Comparison of lung aeration loss in open abdominal oncologic surgeries after ventilation with electrical impedance tomography-guided PEEP versus conventional PEEP: a pilot feasibility study.

BACKGROUND: Existing literature lacks high-quality evidence regarding the ideal intraoperative positive end-expiratory pressure (PEEP) to minimize postoperative pulmonary complications (PPCs). We hypothesized that applying individualized PEEP derived from electrical impedance tomography would reduce the severity of postoperative lung aeration loss, deterioration in oxygenation, and PPC incidence. METHODS: A pilot feasibility study was conducted on 36 patients who underwent open abdominal oncologic surgery. The patients were randomized to receive individualized PEEP or conventional PEEP at 4 cmH2O. The primary outcome was the impact of individualized PEEP on changes in the modified lung ultrasound score (MLUS) derived from preoperative and postoperative lung ultrasonography. A higher MLUS indicated greater lung aeration loss. The secondary outcomes were the PaO2/FiO2 ratio and PPC incidence. RESULTS: A significant increase in the postoperative MLUS (12.0 ± 3.6 vs 7.9 ± 2.1, P < 0.001) and a significant difference between the postoperative and preoperative MLUS values (7.0 ± 3.3 vs 3.0 ± 1.6, P < 0.001) were found in the conventional PEEP group, indicating increased lung aeration loss. In the conventional PEEP group, the intraoperative PaO2/FiO2 ratios were significantly lower but not the postoperative ratios. The PPC incidence was not significantly different between the groups. Post-hoc analysis showed the increase in lung aeration loss and deterioration of intraoperative oxygenation correlated with the deviation from the individualized PEEP. CONCLUSIONS: Individualized PEEP appears to protect against lung aeration loss and intraoperative oxygenation deterioration. The advantage was greater in patients whose individualized PEEP deviated more from the conventional PEEP.

Does the Nightmare of Distressing Complications of Groin Dissection Over with "River Flow" Incision? - Experience of 240 Dissections from Tertiary Referral Oncology Centre, India.

OBJECTIVE: Groin dissection has been a nightmare for many surgeons due to its higher morbidity especially flap necrosis. Various modifications in incisions have been described in the literature to reduce the complications but with variable outcomes. By our novel "River Flow" incision technique, we have significantly reduced the procedure related complications without compromising onco surgical principles. METHODS: A prospective longitudinal clinical observational study was designed after Institutional Ethical Committee clearance, aiming to minimize the rate of complications, especially flap necrosis. All patients who underwent unilateral/bilateral ilio-inguinal block dissection (IIBD) from January 2014 to December 2021 were included in the study. The "River Flow" incision was made and standard ilio-inguinal block dissection was performed. Flap viability, seroma formation, lymphedema, infection, etc. were observed and noted during hospitalization and on followup. Clavien- Dindo classification was used to grade the postoperative complications. We have taken our historical data of 235 groin dissections as a control and compared them with the results of the present study. It is one of the largest studies on groin dissection so far. RESULTS: A total of 138 patients underwent 240 groin dissections. The most common diagnosis was carcinoma penis (44.9%) followed by carcinoma vulva (22.4%). Overall, the outcome of all groin dissections showed no postoperative mortality. None of the patients had complete flap necrosis. But in our historical data, the flap necrosis rate was 38%. The most common complication observed was seroma formation in 13.7% of cases followed by surgical site infection (6.52%). All the complications were managed conservatively. The postoperative stay of the patients was also significantly less. The median hospital stay was 3 days. CONCLUSION: "River Flow" incision technique is a simple but effective novel surgical technique for therapeutic ILND for any surgical setup without the learning curve. It can avoid flap necrosis, and decrease morbidity significantly without compromising the onco surgical principle of standard groin dissection. KEY WORDS: Groin dissection, skin necrosis, river flow incision.

Pattern of Care in Real-World Scenario on Advanced Epithelial Ovarian Cancer in a Tertiary Referral Oncology Centre in India - ISPSM Collaborative Study.

The treatment of advanced epithelial ovarian cancer (EOC) has evolved over time. With advent of platinum-based chemotherapy and hyperthermic intraperitoneal chemotherapy (HIPEC), there is a paradigm shift in the patterns of care with improved survival. In this study, we analysed our advanced EOC patients aiming to gain insights into the pattern of care. An ambispective study of 250 patients of advanced EOC was done from our prospectively maintained computerised database in the Department of Surgical Oncology, tertiary care referral centre from 2013 to 2020. We analysed the demographic profile, treatment patterns, and perioperative outcomes. In this study, there were 83.6% stage III and 16.4% stage IVA. There were 62 (24.8%) upfront and 112 (44.8%) in interval settings. There was a higher number of patients receiving neo-adjuvant chemotherapy. One hundred twenty-six (50.4%) underwent cytoreductive surgery (CRS) only and 124 (49.6%) underwent CRS and HIPEC. CC-0 was achieved in 84.4% and CC-1 in 15.6% patients. HIPEC programme was started in 2013. With advent of RCTs in HIPEC, there was a substantial increase in the number of patients receiving HIPEC from 2015 (n = 10), 2017 (n = 20) to 2019 (n = 41). We offer secondary CRS in a limited subset of patients, n = 76 (30.4%). There was 24.8% early and 8.4% late postop complications. We have median follow-up of 50 months with attrition rate of 4%. With practice changing updates, the treatment of advanced EOC has been evolving over time. Though the primary CRS followed by systemic therapy is the standard to date, there is change in pattern of care with neo-adjuvant chemotherapy followed by interval CRS and HIPEC because of various RCTs. The addition of HIPEC has acceptable morbidity and mortality. There is a definite learning curve and the team has to evolve as a whole. In a tertiary care referral centre from LMIC, good patient selection, logistics, and implementing recent advances will definitely add to improved survival.

Can EPIC Be a Low-Cost Alternative to HIPEC in Advanced Epithelial Ovarian Cancer in Resource-Constraint Settings? Experience from Tertiary Care Oncology Center.

Management of advanced ovarian cancer underwent a paradigm shift with advent of cytoreductive surgery and intraperitoneal chemotherapy. Hyperthermic intraperitoneal chemotherapy requires complex machinery and costly disposables, and increased operative time. Early postoperative intraperitoneal chemotherapy is a relatively less resource-intensive alternative way of intraperitoneal drug delivery. We started our HIPEC programme in 2013. In select cases, we offer EPIC. This study is an audit of outcomes to look into the feasibility of EPIC as alternative to HIPEC. We performed analysis of prospectively maintained database in the Department of Surgical oncology from January 2019 to June 2022. We had 15 patients who underwent CRS + EPIC and 84 CRS+ HIPEC. We did a propensity-matched analysis for demographics, baseline data and PCI and compared 15 CRS + EPIC with 15 CRS + HIPEC patients. We compared the perioperative outcomes-morbidity, mortality, length of ICU and hospital stay. Procedure time was significantly higher in the HIPEC compared to EPIC as HIPEC is an intraoperative procedure. Patients were admitted to intensive care unit (ICU) after surgery for a longer mean duration in HIPEC arm (1.4 + 0.7 days) compared to EPIC arm (1.2 + 0.41 days). Patients in HIPEC arm had a significantly shorter hospital stay (mean 7.93 vs. 9.93 days. Four patients in EPIC arm had Clavien-Dindo grade 3 and 4 morbidity compared to 1 patient in HIPEC arm. Hematological toxicity was more common in EPIC group. CRS with EPIC can be explored as an alternative to HIPEC in centres lacking facilities and expertise for HIPEC.

Evaluation of HE4 as a prognostic biomarker in uterine cervical cancer.

INTRODUCTION: Uterine cervical cancer (UCC) is the fourth most common health problem worldwide among women. Currently available biomarkers CA125, CA199, and CEA for diagnosis or prognostic evaluation of UCC have not got widespread acceptance. METHOD: Whole blood samples of 64 patients with UCC were collected along with 63 healthy females and tested for serum levels of HE4 (sHE4). A cut-off value for positive result 64.0 pmol/L was set. Statistical analysis of different clinical variables was done. RESULT: Serum level of HE4 has a significant role in the diagnosis of uterine cervical cancer. Its level increases with age, higher parity (P < 0.05), stage (P < 0.16), tumor size, and parametrial invasion. Negative result was seen with vaginal invasion, lymph node involvement & cases which had recurrence. Various histological types showed variable results. So the serum level of HE4 (sHE) level may play a role in the diagnosis & therapeutic monitoring of UCC. But the prognostic evaluation needs further studies. CONCLUSION: sHE4 is useful in the diagnosis of cervical cancer, but its prognostic significance is under the question marks. It may be associated with higher values in higher stages. Higher parity of the patient is associated with higher level of HE4 in UCC.

BESFA: bioinformatics based evolutionary, structural & functional analysis of prostrate, Placenta, Ovary, Testis, and Embryo (POTE) paralogs.

The POTE family comprises 14 paralogues and is primarily expressed in Prostrate, Placenta, Ovary, Testis, Embryo (POTE), and cancerous cells. The prospective function of the POTE protein family under physiological conditions is less understood. We systematically analyzed their cellular localization and molecular docking analysis to elucidate POTE proteins' structure, function, and Adaptive Divergence. Our results suggest that group three POTE paralogs (POTEE, POTEF, POTEI, POTEJ, and POTEKP (a pseudogene)) exhibits significant variation among other members could be because of their Adaptive Divergence. Furthermore, our molecular docking studies on POTE protein revealed the highest binding affinity with NCI-approved anticancer compounds. Additionally, POTEE, POTEF, POTEI, and POTEJ were subject to an explicit molecular dynamic simulation for 50ns. MM-GBSA and other essential electrostatics were calculated that showcased that only POTEE and POTEF have absolute binding affinities with minimum energy exploitation. Thus, this study's outcomes are expected to drive cancer research to successful utilization of POTE genes family as a new biomarker, which could pave the way for the discovery of new therapies.

Leveraging epigenetics to enhance the efficacy of cancer-testis antigen: a potential candidate for immunotherapy.

Ovarian cancer is the most lethal gynecological malignancy in women. The phenotype is characterized by delayed diagnosis, recurrence and drug resistance. Inherent immunogenicity potential, oncogenic function and expression of cancer-testis/germline antigen (CTA) in ovarian cancer render them a potential candidate for immunotherapy. Revolutionary clinical findings indicate that tumor antigen-mediated T-cell and dendritic cell-based immunotherapeutic approaches provide an excellent strategy for targeting tumors. Currently, dendritic cell vaccination for the treatment of B-cell lymphoma and CTA-based T-cell receptor transduced T-cell therapy involving MAGE-A4 and NY-ESO-1 are well documented and shown to be effective. This review highlighted the mechanical aspects of epigenetic drugs that can elicit a CTA-based humoral and cellular immune response and implicate T-cell and dendritic cell-based immunotherapeutic approaches.

Despite substantial advancements in prognosis and diagnostic approaches, epithelial ovarian cancer is still the most lethal gynecological malignancy worldwide. In addition to radiotherapy, chemotherapy, hormonal therapy, and surgery, immunotherapy in the clinical setting is promising. Tumor-restricted expression and strong immunogenic potential make cancer-testis/germline antigen (CTA) a potential candidate for efficient T-cell and dendritic cell-mediated cancer immunotherapy. The expression of CTAs is shown to be modulated by a specific epigenetic fine-tuning mechanism. However, the expression and role of CTA in epithelial ovarian cancer immunotherapy are poorly understood. Therefore, in the current work, the authors thoroughly highlight and explore the possible epigenetic mechanisms associated with CTA expression and their implication in T-cell and dendritic cell-based immunotherapy approaches to ovarian cancer. Understanding such a paradigm is essential to adopting a precision medicine approach for better therapeutic options.

A proposal for changing nomenclature from pseudomyxoma peritonei (PMP) to abdomino-peritoneal mucinous carcinoma (APM) based on its long journey and experience from tertiary oncology center in India.

INTRODUCTION: Pseudomyxoma peritonei (PMP) is a generalized term, usually known as "jelly belly" since 1884. Incidence is very low, 1-3 per million people per year. Because of its indolent nature, it is usually diagnosed at an advanced stage, thereby impacting the quality of life. The 5-year survival rate varies from 23 to 86% in world literature. Even 10 years and 20 years of survival have been described. With our experience, we like to propose rename of PMP as abdomino-peritoneal mucinous carcinoma (APM) as we strongly feel the time has come to specify the term and standardize the management strategy. METHODOLOGY: In the premier institute of India and as a tertiary referral center, we experienced the maximum number of advanced cases of APM. From 2012 to 2021, we analyzed all the APM patients based on a prospectively maintained computerized database in the department of surgical oncology and found the reasons for renaming from this traditional one. RESULTS: We included a total of 87 patients who underwent surgical intervention. Thirty-five patients underwent cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC), and 52 patients underwent debulking. In CRS-HIPEC patients, CC-0 was achieved in 28 patients (80%), CC-1 in 4 patients (11.4%), and CC-2 in 3 patients (8.6%). Palliative intent HIPEC was done in 3 patients (8.6%). Clavien-Dindo grade III and IV morbidity was observed in 18.8% of patients with 90 days mortality of 5.7%. CONCLUSION: With our long-term experience and advancement of scientific evidence, we like to propose a new name for PMP as APM. We strongly believe this paper will give a clear picture of this rare disease and standard management outlines.

Complex and Challenging Surgery like CRS with HIPEC is Easible Midst the COVID 19 Pandemic: Experience from Tertiary Care Center in India.

BACKGROUND: Amidst the COVID pandemic, most guidelines have recommended delaying surgery and giving chemotherapy for with peritoneal surface malignancies. However, when all options are exhausted, complex surgery like CRS with HIPEC can be performed in select patients. METHOD: To facilitate these complex surgeries with maximum safety, RT-PCR test for COVID-19 was performed for each patient. Personal protective equipment including N95 masks and face shields was used. A number of OT personals were limited. Taking these steps minimized the risk of COVID-19 infections among healthcare workers and patients. CONCLUSION: After implementing these steps, we were able to perform complex CRS and HIPEC procedure during the pandemic and thus improve oncological outcomes.

Interplay between genome organization and epigenomic alterations of pericentromeric DNA in cancer.

In eukaryotic genome biology, the genomic organization inside the three-dimensional (3D) nucleus is highly complex, and whether this organization governs gene expression is poorly understood. Nuclear lamina (NL) is a filamentous meshwork of proteins present at the lining of inner nuclear membrane that serves as an anchoring platform for genome organization. Large chromatin domains termed as lamina-associated domains (LADs), play a major role in silencing genes at the nuclear periphery. The interaction of the NL and genome is dynamic and stochastic. Furthermore, many genes change their positions during developmental processes or under disease conditions such as cancer, to activate certain sorts of genes and/or silence others. Pericentromeric heterochromatin (PCH) is mostly in the silenced region within the genome, which localizes at the nuclear periphery. Studies show that several genes located at the PCH are aberrantly expressed in cancer. The interesting question is that despite being localized in the pericentromeric region, how these genes still manage to overcome pericentromeric repression. Although epigenetic mechanisms control the expression of the pericentromeric region, recent studies about genome organization and genome-nuclear lamina interaction have shed light on a new aspect of pericentromeric gene regulation through a complex and coordinated interplay between epigenomic remodeling and genomic organization in cancer.

Hyperthermic intraperitoneal chemotherapy in locally advanced and recurrent ovarian carcinoma: surgical and oncological outcomes in the Indian public healthcare system.

This study analyzed the surgical outcomes after initial implementation of a cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) program in government settings in India. Methods: Ovarian cancer patients undergoing cytoreductive surgery and HIPEC from May 2015 to April 2019 were identified from a prospectively maintained database. Treatment characteristics and surgical outcomes were analyzed. Results: The study identified 101 patients. The mean peritoneal cancer index (PCI) was 7 ± 6, with higher PCI scores in primary and recurrent cases. Major morbidities were recorded in 24.7% of patients. High PCI score, completeness of cytoreduction and major morbidities were independent predictors of overall survival in multivariate analysis. Conclusion: The application of HIPEC in limited-resource settings is feasible with acceptable major morbidities. This program should receive similar priority in government systems.

Oral metronomic chemotherapy for recurrent & refractory epithelial ovarian cancer: A retrospective analysis.

Background & objectives: Advanced epithelial ovarian cancer (EOC) is associated with dismal outcome and progression-free survival (PFS) shortens with each subsequent relapse. For patients with recurrent and platinum refractory disease, therapeutic options are limited. Oral metronomic therapy (OMT) is associated with symptomatic relief and stable response in a significant proportion of patients. We retrospectively evaluated the outcome of patients with EOC treated with OMT at a tertiary care hospital in north India. Methods: Between January 2011 to December 2017, 36 EOC patients received OMT. Patients' median age was 50 yr (range, 38-81 yr) and they had received a median of two lines of prior chemotherapy. OMT regimen included a combination of cyclophosphamide, etoposide (VP-16) and celecoxib with or without pazopanib along with supportive care. Response rates and outcomes were ascertained using the Gynecological Cancer Intergroup Guidelines. The toxicity was graded according to the Common Terminology Criteria for Adverse Events v.4.03. Results: The median CA-125 before initiating OMT was 160 U/ml (range, 42.23-5330 U/ml). The median interval between last chemotherapy and starting OMT regimen was 159 days (range, 1-1211 days). The overall response rate was 50 per cent. The median progression-free survival (PFS) was 8.2 months [95% confidence interval (CI): 5.03-10.33], and the median overall survival was 38 months (95% CI: 25.6-NR). Patients who received two lines of chemotherapy before OMT (P=0.052) and those who received pazopanib-based OMT (P=0.0513) had better PFS. Interpretation & conclusions: For patients with relapse and refractory EOC, OMT could be a reasonable option. A combination of oral etoposide (VP-16) and pazopanib needs further evaluation in a large number of patients in a randomized trial.

Xanthogranulomatous Orchitis Presenting as a Scrotal Mass in an Elderly Male: Malignancy or Mimicker?

Xanthogranulomatous inflammation is a rare, destructive pattern of inflammation, affecting different organs, that often produces a mass-like lesion, simulating malignancy. Although benign, it can coexist with malignancy. We, herein, report the case of a 60-year-old male patient, who presented with a testicular mass that was partly necrotic and showed heterogeneous enhancement on contrast study. Testicular tumor markers were normal. In view of clinicoradiological suspicion of a malignant cause, high inguinal orchidectomy was performed. However, histopathology showed features of a xanthogranulomatous orchitis with no evidence of any malignancy. Pathologists must be aware of this entity as definitive diagnosis requires histopathologic examination and adequate sampling must be done to rule out a coexistent malignancy.

Transfer of the methicillin resistance genomic island among staphylococci by conjugation.

Methicillin resistance creates a major obstacle for treatment of Staphylococcus aureus infections. The resistance gene, mecA, is carried on a large (20 kb to > 60 kb) genomic island, staphylococcal cassette chromosome mec (SCCmec), that excises from and inserts site-specifically into the staphylococcal chromosome. However, although SCCmec has been designated a mobile genetic element, a mechanism for its transfer has not been defined. Here we demonstrate the capture and conjugative transfer of excised SCCmec. SCCmec was captured on pGO400, a mupirocin-resistant derivative of the pGO1/pSK41 staphylococcal conjugative plasmid lineage, and pGO400::SCCmec (pRM27) was transferred by filter-mating into both homologous and heterologous S. aureus recipients representing a range of clonal complexes as well as S. epidermidis. The DNA sequence of pRM27 showed that SCCmec had been transferred in its entirety and that its capture had occurred by recombination between IS257/431 elements present on all SCCmec types and pGO1/pSK41 conjugative plasmids. The captured SCCmec excised from the plasmid and inserted site-specifically into the chromosomal att site of both an isogenic S. aureus and a S. epidermidis recipient. These studies describe a means by which methicillin resistance can be environmentally disseminated and a novel mechanism, IS-mediated recombination, for the capture and conjugative transfer of genomic islands.

Shared borders: achieving the goals of interdisciplinary patient care.

Definitions and components of interdisciplinary care, as well as means of implementing, reasons for adopting, and barriers to interdisciplinary care, are presented. A health care discipline is an area of knowledge and research that is critical to patient care. In multidisciplinary practice, each member of a clinical group practices with an awareness and tolerance of other disciplines. In interdisciplinary practice, members of a team actively coordinate care across disciplines. In an ideal interdisciplinary health care team, decisions are made by consensus and each discipline has an equal opportunity for input into decisions. To make the transition from multidisciplinary to interdisciplinary practice, all disciplines, rather than representing freestanding silos, must have shared borders that represent a common professional interest and knowledge base. Such a practice model will lead to an increased level of trust among professions and a deeper level of understanding about what each profession can contribute. Barriers to interdisciplinary practice include historical factors such as different philosophies of practice and professional training, logistics of team implementation, and resource limitation. To facilitate interdisciplinary practice, pharmacists must be competent, understand what a team is, provide leadership, be prepared to help develop drug therapy outcome objectives, project self-confidence, and demonstrate a readiness for interdisciplinary practice. Interdisciplinary care must be applied in a cost-effective way. Interdisciplinary patient care must be taught in professional schools and postgraduate training programs. Interdisciplinary patient care requires common values, a common vision, and an understanding of teamwork with the ultimate goal of serving the patient with wisdom.

Experience with an automated point-of-use unit-dose drug distribution system.

Two years' experience with an automated, point-of-use unit-dose system at the University of California, San Diego Medical Center (UCSDMC) is described. Growing concerns about the efficiency and cost-effectiveness of the traditional unit-dose drug distribution system at UCSDMC, and the corresponding diversion of professional staff time from pharmaceutical care responsibilities, led us to investigate alternative systems. Criteria for a new system were developed and used in evaluating alternatives. Consideration was given to three possibilities: 1) improving the existing system, 2) automating the unit-dose cassette fill process, or 3) automating the final step in medication delivery at the nursing station. Based on the realization that our traditional unit-dose system was largely inefficient in today's hospital environment, it was concluded that the drug distribution system needed to be re-engineered in a way that simplified delivery and reduced waiting time. The Medstation Rx system marketed by the Pyxis Corporation (San Diego, CA) seemed to meet the need. During a 2-year period a Medstation Rx system was implemented in most of the hospital (in all but three specialty units) and evaluated. This system has resulted in several benefits, including a net savings in labor costs, a significant reduction in waiting time for first doses, and a reduction in dispensing errors. In the process, it was possible to minimize the disruption of pharmacists engaged in the direct provision of pharmaceutical care, thereby increasing their efficiency.