, EGFR-specific shRNA or with a covalent EGFR family inhibitor Afatinib inhibits tumor-associated characteristics of the gallbladder cancer cells. Furthermore, we observe an in vivo reduction in tumor size of gallbladder xenografts in response to Afatinib is paralleled by a reduction in the amounts of phospho-ERK, in tumors harboring KRAS (G13D) mutation but not in KRAS (G12V) mutation, supporting an essential role of the ErbB pathway. In overall, besides implicating ERBB2 as an important therapeutic target under neo-adjuvant or adjuvant settings, we present the first evidence that the presence of KRAS mutations may preclude gallbladder cancer patients to respond to anti-EGFR treatment, similar to a clinical algorithm commonly practiced to opt for anti-EGFR treatment in colorectal cancer.

A cross-sectional study of the distribution of pediatric solid tumors at an Indian tertiary cancer center.

CONTEXT: Pediatric solid tumors include a heterogeneous group of tumors, and the burden of these tumors, especially from resource-challenged countries, is not well described. AIMS: The aim of this study was to describe the distribution of solid tumors in children and the treatment outcome of Wilms tumor and hepatoblastoma. PATIENTS AND METHODS: All patients under 15 years of age with histologically confirmed tumors presenting at a tertiary cancer center from January 2012 to December 2016 were identified from the hospital database. Patients with lymphomas, bone, and central nervous tumors were excluded. The demographic profile including age, sex distribution, and the treatment received were recorded for all patients. RESULTS: The mean age of the eligible 1944 patients was 5.7 years with majority (57.3%) in the 0-4 years age group. The male-to-female ratio was 1.4:1 with a male predominance in all tumors except germ cell tumors. Soft tissue tumors were the most common tumors followed by neuroblastoma and renal tumors, whereas liver tumors formed only 6.7% of all tumors. Seventy percent of the patients received treatment completely or partially at our institute, whereas 18.3% had no cancer-directed treatment. The 3-year overall survival of patients with Wilms tumor and hepatoblastoma was 85.4 and 78.5%, respectively. CONCLUSIONS: Extracranial and extraosseous pediatric solid tumors include a wide range of tumors with a predilection for male sex and children below 4 years of age. Soft tissue tumors, neuroblastoma, and renal tumors are the most common; the outcomes of Wilms tumor and hepatoblastoma are favorable.

Non-typhoidal Salmonella DNA traces in gallbladder cancer.

BACKGROUND: We earlier proposed a genetic model for gallbladder carcinogenesis and its dissemination cascade. However, the association of gallbladder cancer and 'inflammatory stimulus' to drive the initial cascade in the model remained unclear. A recent study suggested infection with Salmonella can lead to changes in the host signalling pathways in gallbladder cancer. FINDINGS: We examined the whole exomes of 26 primary gall bladder tumour and paired normal samples for presence of 143 HPV (Human papilloma virus) types along with 6 common Salmonella serotypes (S. typhi Ty2, S. typhi CT18, S. typhimurium LT2, S. choleraesuis SCB67, S. paratyphi TCC, and S. paratyphi SPB7) using a computational subtraction pipeline based on the HPVDetector, we recently described. Based on our evaluation of 26 whole exome gallbladder primary tumours and matched normal samples: association of typhoidal Salmonella species were found in 11 of 26 gallbladder cancer samples, and non-typhoidal Salmonella species in 12 of 26 gallbladder cancer, with 6 samples were found co-infected with both. CONCLUSIONS: We present the first evidence to support the association of non-typhoidal Salmonella species along with typhoidal strains in gallbladder cancer. Salmonella infection in the chronic carrier state fits the role of the 'inflammatory stimulus' in the genetic model for gallbladder carcinogenesis that may play a role in gallbladder cancer analogous to Helicobacter pylori in gastric cancer.

Hepatoblastoma: a single institutional experience of 18 cases.

Hepatoblastomas are the most common liver tumours in children. However, they are rare as compared to other solid malignancies. Thus, there is a need to integrate data from surgical centers around the world to provide a clearer view on the outcomes of multidisciplinary management of these tumours. We set out to retrospectively review our experience of patients with surgically resected hepatoblastomas looking at primary and secondary outcomes. Children diagnosed with hepatoblastoma and managed surgically (along with chemotherapy) at a single institution between 1 January 2000 and 31 May 2007, were analyzed. Out of the 18 patients, there were 12 male and 6 female patients. The median age was 18 months (range 8-72). A palpable mass in abdomen was the presenting symptom in 88% patients. Sixteen patients (88.8%) underwent major liver resection. Sixteen patients (88.8%) received preoperative chemotherapy. Complete gross resection (stage I and II) was achieved in all 18 patients (100%). The mortality and morbidity rates were 0 and 11.2%, respectively. The 80-month disease-free survival was 67%. This series, the largest from India in terms of surgical resections for hepatoblastoma, reaffirms that major liver resection can be performed with minimal perioperative mortality and morbidity and that the use of chemotherapy has definitely helped in down staging tumours for liver resection.