Genomic and clinical characterization of a familial GIST kindred intolerant to imatinib.

Familial gastrointestinal stromal tumors (GIST) are rare. We present a kindred with multiple family members affected with multifocal GIST who underwent whole genome sequencing of the germline and tumor. Affected individuals with GIST harbored a germline variant found within exon 13 of the KIT gene (c.1965T>G; p.Asn655Lys, p.N655K) and a variant in the MSR1 gene (c.877 C > T; p.Arg293*, pR293X). Multifocal GISTs in the proband and her mother were treated with preoperative imatinib, which resulted in severe intolerance. The clinical features of multifocal GIST, cutaneous mastocytosis, allergies, and gut motility disorders seen in the affected individuals may represent manifestations of the multifunctional roles of KIT in interstitial cells of Cajal or mast cells and/or may be suggestive of additional molecular pathways which can contribute to tumorigenesis.

Abdominal wall reconstruction (AWR) for post-trauma laparotomy ventral hernia and follow-up assessment of functional quality of life (QOL): experience of a level-1 trauma centre in India.

PURPOSE: The aim of this study was to examine the postoperative outcomes and follow-up QOL of patients after AWR at a level-1 trauma centre in India. METHODS: The study cohort included AWR patients treated between January 2011 and July 2022. The Activities Assessment Scale (AAS) was used to measure QOL, and the Ventral Hernia Recurrence Inventory (VHRI) was used to determine the occurrence of recurrence. In patients suspected of having recurrence, thorough clinical examination and relevant imaging were performed to confirm or rule out recurrence. RESULTS: Out of 89 patients, 35 patients whose complete perioperative and follow-up data were available were enrolled. The mean age of the patients was 28 (SD, 9) years. The mean defect size was 14. 9 (SD, 7) cm. The mean time from laparotomy to AWR surgery was 21 months. During the postoperative course, 37% of patients developed complications, such as SSI and seroma. The mean follow-up time was 53 (SD, 43) months. Upon comparing procedures involving the mesh placed in the sublay position with procedures involving the mesh placed in other positions, no statistically significant difference in the recurrence rate (one in each group, p = 0.99), surgical complication rate (33% v/s 66%, p = 0.6), or mean AAS QOL score (94.7 v/s 98, p = 0.4) was observed. The specificity of the VHRI for diagnosing recurrence was 79%. CONCLUSION: Overall, the recurrence rate was low in these patients despite the presence of large hernia defects. Long-term QOL was not affected by the specific procedure used. Timely planning and execution are more important than the specific repair approach for post-trauma laparotomy ventral hernia.

Mandibular reconstruction using an iliac bone flap with perforator-supported external oblique abdominal muscle island: a pilot study.

The deep circumflex iliac artery (DCIA) flap is one of the bone flaps commonly used for mandibular reconstruction. Observation of the skin paddle and Doppler ultrasound are methods that are usually used to monitor DCIA flaps after mandibular reconstruction surgery. The aim of this study was to introduce a novel DCIA flap with a perforator-supported external oblique abdominal muscle (EOAM) island for postoperative flap monitoring. This study included five patients who underwent mandibular reconstruction using this modified technique. The DCIA flap and the EOAM island supplied by the ascending branch of the DCIA were harvested during the surgery. After mandibular reconstruction, the EOAM island was placed in the submandibular region to monitor the blood supply to the DCIA flap after surgery. The blood supply to the DCIA flap was monitored by observing the colour, texture, and bleeding condition of the EOAM island. After the monitoring period, the EOAM was removed and the ascending branch of the DCIA was ligated. The outcome was successful in all patients. The EOAM island supported by the ascending branch of the DCIA is reliable and safe, thus providing a robust option to monitor the blood supply to the DCIA flap.

Potential of dietary polyphenols for protection from age-related decline and neurodegeneration: a role for gut microbiota?

Many epidemiological studies have shown the beneficial effects of a largely plant-based diet, and the strong association between the consumption of a Mediterranean-type diet with healthy aging including a lower risk of cognitive decline. The Mediterranean diet is characterized by a high intake of olive oil, fruits and vegetables and is rich in dietary fiber and polyphenols - both of which have been postulated to act as important mediators of these benefits. Polyphenols are large molecules produced by plants to protect them from environmental threats and injury. When ingested by humans, as little as 5% of these molecules are absorbed in the small intestine with the majority metabolized by the gut microbiota into absorbable simple phenolic compounds. Flavan-3-ols, a type of flavonoid, contained in grapes, berries, pome fruits, tea, and cocoa have been associated with many beneficial effects on several risk factors for cardiovascular disease, cognitive function and brain regions involved in memory formation. Both preclinical and clinical studies suggest that these brain and heart benefits can be attributed to endothelial vascular effects and anti-inflammatory properties among others. More recently the gut microbiota has emerged as a potential modulator of the aging brain and intriguingly polyphenols have been shown to alter microbiota composition and be metabolized by different microbial species. However, there is a need for well controlled studies in large populations to identify predictors of response, particularly given the vast inter-individual variation of human gut microbiota.

Perioperative myocardial injury is associated with increased postoperative non-cardiac complications in patients undergoing vascular surgery: a post hoc analysis of a randomised clinical pilot trial.

BACKGROUND: Elevated cardiac biomarkers, such as high-sensitivity cardiac Troponin T and N-terminal pro-B-type natriuretic peptide improve the prediction of major adverse cardiac events. However, very few trials have investigated the association between perioperative cardiac injury and non-cardiac complications. The primary aim of this study was to determine the association between peri-operative myocardial injury and non-cardiac complications in patients undergoing vascular surgery. Additionally, the association between elevated pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide and non-cardiac complications was explored. METHODS: This study is a post hoc analysis of a multicentre randomised controlled trial. Patients were recruited from three centres in Sweden between 2016 and 2019. Cardiac troponin level was measured pre-operatively and at 4, 24, and 48 h after the start of surgery in patients undergoing vascular surgery. N-terminal pro-B-type natriuretic peptide was measured pre-operatively. The primary outcome was a composite of major postoperative non-cardiac complications assessed at 30 days. RESULTS: A total of 184 patients undergoing peripheral or aortic vascular surgery were included in this study. The primary endpoint occurred in 67 (36%) patients. Perioperative myocardial injury was significantly associated with non-cardiac complications, with an adjusted odds ratio (OR) of 2.71 (95% confidence interval 1.33-5.55, P = 0.01). Sensitivity and specificity were 0.40 and 0.81, respectively. No association was found between pre-operative hs-cTnT or NT-proBNP and non-cardiac complications. CONCLUSION: In this pilot study, we found that new peri-operative myocardial injury is associated with an increased risk of non-cardiac complications within 30 days after index surgery in patients undergoing vascular surgery. Pre-operative high-sensitivity cardiac Troponin T or N-terminal pro-B-type natriuretic peptide did not appear to predict non-cardiac complications. Larger studies are needed to confirm our findings. TRIAL REGISTRATION: EudraCT database: 2016-001584-36.

Local injection of amphotericin B: novel use in the treatment of fungal maxillary sinusitis.

This report highlights the role of local amphotericin B (AMB) injection in cases of maxillary mucormycosis. The COVID-19 pandemic has resulted in a dramatic rise in the number of rhino-orbital mucormycosis cases. Although extensive surgical debridement remains the gold standard treatment, tissue salvage is desirable. The cases of two patients treated with local AMB are reported here, indicating that early intervention for maxillary fungal sinusitis in the form of local AMB may avoid the need for more invasive treatment.

Mucormycosis infection associated with global COVID-19 pandemic - an institutional histopathological study.

BACKGROUND: Coronavirus disease 2019 (COVID-19) in the recent times have instilled signs of immunosuppression globally which has further precipitated increasing range of opportunistic infections. Mucormycosis is a distressing opportunistic fungal infection with a high incidence and is the third commonest acute invasive infection following candidiasis and aspergillosis. The aim of the present observational study is to delineate the enigmatic histopathological profile between mucormycosis cases seen prior to pandemic (PPM) and pandemic associated mucormycosis (PAM). MATERIAL AND METHODS: Tissue archives of 105 histopathologically diagnosed cases of mucormycosis were included and analysed for demographical details and histopathological parameters like fungal load and localization, granuloma formation, necrosis, inflammatory infiltrate and tissue invasion. RESULTS: 0ut of 105 included cases, 11/105 (10.48%) were reported PPM and 94/105 (89.52%) PAM. Among 94 cases of PAM, 51/94 (54%) cases also showed COVID-19 positivity, while 43/94 (46%) did not. Of all the histological variables, increased fungal load and necrosis were observed in PAM relative to PPM cases. CONCLUSIONS: The histopathological variables like fungal load, necrosis, granuloma formation and tissue invasion, could help the clinician in assessing the clinical status at the time of tissue diagnosis and improve the treatment accordingly.

Unilateral sacral erector spinae plane block for lower limb surgery in children.

The erector spinae plane block is a versatile regional anaesthesia technique used for a variety of truncal surgeries. A novel variation is the sacral erector spinae plane block which is gaining popularity for perineal and anorectal procedures. Local anaesthetic injected at this level blocks the sacral dermatomes and has the potential for more proximal spread to involve lumbar nerve fibres via spread to the lumbar plexus or the epidural space. The advantage of a sacral erector spinae plane block over a neuraxial block is that it is less invasive and may have a better safety profile: there is a reduced risk of epidural haematoma, epidural abscess, haemodynamic instability and motor weakness of the lower extremities. Until now, this approach has been used for midline surgical procedures when the local anaesthetic was injected bilaterally. Its application for lower limb procedures with a single unilateral injection has not been described. We report the use of a unilateral sacral erector spinae plane block at the level of the S2 median crest in two children undergoing lower limb procedures of the hip and thigh. The block was found to provide effective peri-operative analgesia with minimal need for any opioid analgesics and without any significant adverse effects.

Maternal and neonatal characteristics, operative details and outcomes in COVID-19 positive parturients undergoing cesarean sections: A retrospective observational study.

Background and Aims: There is a marked inclination towards cesarean sections as the preferred mode of delivery in parturients with COVID-19 disease. However, the challenges associated with planning and performing a surgery in the COVID-19 setup are considerable. These factors may lead to widespread changes in obstetric decision-making, operative planning, and perioperative outcomes. Thus, our study aimed to study the clinical and logistical factors involved in cesarean sections in COVID-19 parturients. Material and Methods: This was a retrospective observational study performed at a dedicated COVID-19 tertiary care center in India. All women undergoing cesarean section in the specially earmarked operating room between 1st May 2020 and 31st December 2020 were included in the study. The clinical characteristics, operative details, and neonatal details, along with maternal and fetal outcomes were noted and analyzed. Results: A total of 44 women underwent cesarean section during the study period, with elective and emergency surgeries numbering 22 each. No indication, apart from COVID-19 status, was listed in over one-fourth of the women (13/44). The most common preoperative comorbidity was hypothyroidism (12/44). Median surgical duration was 117.5 min (IQR 100-133), with a median of 7.5 (IQR 6-8.25) healthcare personnel in the OT. Over one-fourth (12/44) of the delivered babies had low birth weight, while 4.5% (2/44) tested positive for SARS-CoV-2. Conclusion: COVID-19 status alone continues to be a common indication for cesarean section. Operative time is increased, but the number of healthcare personnel involved can be trimmed with proper planning. Maternal and fetal outcomes are largely positive, with low transmission rates, but a considerable proportion of low-birth-weight neonates.

Immunophenotypic Characterization and Ploidy Analysis of Neoplastic Plasma Cells by Multiparametric Flow Cytometry.

Flow cytometric (FCM) immunophenotyping is an important tool for generating diagnostic and prognostic information in plasma cell dyscrasias. This study aimed to evaluate the immunophenotype and ploidy status of plasma cells (PCs) in patients of myeloma and its correlation with other laboratory parameters. Bone marrow of 70 newly diagnosed cases of myeloma were subjected to FCM using a panel of antibodies; CD138, CD38, CD19, CD45, CD28, CD81, CD56, CD200, and CD229. FxCycle Violet (FCV) dye was used for the ploidy analysis of clonal PCs. Median age was 60 years with M:F ratio of 3.2:1. A positive correlation was noted between the morphological and FCM-based PC enumeration (r = 0.4, p = 0.001). Aberrant expression of CD56, CD200, CD28, CD117, CD81 and CD19 and was observed in 88.5%, 77%, 29%, 37%, 23% and 17% cases respectively. Two aberrant antigens were noted in all cases. CD81 + cases had a relatively higher quantity of monoclonal-protein (> 1 g/dl, p < 0.05) and renal insufficiency (Cr > 2 mg/dl, p < 0.05) as compared to the CD81- cases. CD229 was expressed in all the cases, with a median MFI in PCs significantly higher than other hematopoietic elements. Hyperdiploid PCs (median DI-1.59, range, 1.16-2.6) were noted in 80% cases (n = 48), diploid/ near-hyperdiploid PCs in 8% (n = 5) cases and hypodiploidy in 3% (n = 1) cases. Bright CD56/CD200 and CD45- can identify abnormal PC in the majority of the cases. CD81 appears to correlate with disease burden and might be useful as a prognostic marker. CD229 is a reliable gating marker for plasma cells. Ploidy analysis may be incorporated in routine workup to guide in the identification of patients with poor prognosis. Supplementary Information: The online version contains supplementary material available at 10.1007/s12288-021-01477-y.

Culture media, DMSO and efflux affect the antibacterial activity of cisplatin and oxaliplatin.

Cisplatin was originally discovered through its antibacterial action and subsequently has found use as a potent broad-spectrum anticancer agent. This study determines the effect of growth media and solvent on the antibacterial activity of cisplatin and its analogue, oxaliplatin. Escherichia coli MG1655 or MG1655 ΔtolC was treated with the platinum compounds under different conditions and susceptibility was determined. Our results showed that DMSO reduced the activity of cisplatin by fourfold (MIC 12·5 mg l-1 ) compared with 0·9% NaCl-solubilized cisplatin (MIC 3·12 mg l-1 ) when tested in MOPS. Surprisingly, complete loss of activity was observed in Mueller-Hinton Broth II (MHB II). By supplementing MOPS with individual components of MHB II such as the sulphur-containing amino acids, l-cysteine and l-methionine, individually or in combination reduced activity by ≥8-fold (MIC ≥25 mg l-1 ). Oxaliplatin was less active against E. coli (MIC 100 mg l-1 ) but exhibited similar inactivation in the presence of DMSO, MHBII or MOPS spiked with l-cysteine and l-methionine (MIC ≥400 mg l-1 ). Our data suggest that the antibacterial activity of cisplatin and oxaliplatin is modulated by both choice of solvent and composition of growth media. We demonstrate that this is primarily due to sulphur-containing amino acids cysteine and methionine, an essential component of the recommended media for testing antimicrobial susceptibility, MHBII.

Potential use of microwave technology in dermatology.

BACKGROUND: Microwaves are used in medicine for diagnostics, and treatment of cancer. Recently, novel microwave devices (Swift®, Emblation Ltd, UK and miraDry®, Miramar Labs Inc., CA) have been cleared by the FDA and Health Canada for various dermatological conditions. OBJECTIVE AND METHODS: To review the dermatological use of microwave-based treatments (plantar warts, corns, actinic keratosis, dermatophytosis, axillary hyperhidrosis, osmidrosis, and hidradenitis suppurativa). Clinical trials, case reports, or in vitro studies for each condition are summarized. RESULTS AND CONCLUSION: Microwaves are a promising alternative therapy for cutaneous warts, actinic keratosis, axillary hyperhidrosis, and osmidrosis, with favorable safety profiles. However, patients with hidradenitis suppurativa have had negative clinical outcomes. Limited treatment of corns showed good pain reduction but did not resolve hyperkeratosis. A preliminary in vitro study indicated that microwave treatment inhibits the growth of T. rubrum. We present the first case of toenail onychomycosis successfully treated with microwaves. Despite the advancements in the use of microwaves, the mechanism of action in non-ablative treatment is not well understood; further research is needed. More high-quality randomized clinical trials with larger groups and long follow-up periods are also required to evaluate the clinical benefits and possible adverse effects of microwaves in treating dermatological conditions.

Deciphering radiological stable disease to immune checkpoint inhibitors.

BACKGROUND: 'Stable disease (SD)' as per RECIST is a common but ambiguous outcome in patients receiving immune checkpoint inhibitors (ICIs). This study aimed to characterize SD and identify the subset of patients with SD who are benefiting from treatment. Understanding SD would facilitate drug development and improve precision in correlative research. PATIENTS AND METHODS: A systematic review was carried out to characterize SD in ICI trials. SD and objective response were compared to proliferation index using The Cancer Genome Atlas gene expression data. To identify a subgroup of SD with outcomes mirroring responders, we examined a discovery cohort of non-small-cell lung cancer (NSCLC). Serial cutpoints of two variables, % best overall response and progression-free survival (PFS), were tested to define a subgroup of patients with SD with similar survival as responders. Results were then tested in external validation cohorts. RESULTS: Among trials of ICIs (59 studies, 14 280 patients), SD ranged from 16% to 42% in different tumor types and was associated with disease-specific proliferation index (ρ = -0.75, P = 0.03), a proxy of tumor kinetics, rather than relative response to ICIs. In a discovery cohort of NSCLC [1220 patients, 313 (26%) with SD to ICIs], PFS ranged widely in SD (0.2-49 months, median 4.9 months). The subset with PFS >6 months and no tumor growth mirrored partial response (PR) minor (overall survival hazard ratio 1.0) and was proposed as the definition of SD responder. This definition was confirmed in two validation cohorts from trials of NSCLC treated with durvalumab and found to apply in tumor types treated with immunotherapy in which depth and duration of benefit were correlated. CONCLUSIONS: RECIST-defined SD to immunotherapy is common, heterogeneous, and may largely reflect tumor growth rate rather than ICI response. In patients with NSCLC and SD to ICIs, PFS >6 months and no tumor growth may be considered 'SD responders'. This definition may improve the efficiency of and insight derivable from clinical and translational research.

Cholecystitis: association between ultrasound findings and surgical outcomes.

AIM: To identify sonographic signs of cholecystitis that correlate with surgical outcomes. MATERIALS AND METHODS: Three hundred and thirty-three consecutive patients who underwent cholecystectomy between 22/06/2014 and 1/3/2016 and underwent abdominal ultrasound (US) within 7 days of surgery were included. Individual US signs, including gallstones, gallbladder distention, wall thickening, pericholecystic fluid, and abscess, were graded by two radiologists, 1 and 2. Outcomes included operative duration (OD), drain placement, partial cholecystectomy, conversion from laparoscopic to open cholecystectomy, surgical pathology, bile leak, infection, and 30-day readmission. US signs and outcomes were analysed using analysis of variance, chi-square test, or odds ratios (OR). RESULTS: Radiologist 1 reported 141/333 and radiologist 2 reported 128/333 patients showed gallbladder distention. For the subset with OD, radiologist 1 reported 140/320 and radiologist 2 reported 126/320 patients showed gallbladder distention. Distention was predictive of increased OD (radiologist 1, +23.2 minutes, p<0.0001; radiologist 2, +19.4 minutes, p=0.0003). Cases with gallbladder distention were more likely to have surgical drain placement (OR= 2.60; 95% confidence interval [CI]: 1.12-6.08, p=0.027 radiologist 1; OR=2.59; 95% CI: 1.13-5.95, p=0.025 radiologist 2). Wall thickening was present in 126/333 patients reported by radiologist 1 and 120/333 by radiologist 2. Cases with wall thickening were more likely to have drain placement (OR=2.66; 95% CI: 1.16-6.13, p=0.021 radiologist 1; OR=3.49; 95% CI: 1.49-8.16, p=0.004 radiologist 2). For the subset with OD, wall thickening was present for 121/320 reported by radiologist 1 and 116/320 by radiologist 2 and predicted longer OD (radiologist 1, +15.9 minutes, p=0.0033; radiologist 2, +13.3 minutes, p=0.0143). CONCLUSION: Gallbladder distention and wall thickening on US correlate with prolonged OD and surgical drain placement in patients with cholecystitis.

Global Forum of Cancer Surgeons: Cancer Surgery During the COVID-19 Pandemic: Impact and Lessons Learned.

BACKGROUND: The purpose of this article is to summarize the opinions of the surgical oncology leaders from the Global Forum of Cancer Surgeons (GFCS) about the global impact of COVID-19 pandemic on cancer surgery. METHODS: A panel session (virtual) was held at the annual Society of Surgical Oncology 2021 International Conference on Surgical Cancer Care to address the impact of COVID-19 on cancer surgery globally. Following the virtual meeting, a questionnaire was sent to all the leaders to gather additional opinions. The input obtained from all the leaders was collated and analyzed to understand how cancer surgeons from across the world adapted in real-time to the impact of COVID-19 pandemic. RESULTS: The surgical oncology leaders noted that the COVID-19 pandemic led to severe disruptions in surgical cancer care across all domains of clinical care, education, and research. Several new changes/protocols associated with increased costs were implemented to deliver safe care. Leaders also noted that preexisting disparities in care were exacerbated, and the pandemic had a detrimental effect on well-being and financial status. CONCLUSIONS: The COVID-19 pandemic has led to severe disruptions in surgical cancer care globally. Leaders of the GFCS opined that new strategies need to be implemented to prepare for any future catastrophic events based on the lessons learned from the current events. The GFCS will embark on developing such a roadmap to ensure that surgical cancer care is preserved in the future regardless of any catastrophic global events.

Plateletpheresis donation through donor awareness, motivation, and recruitment drives: A unique concept and experience from a tertiary care oncology centre in India.

OBJECTIVES: The majority of blood donor motivational and awareness activities are directed toward whole blood donation and not much emphasis is given to the plateletpheresis. The study was designed to analyze the effectiveness of the unique concept of platelet drives (PD) to increase voluntary plateletpheresis donations. MATERIALS AND METHODS: The study was a retrospective study conducted at a tertiary care oncology hospital-based blood transfusion services (BTS). RESULTS: A total of 13 PDs were conducted from January 2016 to December 2020. A total of 559 potential donors came for the donor registration and 125 donors got deferred on medical history. A total of 434 donors gave their samples for the testing of plateletpheresis. The median age of potential male and female donors was 32 and 30 years respectively. A total of 58 males and two females have donated single donor platelets (14.3% vs. 7.4%, P=0.319). The median age of male and female donors was 36 and 42 years, respectively. In male donors, 48 had donated once, seven donated twice, two donated thrice and one donor donated four times. Out of two female donors, one donor donated twice and the other donor donated four times. The female donors were more committed to repeat donations (P=0.004). Since the start of PDs, the number of voluntary donations has increased considerably over the years. CONCLUSION: PDs have helped in increasing the number of voluntary plateletpheresis donors. All the BTS must have the standard operating procedures in place for these kinds of awareness and motivational drives.

Radiological and clinical correlations of the anterior ethmoidal artery in functional endoscopic sinus surgery.

OBJECTIVES: To correlate computed tomography findings and endoscopic localisation of the anterior ethmoidal artery during surgery, and to analyse the intranasal landmarks and abnormalities of the artery. METHOD: The anterior ethmoidal artery was studied with high-resolution computed tomography and endoscopic surgery in 30 patients undergoing functional endoscopic sinus surgery (group A), and with endoscopic dissection on 30 human cadavers (group B). RESULTS: The anterior ethmoidal artery was demonstrated on computed tomography in 25 patients and intra-operatively in 12 (group A). It was identified in 26 cadavers (group B). Dehiscence of bony canal and branching was noted in 10.53 per cent of cases. The mean (± standard deviation) intranasal length of the anterior ethmoidal artery was 7.29 (± 1.21) mm, the distance of the artery from the axilla of the middle turbinate was 16.24 (± 2.75) mm, and the mean distance from the ground lamella was 8.97 (± 1.46) mm. CONCLUSION: High-resolution computed tomography scanning prior to functional endoscopic sinus surgery is mandatory to identify the anterior ethmoidal artery. Endoscopically, the axilla of the middle turbinate and the ground lamella can serve as dependable reference points to identify the artery. Cadaver dissection improves understanding of anatomy.