Circulatory Cytokine Levels as a Predictor of Disease Severity in COVID-19: A Study from Western India

Objectives: Neuroborreliosis is generally known to be a disease confined to the Western part of the globe. It is not commonly encountered in this part of the world. Interestingly, we recently came across a series of cases of Lyme’s disease with a plethora of neurological presentations. Most of the cases were a diagnostic dilemma, with poor response to immunotherapy and on subsequent evaluation all were found to have positive Borrelia antibodies. Materials and methods: Eight cases were selected from the tertiary care hospital in North western India. Patients were suspected to have Neuroborreliosis whose neurological presentations were atypical for other classical neurological disorders, who had a progressive or relapsing clinical course and had responded poorly to the initial treatment given for the previous neurological diagnosis. Skin lesions were present in some cases. The patients underwent a detailed clinical assessment which comprised of an elaborate history including history of travel, any insect bite or skin rashes along with a complete systemic and neurological examination. All the required blood investigations, Magnetic Resonance Imaging (MRI) Brain, Computer Tomography Angiography (CT), Nerve conduction study (NCS) and Electromyographic (EMG) studies and Cerebrospinal fluid (CSF) studies were done as indicated in each case. Borrelia antibody titre was done in all the patients using immunoblot technique. Results: Among the 8 patients, 6 were male and 2 were females. The age group was between 25-70 years. The clinical presentation was acute, subacute or chronic. One patient gave a clear history of tick bite. Two patients had skin lesions and one had the pathognomic "eschar". All the suspected 8 patients had either IgG or IgM or both IgG and IgM Borrelia antibodies positive. Almost all the patients had previously received either steroids or intravenous immunoglobulins, but had not adequately responded to immunotherapy. These patients were given a trial of injectable Ceftriaxone and oral Doxycycline. Most of them either showed partial or complete clinical improvement. Conclusion: Lyme’s disease, a common disease of the west does exist in the Indian subcontinent as well. Because of increasing global travel and migration and change in vector habitat the disease seems to have percolated in the non endemic areas too. Proper history of travel or exposure to tick bite is important. We want to emphasize, Neuroborreliosis, a great mimicker may have diverse and varied neurological presentations and has a potential for reversibility with appropriate treatment even after a significant delay in diagnosis.

Role of pelvic and para-aortic lymphadenectomy in epithelial ovarian cancers

Background: Lymphadenectomy in epithelial ovarian cancers has remained a controversial subject. Lack of robust evidence on survival benefits and surgical morbidity associated questions its role in the era of adjuvant chemotherapy. The present study assessed pelvic and para-aortic lymph node removal in epithelial ovarian cancer in Indian women and tried to find clinicopathological correlation of nodal involvement and postoperative implications of lymphadenectomy.Methods: Thirty patients with diagnosis of epithelial ovarian cancer posted for primary debulking surgery were recruited and underwent staging laparotomy along with pelvic and para-aortic lymphadenectomy. Nodal involvement was confirmed on histopathology and various parameters which could predict nodal metastasis were assessed. Patients were followed up for 12 months post-surgery.Results: Nodal yield was ten for pelvic and four for paraaortic nodes. Pelvic node involvement was seen in 26.6% (8/30) of the patients and para-aortic in 15% (3/20) of the patients. Serous histology, higher grade, stage 3 and above, positive peritoneal cytology, omental involvement showed a higher lymph node involvement though not statistically significant. Para-aortic lymphadenectomy was associated with increased operating time, blood loss and longer hospital stay.Conclusions: Lymphadenectomy increases morbidity and decision should be based on predictors of nodal involvement.

Peritoneal metastasis in Stage IB1 adenocarcinoma cervix: A rare entity

The presence of ovarian or peritoneal metastasis in early-stage cervical malignancy is a rare entity. It often poses a diagnostic challenge whether it is a synchronous primary tumor or a metastatic lesion. A 63-year-old postmenopausal woman presented with Stage 1B1 carcinoma cervix with ascites, and a 5.8 cm × 4.2 cm × 3.5 cm left solid adnexal mass. She underwent Type III radical hysterectomy, excision of peritoneal mass, with bilateral pelvic and paraaortic lymphadenectomy and infracolic omentectomy. On histopathology, cervix showed features of adenocarcinoma, and the peritoneal mass revealed similar histomorphology as cervical growth with metastatic tumor deposits in omentum. Immunohistochemistry (IHC) was utilized to determine the origin of mass. The early stage disease and histology may not always predict the distant metastasis. Therefore, a thorough pretreatment evaluation, meticulous intraoperative assessment, and IHC are mandatory for optimum management and prognostication

Locally advanced cervical cancer – neoadjuvant chemotherapy followed by concurrent chemoradiation and targeted therapy as maintenance: A phase II study

Aim: The survival in locally advanced cervical cancer remains low. We evaluated the role of neoadjuvant chemotherapy (NACT), chemoradiotherapy (CRT), followed by gefitinib maintenance in locally advanced cervical cancer. Materials and Methods: Twenty-five patients with locally advanced carcinoma cervix were enrolled between July 2012 and May 2013. Patients received 6 weekly doses of NACT Paclitaxel (60 mg/m2) and carboplatin (AUC 2), followed by CRT and brachytherapy. The analysis of epidermal growth factor receptor (EGFR) expression was carried out by immunohistochemistry. Gefitinib (250 mg daily) was given as maintenance therapy for 1 year after completion of chemoradiation. Comparison of EGFR expression and survival outcomes was done. Results: Twenty-four of 25 patients completed the neoadjuvant chemotherapy and concurrent chemoradiotherapy. Post-CRT, all patients were started on gefitinib maintenance, and twenty patients completed the intended 1 year of gefitinib maintenance. Nineteen (76%) patients had a radiological complete response to NACT. EGFR was moderately or strongly expressed in 86.3% of the patients. The 3-year overall survival was 69.8%, and 3-year progression-free survival was 51.4%. Expression of EGFR was not found to be a significant factor affecting overall survival or progression-free survival. Conclusions: Weekly neoadjuvant chemotherapy is associated with a good response rate in locally advanced cervical cancer. Neoadjuvant chemotherapy, chemoradiation, followed by gefitinib maintenance gives good survival outcome in patients with locally advanced cervical cancer.

Optimization of sentinel lymph node identification techniques in the Indian setting: A randomized clinical trial

INTRODUCTION: The recommended technique of sentinel lymph node biopsy (SLNB) in breast cancer is a combination of blue dye and radiotracer. In the Indian scenario, SLNB is still not routinely practiced due to lack of nuclear medicine facilities and unavailability of isosulfan blue or patent blue violet (PBV). This study was conducted for optimizing SLN identification techniques by comparing the identification rate using PBV and methylene blue (MB) in combination with radiotracer. MATERIALS AND METHODS: Single-blinded two-arm parallel design randomized control trial was conducted at an apex teaching and research medical institute in India. Patients with axillary LN–negative breast cancer were included. Blue dye and radio tracer were injected preoperatively, and SLNB was performed using a combination technique. Frozen section was performed. Demographic, clinical, radiological, operative, and histopathological data were recorded. Descriptive statistics were used to represent patient characteristics. Baseline characteristics for entire cohort and between groups were compared using Student's t-test for quantitative variables and Chi-square test for qualitative variables. RESULTS: A total of 119 patients were randomized for mapping with MB and 118 patients with PBV between 2011 and 2015. SLN was identified in 116 patients with MB and 115 with PBV. SLN identification proportions were 97.4% (MB) and 96.6% (PBV). In patients undergoing axillary lymph node dissection, concordance with SLNB was 98.5% and 96.61% in MB and PBV, respectively. False-negative proportion for MB was 2.56% and 7.69% for PBV, respectively. The cost of MB is about INR 15 per ~10-mL vial. The cost of PBV is approximately ~$91 per ampoule (equivalent to approximately INR 8190). CONCLUSION: SLNB using MB can be recommended as the technique of choice in low-resource settings.

Comparison of resection margins and cosmetic outcome following intraoperative ultrasound-guided excision versus conventional palpation-guided breast conservation surgery in breast cancer: A randomized controlled trial

INTRODUCTION: Use of intraoperative ultrasound (IOUS) has been shown to help achieve satisfactory cosmesis and negative margins in breast conserving surgery (BCS). This study has been done to compare the oncological and cosmetic outcomes following BCS using conventional palpatory method and IOUS. MATERIALS AND METHODS: This is a prospective randomized controlled trial conducted at a tertiary care teaching and research institute in India. Patients with early operable breast cancer willing for BCS were included. Tumors were excised with 1 cm margin. In palpatory group, tumor was palpated and 1 cm margin was taken with a measuring scale while in the second group, IOUS was used to mark the margins. Histopathological evaluation was done to assess margins and cosmesis was assessed by patient, resident doctor, and nurse independently. RESULTS: Sixty patients were included, 32 in the ultrasonography-guided and 28 in palpation-guided wide local excision. The mean age of patients was 48.78 years. In both groups, mean tumor size was 3.18 cm. Margin thickness and positivity was higher in palpatory group (though P > 0.05). Most patients were satisfied with cosmesis. There was no significant difference in complications and specimen volume in both groups. Presence of ductal carcinoma in situ component and expression of Her2neu by tumor cells had a significant impact on margin positivity. CONCLUSIONS: Intraoperative use of ultrasound offers a real-time assessment of margin status and may reduce the margin positivity rate compared to conventional palpation-guided method.

Clinico-pathological characteristics and treatment outcome in invasive lobular carcinoma of the breast: An Indian experience

BACKGROUND: Invasive lobular carcinoma (ILC) is the second most common histologic subtype of breast cancer and accounts for 10%–15% of all breast cancers in the west. There is a scarcity of data on ILC from the Indian subcontinent. This report intends to present the patterns of care, survival outcomes, and prognostic factors of ILC treated in a tertiary care institute. MATERIALS AND METHODS: This retrospective analysis included consecutive patients diagnosed with ILC and registered at our Institute between 2009 and 2016. RESULTS: We included 97 patients with a median age of 53 years (range 28–80). American Joint Committee on Cancer (7th edition) stage distribution was stage I-8.24%, stage II-45.36%, stage III- 34.10%, and stage IV-12.30%. Bilateral breast cancer was seen in 8 cases. Estrogen receptor, progesterone receptor, and HER 2/neu positivity was 90%, 85%, and 9%, respectively. Triple-negative breast cancer constituted 5% of cases. Twenty-nine events were recorded (systemic and locoregional relapse) with a median follow-up of 3.5 years. Three years relapse-free survival (RFS) and overall survival were 80% and 60%, respectively. Bones were the most common site of metastasis. Age <45 years [HR-1.4 (0.8–2.1), P < 0.001] and advanced clinical tumor stage [T4, HR-2.1 (1.1–3.8), P = 0.001] were associated with poor RFS. CONCLUSION: ILC constituted 2.5% of breast cancer cases at our institute. Triple negativity and HER-2/neu positivity were seen in 9% and 5% of cases, respectively. Age <45 years and advanced clinical tumor stage were associated with poor RFS.

Clinicopathological profile of breast cancer: An institutional experience

INTRODUCTION: This study was undertaken to evaluate the clinicopathological characteristics of patients with breast cancer at our institute, a tertiary-care cancer center in northern India. MATERIALS AND METHODS: This retrospective study included all patients with breast cancer registered at our institute from January 1st, 2014 to December 31st, 2016. We retrieved data (demographic, baseline clinical characteristics, pathology, and treatment details) from prospectively maintained clinical case records. Patients with incomplete case records or missing baseline information were excluded. RESULTS: We included 550 patients with breast cancer. The median age was 48 years (23–85). The median clinical tumor size was 5.0 cm. The TNM (AJCC-7th edition) stage distribution was stage I, 22 (4%); stage II, 182 (33%); stage III, 247 (44.9%); and stage IV, 99 (18%). Locally advanced breast cancer constituted 40% of the cases. Bone (48 [48.5%]) was the most common site for metastasis followed by lung. Infiltrating ductal carcinoma (528 [96%]) was the most common histologic subtype. Majority of patients, 325 (59%), were positive for estrogen receptor/progesterone receptor whereas 160 (29%) patients were HER2/neu positive. Triple negative breast cancer (TNBC) constituted 28% (154) of patients. In the nonmetastatic subgroup, 343 (76%) patients underwent modified radical mastectomy. Neoadjuvant chemotherapy (NACT) was given in 120 (26.6%) patients, of these 23 (19%) achieved pathological complete remission. Sequential anthracyline and taxane were used as NACT/adjuvant chemotherapy in most cases. Of the eligible patients, 48 (30%) received anti-HER2/neu therapy. CONCLUSION: This is one of the largest comprehensive data from a single center in India. Majority of our patients are younger in age and have advanced disease. TNBC and HER2/neu positive breast cancer are more common in our population.

Image guided versus palpation guided core needle biopsy of palpable breast masses: a prospective study.

Background & objectives: Biopsy of palpable breast masses can be performed manually by palpation guidance or under imaging guidance. Based on retrospective studies, image guided biopsy is considered more accurate than palpation guided breast biopsy; however, these techniques have not been compared prospectively. We conducted this prospective study to verify the superiority and determine the size of beneficial effect of image guided biopsy over palpation guided biopsy. Methods: Over a period of 18 months, 36 patients each with palpable breast masses were randomized into palpation guided and image guided breast biopsy arms. Ultrasound was used for image guidance in 33 patients and mammographic (stereotactic) guidance in three patients. All biopsies were performed using 14 gauge automated core biopsy needles. Inconclusive, suspicious or imaging-histologic discordant biopsies were repeated. Results: Malignancy was found in 30 of 36 women in palpation guided biopsy arm and 27 of 36 women in image guided biopsy arm. Palpation guided biopsy had sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 46.7, 100, 100, 27.3 per cent, respectively, for diagnosing breast cancer. Nineteen of 36 women (52.8%) required repeat biopsy because of inadequate samples (7 of 19), suspicious findings (2 of 19) or imaging-histologic discordance (10 of 19). On repeat biopsy, malignancy was found in all cases of imaging-histologic discordance. Image guided biopsy had 96.3 per cent sensitivity and 100 per cent specificity. There was no case of inadequate sample or imaging-histologic discordance with image guided biopsy. Interpretation & conclusions: Our results showed that in palpable breast masses, image guided biopsy was superior to palpation guided biopsy in terms of sensitivity, false negative rate and repeat biopsy rates.

Evaluation of epidermal growth factor receptor mutations based on mutation specific immunohistochemistry in non-small cell lung cancer: A preliminary study.

Background & objectives: Studies have shown that immunohistochemical (IHC) staining using epidermal growth factor receptor (EGFR) mutation specific antibodies, is an easy and cost-effective, screening method compared with molecular techniques. The purpose of present study was to assess the percentage positivity of IHC using EGFR mutation specific antibodies in lung biopsy samples from patients with primary lung adenocarcinoma (ADC). Methods: Two hundred and six biopsies of primary lung ADC were subjected to EGFR mutation specific antibodies against del E746-A750 and L858R. Detection of EGFR mutation done by high resolution melting analysis (HRM) was used as gold standard. A concordance was established between molecular and IHC results. Frequency of IHC positivity was assessed. Results: Of the 206 patients, 129 were male and 77 were female patients, with a mean age of 54.1 yr. Fifty five (26.6%) patients (36 men; 19 women) showed positivity for IHC of del E746-A750 (33) and L858R (22). HRM results were available in 14 patients which showed EGFR mutations in correspondence with del E746-750 or L858R in 64.2 per cent cases. Positive cases on HRM were further confirmed by DNA sequencing and fragment analysis. Three patients showed exon20 variation. Two cases were negative for mutation. The genotype of del E746-750 mutation was more common than L858R. A concordance was established between molecular mutation and IHC in 85.7 per cent cases. Interpretation & conclusions: In this preliminary study from India mutation specific IHC was used for assessment of mutation status of EGFR. Although the number tested was small, a good concordance was observed between molecular EGFR mutation and IHC expression. IHC methodology is a potentially useful tool to guide clinicians for personalized treatment in lung ADC, especially where facilities for molecular analysis are not readily available and for use in small biopsies where material is scant for molecular tests.

Effect of Pioglitazone on Body Composition in Asian Indian Diabetics Suggest Role of Limb Fat in their High Insulin Resistance.

Aim: To study (1) effect of pioglitazone mono-therapy on body composition in treatment naive type-2 diabetes mellitus patients and (2) relationship between changes in body composition and insulin resistance induced by pioglitazone. Methods: Subjects: 49 newly diagnosed non-obese T2DM patients were recruited. Design: Open label observational study. Drug and Dose: pioglitazone 30 mg orally once daily for at least 6 months. Exclusion: Primary un-responsiveness at 3 months (10 subjects) and adverse effect (2 subjects). Final analysis done on 37 subjects (Mean age 47.9 years, male:female ratio 20:10) Controls: 37 healthy control subjects (Mean age 47 years M:F ratio 27:10) with normal glucose as per American Diabetes Association criteria. Study parameters were: Plasma glucose, Lipid profile, body mass index, HOMA-R, HOMA-B and body composition measured by dual-energy X-ray absorptiometry (DEXA) at start and after at least 6 months of follow up. Results: Treatment with pioglitazone was associated with significantly decreased glycated hemoglobin (HbA1c), fasting and post-prandial plasma glucose, insulin resistance and triglycerides HDL ratio.Significant increase in total body, limb and head fat mass was observed. The trunk composition did not show significant change. The DEXA Parameters of body composition of diabetics became comparable with controls. Significant correlation was seen between decrease in FPG, PPG, insulin resistance and increase in limb fat mass. Conclusions: Pioglitazone alters body composition by increasing limb and head fat content, without altering trunk fat. Decrease in insulin resistance by it is related to increase in limb fat mass.

Primary pulmonary leiomyosarcoma of lung: An unusual entity with brief review.

Primary pulmonary leiomyosarcomas are rare and diagnostically challenging group of neoplasms approximately constituting 0.2-0.5% of all primary lung malignancies. They originate from the smooth muscle cells of the bronchial wall, blood vessels or from the pulmonary interstitium. Here we present a case of 45 year old male with history of chronic cough, breathlessness and chest pain for few months. Clinical and radiological workup showed a left upper lobe lung mass. Endobronchial ultrasound guided (EUS) needle biopsy of the mass on histopathology confi rmed leiomyosarcoma. Further through evaluation ruled out the possibility of metastasis. A fi nal diagnosis of primary leiomyosarcoma of lung was made and patient was planned for surgical management.

Single visit approach for management of cervical intraepithelial neoplasia by visual inspection & loop electrosurgical excision procedure.

Background & objectives: Developing a feasible and sustainable model of cervical cancer screening in developing countries continues to be a challenge because of lack of facilities and awareness in the population and poor compliance with screening and treatment. This study was aimed to evaluate a single visit approach (SVA) for the management of cervical intraepithelial neoplasia (CIN) using visual inspection with acetic acid (VIA) and Lugol's iodine (VILI) along with loop electrosurgical excision procedure (LEEP) in women attending Gynaecology OPD in a tertiary care hospital in north India. Methods: In this hospital-based study, 450 women receiving opportunistic screening by conventional Pap cytology were also screened by VIA and VILI. VIA/VILI positive cases underwent same-day colposcopy and biopsy of all lesions. If the modified Reid score was >3, the patient underwent LEEP at the same visit. Results: Of the 450 women screened, 86 (19.1%) and 92 (20.5%) women were VIA and VILI positive, respectively. Detection rates of VIA, VILI and cytology findings at ASCUS threshold were 33.3, 35.5 and 24.4 per 1000, women, respectively to detect a lesion >CIN1. For detection of CIN2+ lesion, detection rates of VIA, VILI and cytology were 20, 22.2 and 22.2 per 1000 women, respectively. Sixteen patients with Reid score >3 underwent the See-and-treat protocol. The overtreatment rate was 12.5 per cent and the efficacy of LEEP was 81.3 per cent. There were no major complications. Interpretation & conclusions: The sensitivity of VIA/VILI was comparable to cytology. A single visit approach using visual screening methods at community level by trained paramedical personnel followed by a combination of ablative and excisional therapy can help to decrease the incidence of cervical neoplasia.

Leiomyosarcoma of inferior vena cava: A case series of four cases.

Vascular leiomyosarcomas are rare tumors, arising most frequently from inferior vena cava (IVC). They are mostly seen in sixth decade, with a female predominance. Their diagnosis is often challenging, as patients may present with non-specific complaints such as dyspnea, malaise, weight loss, abdominal pain, or back pain, preceding the diagnosis by several years. Leiomyosarcoma of the IVC most frequently occurs in the middle segment. The final diagnosis can be made by an ultrasound or computed tomography guided biopsy. Because of limited experience with this disease, optimal management of IVC leiomyosarcoma is unknown. Curative surgical resection remains the current treatment of choice for primary leiomyosarcoma of IVC. Neoadjuvant therapy may be given to downsize the tumor and increase resectability rates. Nonetheless, when complete resection is not possible, debulking combined with radiation therapy still provides good palliation. We, hereby, report four cases of this rare entity with emphasis on management.

Port site tuberculosis: A case report and review of literature.

Sumrnury: A rare case of port site tubercular infection is reported. A young male patient presented, one month after laparoscopic inguinal hernia repair with discharging sinuses at the port sites. Biopsy of the sinus tract showed features of tuberculosis. Excision of sinus tract was done and the patient was started on anti-tubercular therapy, sinuses healed. Probably, the source of tubercular infection was laparoscopic instruments. Proper sterilization of laparoscopic instruments is necessary.

Anaplastic transformation of metastatic papillary thyroid carcinoma at shoulder mimicking soft tissue sarcoma.

A 52-year-old woman presented with fracture upper end of the left humerus after trivial trauma and aspiration cytology from the lytic lesion in the upper humerus seen on X-ray revealed a metastatic papillary carcinoma from the thyroid. Total thyroidectomy confirmed the papillary carcinoma thyroid. Post-operatively, she was given radioactive iodine (I-131) ablation therapy for 8 years and was asymptomatic during this period; however, for the last 1 year, she has been complaining of swelling in the shoulder, which did not respond to palliative radiotherapy and rapidly increased in size. Disarticulation of the shoulder joint was performed, which showed anaplastic carcinoma on histopathological examination. Anaplastic transformation of papillary carcinoma at the metastatic sites is well documented in the literature and is rare. However, the same has not been reported at the shoulder and from India before. Although soft tissue sarcomas are most common at this site, however, the possibility of anaplastic transformation should be kept in the differential diagnosis of rapidly enlarging painful mass in a known case of metastatic thyroid carcinoma to prevent misdiagnosis.

Calotropis procera root extracts block VEGF-induced angiogenesis: Quantitative analysis.

Angiogenesis is controlled by number of growth factors, including vascular endothelial growth factor (VEGF). Plant derived anti-angiogenic molecules acting via VEGF are being investigated for curtailing angiogenesis dependent diseases. In this study, methanolic (CM), n-hexane (CH), ethylacetate (CE) and water (CW) extracts of the roots of Calotropis procera were tested for anti-angiogenic activity. In the chicken egg chorioallantoic membrane (CAM) assay, CM, CH and CE but not CW inhibited VEGFinduced neovascularization in a dose-dependent manner. Of all the tested extracts, CM at the dose of 10, 5 and 2.5 ng most effectively inhibited over 83, 71 and 64%, of neovascularization induced by 10ng of VEGF, respectively. Sponge implantation assay in mice further showed that at the dose of 100ng CM, CH and CE but not CW significantly inhibited neovascularization induced by VEGF (100 ng). Taken together, this study indicates that the root extracts of C.procera may possess anti-angiogenic activity.

Thoraco-abdominal mature teratoma in a left diaphragmatic hernia.

This case describes a contiguous mediastinal and retroperitoneal mature teratoma in a congenital diaphragmatic defect, a combination that is hitherto unreported in literature. It substantiates embryological chronology of events during the cephalad migration of the primordial germ cells through the developing diaphragm, prior to its closure.