Treatment Outcomes of Incidental Gallbladder Cancer - Results from a High-Volume Tertiary Care Centre in North India.

Gallbladder cancer (GBC) is a lethal disease. Incidentally detected gallbladder cancer (IGBC) presents a unique opportunity for early management and better outcomes. We present the institutional experience of a high-volume tertiary care center in northern India. Retrospective analysis of a prospectively maintained database was performed and data of all IGBC patients between January 2014 to December 2021 was analyzed. There were 125 patients of IGBC among the 750 patients of GBC seen during the study period. Of these 125 patients, 72 (57.6%) patients were not eligible for surgery. Successful completion radical cholecystectomy (CRC) was possible in 37 (69.8%) of the 53 patients who underwent surgery. On univariate analysis, thickness of gallbladder wall 10 mm or more (p < 0.001, OR 19.0, 95% CI 4.58-78.76), pathological stage (p < 0.001, OR 5.8, 95% CI 2.45-14.98) and median delay of 16 weeks or more (p < 0.001, OR 17.0, 95% CI = 4.08-70.76), were associated with inoperability. However, on multivariate analysis only gallbladder wall thickness of 10 mm or more (p < 0.001, AOR 17.9, 95% CI 3.24-98.78) and median delay of 16 weeks or more (p < 0.001, AOR 32.33, 95% CI 6.05-172.66) remained significant. Median time to recurrence (TTR) and overall survival (OS) was not reached after a median follow up of 30 months in patients undergoing successful CRC. Successful outcomes of IGBC are dependent on several factors. Diligent workup of suspicious thickening before simple cholecystectomy for gallstone disease and timely referral of IGBC to tertiary care are the keystones for good outcomes.

Uniportal video-assisted thoracoscopic Ivor Lewis oesophagectomy.

Standard minimally invasive Ivor Lewis oesophagectomy is performed through a multiport technique using carbon dioxide. However, access to video-assisted thoracoscopic surgery (VATS) is increasingly shifting to a single-port approach due to its proven safety and efficacy in lung surgeries. Therefore, the preamble of this submission is to describe, 'How I do differently' uniportal VATS MIO in three major steps: (a) VATS dissection through a single 4-cm incision in a semi-prone position without artificial capnothorax; (b) fluorescence dye to check conduit perfusion and (c) intrathoracic overlay anastomosis with a linear stapler.

Quality of Life in Patients with Recurrent Oral Squamous Cell Carcinoma: A Study from India.

Background: Locoregional recurrence of oral cancer causes significant morbidity. This study aims at assessing the functional outcomes of patients undergoing treatment for recurrent oral squamous cell carcinoma. Methods: This study was done in a tertiary care center in North India and includes prospective cohort of 179 recurrent oral carcinoma patients, from September 2017 to September 2018. Patients undergoing treatment of recurrent oral carcinoma were assessed for quality-of-life score at baseline before starting treatment and two months after the completion of the treatment. For the assessment, EORTC QLQH&N35 questionnaire was used. Results: Of 179 patients included, 71 (39.66%) patients underwent salvage surgery and 104 patients (58.10%) received palliative chemotherapy. One hundred and thirty patients could complete the "EORTC-QOL-H&N-35" questionnaire on required two occasions. Forty-nine patients died before completing second questionnaire. More than half (55.6%) of patients who underwent salvage surgery had improved quality of life after the procedures. They have little or no pain in oral cavity, improved swallowing, less odynophagia, improvement in neck and shoulder pain, less problems with the external appearance and socialization, and enjoyed better sexual life. In patients receiving palliative chemotherapy, the quality of life declined in majority (88.1%) of the patients. Conclusions: Although salvage surgery is the best modality of treatment for recurrent oral carcinoma, only about one-third of patients qualify for surgery and enjoy improved quality of life following surgery. On the other hand, in majority of the patients receiving palliative chemotherapy, the quality of life worsened with time and treatment.

Radical surgery for de novo gallbladder carcinoma-Single-center analysis of prognostic factors and survival outcomes from an endemic region.

BACKGROUND AND OBJECTIVE: Gallbladder cancer (GBC) is an aggressive malignancy where curative resection is possible in few and survival is poor. There are limited data on outcomes in patients with de novo GBC from endemic regions undergoing surgery for curative intent. We report survival outcomes in this group of patients from a region with high incidence of disease. METHODS: We reviewed the records of all GBC patients (2014-2018) and included those who underwent radical cholecystectomy (RC) for de novo GBC. Univariable and multivariable analyses were performed to identify factors influencing recurrence and survival. RESULTS: A total of 649 patients with GBC were evaluated for surgery and curative intent surgery was attempted in 246 (38%) patients. Of these 246 patients, RC was performed in 115 patients, with histologically confirmed de novo GBC. Locally advanced disease (≥stage IIIB) was present in 52 (45.2%) patients. Median time to recurrence and overall survival (OS) were 31 and 36 months, respectively. Lymph node positivity (p = 0.005) and grade significantly influenced OS on multivariable analysis. CONCLUSION: Satisfactory survival outcomes are possible after RC for de novo GBC. Extended resections performed in high volume centers combined with appropriate adjuvant treatment can offer significant survival benefits, with acceptable morbidity and mortality rates.

Surgical outcomes in oral cancer involving the central arch of the mandible in elderly patients: An institutional experience.

BACKGROUNDS: Oral squamous cell cancer (SCC) is one of the most common cancers. The most common age of presentation is fifth to sixth decade. Management of this disease is dictated by stage, age, and related comorbidities. Elderly patients have their own set of limitations as far as their management is concerned. Carcinoma involving central mandibular arch is a challenging disease for surgeons, especially in the elderly. This article describes our experience with the surgical treatment of oral cancer involving the central arch of the mandible in elderly patients. METHODS: Forty elderly (≥60 years) patients with histologically proven SCC of the oral cavity in which disease was involving the central arch of the mandible, were included in our study. Demographic, clinical, and treatment-related factors were recorded. The outcome was assessed in terms of postoperative complications, recurrence, and patient survival. RESULTS: The median age of the patients was 63 years. The male:female ratio was 7:3. A history of oral tobacco use was present in 95% of patients. The most common site of disease was lower alveolus (80%) followed by carcinoma of the lower lip (20%). Majority of our patients (77.3% [30]) were having Stage IV disease. Mandibulectomy was either segmental (62.5%) or marginal (37.5%). Bilateral neck dissection (37/40, 92.5%) was done in most patients. Among all patients, 62.5% (25) received adjuvant radiotherapy. The local recurrence rate after a median follow-up of 30 months was 15% (6). Two-year disease-free survival and overall survival were 89% and 90%, respectively. CONCLUSION: Central arch of the mandible is a difficult disease to treat. It needs a complex and lengthy reconstructive procedure. Comorbidities such as extreme age, diabetes, and pulmonary and cardiac illnesses make it more challenging to manage. With the proper evaluation of comorbidities and avoiding long, cumbersome procedures, we can provide patients a fairly good chance of survival.

Molecular Oncology of Gall Bladder Cancer.

Gall bladder carcinoma (GBC) is a worldwide problem, with a higher incidence in areas of the world where cholelithiasis is common. As GBC is usually diagnosed in an advanced stage, the mortality is high. An understanding of the molecular pathways of carcinogenesis and the mutations involved in the development and progression of GBC could be useful in early diagnosis. Understanding molecular markers of prognosis as well as predictors of outcome could also potentially benefit patients undergoing treatment. New therapies targeting major molecular pathways and immunotherapy are exciting novel therapeutic options. This review focuses on the current understanding of the molecular oncology of GBC.

Continuing cancer surgery through the first six months of the COVID-19 pandemic at an academic university hospital in India: A lower-middle-income country experience.

BACKGROUND: The novel coronavirus pandemic (COVID-19) hinders the treatment of non-COVID illnesses like cancer, which may be pronounced in lower-middle-income countries. METHODS: This retrospective cohort study audited the performance of a tertiary care surgical oncology department at an academic hospital in India during the first six months of the pandemic. Difficulties faced by patients, COVID-19-related incidents (preventable cases of hospital transmission), and modifications in practice were recorded. RESULTS: From April to September 2020, outpatient consultations, inpatient admissions, and chemotherapy unit functioning reduced by 62%, 58%, and 56%, respectively, compared to the same period the previous year. Major surgeries dropped by 31% with a decrease across all sites, but an increase in head and neck cancers (p = .012, absolute difference 8%, 95% confidence interval [CI]: 1.75% - 14.12%). Postoperative complications were similar (p = .593, 95% CI: -2.61% - 4.87%). Inability to keep a surgical appointment was primarily due to apprehension of infection (52%) or arranging finances (49%). Two COVID-19-related incidents resulted in infecting 27 persons. Fifteen instances of possible COVID-19-related mishaps were averted. CONCLUSIONS: We observed a decrease in the operations of the department without any adverse impact in postoperative outcomes. While challenging, treating cancer adequately during COVID-19 can be accomplished by adequate screening and testing, and religiously following the prevention guidelines.

Impact of COVID-19 pandemic on cancer surgery: Patient's perspective.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has impacted cancer care globally. The aim of this study is to analyze the impact of COVID-19 on cancer healthcare from the perspective of patients with cancer. METHODS: A cross-sectional survey was conducted between June 19, 2020, to August 7, 2020, using a questionnaire designed by patients awaiting cancer surgery. We examined the impact of COVID-19 on five domains (financial status, healthcare access, stress, anxiety, and depression) and their relationship with various patient-related variables. Factors likely to determine the influence of COVID-19 on patient care were analyzed. RESULTS: A significant adverse impact was noted in all five domains (p = < 0.05), with the maximal impact felt in the domain of financial status followed by healthcare access. Patients with income levels of INR < 35 K (adjusted odds ratio [AOR] = 1.61, p < 0.05), and 35K- 100 K (AOR = 1.96, p < 0.05), married patients (AOR = 3.30, p < 0.05), and rural patients (AOR = 2.82, p < 0.05) experienced the most adverse COVID-19-related impact. CONCLUSION: Delivering quality cancer care in low to middle-income countries is a challenge even in normal times. During this pandemic, deficiencies in this fragile healthcare delivery system were exacerbated. Identification of vulnerable groups of patients and strategic utilization of available resources becomes even more important during global catastrophes, such as the current COVID-19 pandemic. Further work is required in these avenues to not only address the current pandemic but also any potential future crises.

Paramedian forehead flap reconstruction for skin tumors involving central subunit of face: An analysis of 37 cases.

INTRODUCTION: Tumors of facial skin are common in upper part of central subunit of face. Defects after resection require a flap, which is pliable, thin, and has a good colour match. Among the various local flaps available paramedian forehead flap is a good option. PATIENTS AND METHODS: Patients reconstructed with paramedian forehead flap during the period from January 2015 to March 2020 were included in the study. Data regarding the demographic, clinical characteristics, and treatment details was recorded, and analyzed for postoperative complications and cosmetic outcomes. RESULTS: Paramedian forehead flap reconstruction was performed in 37 patients who were resected for tumor involving upper central subunit of face. Median age of patients was 57 years. Male to female ratio was 1.4:1. All tumors were resected with a negative margin. Nodal disease was managed by superficial parotidectomy only (4/37), superficial parotidectomy along with supra-omohyoid neck dissection (6/37) and modified neck dissection (1/37). In five patients additional buccal mucosa graft was used to reconstruct conjunctiva. Additional flaps were required in two patients in whom nasolabial and mustarde flaps were used. Partial flap loss occurred in one patient. There was no major flap loss. Surgical site infection developed in only one patient, who had partial flap loss. On subjective assessment, nearly 60% patients described their appearance as good. CONCLUSION: Facial reconstruction in area of dorsum of nose and medial aspect of both eyelids using paramedian forehead flaps is a simple and quick procedure.

Study of tumor transglutaminase 2 expression in gallbladder cancer - Is it a novel predictor of survival?

BACKGROUNDS/AIMS: Transglutaminase 2 (TG2) is known to be an important mediator of inflammation induced carcinogenesis pathway. Chronic inflammation is the most important causative factor in Gallbladder cancer (GBC) carcinogenesis. We analyzed the expression of TG2 in GBC and its role as potential prognostic marker, first of its kind study. METHODS: We analyzed TG2 expression in 100 cases of GBC and 28 cases of non-cancer gallbladder specimen (calculus cholecystitis). We studied TG2 expression in GBC in comparison to control group and evaluated its role as a potential prognostic marker. RESULTS: TG2 score (1-9) was calculated by multiplying percentage cytoplasmic expression (P) with intensity of expression (I) in tumor cells. Positive TG-2 expression was observed in 62% of GBC patients compared to only 21% (n=6) in control group (p=0.001). In curative resection subgroup (n=54), TG2 positive patients showed shorter disease free survival rate (p=0.04) and higher rate of recurrence (p=0.03) compared to TG2 negative patients. TG2 positive expression was observed in 15/16 of patients with recurrent disease. In palliative treatment subgroup, patients with strong TG2 positive expression had poorer disease specific survival (p=0.01) as compared to weakly positive group. On multivariate analysis, lymph node status (p=0.03) and TG2 expression (p=0.037), were found to be significant predictor of recurrence and eventual survival. CONCLUSIONS: Positive TG2 expression was related to higher recurrence rates post curative surgery, shorter disease free and overall survival and ultimately portended poor prognosis. It may be helpful in better prognostication and tailoring therapeutic approach for better management of GBC.

Metronomic chemotherapy for scheduling oral cancer surgery during the COVID-19 pandemic.

Worldwide, hospitals are facing problems in managing cancer patients during the ongoing COVID-19 pandemic. Given the immense cancer burden of oral cancer in India, scheduling surgeries are becoming increasingly difficult. Upfront surgeries are recommended for curative treatment of oral cancers and postponing them raises the fear of progression. Metronomic chemotherapy can be considered during the waiting period given its potential oncological benefits and ease of administration without much toxicity.

A Novel and Simple Technique of Reconstructing the Central Arch Mandibular Defects-a Solution During the Resource-Constrained Setting of COVID Crisis.

The current COVID 19 pandemic has a major impact on healthcare delivery globally. Oral cancer involving anterior arch of mandible is difficult to reconstruct and ideally, requires free fibular osteomyocutaneous flap. During this time of resource constraint situation, these free flaps are not a great choice, as it increases exposure of both patient and surgical team to the deadly virus. We are describing a novel method of reconstruction after resection of oral cancer involving anterior arch of mandible. In this new technique, we have reconstructed central arch defect by hanging bipaddle pectoralis major myocutaneous flap with orbicularis oris muscle using ethylene terephthalate suture. Operative time, early postoperative complications and early cosmetic and functional outcome were assessed. We have used this novel technique in eight patients of T4a oral cancer involving anterior arch of mandible and skin over chin. Mean operative time was 180 min. One patient had minor flap loss with surgical site infection (Clavien-Dindo grade I). In all patients, we were able to discharge all patients on eighth postoperative day. Cosmetic outcome and functional outcomes were mostly satisfactory. All patients were able to oppose their lips without any oral incompetence and drooling. Tongue mobility was good. There was no incidence of 'Andy Gump deformity'. This is a feasible option for reconstructing anterior arch defect in resource- and time-limited setting of COVID 19 pandemic. This technique can also be used in comorbid conditions where it is not advisable to do very long surgery.

Differentially expressed full-length, fusion and novel isoforms transcripts-based signature of well-differentiated keratinized oral squamous cell carcinoma.

Highly keratinized oral squamous cell carcinoma (OSCC) exhibits an improved response to treatment and prognosis compared with weakly keratinized OSCC. Therefore, we aimed to develop gene transcript signature and to identify novel full-length isoforms, fusion transcript and non-coding RNA to differentiate well-differentiated (WD) with Moderately Differentiated (MD)/Poorly Differentiated (PD)/WD-lymphadenopathy OSCC through, HTA, Isoform sequencing, and NanoString. Additionally, specific copy number gain and loss were also identify in WD keratinized OSCC through Oncoscan array and validated through Real-time PCR in histopathologically characterized FFPE-WD keratinized OSCC. Three-hundred-thirty-eight (338) differentially expressed full-length (FL) transcript isoforms (317 upregulated and 21 down-regulated in OSCC) were identified through Isoform Sequencing using the PacBio platform. Thirty-four (34) highly upregulated differentially expressed transcripts from IsoSeq data were also correlated with HTA2.0 and validated in 42 OSCC samples. We were able to identify 18 differentially expressed transcripts, 12 fusion transcripts, and two long noncoding RNAs. These transcripts were involved in increased cell proliferation, dysregulated metabolic reprogramming, oxidative stress, and immune system markers with enhanced immune rearrangements, suggesting a cancerous nature. However, an increase in proteasomal activity and hemidesmosome proteins suggested an improved prognosis and tumor cell stability in keratinized OSCC and helped to characterize WD with MD/PD/WD with lymphadenopathy OSCC. Additionally, novel isoforms of IL37, NAA10, UCHL3, SPAG7, and RAB24 were identified while in silico functionally validated SPAG7 represented the premalignant phenotype of keratinized (K4) OSCC. Most importantly we found copy number gain and overexpression of EGFR suggest that TKIs may also be used as therapeutics in WD-OSCCs.

Mitochondrial Stress-Mediated Targeting of Quiescent Cancer Stem Cells in Oral Squamous Cell Carcinoma.

INTRODUCTION: Despite improved therapeutics in oral squamous cell carcinoma (OSCC), tumor cells that are either quiescent and/or endowed with stem cell-like attributes usually survive treatment and recreate tumor load at relapse. Through this study, we aimed strategically to eliminate these stem cell-like cancer cells using a combination drug approach. METHODS: Primary cultures from 15 well-moderately differentiated OSCC were established, and the existence of cancer cells with stem cell-like characteristics using five cancer stem cell (CSC) specific markers - CD44, CD133, CD147, C166, SOX2 and spheroid assay was ascertained. Next, we assessed quiescence in CSCs under normal and growth factor-deprived conditions using Ki67. Among several gene signatures regulating quiescent cellular state, we evaluated the effect of inhibiting Dyrk1b in combination with topoisomerase II and histone deacetylase inhibitors in targeting quiescent CSCs. Multiple drug-effect analysis was carried out with CompuSyn software to determine combination-index values. RESULTS: We observed that CD44+CD133+ showed the highest level of SOX2 expression. CSCs showed varying degrees of quiescence, and inhibition of Dyrk1b decreased quiescence and sensitized CSCs to apoptosis. In the drug-combination study, Dyrk1b inhibitor was combined with topoisomerase II and histone deacetylase inhibitors to target quiescent CSCs. In combination, a synergistic effect was seen even at a 16-fold lower dose than IC50. Furthermore, combined treatment decreased glutathione levels and increased ROS and mitochondrial stress, leading to increased DNA damage and cytochrome c in CSCs. CONCLUSION: We report marker-based identification of CSC subpopulations and synergy of Dyrk1b inhibitor with topoisomerase II and HDAC inhibitors in primary OSCC. The results provide a new therapeutic strategy to minimize quiescence and target oral CSCs simultaneously.