Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study.

Introduction: The objective of the study was to evaluate the clinical profile and outcome of patients with secondary hemophagocytic lymphohistiocytosis (HLH) in critically ill patients. Materials and methods: A prospective observational study was conducted where critically ill adult patients presenting with fever and bicytopenia were evaluated according to the HLH-2004 diagnostic criteria for the presence of secondary HLH. The underlying trigger, clinical profile, treatment, and outcome of patients with HLH were analyzed. Results: Of the 76 critically ill patients with fever and bicytopenia, 33 (43%) patients were diagnosed with HLH. The following triggers for HLH were identified: bacterial infections (23%), fungal infections (10%), viral infections (10%), parasitic infections (10%), autoimmune diseases (13%), and malignancy (8%). A total of 78% of the HLH cases received steroids, but the use of steroids was not associated with improvement in mortality. Conclusion: There is a high prevalence of HLH in patients presenting with fever and bicytopenia in critically ill adult patients. Infections were identified as the most common trigger of HLH. How to cite this article: Fazal F, Gupta N, Soneja M, Mitra DK, Satpathy G, Panda SK, et al. Clinical Profile, Treatment, and Outcome of Patients with Secondary Hemophagocytic Lymphohistiocytosis in Critically Ill Patients: A Prospective Observational Study. Indian J Crit Care Med 2022;26(5):564-567.

Taxane-based Induction Chemotherapy Plus Concurrent Chemoradiotherapy in Nasopharyngeal Carcinoma: Prospective Results from a Non-endemic Cohort.

AIMS: To report the outcomes of induction chemotherapy (ICT) followed by chemoradiotherapy (CTRT) for a large cohort of locoregionally advanced nasopharyngeal cancer (LA-NPC) from a non-endemic region. MATERIALS AND METHODS: Between January 2008 and July 2015, 201 patients with histologically proven, non-metastatic NPC were treated with ICT followed by CTRT at our institute. All the patients received two to three cycles of a taxane-based ICT regimen. Radiotherapy was delivered using an intensity-modulated radiotherapy (IMRT) technique in all patients. RESULTS: After a median follow-up of 37 months (range: 7-110 months), the 3-year disease-free survival (DFS), locoregional relapse-free survival (LRFS), distant metastasis-free survival (DMFS) and overall survival of the entire cohort was 72, 85, 83 and 87.4%, respectively. On multivariate analysis, histology was an independent predictor of DFS, LRFS and overall survival, with keratinising squamous cell carcinoma histologies predicting a worse outcome. The nodal stage was an independent predictor of DFS, DMFS and overall survival. Age, gender, ethnicity, tumour stage and response to ICT did not significantly affect any of the outcomes. Grade 2 or worse subcutaneous fibrosis was seen in 19% of patients at last follow-up and grade 2 or worse xerostomia was seen in 24% of patients. Thirty-nine per cent of patients developed clinical hypothyroidism at last follow-up. CONCLUSION: ICT followed by concurrent CTRT in the IMRT era provides excellent locoregional control, distant control and overall survival rates in patients with LA-NPC. However, distant failure continues to be a problem and may require further systemic intensification.

Prevalence and reproductive manifestations of macroprolactinemia.

PURPOSE: Macroprolactinemia is characterized by predominance of macroprolactin molecules in circulation and generally has extra-pituitary origin. Macroprolactin is viewed as biologically inactive, therefore asymptomatic, and thus may not require any treatment or prolonged follow-up. In addition, data on prevalence of macroprolactinemia and its clinical manifestation are also rare. Therefore, the present study was aimed to find out prevalence of macroprolactinemia and its association, if any, with reproductive manifestations. MATERIAL AND METHODS: Macroprolactin was measured in 102 hyperprolactinemia cases (>100 ng/ml prolactin level), 135 physiological hyperprolactinemia cases (50 pregnant and 85 lactating females; >100 ng/ml prolactin level) and 24 controls. Poly ethylene glycol (PEG) precipitation method was carried out to screen macroprolactin. Prolactin recovery of <25% was considered overt macroprolactinemia. Detailed clinical data was recorded which included complete medical history, physical examination and hormone measurements besides CT/MRI for pituitary abnormalities. RESULTS: Prevalence of macroprolactinemia was 21.57% (22/102) in hyperprolactinemia (prolactin >100 ng/ml). There was no case of macroprolactinemia in physiological hyperprolactinemia, or healthy control females. Reproductive manifestations were present in 72.73% (16/22) macroprolactinemia cases, out of which macroprolactinemia was the sole cause of associated reproductive manifestations in 68.7% (11/16) cases. Reversal of reproductive dysfunction/s was observed in five cases with appropriate treatment for high macroprolactin. CONCLUSION: Macroprolactinemia prevalence was found to be 21.5%, out of which 72.73% cases had associated reproductive dysfunctions.

Role of microscopic spread beyond gross disease as an adverse prognostic factor in oral squamous cell carcinoma.

INTRODUCTION: Despite meticulous surgery and proper adjuvant treatment, outcome of oral squamous cell carcinoma remains unpredictable. This shows that there may be other factors which should be considered while prognosticating these patients. Many a times there is spread of disease beyond the gross margin which can alter the margin status. We hypothesized that microscopic spread beyond gross disease may portend a poor prognosis. METHOD: This is a retrospective study of prospectively collected data of 1025 treatment naïve oral squamous cell carcinoma patients. All patients underwent surgery from January 2012 to October 2013, this was followed by appropriate adjuvant treatment. Demographic and histopathological details were noted from the electronic medical records. RESULTS: Microscopic spread beyond gross disease (MSGD) is associated with higher incidence of nodal positivity (p < 0.046), peri-neural invasion (p < 0.001), thicker tumours (p < 0.024) and poor differentiation (p < 0.060). The overall survival in patients with MSGD was 32.45 months vs. 37.5 months in patients without MSGD (p < 0.002). CONCLUSION: Tumours with MSGD tend to have a higher incidence of nodal metastasis, PNI and thicker tumours. Presence of MSGD was associated with lower overall survival as compared to those without.

Role of the pectoralis major myofascial flap in preventing pharyngocutaneous fistula following salvage laryngectomy.

OBJECTIVE: This study aimed to assess the utility of onlay pectoralis major myofascial flap in preventing pharyngocutaneous fistula following salvage total laryngectomy. METHODS: A retrospective analysis was performed of 172 patients who underwent salvage laryngectomy for recurrent carcinoma of the larynx or hypopharynx between 1999 and 2014. One hundred and ten patients underwent primary closure and 62 patients had pectoralis major myofascial flap onlay. RESULTS: The overall pharyngocutaneous fistula rate was 43 per cent, and was similar in both groups (primary closure group, 43.6 per cent; onlay flap group, 41.9 per cent; p = 0.8). Fistulae in the onlay flap group healed faster: the median and mean fistula duration were 37 and 55 days, respectively, in the primary closure group and 20 and 25 days, respectively, in the onlay flap group (p = 0.008). CONCLUSION: Use of an onlay pectoralis major myofascial flap did not decrease the pharyngocutaneous fistula rate, although fistula duration was shortened. A well-designed randomised-controlled trial is needed to establish parameters for its routine use in clinical practice.

Squamous cell carcinoma of the upper aerodigestive tract in exclusive smokers, chewers, and those with no habits.

BACKGROUND: Tobacco consumption is the major risk factor for developing head and neck squamous cell cancer (SCC). The site of development of HNSCC may depend on the way the tobacco is consumed. While laryngeal cancers are more common among smokers, oral cancers are more common among tobacco chewers. Since the use of smokeless tobacco is increasing, it is important to know whether this difference is restricted only to site wise distribution or it has other clinical and pathological implications. PATIENTS AND METHODS: We analyzed a prospectively collected dataset of HNSCC patients other than nasopharyngeal cancers attending our outpatient department at a single unit of the head and neck services at Tata Memorial Hospital, Mumbai, India, between January 2010 and September 2011. There were 747 eligible patients and were divided into three groups: Those with chewing as the only habit (chewers), those with smoking as the only habit (smokers), and those with no habits. Patients with regular use of alcohol were excluded from the study. The clinical and pathological parameters were analyzed. RESULTS: Of the 747 patients, the tobacco chewers formed 69.3% followed by smokers (19.5%) and patients with no habits (11.1%). Majority of smokers were men (98%). Site distribution revealed patients with chewing as the only habit had oral cancers (most commonly gingivobuccal complex cancers) as the most common site and those with smoking as the only habit had larynx as the most common site. In patients with no habits, oral tongue was found to be the most common site. No statistically significant pathological differences were observed in between these groups in patients who underwent surgery (n = 366) at the initial modality of treatment. CONCLUSIONS: There is a direct relationship between the form of tobacco use and site of appearance of HNSCC. However, there are no differences in clinical or pathological parameters between HNSCC caused by tobacco chewing or tobacco smoking.

Skin involvement and ipsilateral nodal metastasis as a predictor of contralateral nodal metastasis in buccal mucosa cancers.

CONTEXT: In view of low incidence of contralateral nodal metastasis and increase in the morbidity, the opposite neck is not routinely addressed. However, contralateral nodal metastasis is seen frequently in a certain group of patients. Identifying those factors associated with higher chances of contralateral nodal metastasis may help in optimizing the treatment. AIMS: The aim of this study was to identify prognostic factors associated with contralateral nodal metastasis in cases of buccal mucosa cancers. SETTINGS AND DESIGN: A retrospective audit of 125 patients with squamous cell carcinoma of buccal mucosa at a tertiary cancer center. SUBJECTS AND METHODS: Those cases in which lesions were reaching or crossing midline were included in this study. All cases underwent surgery as primary modality of treatment and had bilateral neck dissection. STATISTICAL ANALYSIS USED: Chi-square test is used for evaluating the variables predicting contralateral nodal metastasis. Finally, a multivariate analysis was performed using binomial logistic regression to identify those variables that were independently associated with the risk of contralateral nodal metastasis. RESULTS: Among 125 patients, 53 cases were node negative. Ipsilateral nodal metastasis was seen in 44/125 (35.2%) patients, 26/125 (20.8%) had bilateral neck node metastasis, and 2/125 (1.6%) had isolated contralateral nodal metastasis. Among these 28 patients with contralateral nodal metastasis, 26 patients had ipsilateral nodal metastasis. Ipsilateral nodal metastasis and skin involvement were independently predictive of contralateral nodal metastasis. CONCLUSIONS: Contralateral nodal metastasis in the absence of ipsilateral nodal metastasis is very rare and frozen section of ipsilateral neck dissection specimen can be an important pointer for addressing contralateral neck.

Prognostic Performance of Current Stage III Oral Cancer Patients After Curative Intent Resection: Evidence to Support a Revision of the American Joint Committee on Cancer Staging System.

BACKGROUND: The American Joint Committee on Cancer (AJCC) stage III classification of oral cavity squamous cell carcinoma (OCSCC) represents a heterogeneous group of patients with early local disease with regional metastases (T1N1 and T2N1) and advanced local disease with or without regional metastasis (T3N0 and T3N1). OBJECTIVE: The aim of this study was to evaluate prognostic heterogeneity in the stage III category. METHODS AND PATIENTS: An international retrospective multicenter study of 1815 patients who were treated for OCSCC from 2003 to 2011. RESULTS: Kaplan-Meier survival analysis and multivariate models of stage III patients revealed better overall survival (OS; HR 2.12, 95 % CI 1.03-4.15; p = 0.01) and disease-specific survival (DSS; HR 1.7, 95 % CI 1.16-4.12; p = 0.04) rates for patients with T1-2N1/T3N0 disease than for patients with T3N1 disease. The outcomes of patients with T3N1 and stage IVa disease were similar (p = 0.89 and p = 0.78 for OS and DSS, respectively). Modifying stage classification by transferring the T3N1 category to the stage VIa group resulted in a better prognostic performance [Harrell's concordance index, C index 0.76; Akaike's Information Criterion (AIC) 4131.6] compared with the AJCC 7th edition staging system (C index 0.65; AIC 4144.9) for OS. When DSS was assessed, the suggested staging system remained the best performing model (C index 0.71; AIC 1061.3) compared with the current AJCC 7th edition staging (C index 0.64; AIC 1066.2). CONCLUSIONS: The prognosis of T3N1 and stage IVa disease are similar in OCSCC, suggesting that these categories could be combined in future revisions of the nodal staging system to enhance prognostic accuracy.

A review on harmful effects of pan masala.

Pan masala (PM) is a mixture of areca nut with slaked lime, catechu and other flavoring agents. It is widely available and used by all the sections of the Indian society. It is genotoxic as it increases sister chromatin exchange and chromatin aberrations. Among humans, it is a leading cause of oral submucous fibrosis that often progresses to oral cancer. Among experimental animals, it leads to neoplastic lesions in lung, liver and stomach. It is hepatotoxic leading to increased level of enzymes, deranged carbohydrate and lipid metabolism. It is harmful to kidneys and testes leading to increased creatinine and sperm deformities respectively. PM is a very harmful substance affecting almost all organ systems, and there is immediate need for a national policy on complete ban on the production, storage, sale and marketing of PM.

Correlation between lead and cadmium concentration and semen quality.

There are contrary reports of association of lead and cadmium with the decline in semen quality. This study evaluates whether seminal lead (Pb) and cadmium (Cd) at environmental concentration are associated with altered semen quality. We conducted a study of healthy fertile and infertile men 20-43 years of age attending the Andrology Laboratory of Reproductive Biology Department for semen analysis. The semen analysis was carried out according to the WHO 2010 guidelines. Seminal lead and cadmium were estimated by ICP-AES. The lead and cadmium values were significantly higher in infertile subjects. A negative association between seminal lead or cadmium concentration and sperm concentration, sperm motility and per cent abnormal spermatozoa was found. This study shows that exposure to Pb (5.29-7.25 µg dl(-1) ) and cadmium (4.07-5.92 µg dl(-1) ) might affect semen profile in men. Age, diet, smoking and tobacco chewing habits may have an influence on the increase in exposure to Pb and Cd in the individual subjects.

Is taxane/platinum/5 fluorouracil superior to taxane/platinum alone and does docetaxel trump paclitaxel in induction therapy for locally advanced oral cavity cancers?

BACKGROUND: Cisplatin and 5 fluorouracil drug combination is inferior to the combination of taxane with these 2 drugs. However, often in clinical practice at our center giving TPF (docetaxel, cisplatin, 5 fluorouracil) is difficult in view of logistics and tolerance issues. In such a scenario, we prefer to use the 2 drugs combination of platinum and taxane. However, no study has addressed whether a 2 drugs combination, which includes taxane is inferior to the 3 drugs combination and which the taxane of choice is in the 2 drugs combination of taxane and platinum. METHODS: This is a retrospective analysis of prospectively collected data of patients undergoing induction chemotherapy (IC) in oral cavity cancers from 2010 to 2012. We chose for analysis those patients who had a baseline scan done within 4 weeks of starting therapy and a follow-up scan done within 2 weeks of completion of the second cycle of IC. Response was scored in accordance with RECIST version 1.1. Chi-square analysis was done to compare response rates (RRs) between regimens. RESULTS: Two hundred and forty-five patients were identified. The median age was 45 years (24-70 years), 208 (84.9%) were male patients, and 154 patients (62.9%) had primary in the Buccal mucosa. The regimens received were TPF 22 (9%), docetaxel + cisplatin 97 (39.6%), paclitaxel + cisplatin 89 (36.3%), docetaxel + carboplatin 16 (6.5%) and paclitaxel + carboplatin 21 (8.6%). The overall RRs were complete response, partial response, stable disease and progressive disease in 4 (1.6%), 56 (22.9%), 145 (59.2%) and 40 (16.3%). The 3 drugs regimen (TPF) had 50% RR as compared to 22% RR with 2 drugs regimen (P = 0.004). Docetaxel containing regimens had 30.3% RR as compared to 17.2% RR with paclitaxel containing regimens (P = 0.094). CONCLUSIONS: TPF has better RR than a 2 drugs taxane-containing regimen and docetaxel leads to a better RR than paclitaxel for IC in locally advanced oral cavity cancers.

A review of Indian literature for association of smokeless tobacco with malignant and premalignant diseases of head and neck region.

In India, about 60% of tobacco users use smokeless tobacco (ST) alone. Head and neck squamous cell carcinoma is one of the most common cancers in India. International Agency for Research on Cancer (IARC) monograph (Vol 89) found a significant association between ST use and oral cancer. However, only a few articles from India were included in this monograph. To overcome this lacuna, we have reviewed the articles published from India investigating the association between ST use and malignant and premalignant diseases of head and neck region. Data collection has been performed by computer-aided search of the MedLine and PubMed databases using different combinations of the key words. For malignant lesions, only cohort and case control studies were considered for review. For premalignant lesions and dental diseases other than case control studies, some cross-sectional studies have also been reviewed. Studies found a significant association between ST use and cancer of the oral cavity. The association was stronger for the buccal mucosa compared to tongue and for females compared to males. Significant association noted between cancer of the hypopharynx and oropharynx with ST use but no definitive association noted for cancer of the larynx and nasopharynx. Some dental disease and oral premalignant conditions were also associated with ST use. Indian studies suggest ST use is strongly associated with cancer of the oral cavity, oropharynx and hypopharynx.

Factors predicting 'time to distant metastasis' in radically treated head and neck cancer.

Context: Various studies have shown the important risk factors for distant metastasis in head and neck cancer (HNC) which are present in most of the patients in developing countries. Identification of factors on the basis of time to distant metastasis (TDM) can help in future trials targeting smaller subgroups. Aims and Objectives: To identify the factors that predict TDM in radically treated HNC patients. Settings and Design: Retrospective audit. Materials and Methods: Retrospective audit of the prospectively maintained electronic database of a single HNC radiotherapy clinic from 1990 to 2010 was done to identify radically treated patients of HNC who developed distant metastasis. Univariate and multivariate analysis were done to identify baseline (demographic, clinical, pathological, and treatment) factors which could predict TDM, early time to metastasis (ETM; <12 months), intermediate time to metastasis (ITM; 12-24 months), and late time to metastasis (LTM; >2 years) using Kaplan Meier and Cox regression analysis, respectively. Results: One hundred patients with distant metastasis were identified with a median TDM of 7.4 months; 66 had ETM, 17 had ITM, and 17 had LTM. On multivariate analysis, the nodal stage 2-3 (N2/3) was the only baseline factor independently predicting TDM, ETM, and ITM, whereas none of the baseline factors predicted LTM. Conclusions: Higher nodal burden (N2/3) is associated with both ETM and ITM, and calls for aggressive screening, systemic therapy options, and surveillance. It is difficult to predict patients who are at a risk of developing LTM with baseline factors alone and evaluation of biological data is needed.

Delay in seeking specialized care for oral cancers: experience from a tertiary cancer center.

OBJECTIVE: Advanced oral cancers are a challenge for treatment, as they require complex procedures for excision and reconstruction. Despite being occurring at a visible site and can be detected easily, many patients present in advanced stages with large tumors. Timely intervention is important in improving survival and quality of life in these patients. The aim of the present study was to find out the causes of delay in seeking specialist care in advanced oral cancer patients. MATERIALS AND METHODS: A prospective questionnaire based study was done on 201 consecutive advanced oral squamous cancer patients who underwent surgery at our hospital. All patients had either cancer of gingivobuccal complex (GBC) or tongue and had tumors of size more than 4 cm (T3/T4) and were treatment naοve at presentation. RESULTS: Even though most patients observed abnormal lesions in their mouth, majority delayed the decision to visit a physician early. A significant percentage of patients (50%) also reported a delayed diagnosis by the primary care physician before being referred to a tertiary care center for definitive treatment. The average total duration from symptoms to treatment was 7 months. CONCLUSION: The main reasons of this delay in receiving treatment were due to patients themselves (primary delay) or due to time taken by the primary physician to diagnose the condition (secondary delay). Oral self-examination can be helpful in detecting oral cancers early.

Microbial colonization of Provox voice prosthesis in the Indian scenario.

INTRODUCTION: Tracheoesophageal speech using the voice prosthesis is considered to be the "gold standard" with success rates as high as 90%. Despite significant developments, majority eventually develop dysfunction due to microbial deterioration. We did a pilot study of 58 laryngectomy patients who developed prosthesis dysfunction. MATERIALS AND METHODS: A total of 58 laryngectomy patients who had their dysfunctional prosthesis removed were included in this study. Dysfunctional prostheses were removed and examined. Esophageal and tracheal flanges were examined separately. After obtaining pure fungal and bacterial cultures, the yeast strains were identified. Bacteria were identified with the light microscope and gram staining. We analyzed prosthesis lifespan and probable factors affecting it. RESULTS: Central leak was found in 43% cases while in 57% peri-prosthetic leakage was the most common reason for prosthesis replacement. Microbial analysis revealed a combination of yeast and bacteria in approximately 55% culture samples. Out of these, almost 90% had the presence of single yeast species with bacteria. Pure fungal culture was identified in rest of the 45% cultures while none detected pure bacterial forms. Candida tropicalis was the solitary yeast in 81% while Candida albicans was seen in 10% as the solitary yeast. Bacterial isolates revealed Klebsiella pneumonia in 19%, Escherichia coli in 8% while Staphylococcus aureus was grown in 1% cultures. The consumption of curd (P = 0.036, 95% confidence intervals [CI]: 2.292-64.285) to have a significant correlation of the mean prosthesis lifespan. Consumption of curd (P = 0.001, 95% CI: 0.564-2.008) and history of prior radiotherapy (P = 0.015, 95% CI: 0.104-0.909) had a significant bearing on the Provox prosthesis lifespan. CONCLUSIONS: Candida is the most common organism grown on voice prosthesis in Indian scenario. Consumption of curd and history of prior radiotherapy significantly affect Provox prosthesis lifespan.

Neoadjuvant chemotherapy followed by surgery in very locally advanced technically unresectable oral cavity cancers.

BACKGROUND: The median survival of technically unresectable oral-cavity cancers (T4a and T4b) with non surgical therapy is 2-12 months. We hypothesized that neoadjuvant chemotherapy (NACT) could reduce the tumour size and result in successful resection and ultimately improved outcomes. We present a retrospective analysis of consecutive patients who received NACT at our centre between January 2008 and August 2012. PATIENTS AND METHODS: All patients with technically unresectable oral cancers were assessed in a multidisciplinary clinic and received 2 cycles of NACT. After 2 cycles, patients were reassessed and planned for either surgery with subsequent CTRT or nonsurgical therapy including CT-RT, RT or palliation. SPSS version 16 was used for analysis of locoregional control and overall survival (OS). Univariate and multivariate analysis was done for factors affecting the OS. RESULTS: 721 patients with stage IV oral-cavity cancer received NACT. 310 patients (43%) had sufficient reduction in tumour size and underwent surgical resection. Of the remaining patients, 167 received chemoradiation, 3 radical radiation and 241 palliative treatment alone The locoregional control rate at 24 months was 20.6% for the overall cohort, 32% in patients undergoing surgery and 15% in patients undergoing non surgical treatment (p=0.0001). The median estimated OS in patients undergoing surgery was 19.6 months (95% CI, 9.59-25.21 months) and 8.16 months (95%, CI 7.57-8.76) in patients treated with non surgical treatment (p=0.0001). CONCLUSION: In our analysis, NACT led to successful resection and improved overall survival in a significant proportion of technically unresectable oral-cancer patients.