Statins abrogate gemcitabine-induced PD-L1 expression in pancreatic cancer-associated fibroblasts and cancer cells with improved therapeutic outcome.

A combination of chemotherapy with immunotherapy has been proposed to have better clinical outcomes in Pancreatic Ductal Adenocarcinoma (PDAC). On the other hand, chemotherapeutics is known to have certain unwanted effects on the tumor microenvironment that may mask the expected beneficial effects of immunotherapy. Here, we have investigated the effect of gemcitabine (GEM), on two immune checkpoint proteins (PD-L1 and PD-L2) expression in cancer associated fibroblasts (CAFs) and pancreatic cancer cells (PCCs). Findings of in vitro studies conducted by using in-culture activated mouse pancreatic stellate cells (mPSCs) and human PDAC patients derived CAFs demonstrated that GEM significantly induces PD-L1 and PD-L2 expression in these cells. Moreover, GEM induced phosphorylation of STAT1 and production of multiple known PD-L1-inducing secretory proteins including IFN-γ in CAFs. Upregulation of PD-L1 in PSCs/CAFs upon GEM treatment caused T cell inactivation and apoptosis in vitro. Importantly, Statins suppressed GEM-induced PD-L1 expression both in CAFs and PCCs while abrogating the inactivation of T-cells caused by GEM-treated PSCs/CAFs. Finally, in an immunocompetent syngeneic orthotopic mouse pancreatic tumor model, simvastatin and GEM combination therapy significantly reduced intra-tumor PD-L1 expression and noticeably reduced the overall tumor burden and metastasis incidence. Together, the findings of this study have provided experimental evidence that illustrates potential unwanted side effects of GEM that could hamper the effectiveness of this drug as mono and/or combination therapy. At the same time the findings also suggest use of statins along with GEM will help in overcoming these shortcomings and warrant further clinical investigation.

Impact of personal protective equipment on patient safety and health care workers.

Background: The study aims to assess the effect of personal protective equipment (PPE) on the physical and psychological well-being of health care workers (HCWs) and its impact on patient safety. Methods: After ethical approval, a 14-point questionnaire was circulated offline and online among the HCWs of ours institute, who were involved in performing invasive procedures while wearing a PPE. The responses were analysed using the SPSS software version 26. Results: Of 198 responses, the mean duration of PPE use was 4.6 ± 1.52 h. Seventy percent of respondents suggested <4 h of continuous use of PPE. Seventy-seven percent found difficulties during the procedures while wearing PPE and agreed to errors while performing a procedure. Poor visibility (95.5%), fogging (84.9%), communication difficulty (75.3%), sweating (74.2%), posture-related discomfort (56.1%) and poor concentration (51%) were major causes. Anxiety (39.9%) and fear of spreading an infection to the family (42.9%) were major psychological effects. Eighty percent of HCWs raised concern over the quality of PPE, N95 mask and eye protector. The HCWs felt the need to improve the quality of PPEs, use extra padding around the ears, sealing the N95 mask with adhesive tape, besides using sign language for communication for more safety. Fifty percent graded the procedure-related difficulty level >6 on a Likert scale of 1-10. Conclusion: PPE-related discomfort is common among the HCWs and could contribute to errors during an invasive procedure. Efforts to alleviate the physical and psychological well-being of the HCWs will be essential for reducing procedural error while wearing a PPE.

Ligation of Intersphincteric Fistulous Tract vs Endorectal Advancement Flap for High-Type Fistula in Ano: A Randomized Controlled Trial.

BACKGROUND: This study aimed to compare the postoperative outcomes and success rate of the endorectal advancement flap and ligation of intersphincteric fistulous tract (LIFT) in high-type fistula in ano. STUDY DESIGN: This randomized control trial included patients with high-type fistula in ano of cryptoglandular origin. The primary endpoint was complete fistula healing at the end of 6 months. However, the patients were followed up for 2 years. Other parameters studied were perioperative complications, duration of surgery, postoperative pain, hospital stay in hours, continence, and quality of life at 6 months. RESULTS: A total of 84 patients were recruited (42 in each group). The healing rate in the LIFT arm was better than that in the endorectal advancement flap arm (76.2.% vs 54.7%, p = 0.039). Four patients in the endorectal advancement flap group and two in the LIFT group had flatus incontinence at the end of 6 months, but all were continent at 2 years. At the end of the first week, the Visual Analog Scale score and quality of life at 6 months were better in the LIFT arm (3.7 ± 1.16 vs 4.7 ± 0.81 and 0.7 vs 0.6, p < 0.05). The mean duration of surgery was significantly less in the LIFT group (46.43 ± 9.32 vs 89.29 ± 10.90 minutes). None had any postoperative complications, and >80% were discharged within 24 hours. CONCLUSIONS: The shorter operative duration, better quality of life at 6 months, and higher healing rate make LIFT a superior treatment option for high fistula in ano. However, studies with a large sample size will be needed to verify these results.

MIF confers survival advantage to pancreatic CAFs by suppressing interferon pathway-induced p53-dependent apoptosis.

The presence of activated pancreatic stellate cells (PSCs) in the pancreatic ductal adenocarcinoma (PDAC) microenvironment plays a significant role in cancer progression. Macrophage migration inhibitory factor (MIF) is overexpressed in PDAC tissues and expressed by both cancer and stromal cells. The pathophysiological role of MIF in PDAC-associated fibroblasts or PSCs is yet to be elucidated. Here we report that the PSCs of mouse or cancer-associated fibroblast cells (CAFs) of human expresses MIF and its receptors, whose expression gets upregulated upon LPS or TNF-α stimulation. In vitro functional experiments showed that MIF significantly conferred a survival advantage to CAFs/PSCs upon growth factor deprivation. Genetic or pharmacological inhibition of MIF also corroborated these findings. Further, co-injection of mouse pancreatic cancer cells with PSCs isolated from Mif-/- or Mif+/+ mice confirmed the pro-survival effect of MIF in PSCs and also demonstrated the pro-tumorigenic role of MIF expressed by CAFs in vivo. Differential gene expression analysis and in vitro mechanistic studies indicated that MIF expressed by activated CAFs/PSCs confers a survival advantage to these cells by suppression of interferon pathway induced p53 dependent apoptosis.

Squamous Metaplasia in a Borderline Phyllodes Tumor-an Undocumented Histological Finding in Male Breast: Report of a Case and Review of Literature.

Phyllodes tumor is a paradigm of fibroepithelial neoplasm that accounts for <1% of the breast neoplastic lesions usually detected in females and uncommonly in the male breast. The World Health Organization classifies the tumor into benign, borderline, and malignant based on the predefined morphological criteria. Squamous differentiation in phyllodes tumor is epithelial metaplasia, which has been occasionally documented in English literature. We report the first undocumented case of a recurrent borderline phyllodes tumor with cystic squamous metaplastic change in a 32-year-old male patient. The histology was that of a fibroepithelial neoplasm with the typical leaf-like projections and cystic spaces lined by squamous epithelium containing keratin debris. The purpose of presenting this case is to elucidate the pathogenesis and discuss other malignant and benign breast lesions that may be included in the differential diagnosis when evaluating a breast lesion with squamous metaplasia, particularly in the context of fine-needle aspirates.

CT Imaging in Predicting Ovarian Torsion: Report of Two Cases, With and Without Infarction.

Ovarian torsion is one of the common abdominal and gynecologic surgical emergencies with serious morbidity in the form of ovarian infarct or necrosis. Various imaging modalities like USG, CT, and MRI have been used in the evaluation of ovarian torsion. Two middle-aged females presented with lower abdominal pain. Imaging showed an ovarian cystic lesion in the first patient and thickened and twisted ovarian pedicle or 'helical swirling' sign in the second. Intraoperatively, the first case turned out to be a 180* twist with mild ovarian edema and the second showed more than 720* torsion with ovarian infarction. The CT findings of twisted pedicle with pericystic fat stranding might be predictive of hemorrhagic infarction in cases of torsion.

Pure primary ovarian carcinoid tumor with carcinoid syndrome and cervical carcinoma: A rare concoction of dual primary malignancies.

Carcinoid tumors are defined as rare slow-growing neuroendocrine tumors. A majority of primary ovarian carcinoids occur in association with mature cystic teratoma or are metastatic to the ovary. A 48-year-old post-menopausal woman presented with progressive facial puffiness, and intractable diarrhea. Radiological imaging suggested a 10 × 9 × 9.2 cm right ovarian mass. She underwent a total abdominal hysterectomy and bilateral salpingo-oophorectomy. Histopathological examination revealed primary pure carcinoid tumor of the ovary with the synchronous presence of early invasive squamous cell carcinoma of the cervix, along with the icthyosis uteri. The patient is doing well on 5 years of follow-up post-surgery without any recurrence or metastasis. In this report, we intend to highlight the rare association of cervical carcinoma and ichthyosis uteri with this tumor. In addition, we present a short review of the literature, over a decade of ovarian carcinoids associated with carcinoid heart disease.

Nicolau Syndrome: An Unforeseen Yet Evadable Consequence of Intramuscular Injection.

An intramuscular (IM) injection is one of the common routes for administering drugs, commonly analgesics and vaccines. Nicolau syndrome refers to the rapid-onset painful, extensive cutaneous discoloration progressing to necrosis and ulceration, reported after IM injections. This case report highlights a rare but avoidable complication of such injections. An elderly man presented with extensive cutaneous necrosis and discoloration over the buttocks extending to the thigh, within few days after receiving a single shot of IM injection of diclofenac. Management involved wound care, biopsy, and cultures with supportive antibiotics to control superadded infection. After multiple sittings of extensive surgical debridement, the wound showed signs of healing and was ultimately amicable for skin grafting in a month. Health care workers need sensitization toward such a complication that can occur out of a routine procedure like an IM injection. They should follow standard IM injections techniques and take precautions to avoid this mishap, which adds to the patient's morbidity.

The effect of 'THE MOTOR VEHICLES (AMENDMENT) ACT, 2019' on the clinico-epidemiological profile of road traffic accident patients presenting to a tertiary care trauma centre in Bhubaneswar.

CONTEXT: Road traffic accidents (RTA) are a foremost rising cause of morbidity and mortality in developing countries like India. The Government of India enacted a new motor vehicle amendment act (MVA) on September 1st 2019 that permits heavy penalties for traffic rule offenders. AIMS: To find out the early impact of "THE MOTOR VEHICLES (AMENDMENT) ACT, 2019". SETTINGS AND DESIGN: A retrospective observational study was performed during the time period July to October 2019 on RTA patients admitted to the Trauma and Emergency department. METHODS AND MATERIALS: Patients studied in two groups - One Pre MVA group (n = 371) and one Post MVA group (n = 415). The data were extracted from medical case records of the department and filled up in a structured format. Detailed demographic profile, including the use of safety measure and clinical variables such as the pattern of injury and injury severity scores, were recorded. STATISTICAL ANALYSIS USED: Statistical analysis was done by R version 3.6.1. RESULTS: There is a 41% drop in RTA victims post MVA implementation. Polytrauma reduced (25% vs 45.5%) significantly (P = 0.002) and so was Injury severity score (6.00 vs 13.00). More RTA victims were wearing helmets as compared to previous (42% vs 18%), and there was a steep decline in the alcohol driving (25% vs 10%) between the pre and post MVA group. A significant reduction noted in the under 18 yrs. Two-wheeler riders in the post MVA group compared to earlier (P = 0.016). CONCLUSIONS: The study reveals that there is a commendable reduction in the injury severity, violation of safety gears, alcohol use and rash driving following the implementation of MVA September 2019. Primary care and family physician can play a crucial role in creating public awareness about the personal safety measures, which will help in strengthening of this law to reduce the incidence of RTA and the associated mortality and morbidity.

Malignant Extra-Gastrointestinal Stromal Tumor of the Mesentery.

Gastrointestinal stromal tumors (GISTs), the commonest mesenchymal tumors of gastrointestinal tract are often described to take origin from the interstitial cells of Cajal (ICC) or its precursor cells. Rarely these tumors do arise in structures other than the alimentary tract like omentum, mesentery, retroperitoneum, etc., of varying malignant potential and are known as extra-gastrointestinal stromal tumors (eGISTs). This is a case report of a 70-year-old female with multicentric malignant eGISTs arising in the mesentery of ileum. On laparotomy, a large mass of 20 × 15 cm was found in the small bowel mesentery without involvement of the adjacent ileum, with multiple other small nodules resembling lymph nodes, present adjacent to it. Histopathological study of the excised lump, confirmed the mass to be malignant eGIST without involvement of the adjacent ileum, with cluster differentiation (CD)117 positive and of high-risk stratification. The mesenteric nodule was confirmed on histopathology to be malignant eGIST, similar to that of that of the primary, without any lymphoid tissue. Adjuvant imatinib mesylate treatment was started immediately postoperation with the patient doing well at 1 year of follow-up. We report this case, due to the rare occurrence of multifocal malignant eGISTS of small bowel mesentery, which is yet to be reported. The existing literature is unclear regarding the clinicopathology and management of multifocal malignant stromal tumors of the mesentery.

Inadvertent detection of massive Enterobius vermicularis infection in an asymptomatic adult with rectal blowout following barotrauma

Enterobius vermicularis (pin worm) is a common intestinal parasite infection which usually affects children and rarely causes significant illness. However, of the few reports of extra-intestinal E. vermicularis infection reported in the literature, patients can have significant morbidity and mortality, thus stressing the need for appropriate management of pin worm infection. We report a case of massive E. vermicularis infection in a 20-year-old male which was inadvertently discovered during an emergency abdominal surgery. The case emphasizes the need to perform routine ova-parasite screening at periodic intervals to detect intestinal parasitic infections, to promote adequate practices to improve sanitation facilities and to direct appropriate therapeutic measures to eliminate the worm burden in case of infections.

Melioidosis in Odisha: A clinico-microbiological and epidemiological description of culture-confirmed cases over a 2-year period.

Melioidosis is an emerging infectious disease in India mostly reported from South-western coastal Karnataka and North-eastern Tamil Nadu. We speculate the existence of another major hidden focus in Odisha, one of the eastern coastal states. The clinico-epidemiological features of 47 culture-confirmed melioidosis at a tertiary care teaching hospital over a period of 2 years are reported. Septicaemia was the most common clinical presentation. Diabetes mellitus (DM) was present in 72.3% of our cases. The geo-climatic conditions of Odisha and other coastal states of India and the rise in the incidence of DM demand a nationwide surveillance of melioidosis and creation of melioidosis registry.

Experimental models of pancreatic cancer desmoplasia.

Desmoplasia is a fibro-inflammatory process and a well-established feature of pancreatic cancer. A key contributor to pancreatic cancer desmoplasia is the pancreatic stellate cell. Various in vitro and in vivo methods have emerged for the isolation, characterization, and use of pancreatic stellate cells in models of cancer-associated fibrosis. In addition to cell culture models, genetically engineered animal models have been established that spontaneously develop pancreatic cancer with desmoplasia. These animal models are currently being used for the study of pancreatic cancer pathogenesis and for evaluating therapeutics against pancreatic cancer. Here, we review various in vitro and in vivo models that are being used or have the potential to be used to study desmoplasia in pancreatic cancer.

Ancient Schwannoma of Ansa Cervicalis: A Rare Clinical Entity and Review of the Literature.

Ancient schwannoma is an uncommon variant of schwannoma, a benign tumor arising from the nerve sheath. It is reported to arise from any nerves except optic and olfactory. However, only six cases of ancient schwannomas arising from ansa cervicalis nerve have been reported to date in English literature. Proper preoperative evaluation is necessary to rule out other causes of neck mass such as thyroid lesions, lymphadenopathy, and carotid body tumor. We report a case of ancient schwannoma arising from the ansa cervicalis nerve. The origin of the lesion from ansa cervicalis was confirmed by intraoperative finding. Postoperative histopathological examination revealed degenerative changes including pleomorphism, cellular atypia, large nuclei with prominent nucleoli, and paucity of mitotic figures. Periphery of the mass showed nuclear palisading with characteristic verocay bodies. Immunohistochemical evaluation for S-100 showed diffuse positivity of the tumor cells, thereby confirming the diagnosis of schwannoma. We consider that schwannoma of cervical region can have origin from any nerve and should try to identify the origin pre- and intraoperatively. The postoperative complications depend on the nerve of origin and the precision of the surgery performed.

Sternalis Muscle: An Unexpected Finding during Mastectomy.

Sternalis muscle also called rectus sternalis, rectus thoracis, or episternalis is an anomalous muscle of the anterior chest wall with unknown anatomical function. It is regularly observed in lower animal but infrequently in humans. Presence of this muscle can create confusion with tumours of the anterior chest wall during routine mammography. Although less is known about its origin and innervations, knowledge about this muscle can have many clinical implications. A case of unilateral sternalis muscle detected during mastectomy, in a female with carcinoma of the right breast, is being reported with a brief review of the literature and highlighting its clinical significance.

Port site infection in laparoscopic surgery: A review of its management.

Laparoscopic surgery (LS), also termed minimal access surgery, has brought a paradigm shift in the approach to modern surgical care. Early postoperative recovery, less pain, improved aesthesis and early return to work have led to its popularity both amongst surgeons and patients. Its application has progressed from cholecystectomies and appendectomies to various other fields including gastrointestinal surgery, urology, gynecology and oncosurgery. However, LS has its own package of complications. Port site infection (PSI), although infrequent, is one of the bothersome complications which undermine the benefits of minimal invasive surgery. Not only does it add to the morbidity of the patient but also spoils the reputation of the surgeon. Despite the advances in the field of antimicrobial agents, sterilization techniques, surgical techniques, operating room ventilation, PSIs still prevail. The emergence of rapid growing atypical mycobacteria with multidrug resistance, which are the causative organism in most of the cases, has further compounded the problem. PSIs are preventable if appropriate measures are taken preoperatively, intraoperatively and postoperatively. PSIs can often be treated non-surgically, with early identification and appropriate management. Macrolides, quinolones and aminoglycosides antibiotics do show promising activity against the atypical mycobacteria. This review article highlights the clinical burden, presentations and management of PSIs in LS as shared by various authors in the literature. We have given emphasis to atypical mycobacteria, which are emerging as a common etiological agent for PSIs in LS. Although the existing literature lacks consensus regarding PSI management, the complication can be best avoided by strictly abiding by the commandments of sterilization techniques of the laparoscopic instruments with appropriate sterilizing agent.

Acute small intestinal obstruction-an unusual complication of capsule endoscopy.

We report a case of endoscopic capsule impaction causing acute small intestinal obstruction in a patient with Crohn's disease (CD), having obscure gastrointestinal bleeding. A 57-year old female presented with features of acute small bowel obstruction 2 days after capsule endoscopy elsewhere for the evaluation of intermittent bleeding per rectum and iron deficiency anemia. Patient underwent an exploratory laparotomy with right hemicolectomy for the diseased ileocecal region which mimicked malignancy. The capsule was found to be impacted in the strictured lumen of the terminal ileum. Post operative histopathological examination revealed it to be Crohn's disease.

Omental torsion and infarction: a diagnostic dilemma and its laparoscopic management.

Vascular disturbances of the omentum, described variously as acute epiploitis, primary omental torsion, idiopathic segmental infarction, etc., is an infrequent cause of acute abdomen, often mimicking acute appendicitis, cholecystitis, or pancreatitis. In this retrospective article, we share our experiences about the incidence, diagnostic dilemma, and management of patients with omental torsion or infarction and discuss the diagnostic and therapeutic role of laparoscopy. From January 2003 to December 2008, 9 patients (7 men and 2 women; median age, 26 years; range, 5-71) with omental gangrene, including omental torsion and infarction, were operated on at our institute. Of these, 8 patients had a preoperative provisional diagnosis of acute appendicitis and 1 patient of acute calculus cholecystitis. During this period, a total of 1502 patients were diagnosed and operated on laparoscopically for acute appendicitis and acute cholecystitis. Of them, 2 patients were intraoperatively diagnosed to have omental torsion and 7 patients had segmental omental infarction. Incidences of omental gangrene presenting as acute cholecystitis and acute appendicitis were 0.11 and 1.1%, respectively. The suspected preoperative pathology was grossly normal, and histopathology of the same was noncontributory to the cause of acute abdomen. All 9 cases were managed laparoscopically, with the gangrenous omentum excised along with appendectomy in 8 patients and cholecystectomy in 1 patient. In conclusion, inspection of the omentum should be a routine part of exploration in suspected acute appendicitis.

Laparoscopic repair of spigelian hernia: our experience.

BACKGROUND: Spigelian hernias are rare abdominal wall hernias occurring through a defect in the spigelian fascia lateral to the semilunar lines and pose great difficulty in diagnosis due to their location and varied presentations. The treatment of spigelian hernia has evolved from open surgical repair to laparoscopic hernioplasty. In this article, we share our experience of 6 patients with spigelian hernia managed by laparoscopic mesh repair and review the related literature on the topic. METHODS: A retrospective data collection of patients of spigelian hernia operated on between January 2005 and December 2008 was done. The data were evaluated regarding patient presentation, age group, methods of surgical repair, and the outcome of the procedures. The patients had follow-up at 1 week, 6 months, 1 year, and 2 years after the surgery and were evaluated for any recurrence or mesh-related complications. RESULTS: In total, 6 patients of spigelian hernia were operated on in 4 years, from January 2005 to December 2008, with most of them presenting with either a lump or pain. All patients were operated by the transabdominal preperitoneal (TAPP) method with satisfactory results. No recurrences were found in 2 years of follow-up. CONCLUSIONS: Laparoscopic TAPP is an acceptable method of spigelian hernia repair with good results and low recurrence rates. However, long-term follow-up studies are required to assess the late recurrence rate.