Evidence for possible non-canonical pathway(s) driven early-onset colorectal cancer in India.

Two genetic instability pathways viz. chromosomal instability, driven primarily by APC mutation induced deregulated Wnt signaling, and microsatellite instability (MSI) caused by mismatch repair (MMR) inactivation, together account for >90% of late-onset colorectal cancer (CRC). Our understanding of early-onset sporadic CRC is however comparatively limited. In addition, most seminal studies have been performed in the western population and analyses of tumorigenesis pathway(s) causing CRC in developing nations have been rare. We performed a comparative analysis of early and late-onset CRC from India with respect to common genetic aberrations including Wnt, KRAS, and p53 (constituting the classical CRC progression sequence) in addition to MSI. Our results revealed the absence of Wnt and MSI in a significant proportion of early-onset as against late-onset CRC in India. In addition, KRAS mutation frequency was significantly lower in early-onset CRC indicating that a significant proportion of CRC in India may follow tumorigenesis pathways distinct from the classical CRC progression sequence. Our study has therefore revealed the possible existence of non-canonical tumorigenesis pathways in early-onset CRC in India.

Accuracy of Tumor Bed Biopsy for Predicting Pathologic Complete Response After Chemotherapy Among Women With Breast Cancer: Complete Responders in the Breast Study.

PURPOSE: With the advent of taxanes and targeted agents in neoadjuvant chemotherapy (NACT) for breast cancer, the rates for pathologic complete response (pCR) have been steadily increasing. Surgery in these women serves as a biopsy to confirm or negate a pCR. METHODS: All newly diagnosed patients with nonmetastatic breast cancer, planned for NACT, were screened. Eligible patients with a complete or near-complete response to NACT as seen on a mammogram and ultrasound (US) were recruited. A magnetic resonance imaging was performed for these patients for documentation. US-guided core biopsies of the tumor bed (Core Bx) using a 14G needle was performed (minimum four in number), and the results were compared with the final histopathology report after surgery for standard performance parameters. RESULTS: This study recruited 65 women of whom 94% were node-positive, and 60% were hormone receptor-negative. The pCR rate was 41.5% and 53.8% for the whole cohort and the hormone receptor-negative subgroup, respectively. The false-negative rate (FNR) for Core Bx was 42.1% (95% CI, 26.3 to 59.2), with a negative predictive value of 59.0% (95% CI, 42.1 to 74.4). Among the hormone receptor-negative tumors, the FNR was 44.4% (95% CI, 21.5 to 69.2) with a negative predictive value of 70.4% (95% CI, 49.8 to 86.2). CONCLUSION: The Complete Responders in the Breast study results suggest that ultrasound-guided 14G core needle biopsy of the tumor bed may not be a reliable predictor of pCR in the breast. These results highlight the importance of further research into the omission of surgery in the breast after chemotherapy. This study is registered with Clinical Trials Registry of India (CTRI/2018/01/011122).

p16 gene alterations in human ovarian cancers: comparison between tissue and blood samples.

OBJECTIVE: To determine the alterations of tumor suppressor gene p16INK4A in human ovarian cancers to explore the possibilities of identifying potential minimally invasive markers in blood of the patients, which could help in the clinical practice as a diagnostic and prognostic marker. METHODS: Ovarian cancer tissue and corresponding blood samples were collected from patients (n = 50). The promoter methylation and mutation status of p16 gene in blood and ovarian tissue DNA was then assessed using methylation-specific polymerase chain reaction and denaturing high-performance liquid chromatography along with DNA sequencing method. In addition, the protein expression in ovarian cancer tissue samples was detected by immunostaining method using monoclonal antibodies against p16. RESULTS: Methylation of p16 was observed in 56% (28/50) of the cases. The data showed concordance in promoter methylation status of p16 gene between the tumor tissue and the corresponding blood DNA samples of the patients with ovarian cancer. There was a weak statistical agreement (Kendall tau b = +0.31), and a perfect correspondence was observed in 50% of the cases. The p16 mutations were comparatively low, revealing only 2 variations among the samples analyzed. The percentage of protein expression was inversely correlated with the p16 gene promoter methylation. CONCLUSIONS: This study demonstrates that the p16 gene plays a role in the progression of human ovarian cancers and the blood DNA methylation of p16 gene promoter region is a weak predictor of tumor tissue methylation status.

A novel 11;18 translocation in a case of acute myeloid leukemia with maturation.

Acute myeloid leukemia with maturation (AML-M2) is associated with the 8;21 translocation. For the first time in an adult patient with AML-M2, a novel unbalanced translocation involving the short arm of chromosome 11 and long arm of chromosome18 with new breakpoints is presented. CD82 on band 11p11.2 and GATA 6 on 18q11.2 may play a role in the pathogenesis of de novo AML M2. The report with translocation (11;18)(p11.2;q11.2), as the sole cytogenetic abnormality provides more data on the leukemogenesis of de novo AML M2.

Accuracy of digital mammography, ultrasound and MRI in predicting the pathological complete response and residual tumor size of breast cancer after completion of neoadjuvant chemotherapy.

Background: Neoadjuvant chemotherapy (NACT) is the standard of care for the treatment of locally advanced or non-metastatic breast cancer, which may increase the chances of breast conservative surgery (BCS) in place of radical mastectomy without compromising on the overall survival. The aim of this study was to evaluate the accuracy of mammography (MG), ultrasound (US), and magnetic resonance imaging (MRI) in predicting the complete response and to assess the extent of residual breast cancer in women treated with NACT. Materials and Methods: Fifty-six consecutive patients with stage II or III breast cancer, who underwent imaging evaluation of breast with digital mammogram, US, and MRI after NACT and before the breast surgery, were included in the study. For each patient, pathologic complete response (pCR) or residual tumor (non-pCR) was predicted and the maximum extent of the residual tumor was measured on each imaging modality. These measurements were subsequently compared with the final histopathology results. Results: Of 56 patients, 22 showed pCR with MRI having better accuracy for predicting complete response than the MG and US (area under the receiver operating characteristic curve: 0.86, 0.68, and 0.65, respectively; p = 0.0001 for MRI; p = 0.06 for MG, and p = 0.02 for US). The sensitivity of MRI for detecting pCR was 72.7%; specificity and positive predictive value were 100%. For pathological residual tumor, the size measured on MRI showed significantly higher correlation with the pathologic size (correlation coefficient, r = 0.786), than the MG (r = 0.293) and US (r = 0.508) with P < 0.05. Conclusions: Accuracy of MRI for predicting pathological complete response was significantly higher than the MG and US. Pathologic residual tumor size was also more precisely reflected by the longest tumor dimension on MRI with the strong positive correlation coefficient.

Circulating tumor cell assay to non-invasively evaluate PD-L1 and other therapeutic targets in multiple cancers.

Biomarker directed selection of targeted anti-neoplastic agents such as immune checkpoint inhibitors, small molecule inhibitors and monoclonal antibodies form an important aspect of cancer treatment. Immunohistochemistry (IHC) analysis of the tumor tissue is the method of choice to evaluate the presence of these biomarkers. However, a significant barrier to biomarker testing on tissue is the availability of an adequate amount of tissue and need for repetitive sampling due to tumor evolution. Also, tumor tissue testing is not immune to inter- and intra-tumor heterogeneity. We describe the analytical and clinical validation of a Circulating Tumor Cell (CTC) assay to accurately assess the presence of PD-L1 22C3 and PD-L1 28.8, ER, PR and HER2, from patients with solid tumors to guide the choice of suitable targeted therapies. Analytically, the test has high sensitivity, specificity, linearity and precision. Based on a blinded case control study, the clinical sensitivity and specificity for PD-L1 (22C3 and 28.8) was determined to be 90% and 100% respectively. The clinical sensitivity and specificity was 83% and 89% for ER; 80% and 94% for PR; 63% and 89% for HER2 (by ICC); and 100% and 92% for HER2 (by FISH), respectively. The performance characteristics of the test support its suitability and adaptability for routine clinical use.

Frequency of Nucleophosmin 1 Expression by Immunohistochemistry in Acute Myeloid Leukemia.

Nucleophosmin (NPM1) mutation is one of the most common recurring genetic abnormalities seen in acute myeloid leukemia (AML). Immunohistochemistry serves as a cost effective and simple surrogate testing method for detection of NPM1 mutation. This study was conducted to evaluate the frequency of aberrant cytoplasmic nucleophosmin 1 expression in leukemic blast cells on formalin fixed bone marrow trephine biopsy (BMB) sections and also to correlate this data with the reference molecular method (reverse transcriptase-polymerase chain reaction; RT-PCR and gene sequencing), where available. Immunostains were performed using mouse anti-NPM1 monoclonal antibody on 71 paraffin embedded bone marrow biopsies (BMB) of patients with AML of any French-American-British (FAB) subtype. Results of immunohistochemistry (IHC) were then compared with the reference molecular method. The proportion of NPM1 expression by immunostaining in AML cases was found to be 17%. Twelve of the total 71 cases demonstrated cytoplasmic nucleophosmin (NPMc+) on immunostaining. Eleven of the positive cases that were correlated with the molecular standard demonstrated mutation in exon 12 of NPM1 gene. Cytoplasmic nucleophosmin expression by immunostaining was found to be in complete agreement with the standard molecular method. In a resource restricted setup, the information from this study might help in providing an inexpensive and accurate detection method to facilitate introduction of this marker in diagnostic and prognostic workup of AML especially in patients showing normal karyotype and no common recurrent translocations.

Primary intracranial extra-skeletal myxoid chondrosarcoma of right lateral ventricle with EWSR1 gene fusion: a case report and review of literature.

BACKGROUND: Primary intracranial malignancies with extra-skeletal myxoid chondrosarcoma (EMC) features are extremely rare. EMC constitutes a distinct genomic entity characterised by reciprocal translocation of fusion genes, most commonly EWS RNA Binding Protein 1 (EWSR1) in 22q12 with Nuclear Receptor Subfamily 4 Group A Member 3 (NR4A3) in 9q2-q31.1. It is reported to have a high propensity for local recurrence and has potential for metastasis. So far in 28 years since its first description, only 17 cases of primary intracranial EMC were reported in literature. This would be the second case of intraventricular origin and first case from lateral ventricle. CASE PRESENTATION: A 27-year-old male presenting with complaints of headache, seizures and pain in neck was diagnosed to have a mass lesion in right lateral ventricle in Magnetic Resonance Imaging of brain. He underwent right parieto-occipital craniotomy with total excision of the lesion. Initial histopathological examination was reported as Ependymoma, WHO grade II. However, blocks and slides review with immunohistochemistry (IHC) markers revealed neoplastic aetiology with extensive myxoid changes. Hence, fluorescent in-situ hybridisation (FISH) testing was done with EWSR1 break apart probe, which demonstrated EWSR1 break apart signals. Therefore, correlating the clinical findings with morphology, IHC and FISH, the diagnosis of primary intracranial EMC was rendered. Patient received adjuvant external beam radiation of 54 Gy in 30 fractions to the post-op region. At 29-month follow-up, there was no evidence of disease recurrence. CONCLUSIONS: Owing to the rarity of the condition, there are no standard treatment guidelines available for primary intracranial EMC. A combined treatment approach with surgery followed by adjuvant radiotherapy provides good local control with less morbidity.

Diagnosis of pseudomyogenic hemangioendothelioma of scapula on limited biopsy: A rare and challenging entity.

Pseudomyogenic hemangioendothelioma (PHE) is a soft-tissue tumor of intermediate malignant potential, recognized as a separate entity in the WHO (World Health Organization) classification of tumors of soft tissue and bone, in 2013. This is a case report of a 33-year-old man with intraosseous scapular PHE reported on small biopsy and immunohistochemistry. The patient presented with local recurrence and metastases even after wide local excision and adjuvant radiotherapy after 14 months. The rarity of this lesion at this site and morphologic clues to diagnosis are important for optimizing the treatment protocol.

FISH for EWSR1 in Ewing's sarcoma family of tumors: Experience from a tertiary care cancer center.

BACKGROUND: : Molecular confirmation of histologic diagnosis has become mandatory for the diagnosis of Ewing sarcoma family of tumors (ESFT). AIM: To validate the diagnosis made by morphology and immunohistochemistry (IHC) by fluorescence in-situ hybridization (FISH) for EWSR1 rearrangement on formalin fixed paraffin embedded (FFPE) tissues. Settings and design: A retrospective and prospective observational study. Material and methods: All patients who had FISH studies for EWSR1 rearrangement for small round cell tumors during 10 years period were included. Demographic, clinical and radiological details were obtained from medical records. Morphology was reviewed with IHC by CD99, FLI1 and others. FISH studies were performed using the break apart probe. Additional molecular studies and IHC were done to resolve the diagnosis in EWSR1 rearranged tumors. Final diagnosis was made by integrating clinical, morphology, IHC and molecular features. RESULTS: There were 81 patients (M: F 45:36, median age 21 years) with 32 skeletal and 49 extra skeletal tumors. CD 99 was positive in 94.52%. FISH for EWSR1 were positive in 59, negative in 13 and failed in 9. The final diagnosis was made as ESFT in 67, angiomatoid fibrous histiocytoma in 3, desmoplastic small round cell tumor in 3, myxoid chondrosarcoma in 2, unclassified in one, synovial sarcoma in 3, and one each of lymphoma and small cell neuroendocrine carcinoma. FISH was positive for ESFT in 89.83% of EWSR1 rearranged tumors. FISH validated the diagnosis made on IHC in 79.10%. FISH resolved the diagnosis in 1.49% CD99 negative tumors. CONCLUSION: FISH is a reliable ancillary technique for the diagnosis of ESFT on FFPE tissues.

Immunohistochemical and Molecular Characterization of Endometrial Stromal Sarcomas.

INTRODUCTION: Endometrial stromal sarcomas (ESSs) are rare and characterized by translocations t(7;17)(p15;q11.2) and t(10;17)(q22;p13), resulting in JAZF1-SUZ12 and YWHAE-FAM22 gene fusions used for defining low-grade (LG-ESS) and high-grade (HG-ESS) tumours. AIM: The objective of the study was to characterize ESSs using immunohistochemical and molecular markers. MATERIAL AND METHODS: Patients diagnosed as having ESSs between January 2014 and December 2018 were included in the study. The slides were reviewed along with a panel of immunohistochemical markers, CD10, cyclin D1, oestrogen receptor (ER) and progesterone receptor (PR), Ki67, and vimentin and classified according to World Health Organization (2014) criteria into LG-ESS, HG-ESS, and undifferentiated uterine sarcoma (UUS). Molecular characterization was performed by fluorescence in situ hybridization using relevant probes. RESULTS: Over a 4-year period, 552 cases of endometrial malignancies were reported, 10 of which were ESS (1.8%). Of these, 5 were LG-ESS, 3 HG-ESS, and 2 UUS. CD10 was 100% sensitive and 75% specific for LG-ESS. Oestrogen receptor and PR were 100% specific but less sensitive (80%) for LG-ESS. Forty per cent (2/5) of LG-ESS demonstrated JAZF1-SUZ12 gene rearrangement. All 3 cases of HG-ESS showed diffuse strong cyclin D1 (>70% nuclei) positivity and were negative for cluster differentiation 10, ER, and PR and demonstrated YWHAE gene rearrangement. None of the UUS cases demonstrated this gene rearrangement. CONCLUSION: Endometrial stromal sarcomas are rare tumours (1.8% in this study). JAZF1-SUZ12 and YWHAE-FAM22 gene rearrangement helps in accurate characterization of ESS and can be used as diagnostic tools especially when the diagnosis is unclear or difficult. Cyclin D1 can be used as an adjuvant immunomarker for YWHAE gene-rearranged HG-ESS.

Plasmablastic Lymphoma: A Clinicopathological Study from a Tertiary Care Cancer Center in South India.

Background Plasmablastic lymphoma (PBL) is a rare aggressive B cell lymphoma that is commonly encountered in patients with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). In this case series, we describe the clinicopathological features of cases of PBL seen at a tertiary care center in South India. Materials and Methods Medical records of patients diagnosed with PBL between January 2009 and November 2017 were reviewed. PBL was defined as per the World Health Organization 2016 classification for hematopoietic and lymphoid neoplasms. The slides were reviewed with hematoxylin and eosin along with immunohistochemistry (IHC) including CD45, CD20, PAX5, CD79a, CD3, CD5, CD138, MUMI, EMA, ALK, and Ki67. Epstein-Barr virus (EBV) association was documented by rapid in situ hybridization (RISH) studies wherever possible. The demographic data, clinical presentation, treatment details, and outcomes are elaborated using descriptive statistics. Results During the study period, nine patients with PBL were identified. The median age at presentation was 47 years (range: 36-54 years). All patients had associated HIV/AIDS, eight (89%) had extranodal disease, and six (66%) had advanced clinical stage (stage III). All biopsies were positive for CD45, CD138, and MUM1, and negative for CD79a and T cell markers with a high Ki67 proliferation index (85-90%); CD20 was faint positive in one patient, and CD56 was positive in one (11%) patient. EBV-RISH was tested in two patients and was positive in one. Bone marrow was uninvolved in all the cases. At the time of last follow-up, three patients were alive. Treatment details were available in six patients. With frontline therapy, four patients achieved a complete remission (CR) and one patient developed progressive disease. Three of four patients in CR are alive till the last follow-up. Conclusion PBL is a rare form of lymphoma with predominant association with HIV, extranodal location, and characteristic IHC pattern.

Gingival Angiosarcoma: A Case Report and Clinicopathologic Review of 32 Cases of Primary Gingival Angiosarcoma.

Angiosarcoma is a malignant neoplasm of mesenchymal origin arising from vascular endothelium and most commonly involves extremities. Gingival angiosarcoma is a rare sporadic occurring tumor. We report a case of primary angiosarcoma of gingiva along with a review of 31 cases of primary gingival angiosarcoma reported in literature till 2018. A 30-year-old lady presented with recurrent gingival swelling over central mandible. She had no palpable cervical lymphadenopathy. She underwent central marginal mandibulectomy. Final histological analysis with immunohistochemistry was suggestive of the angiosarcoma of the gingiva. She is 50 months postoperative and doing well.

Differentiation of renal cell tumors with morphological cocktails using a minimal panel of immunohistochemical markers.

CONTEXT: Morphological cocktails in renal cell carcinoma (RCC). AIMS: Minimal immunohistochemistry (IHC) panel to resolve the diagnosis of renal cell cacinoma (RCC) with morphological overlaps. SETTINGS AND DESIGN: RCC is the most common malignancy in kidney accounting for 90% of all kidney cancers. Clear cell RCC is the most common histological type followed by papillary RCC. However, many of the RCCs show morphological cocktails which may pose diagnostic difficulties in small biopsies and even in the resection specimens. Accurate diagnosis has both prognostic and therapeutic implications; hence, correct differentiation is necessary. SUBJECTS AND METHODS: This retrospective study includes all renal cell tumors diagnosed on core biopsies, radical and partial nephrectomies between January 2015 and September 2017 were studied. The demographic, clinical, and gross findings were noted. The cases that had morphological overlap among the subtypes were subjected to a panel of IHC markers, including CD10, CK7, alpha-methyl acyl-coenzymeA racemase (AMACR), and CD117. RESULTS: There were 128 RCC in the study period, and morphological overlap was seen in 36 (27.9%) specimens including 13 core biopsies, 16 radical, and 7 partial nephrectomies. IHC resolved 35/36 (97.2%) cases rendering a diagnosis of clear cell (11), papillary (15), chromophobe (4), and oncocytoma (5). However, in one case where the provisional diagnosis was oncocytic tumor, all IHC markers were negative rendering IHC noncontributory. CONCLUSIONS: Difficulty in diagnosis was encountered in many core biopsies, resection specimens which when subjected to IHC panel of CD10, CK7, AMACR, and CD117 helped in resolving the diagnosis of subtypes of RCC.

Ewing Sarcoma With Emphasis on Extra-skeletal Ewing Sarcoma: A Decade's Experience From a Single Centre in India.

INTRODUCTION: The diagnosis of Ewing sarcoma family of tumours (ESFT) is challenging, especially in adults and in extra-skeletal or visceral location. Several morphologic mimics with varied treatment options and prognosis confer diagnostic dilemmas. Application of ancillary diagnostic modalities in surgical pathology in clinical routine has enabled accurate diagnosis of ESFT in bone, soft tissues, and viscera. AIM: The study aims to assess the clinicopathological features including molecular test results of ESFT with emphasis on sex, age, and location, especially extra-skeletal soft tissue and visceral location. MATERIAL AND METHODS: Data of clinicopathological, molecular tests (wherever performed), diagnosis rendered in 302 ESFT over a decade from our centre were reviewed. Statistical comparison of skeletal and extra-skeletal tumours with reference to age and sex was done using SPSS package. The P value of <.05 was considered significant. RESULTS: The cohort included 302 ESFTs with 49% skeletal and 51% extra-skeletal tumours. Thigh was most common site among skeletal tumours; chest wall, paraspinal location, and retroperitoneum among soft tissues (39.4%); and kidney, ovary, and cervix among visceral tumours (11.3%). Fluorescence in situ hybridisation for EWSR1 gene rearrangement was positive in 54 patients and reverse-transcriptase polymerase chain reaction in 19 patients. Predominance of male sex, younger age and location in extremities among skeletal tumours and lack of gender predilection, higher age and axial location in extra-skeletal tumours were noted, which were statistically significant. Molecular tests were performed more frequently in extra-skeletal tumours, especially in visceral tumours to establish the diagnosis. CONCLUSIONS: The study showed statistically significant differences in the age, sex, and location between skeletal and extra-skeletal ESFT. The increased percentage of extra-skeletal tumours especially in viscera was attributed to the increased awareness and availability of ancillary techniques.

Prospective Randomized Controlled Study Comparing Primary Surgery Versus Neoadjuvant Chemotherapy Followed by Surgery in Gastric Carcinoma.

Neoadjuvant chemotherapy in gastric cancer can treat micro metastatic disease and can increase the resectability rate. The trial was to compare early outcomes after primary surgery versus neoadjuvant chemotherapy followed by surgery in gastric adenocarcinoma. The primary aim of the study was to compare resectability and R0 resection rates in upfront surgery v/s chemotherapy followed by surgery arm. A secondary aim was to see if neoadjuvant chemotherapy is well tolerated or not by comparing postoperative morbidity and mortality. The study consisted of 60 consecutive patients of carcinoma stomach randomized into primary surgery and neoadjuvant chemotherapy followed by surgery arms. Morbidity, pathological status, and mortality data were collected and analyzed. Mean operating time in primary surgery arm was 290 ± 46.5 min, while in NACTarm, it was 316.7 ± 56.6 min, respectively. When postop complications were compared between the arms, it was not significant. Comparing the histopathological report of two groups, there was no significant difference between differentiated, T stage, mean lymph node harvest, R0 resection, PNI, and LVI. Neoadjuvant chemotherapy showed a trend towards improving in the R0 resection rate. There is no increase in postoperative morbidity and mortality with neoadjuvant chemotherapy.

Isolated cerebral aspergillus abscess as a complication of pulmonary alveolar proteinosis in a child.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) poses a risk of opportunistic infections with a variety of organisms with Nocardia being the most common pathogen followed by mycobacteria and fungi. CASE PRESENTATION: A 7-year-old female child, presented with headache and multiple episodes of vomiting. There was no fever or altered sensorium. On examination, there were no focal deficits or cranial nerve palsies. An MRI brain showed a small T2 hyperintense lesion in the left superior parietal lobe suggestive of an abscess. She was diagnosed as PAP based on CT chest and bronchioloalveolar lavage 7 months earlier and treated with corticosteroids. A left parieto-occipital craniotomy was done with drainage of abscess and abscess wall excision. Histopathology revealed a suppurative lesion with slender septate acute angle branching hyphae which were positive on fungal stains. Culture done on the pus was positive for Aspergillus fumigatus. The patient was treated with voriconazole and stable at 1 year follow-up. CONCLUSION: Opportunistic infections are common in patients diagnosed with PAP. High index of clinical suspicion and early diagnosis are important for favorable outcome.

Short-term Outcomes in Patients with Carcinoma of the Esophagus and Gastroesophageal Junction Receiving Neoadjuvant Chemotherapy or Chemoradiation before Surgery. A Prospective Study.

BACKGROUND: Neoadjuvant chemotherapy (NACT) and neoadjuvant chemoradiotherapy (NACRT) have been demonstrated to improve survival compared to surgery alone in esophageal carcinoma, but the evidence is scarce on which of these therapies is more beneficial, particularly with regard to resectability rates, postoperative morbidity and mortality, and histological responses. OBJECTIVE: This study compares the resectability, pathological response rates, and short-term surgical outcomes in patients with carcinoma of the esophagus or gastroesophageal junction receiving NACT or NACRT prior to surgery. METHODS: Patients with resectable carcinoma of the esophagus or gastroesophageal junction adenocarcinoma, squamous cell carcinoma, and adenosquamous histologies were enrolled in this well-matched prospective non-randomized study. Thirty-five patients were given NACT, and 35 NACRT. In the NACT group, 25 patients received three cycles of three-weekly carboplatin and paclitaxel, and 10 received three cycles of cisplatin/5-fluorouracil, while all the patients in the NACRT group received 41.4 Gy of radiotherapy concomitant with five cycles of weekly paclitaxel and carboplatin-based chemotherapy. RESULTS: Twenty-two patients in the NACT group and 33 patients in NACRT group had resection (P value = 0.0027). The percentage of microscopically margin-negative resection (R0 resection) was similar in both the groups (86% versus 88%). The incidences of surgical and non-surgical complications were similar in both the groups (P=0.34). There was no 30-day mortality. There was a trend toward more pathological complete regression in the NACRT group (P=0.067). The percentage of patients achieving complete tumor regression at the primary site (pT0) was significantly higher in the NACRT group. The down-staging effect on nodal status was similar in both the groups (P=0.55). There was a statistically significant reduction in tumor size in the NACRT group. The median numbers of nodes harvested and positive nodes were similar in both the groups. CONCLUSION: Patients receiving NACRT had better resectability rates and pathological response rates, but similar postoperative morbidity compared to the NACT group.

Uterine Sarcomas: Experience from a Tertiary Cancer Care Center from India.

Uterine sarcomas are uncommon and aggressive tumors comprising 3-7% of all uterine malignancies. The aim is to evaluate clinical presentation, histopathologic pattern, recurrence pattern, and outcome of patients with uterine sarcomas presenting to a tertiary care cancer center over an 8-year period. A total of 11 cases of uterine sarcoma were diagnosed. The median age of patients at presentation was 51 years (range 30-67 years). Six patients had leiomyosarcoma (54.5%), 4 had endometrial stromal sarcoma (36%), and 1 had adenosarcoma (9%). The main presenting symptoms were abnormal vaginal bleeding, low abdominal pain, and white discharge. Median follow-up was 11 months ranging from 3 to 200 months. Median survivals for leiomyosarcoma, endometrial stromal sarcoma, and adenosarcoma were 6.5, 18, and 56 months. The 3- and 5-year survival by Kaplan-Meier survival analysis of the entire cohort was 30 and 20%. The mitotic index, age, adjuvant therapy (chemotherapy, radiotherapy), and performance of pelvic nodal dissection did not impact survival significantly in the patient with leiomyosarcoma. Stage and histology had the strongest bearing on survival and leiomyosarcoma has the worst survival, whereas adenosarcoma had the best prognosis. Adequately powered prospective studies are required to define the role of radiation therapy and chemotherapy in this rare disease.

The Impact of Stage and Molecular Subtypes on Survival Outcomes in Young Women with Breast Cancer.

Young women form a unique cohort in breast cancer, with evidence suggesting a later stage at presentation with more aggressive cancers. We aimed at evaluating the prognostic significance of young age and the impact of stage and molecular subtypes on survival. We conducted an audit of a prospectively maintained database at our institute between 2010 and 2014. All women with available receptor status and documented follow-up were included. The young breast cancer (YBC) cohort comprised 103 women and 230 women constituted the comparator arm (45-55 years). The median follow-up was 4 years. The YBC had a higher incidence of hormone negative tumors (61.1% vs. 46.3%, p = 0.012, significant [S]); however, both groups were similar in their stage at presentation. On classification into luminal subtypes, triple negative breast cancer was more common in the YBC cohort (50.5% vs. 29.6%, p = 0.001, S). The 5-year disease-free survival (DFS) was significantly worse in the YBC cohort (70.3% vs. 78%, p = 0.03, S). This detriment appeared to be significantly more in women presenting with operable breast cancer (77.2% vs. 82.6%, p = 0.012, S). Among the Luminal subtypes, there was no significant difference in the DFS between the two groups. Young age is a negative prognostic factor among women presenting with breast cancer. Further studies are required to evaluate whether any specific stage or molecular sub-type is particularly vulnerable to a poor outcome despite treatment.