Trends in Surgical Management of Esophageal Cancer.

BACKGROUND: Management of esophageal cancer has changed to a combined modality approach over the past two decades due to poor outcome. Recently, multimodal treatment has become the standard practice. The aim of this study was to evaluate the changing trends in management and outcomes of esophagectomy over 15 years from a single center in Nepal. METHODS: Patients with squamous cell carcinoma and adenocarcinoma of esophagus/ gastroesophageal junction who underwent surgery between 2001-2018 were analyzed. Patients were grouped into three successive 5-year periods. RESULTS: 547 patients underwent esophagectomy during 2001-2018. There was increased trend of neoadjuvant treatment from 9-13% to 52% (p<.001) and minimally invasive surgery (MIS) from 0% to 80% (p<.001). 30-day mortality decreased from 8% to 1% (p=.01). The 5-overall survival was 24% which increased from 17% to 27% (p=.003). CONCLUSIONS: Long term outcome has improved over last 15 years with decreasing mortality which appears to be due to incorporation of MIS and neoadjuvant treatment.

REcovery and SURvival of patients with moderate to severe acute REspiratory distress syndrome (ARDS) due to COVID-19: a multicenter, single-arm, Phase IV itolizumab Trial: RESURRECT.

BACKGROUND: Itolizumab, an anti-CD6 monoclonal antibody, down-regulates COVID-19-mediated inflammation and the acute effects of cytokine release syndrome. This study aimed to evaluate the safety and efficacy of itolizumab in hospitalized COVID-19 patients with PaO2/FiO2 ratio (PFR) ≤200 requiring oxygen therapy. RESEARCH DESIGN AND METHODS: This multicenter, single-arm, Phase 4 study enrolled 300 hospitalized adults with SARS-CoV-2 infection, PFR ≤200, oxygen saturation ≤94%, and ≥1 elevated inflammatory markers from 17 COVID-19 specific tertiary Indian hospitals. Patients received 1.6 mg/kg of itolizumab infusion, were assessed for 1 month, and followed-up to Day 90. Primary outcome measures included incidence of severe acute infusion-related reactions (IRRs) (≥Grade-3) and mortality rate at 1 month. RESULTS: Incidence of severe acute IRRs was 1.3% and mortality rate at 1 month was 6.7% (n = 20/300). Mortality rate at Day 90 was 8.0% (n = 24/300). By Day 7, most patients had stable/improved SpO2 without increasing FiO2 and by Day 30, 91.7% patients were off oxygen therapy. Overall, 63 and 10 patients, respectively, reported 123 and 11 treatment-emergent adverse events up to Days 30 and 90. No deaths were attributable to itolizumab. Patient-reported outcomes showed gradual and significant improvement for all five dimensions on EQ-5D-5L. CONCLUSION: Itolizumab demonstrated acceptable safety with a favorable prognosis in hospitalized COVID-19 patients. CLINICAL TRIAL REGISTRATION: CTRI/2020/09/027941 (Clinical Trials Registry of India).

Management of Locally Advanced Esophageal Cancer.

Esophageal cancer is diagnosed usually at a locally advanced stage. Surgery alone has less optimal results and a multimodality approach has been established as the standard of care for cII-III stages of esophageal cancer. This review focuses on the recent evidences of management of esophageal cancer with various variations in approaches in Eastern and Western countries. The major difference is the selection of induction treatment. Till the results of some ongoing trials become available, most of the evidences support neoadjuvant chemoradiation followed by surgery for squamous cell carcinoma and perioperative chemotherapy and surgery for adenocarcinoma.

Medical Thoracoscopy for Undiagnosed Exudative Pleural Effusion: Experience from Two Tertiary Care Hospitals of Nepal.

INTRODUCTION: Medical thoracoscopy has recently gained renewed interest due to its minimal invasive nature and high yield diagnostic outcome. This study aims to observe diagnostic yield and safety of medical thoracoscopy in undiagnosed exudative pleural effusion. METHODS: This is a descriptive cross-sectional study conducted in two tertiary care hospitals in Chitwan from March 2018 to May 2018. Ethical approval from the Institutional Review Board was obtained. Convenient sampling was done that included all the patients who met criteria for undiagnosed exudative pleural effusion after diagnostic thoracocentesis. Patients having contraindication to procedure and who refused consent were excluded. Statistical analysis was performed using IBM SPSS Statistics 20 and data are presented as mean ±SD and frequency (percentage). RESULTS: A total of 14 patients underwent rigid medical thoracoscopy. All 14 patients had unilateral pleural effusion. The overall diagnostic yield was 100%. Malignancy was the most frequent histopathology diagnosis seen in 11 (78.57%) patients, the commonest being metastatic adenocarcinoma in 8 (57.1%). Pleural tuberculosis and acute-on-chronic pleuritis were seen in 2 (14.3%) and 1 (7.1%) patients, respectively. Pleural deposits and hemorrhagic pleural fluid were the two commonest findings, seen in 10 (70.1%) and 9 (64.3%) patients, respectively. Two (14.3%) patients clinically treated as tuberculous pleural effusion was re-diagnosed to have metastatic adenocarcinoma. Procedure related mortality and major complications were nil. Common procedure-related minor complications observed were mild to moderate pain and mild bleeding, observed in 3 (21.4%) and 2 (14.3%) patients, respectively. CONCLUSIONS: Medical thoracoscopy is a safe, well-tolerated and high yield procedure in undiagnosed exudative pleural effusion. This art of medicine should be promoted in daily medical practice.

Medical Thoracoscopy for Undiagnosed Exudative Pleural Effusion: A Descriptive Cross-sectional Study.

INTRODUCTION: Medical thoracoscopy has recently gained renewed interest due to its minimal invasive nature and high yield diagnostic outcome. This study aims to observe diagnostic yield and safety of medical thoracoscopy in undiagnosed exudative pleural effusion. METHODS: This is a descriptive cross-sectional study conducted in two tertiary care hospitals in Chitwan from March 2018 to May 2018. Ethical approval from the Institutional Review Board was obtained. Convenient sampling was done that included all the patients who met criteria for undiagnosed exudative pleural effusion after diagnostic thoracocentesis. Patients having contraindication to procedure and who refused consent were excluded. Statistical analysis was performed using IBM SPSS Statistics 20 and data are presented as mean±SD and frequency (percentage). RESULTS: A total of 14 patients underwent rigid medical thoracoscopy. All 14 patients had unilateral pleural effusion. The overall diagnostic yield was 100%. Malignancy was the most frequent histopathology diagnosis seen in 11 (78.57%) patients, the commonest being metastatic adenocarcinoma in 8 (57.1%). Pleural tuberculosis and acute-on-chronic pleuritis were seen in 2 (14.3%) and 1 (7.1%) patients, respectively. Pleural deposits and hemorrhagic pleural fluid were the two commonest findings, seen in 10 (70.1%) and 9 (64.3%) patients, respectively. Two (14.3%) patients clinically treated as tuberculous pleural effusion was re-diagnosed to have metastatic adenocarcinoma.  Common procedure-related minor complications observed were mild to moderate pain and mild bleeding, observed in 3 (21.4%) and 2 (14.3%) patients, respectively. CONCLUSIONS: Medical thoracoscopy is a safe, well-tolerated and high yield procedure in undiagnosed exudative pleural effusion. This art of medicine should be promoted in daily medical practice.

Evidence Based Surgical Approach to Locally Advanced Gastric Cancer.

Gastric cancer is endemic in China, Japan, Korea, Brazil and Former Soviet Union. Patients are diagnosed usually in locally advanced stage. Endoscopy, Positron Emission Therapy- Computed Tomography, Endoscopic ultrasound and staging laparoscopy are the tools for proper evaluation of such patients. Locally advanced gastric cancer (T2-4N0 or TanyN+) requires multimodality treatment including surgery. Resection is the cornerstone of cure for gastric adenocarcinoma; however, several aspects of surgical intervention remain controversial or are suboptimally applied at a population level. Current evidence shows a D2 gastrectomy has got the best survival results. At least 15 lymph nodes should be assessed for adequate staging. Laparoscopic resections should be performed to the same standards as those for for open resections, by surgeons who are experienced in both advanced laparoscopic surgery and gastric cancer management. Keywords: Curative surgery; gastrectomy; stomach neoplasms.

Reproductive and Hormonal Factors in Relation to Lung Cancer Among Nepali Women.

Background: Of the 1.8 million global incident lung cancer cases estimated in 2012, approximately 60% occurred in less developed regions. Prior studies suggest sex differences in lung cancer risk and a potential role for reproductive and hormonal factors in lung cancer among women. However, the majority of these studies were conducted in developed regions. No prior study has assessed these relationships among Nepali women. Methods: Using data from a hospital-based case-control study conducted in B. P. Koirala Memorial Cancer Hospital (Nepal, 2009-2012), relationships between reproductive and hormonal factors and lung cancer were examined among women aged 23-85 years. Lung cancer cases (n = 268) were frequency-matched to controls (n = 226) based on age (±5 years), ethnicity and residential area. The main exposures in this analysis included menopausal status, age at menarche, age at menopause, menstrual duration, gravidity, and age at first live-birth. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression. Results: Among postmenopausal women, those with a younger age at menopause (<45 years; 45-49 years) had an increased odds of lung cancer compared to those with an older (≥50 years) age at menopause [OR (95%CI): 2.14 (1.09, 4.17); OR (95% CI): 1.93 (1.07, 3.51)], after adjusting for age and cumulative active smoking years. No statistically significant associations were observed with the other reproductive and hormonal factors examined. Conclusion: These results suggest that Nepali women with prolonged exposure to endogenous ovarian hormones, via later age at menopause, may have a lower odds of lung cancer.

Evolutionary selected Tibetan variants of HIF pathway and risk of lung cancer.

Tibetans existed in high altitude for ~25 thousand years and have evolutionary selected unique haplotypes assumed to be beneficial to hypoxic adaptation. EGLN1/PHD2 and EPAS1/HIF-2α, both crucial components of hypoxia sensing, are the two best-established loci contributing to high altitude adaptation. The co-adapted Tibetan-specific haplotype encoding for PHD2:p.[D4E/C127S] promotes increased HIF degradation under hypoxic conditions. The Tibetan-specific 200 kb EPAS1 haplotype introgressed from an archaic human population related to Denisovans which underwent evolutionary decay; however, the functional variant(s) responsible for high-altitude adaptation at EPAS1/HIF-2α have not yet been identified. Since HIF modulates the behavior of cancer cells, we hypothesized that these Tibetan selected genomic variants may modify cancer risk predisposition. Here, we ascertained the frequencies of EGLN1D4E/C127S and EGLN1C127S variants and ten EPAS1/HIF-2α variants in lung cancer patients and controls in Nepal, whose population consists of people with Indo-Aryan origin and Tibetan-related Mongoloid origin. We observed a significant association between the selected Tibetan EGLN1/PHD2 haplotype and lung cancer (p=0.0012 for D4E, p=0.0002 for C127S), corresponding to a two-fold increase in lung cancer risk. We also observed a two-fold or greater increased risk for two of the ten EPAS1/HIF-2α variants, although the association was not significant after correcting for multiple comparisons (p=0.12). Although these data cannot address the role of these genetic variants on lung cancer initiation or progression, we conclude that some selected Tibetan variants are strongly associated with a modified risk of lung cancer.

Household air pollution and lung cancer risk among never-smokers in Nepal.

More than half of the global population relies on biomass fuels (wood, charcoal, crop residue, dung) for cooking and/or heating purposes. Household air pollution (HAP) resulting from the use of these solid fuels is of particular concern, given the overall prevalence as well as the intensity of exposure and the range of potential adverse health outcomes. Long term exposure to HAP is a major public health concern, particularly among women and children in low and middle income countries. In this study, we investigated the association between exposure to HAP resulting from combustion of biomass and lung cancer risk among Nepalese population. Using a hospital-based case-control study (2009-2012), we recruited 606 lung cancer cases and 606 healthy controls matched on age (±5 years), gender, and geographical residence. We used unconditional logistic regression to compute odds ratios (ORs) and 95% Confidence Intervals (95% CI) for lung cancer risk associated with HAP exposures, adjusting for potential confounders (tobacco use, TB status, SES, age, gender, ethnicity, and exposure to second hand smoke. In our overall analysis, we observed increased risk of lung cancer among those who were exposed to HAPs (OR: 1.77, 95% CI: 1.00-3.14). A more detailed analysis stratified by smoking status showed considerably higher risk of lung cancer associated with increasing duration of exposure to HAP from biomass combustion, with evidence of a borderline exposure-response relationship (Ptrend=0.05) that was more pronounced among never-smokers (Ptrend=0.01). Our results suggest that chronic exposure to HAP resulting from biomass combustion is associated with increased lung cancer risk, particularly among never-smokers in Nepal.

Ethnic Variation in Consumption of Traditional Tobacco Products and Lung Cancer Risk in Nepal.

Lung cancer is the leading contributor to cancer deaths in the developing world. Within countries, significant variability exists in the prevalence of lung cancer risk, yet limited information is available whether some of the observed variability is associated with differences in the consumption pattern of local tobacco products with differing potency. We recruited 606 lung cancer cases and 606 controls from the B.P. Koirala Memorial Cancer Hospital in Nepal from 2009-2012. We estimated odds ratios (ORs) and 95% confidence intervals (CI) for lung cancer risk associated with different tobacco products, using unconditional logistic regression. Unfiltered cigarettes tended to be the most frequently used products across ethnic subgroup with about 53.7% of Brahmins, 60.1% of Chettris, and 52.3% of Rai/Limbu/Magar/others. In contrast, about 39.9% of Madishe/Tharu smokers reported using bidi compared with only 27.7% who smoked unfiltered cigarettes. Among those who only smoked one type of product, choor/kankat smokers had the highest lung cancer risk (OR 10.2; 95% CI 6.2-16.6), followed by bidi smokers (OR 5.6; 95% CI 3.6-8.7), unfiltered cigarettes (OR 4.9; 95% CI 3.4-7.2), and filtered cigarettes (OR 3.4; 95% CI 2.2-5.3). A clear dose-response relationship was observed between increased frequency of smoking and lung cancer risk across all ethnic subgroups. These results highlight the important role of traditional tobacco products on lung cancer risk in the low income countries.

Results of management of esophageal and GE junction malignancies in Nepalese context.

BACKGROUND: Optimal management of esophageal and GE junction cancer in Nepal has not been studied properly. We reviewed our results to recommend some practical guidelines. METHODS: An institutional review of 327 patients was done. Locally advanced cases were subjected to neoadjuvant treatment prior to surgery, whereas resectable cases were directly subjected to surgery or surgery followed by adjuvant treatment. Open and minimally invasive approaches were used in 246 (75%) and 81 (25%) patients, respectively. RESULTS: Final stages showed Ia (0.3%), Ib (2%), IIa (13%), IIb (8%), IIIa (17%), IIIb (11%), IIIc (41.7%) and IV (7%). The post operative mortality was 5.8%. Pneumonia/ pneumonitis, anastomotic leak and hoarseness of voice were observed in 21%, 11.6% and 7.6%, respectively. Median survival (in months) was as follows: St Ia - 60, Ib - 15, IIa - 23, IIb - 18, IIIa - 15, IIIb - 15, IIIc - 11 and IV - 8.5 (P<0.001). R0 and R+ resection was achieved in 299 (91%) and 28 (9%) cases, respectively with median survival of 27 and 9 months in R0 and R+ resections, respectively (P<0.001). 5-year overall survival was 22% with median survival of 25 months. After neoadjuvant treatment, Complete responders had median survival of 25.1 vs. 12.6 months for non-responders (P=0.042). CONCLUSION: Though the postoperative complications remain in acceptable range, the overall survival remains poor mainly due to the advanced stage of the disease at the time of diagnosis. Therefore, an approach of neoadjuvant chemoradiation/ chemotherapy prior to the surgery should be encouraged whenever feasible in order to achieve the best results.

Socioeconomic status and lung cancer risk in Nepal.

BACKGROUND: Lung cancer is the most common cancer among men and the third most common cancer among women in Nepal. Socioeconomic disparities in lung cancer have not been studied in the Nepalese population. METHODS: We conducted a lung cancer case-control study, including 209 cases and 313 controls at the main cancer hospital in Nepal, the B.P. Koirala Memorial Cancer Hospital (BPKMCH). RESULTS: We observed differences in lung cancer risk by ethnicity; the Rai, Limbu and Magar groups had a higher risk of lung cancer than Brahmin (OR=3.11, 95%CI=1.55-6.23). An inverse association was observed between education and lung cancer risk (p for trend=0.0008). We also observed greater lung cancer risk among unmarried individuals (OR=2.25, 95%CI=1.12-4.53), and lower risk in individuals who lived in the Central region compared to the West (OR=0.47, 95%CI=0.26-0.85). There were greater proportions of late stage cancers among women compared to men, in the Rai/Limbu/Magar ethnic groups, in individuals with lower education and in older age groups. CONCLUSIONS: Disparities in lung cancer risk were observed by race/ethnicity, education, marital status, and by region of residence. Further research on socioeconomic influence on lung cancer in Nepal is warranted to develop better prevention efforts against the disease.

Comparison Between Concurrent Chemoradiation Followed by Surgery vs. Surgery for Locally Advanced Cancer of Esophagus.

Surgery is an accepted standard in the treatment of localized stage cancer of esophagus. But the ideal approach for locally advanced lesions still remains unknown. Patients with locally advanced lesions (cT3-4N1M0) on the basis of CT chest were subjected either to primary surgery or to preoperative chemoradiation followed by surgery. Major postoperative complications (mortality, anastomotic leak and recurrent laryngeal nerve palsy) did not differ in either arm (P = not significant). Complete pathological response was achieved in 31.2% cases in multimodality arm. Four year overall survival was 10% for whole group. Median survival was 14 months and 20 months in surgery and multimodality arm, respectively (p = .288). In multimodal arm, there was significant survival difference between complete responders and nonresponders (p = .02). For locally advanced lesions, surgery alone gives poor outcome and preoperative chemoradiation followed by surgery should be considered for complete responders.

Initial experience in a cancer hospital in Nepal with sentinel lymph node mapping and biopsy for evaluation of axillary lymph node status in palpable invasive breast cancer.

To evaluate the performance and feasibility of sentinel lymph node biopsy in early breast cancer patients using patent blue dye. From March 2004, we are consecutively enrolling breast cancer patients with tumor size less than 5 cm with no clinically palpable axillary lymph nodes in this feasibility study. So far, 21 patients underwent sentinel lymph node biopsy using 1.0% patent blue dye injection around the tumor followed by axillary dissection. Sentinel lymph node biopsy was compared with axillary dissection for its ability to accurately reflect the final pathological status of the axillary nodes. Age of patients ranged form 32-67 years old with mean age of 46.72 years. Fifty seven percent of patients were postmenopausal. Patients with T1 lesions were 8 and T2 were 13. The sentinel lymph node/s were successfully identified in 20 out of 21 patients (95.0%). The number of sentinel lymph nodes ranged from 1 to 5 (average 2.0) and non-sentinel nodes ranged from 5-22 (average 12.0). Infiltrating ductal carcinoma was diagnosed in 15 patients, DCIS with early invasion in 4 patients, invasive lobular carcinoma in 1 and medullary carcinoma in 1 patient. Of the 20 patients in whom sentinel lymph nodes were successfully identified, nodes were positive in 35.0% (7/20) of patients. All the positive nodes were detected in group with T2 lesions. SLNs were the only positive nodes in 2 patients. There were no false negative patients, yielding an accuracy of 100.0%. Lymphatic mapping using patent blue dye alone is technically feasible for patients with small (T1 or T2) palpable breast tumors. The sentinel node can be reliably identified in the majority of these patients, and its histology reflects that of the axilla with a high degree of accuracy. This method is very useful in economically backward countries as it involves less expensive material.

Gastric trichobezoar presenting as gastric outlet obstruction--a case report.

Trichobezoars are impactions of swallowed hairs in the stomach and occasionally in the intestine. They occur in emotionally disturbed, depressed, or mentally retarded patients who have trichotillomania and trichophagia. Removal of gastric trichobezoar by open surgery (gastrotomy) is a standard approach. Psychiatric follow-up is needed to diminish the recurrence of trichotillomania and trichophagia. Here, we report a case of large gastric trichobezoar presenting as gastric outlet obstruction in a 13-years-old girl. She was treated with open surgical extraction of the bezoar and behavioral therapy.

Retrospective study of chest wall tumors at a cancer hospital in Nepal.

Primary and metastatic tumors of both soft tissues and bony skeleton, and primary tumors of adjacent organs invading the chest wall constitute chest wall tumors. A retrospective review of all the patients with chest wall tumors was done at BP Koirala Memorial Cancer Hospital (BPKMCH). Primary tumors of breast were excluded. Surgical treatment consisted of wide local excision (WLE). Chest wall reconstruction, if needed, was achieved by a muscular flap +/- prolene mesh +/- omental transposition. Thirty one patients were treated in the period from October 1999 to October 2003. Age of the patients varied from 3 years to 72 years (mean age--38 years). Presenting complaint was mass in 96.8% and pain in 48.4% cases. The mass was 5 cm or less in 34.4%, from 5 to 10 cm in 32.3%, and more than 10 cm in 32.3% cases. The lesions were located in sternal region, anterior, lateral, posterior, and vertebral chest wall in 6.5%, 32.3%, 41.9%, 16.1% and 3.2% respectively. WLE was done in 29 cases. Chest wall reconstruction using both muscular flaps and prolene mesh (15x15 cm) was done in 8 cases. In three of them, where concomitant wedge resection of the lung was done, omental transposition was added. In rest of the cases, primary closure, muscular/myocutaneous flap or skin grafting was done. Minor complications were observed in 31.0% cases, which were managed conservatively. Two patients received adjuvant radiotherapy and four patients--adjuvant chemotherapy. There were no postoperative deaths. The rate of malignancy was 48.4%.

Omentoplasty versus no omentoplasty for esophagogastrostomy after surgery for cancer of cardia and esophagus.

BACKGROUND: The standard of care of patients with cancer of cardia and esophagus still remains surgery in early stage. One of the most feared complications after such procedure is anastomotic leak. AIM: We present our experience with omental wrapping of anastomosis (omentoplasty) to decrease the anastomotic leak. SETTINGS AND DESIGN: Retrospective study. MATERIALS AND METHODS: An analysis of 50 consecutive patients, who underwent surgical resection for cancer of cardia and esophagus at BPKMCH, is done. For cancer of esophagus, a 10 cm proximal tumor free margin and for lesions of cardia, at least 5 cm margin was achieved. A 5 cm distal tumor free margin was achieved in each case. A subset of patients was considered for omentoplasty after completion of anastomosis. RESULTS: There were 29 male and 21 female with a mean age of 56.3 years. The average postoperative stay was 13.14 days. The stomach was the organ of substitute in 48 and jejunum in 2 cases. Omentoplasty was done in 37 cases, whereas in 13 cases, no omental wrapping was done. The rate of anastomotic leak was 6%. There was no leak from anastomosis placed at chest, whereas three cases of leak was observed in the anastomosis at the level of neck (P=.013). Overall, there was no leak in omentoplasty group, whereas there were three cases with leak in the group without omentoplasty (P=0.003). CONCLUSION: Omentoplasty should be considered in every case after surgical resection for cancer of cardia and esophagus.