Diagnosis of Pancreatic Cancer after Cholecystectomy in the Elderly.

BACKGROUND: Previous studies evaluating whether recent cholecystectomy is associated with a pancreas cancer diagnosis are limited. We aimed to examine if cholecystectomy was performed more frequently in the year prior to cancer diagnosis than would be expected in a similar non-cancer population. METHODS: SEER-Medicare linked files were used to identify patients with pancreatic adenocarcinoma. Cancer diagnoses were considered to be "timely" if within 2 months of cholecystectomy or "delayed" if 2-12 months after cholecystectomy. Clinical factors and survival outcomes were compared using chi-square and Kaplan-Meier analyses. RESULTS: Rate of cholecystectomy in the year prior to diagnosis of cancer was 1.9% for the cancer group, compared to .4% in the non-cancer group (OR = 4.7, 95% CI 4.4-5.1). Differences in the cancer vs non-cancer cohorts at the time of cholecystectomy included a higher age (74 vs 70, P < .0001), more males (49.9% vs 41.7%, P < .0001), and more frequent open technique (21.0% vs 9.4%, P < .0001). Acute pancreatitis was nearly twice as common in the cancer cohort (19.1%) vs the non-cancer cohort (10.7%), P < .0001. There were no differences between patients who had a timely diagnosis after cholecystectomy compared to a delayed diagnosis with regard to age, gender, comorbidity index, race, or rural/urban designation. The rates of localized disease and subsequent resection were also similar between the delayed and timely groups. Overall unadjusted survival was no different between timely and delayed diagnoses, P = .96. DISCUSSION: Elderly patients diagnosed with pancreatic adenocarcinoma are more likely to have had a recent cholecystectomy compared to those without.

Variation in Lymph Node Assessment for Colon Cancer at the Tumor, Surgeon, and Hospital Level.

BACKGROUND: We hypothesized that tumor- and hospital-level factors, compared with surgeon characteristics, are associated with the majority of variation in the 12 or more lymph nodes (LNs) examined quality standard for resected colon cancer. STUDY DESIGN: A dataset containing an anonymized surgeon identifier was obtained from the National Cancer Database for stage I to III colon cancers from 2010 to 2017. Multilevel logistic regression models were built to assign a proportion of variance in achievement of the 12 LNs standard among the following: (1) tumor factors (demographic and pathologic characteristics), (2) surgeon factors (volume, approach, and margin status), and (3) facility factors (volume and facility type). RESULTS: There were 283,192 unique patient records with 15,358 unique surgeons across 1,258 facilities in our cohort. Achievement of the 12 LNs standard was high (90.3%). Achievement of the 12 LNs standard by surgeon volume was 88.1% and 90.7% in the lowest and highest quartiles, and 86.8% and 91.6% at the facility level for high and low annual volume quartiles, respectively. In multivariate analysis, the following tumor factors were associated with meeting the 12 LNs standard: age, sex, primary tumor site, tumor grade, T stage, and comorbidities (all p < 0.001). Tumor factors were responsible for 71% of the variation in 12 LNs yield, whereas surgeon and facility characteristics contributed 17% and 12%, respectively. CONCLUSIONS: Twenty-nine percent of the variation in the 12 LNs standard is linked to modifiable factors. The majority of variation in this quality metric is associated with non-modifiable tumor-level factors.

Expression of nonmuscle myosin IIC is regulated by non-canonical binding activity of miRNAs.

The expression of mechanoresponsive nonmuscle myosin II (NMII)C is found to be inducible during tumor progression, but its mechanism is yet to be explored. Here, we report a group of microRNAs (mmu-miR-200a-5p, mmu-miR-532-3p, mmu-miR-680, and mmu-miR-1901) can significantly repress the expression of nonmuscle myosin IIC (NMIIC). Interestingly, these microRNAs have both canonical and non-canonical binding sites at 3/UTR and coding sequence (CDS) of NMIIC's heavy chain (HC) mRNA. Each of the miRNA downregulates NMHC-IIC to a different degree as assessed by dual-luciferase and immunoblot analyses. When we abolish the complementary base pairing at canonical binding site, mmu-miR-532-3p can still bind at non-canonical binding site and form Argonaute2 (AGO2)-miRNA complex to downregulate the expression of NMIIC. Modulating the expression of NMIIC by miR-532-3p in mouse mammary tumor cells, 4T1, increases its tumorigenic potential both in vitro and in vivo. Together, these studies provide the functional role of miRNA's non-canonical binding mediated NMIIC regulation in tumor cells.

Post-partum paraplegia following spinal anaesthesia: a report of two rare cases.

Pregnancy and lumbar puncture are rare instances that can precipitate sudden onset paraplegia in patients with otherwise slow-growing intradural tumours. Surgeons and anaesthesiologists should be aware of the etiological factors leading to pregnancy- and delivery-related rapid tumour growth and its complications. Lumbar puncture-related complications leading to acute precipitation of neurological symptoms must be addressed promptly for favourable outcome in such patients. We describe the report of two patients who developed acute onset paraparesis after spinal anaesthesia for caesarean section. Both were found to be having undiagnosed spinal tumours and managed surgically. We recommend urgent MRI in cases of acute onset non-resolving paraparesis in the peripartum period, for timely diagnosis and management of this rare clinical entity.

2D Nano-Sonosensitizers Facilitate Energy Transfer to Enhance Sonodynamic Therapy.

Although sonodynamic therapy (SDT) has shown promise for cancer treatment, the lack of efficient sonosensitizers (SSs) has limited the clinical application of SDT. Here, a new strategy is reported for designing efficient nano-sonosensitizers based on 2D nanoscale metal-organic layers (MOLs). Composed of Hf-oxo secondary building units (SBUs) and iridium-based linkers, the MOL is anchored with 5,10,15,20-tetra(p-benzoato)porphyrin (TBP) sensitizers on the SBUs to afford TBP@MOL. TBP@MOL shows 14.1- and 7.4-fold higher singlet oxygen (1 O2 ) generation than free TBP ligands and Hf-TBP, a 3D nanoscale metal-organic framework, respectively. The 1 O2 generation of TBP@MOL is enhanced by isolating TBP SSs on the SBUs of the MOL, which prevents aggregation-induced quenching of the excited sensitizers, and by triplet-triplet Dexter energy transfer between excited iridium-based linkers and TBP SSs, which more efficiently harnesses broad-spectrum sonoluminescence. Anchoring TBP on the MOL surface also enhances the energy transfer between the excited sensitizer and ground-state triplet oxygen to increase 1 O2 generation efficacy. In mouse models of colorectal and breast cancer, TBP@MOL demonstrates significantly higher SDT efficacy than Hf-TBP and TBP. This work uncovers a new strategy to design effective nano-sonosensitizers by facilitating energy transfer to efficiently capture broad-spectrum sonoluminescence and enhance 1 O2 generation.

A residual driven ensemble machine learning approach for forecasting natural gas prices: analyses for pre-and during-COVID-19 phases.

The natural gas price is an essential financial variable that needs periodic modeling and predictive analysis for many practical implications. Macroeconomic euphoria and external uncertainty make its evolutionary patterns highly complex. We propose a two-stage granular framework to perform predictive analysis of the natural gas futures for the USA (NGF-USA) and the UK natural gas futures for the EU (NGF-UK) for pre-and during COVID-19 phases. The residuals of the previous stage are introduced as a new explanatory feature along with standard technical indicators to perform predictive tasks. The importance of the new feature is explained through the Boruta feature evaluation methodology. Maximal Overlap Discrete Wavelet Transformation (MODWT) is applied to decompose the original time-series observations of the natural gas prices to enable granular level forecasting. Random Forest is invoked on each component to fetch the respective predictions. The aggregated component-wise sums lead to final predictions. A rigorous performance assessment signifies the efficacy of the proposed framework. The results show the effectiveness of the residual as a feature in deriving accurate forecasts. The framework is highly efficient in analyzing patterns in the presence of a limited number of data points during the uncertain COVID-19 phase covering the first and second waves of the pandemic. Our findings reveal that the prediction accuracy is the best for the NGF-UK in the pre-COVID-19 period. Also, the prediction accuracy of the NGF-USA is better in the COVID-19 period than the pre-COVID-19 period.

[18F]FDG PET-CT findings in an unusual case of synchronous double primary lung cancer of different histologies.

Double primary lung cancer (DPLC) is a rare occurrence of primaries of different histologies or the same histology in different lobes in absence of advanced nodal or distant metastasis. It could be synchronous or metachronous. They are frequently misdiagnosed as metastasis or recurrence. This study presents the staging [¹8F]Fluorodeoxyglucose positron emission tomography-computed tomography findings in a case of a 74-year-old man with DPLC of different histologies.

18F-FDG PET/CT for Staging and Response Evaluation in a Rare Case of Childhood Ovarian Primitive Neuroectodermal Tumor.

ABSTRACT: Primitive neuroectodermal tumor (PNET) is an aggressive small cell malignancy. Apart from the central nervous system, they can arise from peripheral sites as well. Ovarian PNETs are extremely rare neoplasms. We here present a case of childhood ovarian PNET, where 18F-FDG PET/CT was efficiently used for staging and response evaluation.

Transcriptome analysis identifies putative multi-gene signature distinguishing benign and malignant pancreatic head mass.

BACKGROUND: Most often, the patients with pancreatic diseases are presented with a mass in pancreatic head region and existing methods of diagnosis fail to confirm whether the head mass is malignant or benign. As subsequent management of the disease hugely depends on the correct diagnosis, we wanted to explore possible biomarkers which could distinguish benign and malignant pancreatic head masses. METHODS: In order to address that gap, we performed a case-control study to identify genome-wide differentially expressed coding and noncoding genes between pancreatic tissues collected from benign and malignant head masses. These genes were next shortlisted using stringent criteria followed by selection of top malignancy specific genes. They subsequently got validated by quantitative RT-PCR and also in other patient cohorts. Survival analysis and ROC analysis were also performed. RESULTS: We identified 55 coding and 13 noncoding genes specific for malignant pancreatic head masses. Further shortlisting and validation, however, resulted in 5 coding genes as part of malignancy specific multi-gene signature, which was validated in three independent patient cohorts of 145 normal and 153 PDAC patients. We also found that overexpression of these genes resulted in survival disadvantage in the patients and ROC analysis identified that combination of 5 coding genes had the AUROC of 0.94, making them potential biomarker. CONCLUSIONS: Our study identified a multi-gene signature comprising of 5 coding genes (CDCA7, DLGAP5, FOXM1, TPX2 and OSBPL3) to distinguish malignant head masses from benign ones.

Role of Cresp® in the management of chemotherapy-induced anemia in cancer patients: A real-world clinical practice audit.

INTRODUCTION: Anemia is a common, underestimated problem in cancer patients receiving myelosuppressive chemotherapy and has significant adverse effect on the quality of life and outcome. Darbepoetin has been shown to be effective in this setting, but controversy surrounds it actual use. METHODS: We analyzed prospectively collected clinical practice data of patients receiving darbepoetin in a real-world setting for this retrospective audit. Patients with baseline hemoglobin (Hb) of <11 g/dl were included in this analysis. Their medical records were audited using a predetermined 35-point pro forma. RESULTS: There were a total of 274 patients with advanced cancer receiving myelosuppressive chemotherapy who had baseline Hb <11 g/dl and who were given darbepoetin. Head-and-neck squamous cell carcinoma, lung cancer, and breast cancer were the most common cancers. Their median baseline Hb was 8.9 g/dl which rose to 11.2 g/dl at the end of commenced therapy, along with improved symptomatology. There were no new toxicities, and only two patients required discontinuation of darbepoetin due to toxicity. CONCLUSION: Darbepoetin is safe and effective in the prevention and management of anemia among patients receiving myelosuppressive chemotherapy.

Nonmuscle myosin IIA and IIB differentially modulate migration and alter gene expression in primary mouse tumorigenic cells.

Though many cancers are known to show up-regulation of nonmuscle myosin (NM) IIA and IIB, the mechanism by which NMIIs aid in cancer development remains unexplored. Here we demonstrate that tumor-generating, fibroblast-like cells isolated from 3-methylcholanthrene (3MC)-induced murine tumor exhibit distinct phospho-dependent localization of NMIIA and NMIIB at the perinuclear area and tip of the filopodia and affect cell migration differentially. While NMIIA-KD affects protrusion dynamics and increases cell directionality, NMIIB-KD lowers migration speed and increases filopodial branching. Strategically located NMIIs at the perinuclear area colocalize with the linker of nucleoskeleton and cytoskeleton (LINC) protein Nesprin2 and maintain the integrity of the nuclear-actin cap. Interestingly, knockdown of NMIIs results in altered expression of genes involved in epithelial-to-mesenchymal transition, angiogenesis, and cellular senescence. NMIIB-KD cells display down-regulation of Gsc and Serpinb2, which is strikingly similar to Nesprin2-KD cells as assessed by quantitative PCR analysis. Further gene network analysis predicts that NMIIA and NMIIB may act on similar pathways but through different regulators. Concomitantly, knockdown of NMIIA or NMIIB lowers the growth rate and tumor volume of 3MC-induced tumor in vivo. Altogether, these results open a new window to further investigate the effect of LINC-associated perinuclear actomyosin complex on mechanoresponsive gene expression in the growing tumor.

Ameloblastic Fibrosarcoma in Pregnancy: an Unreported Entity!

AFS is a rare tumor of odontogenic origin. Less than 100 cases have been reported so far in the literature. Due to its extreme rarity, we do not have clear management guidelines at present. The entire clinical spectrum and natural history of this uncommon malignancy is unknown. Most of the cases present with facial swelling along with varying degrees of oral signs and symptoms. AFS has higher incidence in male and common in third decade of life. However, presentation in female can be unique and may have a different course and outcome then what is known to us. The association of pregnancy and AFS is interesting and has hardly been emphasized before. Pregnancy can dramatically boost the growth of this tumor leading to impending airway obstruction or fatal hemorrhage. We report a case of an 18-year-old pregnant female who presented with rapidly enlarging bleeding mandibular mass and respiratory distress and present the challenges in its surgical management along with it long-term outcome on follow-up. We also discuss and explore the probable role of AFS in context of pregnancy and its oncological outcome.

Metastatic perivascular epithelioid cell tumor responding to mammalian target of rapamycin inhibition.

Perivascular epithelioid cell tumors (PEComa) are a family of rare mesenchymal tumors composed of histologically and immunohistochemically distinctive perivascular epithelioid cells. Female genital tract and retroperitoneum are common sites of origin of PEComa-not otherwise specified. Diagnosis depends upon characteristic morphology and immunohistochemistry findings. Prognosis of unresectable or metastatic disease is poor. Responses to mammalian target of rapamycin (mTOR) inhibition are encouraging but mostly short-lived. We report a case of metastatic PEComa who responded to mTOR inhibition, albeit for a short duration. We also review the existing literature on mTOR inhibitors in PEComa.

Serum galactomannan assay for diagnosis of probable invasive Aspergillosis in acute leukemia and hematopoietic stem cell transplantation.

BACKGROUND: Invasive aspergillosis (IA) is a leading cause of mortality in acute leukemia and hematopoietic stem cell transplantation (HSCT). AIMS: To determine the yield of galactomannan (GM) assay for the diagnosis of probable IA, its temporal relationship with the computed tomography (CT) scans and correlation with mortality in AL and HSCT. PATIENTS AND METHODS: Consecutive neutropenic episodes (n=150) among inpatients aged ≥15 years with AL or recipients of HSCT were prospectively evaluated over 1½ years. All patients underwent weekly serum GM assay and optical density index >0.5 for ≥2 samples was defined as positive. IA was diagnosed according to EORTC 2008 guidelines. RESULTS: Of the 150 episodes enrolled, 43 (28.7%) were diagnosed with IA: possible 25 (16.7%), probable 17 (11.3%) and proven 1 (0.7%). The yield of GM assay in diagnosing probable IA was 17/42 (40.5%). In 88.2% of probable IA episodes, GM was positive before high-resolution CT at a median of 10 days (range 1-16). In the episodes with ≥2 samples tested, fatality was higher in those ≥2 values positive for GM, compared to the rest (31% vs. 13.2%, odd ratio 2.96, 95% CI 1.09-8.00; P=0.04). CONCLUSIONS: In AL and HSCT, GM assay could identify patients with probable IA earlier than CT chest and also predicted a higher risk of death.

Profile of infections and outcome in high-risk febrile neutropenia: experience from a tertiary care cancer center in India.

Objective of the present study was to describe the profile of infections in febrile neutropenia (FN) in acute leukemia and hematopoietic stem cell transplant (HSCT) with emphasis on response to therapy and outcome. In a prospective, observational single-institutional study, consecutive episodes of high-risk FN were enrolled over a 1½-year period. Uniform antibiotic policy and response criteria were used. Of the 200 episodes enrolled, acute leukemia induction comprised 40.5%, consolidation with high-dose cytarabine 22.5%, HSCT 29% (auto-HSCT 84%), and others 8% of the episodes, respectively. Microbiologically documented infections comprised 30% episodes, while bacteremia was documented in 26% episodes. Gram-negative isolates were more common (55.7%). Cefoperazone-sulbactam had the highest in vitro efficacy against Gram-negative rods. Carbapenem resistance was most prevalent among Acinetobacter spp. (80%) and Pseudomonas aeruginosa (50%). All Gram-positive cocci other than enterococci were susceptible to vancomycin, while 2/8 enterococci were resistant to it. Cefoperazone-sulbactam and amikacin were used as first-line antibiotics. Overall mortality was 8%. On multivariate analysis, mortality was associated with a nadir leukocyte count < 200/µl and an abnormal chest radiograph. Among high-risk FN patients, inspite of a high-level of resistance to antibiotics, a frontline regime containing cefoperazone-sulbactam could restrict the use of imipenem and resulted in an acceptable mortality of 8%.

Testicular germ cell tumor fungating through anterior abdominal wall.

Retroperitoneal lymph node metastases from testicular germ cell tumor are common, but fungation of such mass through the anterior abdominal wall is extremely rare. We report such a case which had a favorable response to chemotherapy.