Rohini W Hawaldar

Omission of nitrous oxide during anesthesia reduces the incidence of postoperative nausea and vomiting - A meta-analysis

Background Postoperative nausea and vomiting are important causes of morbidity after general anesthesia. Nitrous oxide has been implicated as an emetogenic agent in many studies. However, several other trials have failed to sustain this claim. The authors tried to resolve this issue through a meta-analysis of randomized controlled trials comparing the incidence of postoperative nausea and vomiting after anesthesia with or without nitrous oxide. Methods Of 37 published studies retrieved by a search of articles indexed on the MEDLINE database from 1966 to 1994, 24 studies (26 trials) with distinct nitrous-oxide and non-nitrous oxide groups were eligible for the meta-analysis. The pooled odds ratio and relative risk were calculated. Post hoc subgroup analysis was also performed to qualify the result. Results The pooled odds ratio was 0.63 (0.53 to 0.75). Omission of nitrous oxide reduced the risk for postoperative nausea and vomiting by 28% (18% to 37%). In the subgroup analysis, the maximal effect of omission of nitrous oxide was seen in female patients. In patients undergoing abdominal surgery and general surgical procedures, the effect of omission of nitrous oxide, although in the same direction, was not significant. Conclusion Omission of nitrous oxide reduced the odds of postoperative nausea and vomiting by 37%, a reduction in risk of 28%.

Abstract S2-02: Surgical removal of primary tumor and axillary lymph nodes in women with metastatic breast cancer at first presentation: A randomized controlled trial

BACKGROUND: The role of loco-regional treatment, in women with metastatic breast cancer (MBC) at first presentation, is debatable. Preclinical evidence suggests that such treatment may facilitate growth of metastatic disease. On the other hand, many retrospective analyses in clinical cohorts have suggested favorable impact of loco-regional treatment in these patients. However, these results are likely to be influenced by selection bias. We conducted a prospective randomized controlled trial to assess the impact of loco-regional treatment on outcome in women with metastatic breast cancer at initial diagnosis. [NCT00193778] METHODS: Women with metastatic breast cancer at initial diagnosis and planned to be treated with anthracycline based chemotherapy (CT) were registered for the study. Those who had objective tumor response after 6 cycles of CT were randomized to one of the following arms: ‘LRT’ (loco-regional treatment) or ‘No-LRT’ (no loco-regional treatment). Patients were stratified by endocrine receptor (ER) status, site of metastases (visceral Vs bone Vs both) and number of metastatic lesions ( 3). Women in LRT arm received surgery (breast conservation or mastectomy plus axillary lymph node dissection) followed by radiation therapy (RT), as per standard adjuvant guidelines. Women in No-LRT arm were followed up without surgery and RT. Both groups received standard endocrine therapy after last cycle of chemotherapy, if indicated. They were regularly followed up with clinical evaluation. Appropriate imaging was performed within 6 months after randomization and thereafter as clinically indicated. The primary endpoint was overall survival (OS). RESULTS: Between Feb 2005 and Jan 2013, 350 women were randomized, 173 in LRT and 177 in No-LRT arm. The data cutoff was in May 2013. The two arms were balanced with respect to age, clinical tumor size, HER2 receptor status and stratification factors. Eight (5.8%) patients in the LRT arm did not undergo loco-regional therapy while 19 (10.7%) patients in the No-LRT arm underwent surgical removal of primary tumor because of palliative reasons. The median follow-up was 17 months and 218 deaths (LRT = 111/173, No-LRT = 107/177) had been recorded at data cutoff. The median OS in LRT and No-LRT arms were 18.8 and 20.5 months (HR = 1.07, 95%CI = 0.82-1.40, p = 0.60) and the corresponding 2-year OS were 40.8% and 43.3%, respectively. After adjusting for age, ER status, HER2 receptor status, site of metastases and number of metastatic lesions in a Cox regression model, there was no significant difference in OS between LRT and No-LRT arms (HR = 1.00, 95%CI = 0.76-1.33, p = 0.98). There was no interaction between the effect of LRT and covariates in the model. CONCLUSIONS: Loco-regional treatment of the primary tumor and axillary nodes has no impact on OS in patients diagnosed with MBC at initial presentation, who have responded to frontline chemotherapy. We were unable to identify any subgroups that are likely to benefit from LRT. Such treatment should be reserved for women who need it for palliative reasons. Detailed analysis will be presented at the Symposium. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr S2-02.

Estrogen, progesterone and HER2 receptor expression in breast tumors of patients, and their usage of HER2-targeted therapy, in a tertiary care centre in India

BACKGROUND This study was undertaken to document the pattern of expression of estrogen (ER), progesterone (PR) and human epidermal growth factor receptor-2 (HER2) and the usage of HER2-targeted therapy in a large tertiary care hospital in India in the year 2008. MATERIALS AND METHODS The histopathology reports of all breast cancer patients registered in the hospital in 2008 were extracted from the electronic medical record system. All the cases were immunohistochemically evaluated for estrogen and progesterone receptor status (ER and PR), and c-erbB-2 protein (HER2) expression using standard immunoperoxidase method. The use of HER2-targeted therapies was evaluated by extracting relevant information from the database of the hospital pharmacy and case charts of patients enrolled in ongoing approved trials. RESULTS A total of 2001 new patients of invasive breast cancers with available pathology reports were registered in the hospital in the year 2008. ER and/or PR expression was positive in tumors of 1025 (51.2%) patients. HER2 3+ expression by immunohistochemistry (IHC) was found in 335 (16.7%) and HER2 2+ in 163 (8.1%). The triple negative phenotype was found in 596 (29.8%) patients. An estimated 441 patients were eligible to receive HER2-targeted therapy based on their HER2 status. Of these 38 (8.6%) patients received some form of HER2-targeted therapy; 20 patients (4.5%) as part of ongoing clinical trials and 18 (4.1%) as part of routine care. CONCLUSIONS The overwhelming majority of patients eligible for HER2-targeted therapy in our institution are unable to receive it because of financial constraints and limited access to health insurance. There is a higher fraction of patients with the triple negative phenotype compared to the Western population.

Evaluation of the radioprotective effect of turmeric extract and vitamin E in mice exposed to therapeutic dose of radioiodine

The aim of this study was to evaluate the radioprotective effect of turmeric extract (40 mg/kg body weight) and vitamin E (α- tocopherol acetate, 400 IU/kg body weight) supplementation on lipid peroxidation, reduced glutathione and antioxidant defense enzymes in various organs like liver, kidney and salivary glands at 24 h in adult Swiss mice. 131Iodine exposure significantly increased lipid peroxidation in kidney and salivary glands in comparison to control animals. Pre supplementation with turmeric extract for 15 days showed significant lowering of lipid peroxidation in kidney. On the other hand vitamin E pre supplementation showed marked reduction in lipid peroxidation in salivary glands. Reduced glutathione levels decreased significantly in liver after radiation exposure. However, pre supplementation with turmeric extract and vitamin E did not improve glutathione levels in liver. In conclusion, we have observed differential radioprotective effect of turmeric extract and vitamin E in kidney and salivary glands. However, Vitamin E seems to offer better radioprotection for salivary glands which is known to be the major site of cellular destruction after radioiodine therapy in patients.

Radioprotective Effect of Ocimum sanctum and Amifostine on the Salivary Gland of Rats After Therapeutic Radioiodine Exposure

The current study investigated the radioprotective effect of Ocimum sanctum on the salivary gland of rats administered radioiodine ((131)I) and compared its efficacy with a known radioprotectant, amifostine. The experimental rats were divided in four groups and sacrificed in three different batches at 1, 3, and 6 months of time interval after 18.5 MBq/100g (i.p.) (131)I exposure. Six months duration batch received (131)I exposure twice with the gap of 3 months. Two groups of experimental rats were presupplemented with O. sanctum (40 mg/kg for 5 days, orally) and amifostine (200 mg/kg, s.c) before (131)I exposure separately. Increased Technetium-99m-pertechnetate ((99m)TcO(4)(-)) uptake at 30 minutes post injection in salivary glands of only (131)I exposed rats may imply delay in clearance at 6 months of exposure in comparison to their counterparts sacrificed at 1 month. Parotid gland histology showed atrophy with lipomatosis in only (131)I exposed rats at 3 and 6 months of duration. O. sanctum and amifostine presupplemented and subsequently exposed to (131)I rats at 3 and 6 months duration exhibited comparable histopathology with controls. Our study indicates possible radioprotective effect of O. sanctum and amifostine against high-dose (131)I exposure.

Micronuclei frequency in peripheral blood lymphocytes of thyroid cancer patients after radioiodine therapy and its relationship with metastasis.

In most cancers peripheral blood lymphocytes exhibit DNA damage. In the case of thyroid cancer the micronucleus (MN) assay has been used to assess DNA damage before and after exposure to iodine-131 ((131)I). The aim of our study was to use this method to assess DNA damage in peripheral blood lymphocytes of thyroid cancer patients and search for its relationship with metastasis as well as (131)I exposure. A significant increase in micronuclei frequency was observed in peripheral blood lymphocytes of 54 thyroid cancer patients in comparison to 38 controls (p=0.000). Further analysis revealed significant elevation in micronuclei index from 48.5 MN/1000 BN cells (range: 25.1-111.2, n=25) in patients without metastasis to 68.1 MN/1000 BN cells (range: 26.2-135.5, n=29, p=0.001) in group of patients with metastasis to one or more sites. There was no clear correlation between the micronuclei frequency and the therapeutic (131)I dose ranging from 0.41 to 31.5 GBq with the exposure interval of <1 to 126 months. In addition, age and sex did not show any influence on micronuclei frequency in either patients or control population. These findings are indicative of increased basal DNA damage in thyroid cancer patients before treatment. Radioiodine treatment did not increase DNA damage measured by the micronuclei frequency for the interval between the last radioiodine dose administered and analysis of blood sample. However a significant increase of peripheral blood lymphocytes micronuclei was observed in thyroid cancer patients with metastasis.

Immune functions, clinical parameters and hormone receptor status in breast cancer patients.

Abstract We have carried out a detailed analysis of the cellular immune functions of breast cancer patients in comparison with healthy controls. A possible correlation between immune and clinical parameters was analysed in 50 breast cancer patients. Immune parameters, natural killer cell and T lymphocyte functions and the numbers of circulating T lymphocytes were analysed against the clinical parameters comprising the tumour burden, the stage of the disease and the expression of hormone receptors on the tumour. In order to analyse the immune function data effectively, low responders were identified with stringent cut-off values. Considerably higher proportions of low responders were found among the patient population. Elevated numbers of circulating T lymphocytes and CD3-directed cytolysis correlated with the expression of oestrogen receptors independently of the clinical/histological parameters.

Does tranexamic acid reduce blood loss during head and neck cancer surgery

Background and Aims: Transfusion of blood and blood products poses several hazards. Antifibrinolytic agents are used to reduce perioperative blood loss. We decided to assess the effect of tranexamic acid (TA) on blood loss and the need for transfusion in head and neck cancer surgery. Methods: After Institutional Review Board approval, 240 patients undergoing supramajor head and neck cancer surgeries were prospectively randomised to either TA (10 mg/kg) group or placebo (P) group. After induction, the drug was infused by the anaesthesiologist, who was blinded to allocation, over 20 min. The dose was repeated every 3 h. Perioperative (up to 24 h) blood loss, need for transfusion and fluid therapy was recorded. Thromboelastography (TEG) was performed at fixed intervals in the first 100 patients. Patients were watched for post-operative complications. Results: Two hundred and nineteen records were evaluable. We found no difference in intraoperative blood loss (TA - 750 [600–1000] ml vs. P - 780 [150–2600] ml, P = 0.22). Post-operative blood loss was significantly more in the placebo group at 24 h (P - 200 [120–250] ml vs. TA - 250 [50–1050] ml, P = 0.009), but this did not result in higher number of patients needing transfusions (TA - 22/108 and P - 27/111 patients, P = 0.51). TEG revealed faster clot formation and minimal fibrinolysis. Two patients died of causes unrelated to study drug. Incidence of wound complications and deep venous thrombosis was similar. Conclusion: In head and neck cancer surgery, TA did not reduce intraoperative blood loss or need for transfusions. Perioperative TEG variables were similar. This may be attributed to pre-existing hypercoagulable state and minimal fibrinolysis in cancer patients.

Elective versus therapeutic neck dissection in the clinically node negative early oral cancer: A randomised control trial (RCT).

LBA3 Background: Management of the neck in early oral cancers has been a matter of debate with clinical equipoise between elective (END) or therapeutic neck dissection (TND). METHODS This is a prospective phase III RCT (NCT00193765) to test the superiority of END at the time of primary surgery over TND (neck dissection at the time of nodal relapse) in patients with lateralized T1 or T2 squamous carcinoma of oral cavity, amenable to peroral excision. Patients were stratified based on size, site, sex and preoperative neck ultrasound. The primary end point was overall survival (OS) and secondary end point was disease-free survival (DFS). The trial was planned to demonstrate a 10% superiority (1-sided α = 0.05 and β = 0.2) in OS for END vs. TND, assuming 60% 5-year OS in TND arm, with a planned sample size of 710. RESULTS This trial was terminated after 596 patients were randomized between January 2004 and June 2014. An interim intent-to-treat analysis of initial 500 patients (255 in TND, 245 END) with a minimum follow-up of 9 months was performed as mandated by Data and Safety Monitoring Committee based on the number of observed deaths in each arm. Both arms were balanced for site and stage. There were 427 tongue, 68 buccal mucosa and 5 floor of mouth tumors; 221 were TI and 279 T2. At a median follow-up of 39 months there were 146 recurrences in TND and 81 in END arms respectively. The 3-year OS was significantly higher in END compared to TND arm (80.0% vs. 67.5%, HR = 0.63, 95%CI 0.44-0.89, p = 0.01) as was 3-year DFS (69.5% vs. 45.9%, HR = 0.44, 95%CI 0.34-0.58, p < 0.001). After adjusting for stratification factors in Cox regression, END continued to be significantly superior to TND for both OS and DFS. CONCLUSIONS There were 8 excess deaths for every 15 excess recurrences in the TND arm. Elective neck dissection in patients with early oral SCC results in 37% reduction in mortality and should be considered the standard of care. CLINICAL TRIAL INFORMATION NCT00193765.

A Prospective Study of Computerized Digital Infrared Image Analysis (NoTouch BreastScanTM) in Biopsy Proven Breast Cancers.

Introduction: Early detection of breast cancer is known to have a more favourable outcome. Currently clinical breast examination and imaging modalities, primarily mammography are used for screening purposes. In India, more than 85% of the population is below the age of 50 years, wherein the sensitivity of mammography is at best 64%. Additional drawbacks of the procedure are physical discomfort and ionizing radiation dose to the patient. So newer techniques have been investigated which detect cancer induced neovascularity with digital thermal imaging. The purpose of this clinical study was to determine the efficacy of a software assisted thermal image analysis tool to distinguish between benign and malignant lesions of the breast.Methods: A prospective study was conducted in women who presented to the breast clinic with clinically or mammographically suspicious breast lesions. They also underwent thermal imaging of the breast. All mammographically suspicious lumps were subjected to histopathological confirmation. The mammography and infrared (IR) reports were compared to the histopathology.Results: In 90 women, 180 breasts were independently analyzed by both digital IR software analysis and mammography. Eighty five out of these 180 had suspicious lesions on mammography or clinical examination which were subjected to pathological confirmation. Mammography being the present diagnostic gold standard, all normal mammograms in clinically normal breast were considered as non-malignant. The sensitivity and specificity of digital thermography in detecting malignant lesions was 88.24% and 70.52% respectively with NPV of 87.01% and PPV of 72.82%. While for mammography the sensitivity and specificity were 96.25% and 96.7% with NPV of 96.7% and PPV of 96.25%. In women below 50 years of age (62/90) the sensitivity and specificity of digital thermography was 89.83% and 64.61% with NPV of 87.5% and PPV of 69.74%. Further, in the same subset no statistically significant difference was detected in the sensitivity of digital thermography to that of mammography (p = 0.7263).Conclusion: Our initial experience shows that the detection rate by digital thermal imaging is comparable to mammography in clinically palpable breast tumors. We also note that there is no significant difference in sensitivity of thermal imaging in women on either side of 50 making it a potentially testable tool for screening in younger women. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5028.