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The fascia of the pancreatic head is referred to as the retropancreatic fascia of Treitz, and that of the body and tail of the pancreas is named the retropancreatic fascia of Toldt. However, the spatial relationship between the nerves, fascia, and the distribution of the fascia on the dorsal side of the pancreas remains unclear. Therefore, this study aimed to explore the distribution of these fasciae and elucidate the spatial relationship between the nerves and arteries connecting the retroperitoneal space and the peritoneal organs by studying eight cadavers using macroscopic anatomical examination, wide‐range serial sectioning, and three‐dimensional reconstruction. The fasciae of Treitz and Toldt converge caudally to the root of the superior mesenteric artery (SMA), forming a narrower gap around the roots of the celiac trunk and SMA than in the celiac plexus. The fasciae eventually get closer to each other, and the boundary between them becomes obscured, providing coverage to the anterior surface of the aorta between the SMA and the inferior mesenteric artery. The celiac plexus does not penetrate the fascia but converges before spreading into the pancreas. Similarly, the arteries pass through this gap in the fasciae. Our findings suggest that the retroperitoneal space and peritoneal organs are connected through a narrow no‐fascia area, with the distribution of the fascia relating to nervous and vascular pathways. Our findings reveal that the distribution of the avascular plane may provide a crucial anatomical foundation for abdominal digestive organ surgery by reducing bleeding volume and determining the dissection region. [ABSTRACT FROM AUTHOR]

Simple Summary: The celiac plexus (CP) is a dense network of ganglia and sensitive fibres receiving nociceptive inputs from most abdominal viscera. In human medicine, the CP is a therapeutic target to control pain originating from pancreatic tumours and chronic pancreatitis. The fluoroscopic-guided block and neurolysis of the CP are commonly used in human analgesia but they have not been described in animals. We describe a fluoroscopically guided transcutaneous approach to the CP in swine cadavers to assess the feasibility of the technique in veterinary species. This technique is shown to be feasible, and its application in veterinary subjects suffering abdominal pain should be assessed. Celiac plexus block (CPB) and neurolysis (CPN) are used for pain management in people suffering from abdominal tumours or chronic pancreatitis. The fluoroscopically guided approach common in human medicine has not been described in veterinary settings. The aim of this study was to describe a fluoroscopic approach to the celiac plexus (CP) in fresh pig cadavers. Twelve animals were included in the procedure. Cadavers were positioned in sternal position and, under fluoroscopic guidance, a Chiba needle was inserted parasagittal at 6 cm from the spinal midline at the level of the last thoracic vertebra. From the left side, the needle was directed medio-ventrally with a 45° angle towards the T15 vertebral body; once the vertebral body was contacted, the needle was advanced 1 cm ventrally towards the midline. Iodinated contrast was injected to confirm the location. Following this, 2 mL of dye (China ink) was injected. A laparotomy was performed, and dyed tissue was dissected and prepared for both histochemical and immunohistochemical techniques. In 10 out of 12 samples submitted for histological evaluation, nervous tissue belonging to CP was observed. Fluoroscopy guidance allows for feasible access to the CP in swine cadavers in this study. Further studies are warranted to determine the efficacy of this technique in swine and other veterinary species. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Treatment with corticosteroids can lead to iatrogenic Cushing's syndrome when used for longer intervals and in high doses. Less common administration routes may conceal the exposure, raising the possibility of misdiagnosis and mismanagement. [ABSTRACT FROM AUTHOR]

Depression is a common non-motor symptom in Parkinson's disease (PD) that includes anhedonia and impacts quality of life but is not effectively treated with conventional antidepressants clinically. Vagus nerve stimulation improves treatment-resistant depression in the general population, but research about its antidepressant efficacy in PD is limited. Here, we administered peripheral non-invasive focused ultrasound to hemiparkinsonian ('PD') and non-parkinsonian (sham) rats to mimic vagus nerve stimulation and assessed its antidepressant-like efficacy. Following 6-hydroxydopamine (6-OHDA) lesion, akinesia-like immobility was assessed in the limb-use asymmetry test, and despair- and anhedonic-like behaviors were evaluated in the forced swim test and sucrose preference test, respectively. After, tyrosine hydroxylase immuno-staining was employed to visualize and quantify dopaminergic degeneration in the substantia nigra pars compacta, ventral tegmental area, and striatum. We found that PD rats exhibited akinesia-like immobility and > 90% reduction in tyrosine hydroxylase immuno-staining ipsilateral to the lesioned side. PD rats also demonstrated anhedonic-like behavior in the sucrose preference test compared to sham rats. No 6-OHDA lesion effect on immobility in the forced swim test limited conclusions about the efficacy of ultrasound on despair-like behavior. However, ultrasound improved anhedonic-like behavior in PD rats and this efficacy was sustained through the end of the 1-week recovery period. The greatest number of animals demonstrating increased sucrose preference was in the PD group receiving ultrasound. Our findings here are the first to posit that peripheral non-invasive focused ultrasound to the celiac plexus may improve anhedonia in PD with further investigation needed to reveal its potential for clinical applicability. [ABSTRACT FROM AUTHOR]

Background and Objectives: Patients now live longer thanks to advanced cancer treatments and early cancer identification. In this study, the efficacy of celiac plexus and splanchnic nerve blocks for pain management and quality of life in patients with upper abdominal malignancies at three months is compared. Material and Methods: This prospective, randomized trial compared the efficaciousness of a splanchnic nerve block vs a celiac plexus block for managing excruciating pain, as well as the side effects associated with both neurolytic blocks. This study was carried out at the Department of Anaesthesiology, Kurnool Medical College, Andhra Pradesh, India. From the patients who are part of this investigation, informed permission was acquired. Using data from the pilot study conducted between August 2022 to July 2023, a sample size of 20 was chosen. Results: Out of 60, a total of 20 patients that were evaluated for eligibility, 10 individuals were found to not meet the necessary inclusion criteria, while an additional 10 patients chose not to partake in the study. A total of sixty patients were randomly assigned to groups over the course of the trial. Group SNB consisted of 10 patients, while Group CPB also included 10 patients. In order to elucidate the descriptive data statistics, the frequency analysis method was employed for categorical variables, while the mean and standard deviation were utilized for continuous variables. Conclusion: The statistical data and findings of this study demonstrate that a splanchnic nerve block exhibits clinical comparability to a celiac plexus block, but with statistically significant discrepancies that hold little clinical significance. [ABSTRACT FROM AUTHOR]

Background and Objectives : Endoscopic ultrasound (EUS)-guided celiac plexus block (CPB) for pain relief in chronic pancreatitis (CP) has wide variation in results as reported in the literature. The objective was to find out the efficacy of EUS-CPB in painful CP from our region where phenotype of CP is different from West and to find out factors favoring response to EUS-CPB. Methods and Results : Patients with known CP who underwent EUS-CPB were assessed for response to CPB. Response to EUS-CPB was recorded as more than 50% reduction in visual analogue scale (VAS) score for pain severity at 1 week, 4 weeks, 12 weeks and 24 weeks after procedure. Factors between responders and nonresponders were analyzed. Among 29 patients who underwent EUS-CPB during the study period, response was seen in 72.4% patients after the procedure. The mean time to response to EUS-CPB was 1.22 (± 0.43) days. Mean duration of response was 8 months (± 4.73). Short duration of painful CP (≤2 years) was seen in 15 patients (51.72%) and long duration (>2 years) was seen in 14 (48.27%). Among responders (21/29), those patients who had short duration of disease had significantly lower median VAS score at 12 weeks, (1 versus 3, p- value= 0.026) and at 24 weeks, (1.5 versus 2.5, p -value= 0.049), as compared to those with longer duration of disease. Overall, 83.3% males responded as compared to 54.54% females (p = 0.04). Significant proportion of subjects who responded either stopped or used analgesics occasionally (p < 0.0001). There was no statistically significant difference in response to EUS-CPB with respect to age, prior history of endoscopic retrograde cholangiopancreatography (ERCP), etiology of CP, prior history of surgery, or whether only EUS-CBP was done (p > 0.05 for all). Conclusion : EUS-CPB can be effective when used in select group of painful CP patient who are not immediate candidates for surgery especially in early course of disease. It can be offered to patients with persistent pain despite optimum medical therapy. When effective, it can reduce need for analgesic medication at least in short to medium term. [ABSTRACT FROM AUTHOR]

The Journal of Digestive Endoscopy published a variety of articles in 2023. Some notable findings include the effectiveness of endoscopic ultrasound-guided celiac plexus block for relieving pain in patients with chronic pancreatitis, the importance of patient education to prevent pill esophagitis in developing countries, and the use of rotational thromboelastometry to reduce fresh frozen plasma requirement in patients undergoing therapeutic endoscopic procedures. Other articles discussed topics such as endoscopic biliary drainage, capsule endoscopy, and the management of various gastrointestinal conditions. The journal also featured endoscopy images and case reports, as well as review articles on topics such as endo-hepatology and the impact of artificial intelligence on colorectal polyp detection. The journal aims to continue publishing high-quality articles and increasing its citations in the future. [Extracted from the article]

The concept of Chakras, or Force Centers, is central to Lok Purusha Samya's theory of the infinite universe. These centers are considered loci of life energy or Prana, and are linked to the cycle, circle, and wheel within all humans. The Vedas, particularly the Yoga Upanishad, have significant references to Chakras, which are considered vast pools of energy in human bodies. According to Ayurveda, Chakras are psychic centers present in the subtle body, acting as a bridge between physical existence and the limitless potential of pure consciousness. The subtle body contains energy channels called Nadis, which carry Prana, which flows through these channels and collects in Chakras. Shatchakra Nirupana is a system of six Chakras in the subtle human body, including Muladhara, Swadhisthana, Manipura, Anahat, Vishuddha, and Ajna Chakra. These Chakras are located at regular intervals in various portions of the spinal cord, with the Sahasrara Chakra being the most important. Sthana of Muladhara Chakra and Swadhishthana Chakra is Ling and Gud which can be correlate with inferior hypogastric and sacral plexus. Sthana of Manipura Chakra is Nabhi and is represented by solar plexus. Hrudiya is the Sthana of Anahat Chakra and it is represented by cardiac plexus. Sthana of Visuddha Chakra is Kantha and is represented by cervical plexus. Sthana of Ajna chakra is between eyebrow and it is Avyakta (union of Prakriti and Purush) hence not related to any plexus. These are directly related to physiological as well as physic centers so it is very necessary to explore this yogic knowledge for our physical, mental and spiritual well-being.. [ABSTRACT FROM AUTHOR]

Background: Pancreatic cancer is a devastating disease with less than 5% 5-year survival. Inoperable patients often present with pain. Randomized controlled trial have shown that endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) improves pain control. It is usually performed by injecting bupivacaine followed by absolute alcohol around the celiac axis. Study design: Single center, randomized, double blind controlled trial of EUS-CPN with and without bupivacaine in patients with inoperable malignancy (pancreatic or other) involving the celiac plexus. The study was approved by research ethics board with approval number of 2022-9969, 21.151 and registered on ClinicalTrials.gov (NCT04951804). Discussion: We hypothesize that bupivacaine is superfluous and may actually reduce pain control by diluting the neurolytic effect of alcohol. Bupivacaine is also potentially dangerous in that it may produce serious adverse events such as arrythmias and cardiac arrest if inadvertently injected intravascularly. Conclusion: This randomized trial is designed to assess whether bupivacaine is of any value during EUS-CPN. [ABSTRACT FROM AUTHOR]

Background: Inflammation is a fundamental biological response to injury and infection, which if unregulated can contribute to the pathophysiology of many diseases. The vagus nerve, which primarily originates from the dorsal motor nucleus (DMN), plays an important role in rapidly dampening inflammation by regulating splenic function. However, direct vagal innervation of the spleen, which houses the majority of immune and inflammatory cells, has not been established. As an alternative to direct innervation, an anti-inflammatory reflex pathway has been proposed which involves the vagus nerve, the sympathetic celiac ganglion, and the neurotransmitter norepinephrine. Although sympathetic regulation of inflammation has been shown, the interaction of the vagus nerve and the celiac ganglia requires a unique interaction of parasympathetic and sympathetic inputs, making this putative mechanism of brain–spleen interaction controversial. Body: As neuropeptides can be expressed at relatively high levels in neurons, we reasoned that DMN neuropeptide immunoreactivity could be used to determine their target innervation. Employing immunohistochemistry, subdiaphragmatic vagotomy, viral tract tracing, CRISPR-mediated knock-down, and functional assays, we show that cocaine and amphetamine-regulated transcript (CART) peptide-expressing projection neurons in the caudal DMN directly innervate the spleen. In response to lipopolysaccharide (LPS) stimulation, CART acts to reduce inflammation, an effect that can be augmented by intrasplenic administration of a synthetic CART peptide. These in vivo effects could be recapitulated in cultured splenocytes, suggesting that these cells express the as yet unidentified CART receptor(s). Conclusion: Our results provide evidence for direct connections between the caudal DMN and spleen. In addition to acetylcholine, these neurons express the neuropeptide CART that, once released, acts to suppress inflammation by acting directly upon splenocytes. [ABSTRACT FROM AUTHOR]

Communication between the ovaries and the central nervous system occurs by peripheral innervation through the celiac plexus, superior ovarian nerve, and ovarian plexus nerve. The vagus nerve is involved in regulating the ovaries, but the neuroanatomical pathway that links them is not clear. Adult female rats were used for gross anatomy, acetylcholinesterase histochemistry, and the immunofluorescence analysis of tyrosine hydroxylase (TH), choline acetyltransferase (ChAT), and tryptophan hydroxylase 2 (TPH). The results obtained indicate that the right vagus nerve (RVN) travels parallel and caudal to the esophagus, where three nerve branches were identified. Also, a right vagal plexus (RVP) formed by microganglia was described, establishing communication with the celiac plexus, and was mainly reactive to tyrosine hydroxylase (TH); some serotoninergic and cholinergic neurons were also found. The left vagus nerve (LVN) travels over the esophagus, bifurcates before its insertion into the stomach and enters the RCG. This neuroanatomical and biochemical description of the RVN and LVN in the rat suggests the RVP is formed by presynaptic catecholaminergic terminals and cholinergic neurons. This information could support detailed studies of communication between the vagus nerve and the ovaries and identify the type of neural signaling involved in abdominal control of the vagus nerve. [ABSTRACT FROM AUTHOR]

The aberrant arteries of the lung are very rare abnormalities. It is included in the type 1 sequestration group when it is a single finding without other sequestration features. Sequestrations account for <1% of all lung malformations. Type 1 is the least common form in this group. In 75% of these cases, the aberrant artery (AA) originates from the thoracic aorta. AA originating from the celiac plexus is very rare. Moreover, even if it originates from an abdominal vascular, AA is extended left lower lobe of the lung or the right middle lobe. Our case is atypical with its azygoesophageal recess (AOR) localization. The AOR is a special region that forms the mediobasal segment of the right lung. After the pandemic, this region has been expressed as one of the areas where COVID-19 infection shows affinity. The reason for this condition has not been definitively clarified yet. Therefore, the anatomical details of this segment need to be more probed. Furthermore, the radiological multidetector computed tomography (MDCT) appearance of our case is in the differential diagnosis, with Scimitar syndrome and, as far as we know, this differential diagnosis detail has not been mentioned so far. MDCT plays an important role in the diagnosis and planning of definitive treatment by determining the origin and course of the AA. Definitive treatment may be surgery (lobectomy or segmentectomy) or endovascular. The case of a 62-year-old patient with a lung AA is presented accompanied by radiological and clinical findings. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical efficacy of celiac plexus block (CPB) combined with 125I seeds implantation (ISI) for refractory epigastric pain from abdominal malignancies. Methods: The data of 81 patients with refractory epigastric pain [visual analog scale (VAS) score ≥ 4] from abdominal malignancies were collected in this retrospective case–control study. Group A (n = 40) was treated with CPB alone, while Group B (n = 41) underwent CPB combined with ISI. The primary study endpoints were the VAS score, quality of life (QoL), and local tumor control (LTC) rate. The secondary endpoints were complications, progression-free survival (PFS), and overall survival (OS). Results: The VAS scores at week 2 (T2), week 4 (T4), week 8 (T8), and week 12 (T12) in both groups were significantly lower compared with the pretreatment values (all P < 0.01). VAS scores in Group B showed a sustained decrease, especially for "mild pain" and "moderate pain," while the VAS scores in Group A rebounded at T8 and T12 (both P < 0.01). The QoL in Group B improved significantly from T4 until T12, which better than that at T12 in Group A (all P < 0.01). The LTC rates at T8 were 35.0% and 92.7% in Groups A and B, respectively, with a significant difference (P < 0.01). Group B had a slightly lower complication rate and a slightly longer median PFS/OS than group A, but neither was statistically different (P = 0.09 and P = 0.99, respectively). Conclusion: CPB combined with ISI performs more sustained pain relief (up to 12 weeks) compared to CPB alone, and ultimately improves the patients' QoL. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Persistent hypotension is a rare complication of celiac plexus neurolysis. It is important to know what are the main and rare complications and how to treat these in patients who undergo CPN. Celiac plexus neurolysis is an effective treatment for visceral abdominal pain in oncological patients. Although it rarely has complications, some side effects may occur. A patient with visceral abdominal pain who developed long‐lasting orthostatic hypotension and was treated with the use of corticosteroids after a neurolytic celiac plexus block for intractable pain. We describe a rare complication and its treatment and we emphasize the importance of having a guide for the management and treatment of rare complications. We also suggest that every patient be informed about complications, from the most common to the rarest. [ABSTRACT FROM AUTHOR]

Introduction: The celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. At our affiliated institution, fluoroscopy-guided splanchnic nerve block with a single needle via the transintervertebral disc approach was the first choice of treatment. The short-term efficacy of this technique has been reported, but the long-term efficacy is not clear. In the present study, we investigated the long-term analgesic efficacy of this technique. Methods: This multicenter, retrospective, observational study reviewed the medical records of patients who underwent neurolytic splanchnic nerve block (NSNB) via the transintervertebral disc approach for intractable cancer pain at five tertiary hospitals in Japan from April 2005 to October 2020. The primary outcome was the long-term analgesic efficacy of a one-time NSNB via the transintervertebral disc approach. Results: In total, 76 patients were included in the analysis. The median lowest numerical rating scale (NRS) score was 1 within 14 days. At 1, 2, 3, and 6 months after the nerve block, the median NRS score was also ≤ 2, while the median equivalent oral morphine dose did not show any clinically noticeable increase at those times. Conclusion: The long-term analgesic efficacy of NSNB via the transintervertebral disc approach in patients with intractable cancer pain has been demonstrated. Plain Language Summary: The celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. The celiac plexus nerve block relieves intractable cancer pain arising from the pancreas or other organs in close proximity, and the splanchnic nerve block is considered clinically equivalent to the celiac plexus block for analgesia. At our affiliated institution, fluoroscopy-guided neurolytic splanchnic nerve block with a single needle via the transintervertebral disc approach is the first choice of treatment because it is technically simpler and less invasive than other approaches. While the short-term efficacy of this technique is known, its long-term efficacy remains unclear. Thus, this multicenter, retrospective, observational study aimed to investigate the long-term analgesic efficacy of a neurolytic splanchnic nerve block via the transintervertebral disc approach. The medical records of patients in whom intractable cancer pain was managed using this technique at five tertiary hospitals in Japan were analyzed. The primary outcome was the long-term analgesic efficacy of a one-time neurolytic splanchnic nerve block via the transintervertebral disc approach. The median lowest numerical rating scale score was 1 within 14 days. At 1, 2, 3, and 6 months after the nerve block, the median numerical rating scale score was also ≤ 2, while the median equivalent oral morphine dose did not show any clinically noticeable increase at those times. This technique may reduce opioid dose and associated side effects compared with long-term conventional pharmacotherapy alone. [ABSTRACT FROM AUTHOR]

Considering the prioritization of life-threatening injuries in trauma care, secondary dysfunctions such as ventilator-induced diaphragmatic dysfunction (VIDD) are often overlooked. VIDD is an entity induced by muscle inactivity during invasive mechanical ventilation, associated with a profound loss of diaphragm muscle mass. In order to assess the incidence of VIDD in polytrauma patients, we performed an observational, retrospective, longitudinal study that included 24 polytraumatized patients. All included patients were mechanically ventilated for at least 48 h and underwent two chest CT scans during their ICU stay. Diaphragmatic thickness was measured by two independent radiologists on coronal and axial images at the level of celiac plexus. The thickness of the diaphragm was significantly decreased on both the left and right sides (left side: −0.82 mm axial p = 0.034; −0.79 mm coronal p = 0.05; right side: −0.94 mm axial p = 0.016; −0.91 coronal p = 0.013). In addition, we obtained a positive correlation between the number of days of mechanical ventilation and the difference between the two measurements of the diaphragm thickness on both sides (r =0.5; p = 0.02). There was no statistically significant correlation between the body mass indexes on admission, the use of vitamin C or N-acetyl cysteine, and the differences in diaphragmatic thickness. [ABSTRACT FROM AUTHOR]

1. Participants will familiarize with the available evidence for different opioid rotation strategies when converting between buprenorphine and other opioids. 2. Using a case-based approach, participants will review and self-report the ability to use a conservative strategy for rotation from buprenorphine sublingual to transdermal fentanyl. Buprenorphine may be insufficient for treatment of cancer pain, necessitating opioid rotation. Due to long half-life and high MOR binding affinity, transitions from buprenorphine to other opioids can be complex. Our case study illustrates that published buprenorphine conversions may contribute to potentially harmful dose over-estimation, and we favor a more conservative approach with close interval patient follow up. Buprenorphine is becoming more widely accepted for treating cancer-related pain, however, it may be insufficient, necessitating opioid rotation. Due to long half-life and higher MOR binding affinity, transitions from buprenorphine to other opioids can be complex. Use of equianalgesic conversions has been discouraged due to variation, thus buprenorphine transitions are fraught with uncertainty. A 55 y.o. male with pancreatic cancer and OUD in remission on stable dose of buprenorphine/naloxone SL 8mg daily was referred to clinic for pain. Initially, buprenorphine was increased to 16mg in four divided daily doses, with subsequent addition of oral hydromorphone up to 16mg q3h PRN. Despite celiac plexus neurolysis, the patient's pain continued to increase, and he required transition to transdermal fentanyl (TDF). A stop-start method was used wherein the TDF patch was placed simultaneously with last buprenorphine dose. Two methods were used to estimate starting TDF dosage. First, buprenorphine was converted to TDF using commonly cited TDF:TD buprenorphine conversions 1:1.1 and 1:1.4, along with accounting for poor buprenorphine SL bioavailability 25% (TDF 150-225mcg). Second, total daily hydromorphone use was converted to TDF with further 50% reduction as a precaution (TDF 37mcg). Ultimately, 37mcg was initiated and hydromorphone PRN was continued, assuming buprenorphine would compete with full agonist opioids given high MOR affinity for first 5-7 days, and full agonists would contribute to greater analgesia over time. The patient initially reported uncontrolled pain, requiring a rapid up-titration over six days to TDF 125mcg, at which time his pain was well managed. The patient remained with good pain control and no return to illicit opioids. Given high degree of variability in patient response to buprenorphine and equianalgesic conversions, we favor a conservative approach when transitioning buprenorphine to other opioids with close patient follow-up. Larger case studies will be beneficial in determining best practices for buprenorphine transitions. Management of Medical Interventions / Pharmacotherapeutics / Pharmacopalliation [ABSTRACT FROM AUTHOR]

Background and objective: Chronic pancreatitis is a chronic, fibro-inflammatory condition that damages the pancreas' structural integrity permanently and impairs exocrine and endocrine function. Alcohol is a major part in the multifactorial pathogenesis. Pain in the form of recurrent attacks of pancreatitis or constant and disabling pain is usually the main symptom. Pain management is mainly empirical and involves treatment with potential potent analgesics, and duct drainage by endoscopic or surgical means. Methods: An observational study was conducted at Dr. D.Y. Patil Medical College for a period of two years, from 2020 to 2022. Cases of chronic pancreatitis were chosen for the study after taking informed consent of the patients concerned. This study aims at achieving comprehensive pain management, and seeks to assess the response to different modalities of treatment. Accordingly, a total of 36 patients were studied by commencing a medical line of management, and their responses were documented using the visual analog scale (VAS) on Day 1, Day 3, and Day 5. Pain medications were stepped up in unresponsive cases based on the World Health Organization (WHO) pain relief ladder. Celiac plexus block and surgical intervention (lateral pancreaticojejunostomy) were conducted where the pain could not be subsided by using the medical line of management. Results: Out of 36 cases with chronic pancreatitis, a majority of the cases had moderate pain (VAS score 4-7) at the time of admission, whereas severe pain (VAS > 7) was reported in 11.1% of the cases. Medical management was commenced in all cases by administering a paracetamol injection (1g IV, 8 hourly); however, pain was relieved in only 25% of the cases. In the remainder of cases, the line of treatment had to be stepped up by using a tramadol injection (1 ampule in 100ml NS IV, 8 hourly) in 61.1% (22 out of 27) of the cases, and by using a morphine injection (30mg IV, 8 hourly) in 13.9% (five) of the cases. Furthermore, celiac plexus block was required for managing pain in a total of 9 cases, and recurrence of pain after celiac plexus block was observed in 55% (5 out of 9 cases); these cases underwent lateral pancreaticojejunostomy. Cases that underwent surgical intervention showed satisfactory results with no recurrence of pain in the follow-up period. Conclusion: A majority of the patients responded to various levels of medical analgesia. Only a few required surgical intervention for pain management. Hence, a multidisciplinary approach is required for adequate management of pain to improve the quality of life. [ABSTRACT FROM AUTHOR]

Background: In the rat, studies have shown that ovary innervation arrives via the superior ovarian nerve (SON) and the ovarian plexus nerve, which originates from the celiac plexus (CP). In the present study, we performed a neuroanatomical technique to investigate the anatomy of the SON between the ovary and the CP. Results: We found that the SON fibers were concentrated on the lateral border of the suprarenal ganglion and projected towards, then inserted into the suspensory ligament. Then, it ran parallel to the long axis of the ligament to reach and innervate the ovaries. At this level, the SON was composed of two coiled nerve fibers, each between 10 and 15 µm in diameter. The SON was linked to three different ganglia: the suprarenal ganglia, the celiac ganglia, and the superior mesenteric ganglion. Conclusions: The postganglionic fibers that project to the ovary via the SON emerge from the suprarenal ganglia. The trajectories on the right and left sides to each ovary are similar. The somas of ipsilateral and contralateral SON neurons are located in the prevertebral ganglia, mostly in the celiac ganglia. [ABSTRACT FROM AUTHOR]

Pancreatic cancer (PC) is a fatal malignancy in the human abdominal cavity that prefers to invade the surrounding nerve/nerve plexus and even the spine, causing devastating and unbearable pain. The limitation of available in vitro models restricts revealing the molecular mechanism of pain and screening pain-relieving strategies to improve the quality of life of end-stage PC patients. Here, we report a PC nerve invasion model that merged human brain organoids (hBrO) with mouse PC organoids (mPCO). After merging hBrOs with mPCOs, we monitored the structural crosstalk, growth patterns, and mutual interaction dynamics of hBrO with mPCOs for 7 days. After 7 days, we also analyzed the pathophysiological statuses, including proliferation, apoptosis and inflammation. The results showed that mPCOs tend to approximate and intrude into the hBrOs, merge entirely into the hBrOs, and induce the retraction/shrinking of neuronal projections that protrude from the margin of the hBrOs. The approximating of mPCOs to hBrOs accelerated the proliferation of neuronal progenitor cells, intensified the apoptosis of neurons in the hBrOs, and increased the expression of inflammatory molecules in hBrOs, including NLRP3, IL-8, and IL-1β. Our system pathophysiologically replicated the nerve invasions in mouse GEMM (genetically engineered mouse model) primary and human PCs and might have the potential to be applied to reveal the molecular mechanism of nerve invasion and screen therapeutic strategies in PCs. [ABSTRACT FROM AUTHOR]

Background/Aims: Endoscopic ultrasound (EUS) has become an essential diagnostic and therapeutic tool. EUS was introduced in 2013 in Indonesia and is considered relatively new. This study aimed to describe the current role of interventional EUS at our hospital as a part of the Indonesian tertiary health center experience. Methods: This retrospective study included all patients who underwent interventional EUS (n=94) at our center between January 2015 and December 2020. Patient characteristics, technical success, clinical success, and adverse events associated with each type of interventional EUS procedure were evaluated. Results: Altogether, 94 interventional EUS procedures were performed at our center between 2015 and 2020 including 75 cases of EUS-guided biliary drainage (EUS-BD), 14 cases of EUS-guided pancreatic fluid drainage, and 5 cases of EUS-guided celiac plexus neurolysis. The technical and clinical success rates of EUS-BD were 98.6% and 52%, respectively. The technical success rate was 100% for both EUS-guided pancreatic fluid drainage and EUS-guided celiac plexus neurolysis. The adverse event rates were 10.6% and 7.1% for EUS-BD and EUS-guided pancreatic fluid drainage, respectively. Conclusions: EUS is an effective and safe tool for the treatment of gastrointestinal and biliary diseases. It has a low rate of adverse events, even in developing countries. [ABSTRACT FROM AUTHOR]

Context • Patients with pancreatic cancer (PC) at a late stage often suffer from severe abdominal pain due to the invasion of celiac plexus, and the analgesics they receive often have intolerable side effects. Endoscopic, ultrasoundguided, celiac plexus neurolysis (EUS-guided CPN) can have a good therapeutic effect. Objective • The study intended to evaluate the ability of two nursing cooperation patterns to reduce patients’ pain, decrease operation times, increase operational efficiency, and increase nurses’ satisfaction, for patients with advanced PC and abdominal pain who received EUS-guided CPN. Design • The research team designed a retrospective controlled study. Setting • The study took place at the Shenzhen People’s Hospital of the Second Clinical Medical College of Jinan University in Shenzhen, China, and at the Changhai Hospital of the Second Military Medical University in Shanghai, China. Participants • Participants were 40 patients with advanced PC who received EUS-guided CPN at one of the two hospitals between January 2019 and January 2020. Intervention • Twenty participants at Changhai Hospital received the traditional nursing cooperation pattern and became the control group, and 20 participants at the Shenzhen People’s Hospital received the new nursing cooperation pattern and became the intervention group. Outcome Measures • The study measured clinical data, nursing measures, diagnostic significance, and key points for the two patterns as well as compared the effects of the new nursing cooperation method to that of traditional nursing. If the measurement data met the requirements for normality, the team used the two independent sample t-test for the intergroup comparisons. If normality wasn’t satisfied, the team used medians and interquartile ranges (IQRs) for expression and the rank sum test for the intergroup comparisons. Counting data were expressed using the constituent ratio, and team used the chi-square test for comparisons between groups. P < .05 was considered to be statistically significant. Results • The operations were successful, and no complications occurred. No significant difference existed in the pain scores between the control group and the intervention group (P>.05), while a significant difference occurred in the nurses’ operation times and satisfaction. Not only were the scores for operation times for the control group (97) and the intervention group (59) significantly different, but also the nurses’ satisfaction was significantly higher for the intervention group postintervention, at 83.35 ± 5.25, than for the control group, at 62.25 ± 8.18 (P < .001). Such a new nursing cooperation method could assist in patient’s rehabilitation and increase nurses’ satisfaction. Conclusions • The new nursing cooperation method for patients with advanced PC and abdominal pain undergoing EUS-guided CPN can reduce operation time and improve nurses’ satisfaction. [ABSTRACT FROM AUTHOR]

Background Perforators are typically found in rows in the deep inferior epigastric perforator (DIEP) flap. As methods to assess flap perfusion continue to improve, surgeons may be more likely to select perforators traditionally avoided. The purpose of this article is to describe clinical outcomes based on row and number of perforators to reevaluate flap and abdominal donor site morbidity. Methods A retrospective analysis was performed on patients who underwent breast reconstruction with DIEP flaps by four microsurgeons from 2013 to 2020. The row and number of perforators were determined from operative reports. Chi-square and t -test or nonparametric Fisher's exact test and Wilcoxon two-sample test were used for discrete and continuous variable, respectively, as applicable. Logistic regression was used for multivariable analyses. Results Of 628 flaps, 305 were medial row (58.7%), 159 were lateral row (30.6%), and 55 had both rows (10.6%). Partial flap loss was higher in both rows (p = 0.003). Fat necrosis was higher with medial (p = 0.03) and both rows (p = 0.01) when compared with lateral using multivariable analysis. Hernia or bulge was higher in lateral row flaps (lateral: 8/157, 5.1%; medial, 5/299, 1.7%; both, 0/55; p = 0.05); however, mesh was more commonly used in both row flaps (p = 0.05). There was no difference in fat necrosis or abdominal morbidity between single and multiple perforators. Conclusion There was no difference in fat necrosis based on the number or row of perforators. The lateral row provides adequate perfusion but may be associated with an elevated risk of hernia or bulge. Patients may benefit from mesh, especially when both rows are dissected. [ABSTRACT FROM AUTHOR]

Background: Microglia regulate the response to injury and disease in the brain and spinal cord. In white matter diseases microglia may cause demyelination. However, how microglia respond and regulate demyelination is not fully understood. Methods: To understand how microglia respond during demyelination, we fed mice cuprizone—a potent demyelinating agent—and assessed the dynamics of genetically fate-mapped microglia. We then used single-cell RNA sequencing to identify and track the microglial subpopulations that arise during demyelination. To understand how microglia contribute to the clearance of dead oligodendrocytes, we ablated microglia starting at the peak of cuprizone-induced cell death and used the viability dye acridine orange to monitor apoptotic and lytic cell morphologies after microglial ablation. Lastly, we treated serum-free primary microglial cultures to model distinct aspects of cuprizone-induced demyelination and assessed the response. Results: The cuprizone diet generated a robust microglial response by week 4 of the diet. Single-cell RNA sequencing at this time point revealed the presence of several cuprizone-associated microglia (CAM) clusters. These clusters expressed a transcriptomic signature indicative of cytokine regulation and reactive oxygen species production with altered lysosomal and metabolic changes consistent with ongoing phagocytosis. Using acridine orange to monitor apoptotic and lytic cell death after microglial ablation, we found that microglia preferentially phagocytose lytic carcasses. In culture, microglia exposed to lytic carcasses partially recapitulated the CAM state, suggesting that phagocytosis contributes to this distinct microglial state during cuprizone demyelination. Conclusions: Microglia serve multiple roles during demyelination, yet their transcriptomic state resembles other neurodegenerative conditions. The phagocytosis of cellular debris is likely a universal cause for a common neurodegenerative microglial state. [ABSTRACT FROM AUTHOR]

Introduction: Patients with chronic pancreatitis (CP) often require opioids for pain control. The goal of our study was to characterize opioid use in patients with CP in a real-life practice using a state-mandated online monitoring program and to assess outcomes compared to CP patients without opioid dependency. Methods: CP patients seen in our Pancreas Center from 2016 to 2021 were divided into two groups—with and without chronic opioid use. Details of opioids and other controlled prescriptions were obtained by review of the Massachusetts Prescription Awareness Tool (MassPat). Results: Of the 442 CP outpatients, 216 used chronic opioids. Patients with opioid use had significantly more recurrent acute pancreatitis (76.6% vs. 52.7%), concurrent alcohol use (11.2% vs. 5.8%), tobacco use (37.8% vs. 19.7%), anxiety (22.4% vs. 16.6%), depression (43.5% vs. 23.5%) and daily pain (59.8% vs. 24.8%) (p < 0.001). They also concurrently used more benzodiazepines (43.7% vs. 12.4%), gabapentinoids (66.4% vs. 31.1%) and medical marijuana (14.9% vs. 4.19%) (p < 0.001). They had more celiac plexus blocks (22.0% vs. 6.67%), surgery (18.3% vs. 8.89%) and more hospitalizations for CP flares (3.6 vs. 1.0 visits) (p < 0.001). Less than 13% patients received opioids by means of ED visits; 81.7% patients received their prescriptions from one facility and 75% received them at regular intervals. Conclusion: Opioid-dependent CP patients exhibit polypharmacy and have worse outcomes with higher resource utilization. The state-monitoring program ensures that the majority of patients receive opioids from a single facility, thereby minimizing misuse. [ABSTRACT FROM AUTHOR]

Introduction: Celiac plexus block is effective for treating intractable cancer pain and has been the focus of many studies. Several guiding techniques such as fluoroscopy, computed tomography, and endoscopy have been devised, and the target of the block has varied in previous studies as both the celiac plexus and splanchnic nerve, which is the main origin of the celiac plexus, have been targeted. At our affiliated institution, fluoroscopy-guided splanchnic nerve block with a single needle via transintervertebral disc approach is the first choice. However, there have been few reports on the use of this technique. This study investigated the efficacy and safety of this technique. Methods: This multicenter retrospective observational study reviewed the medical records of patients who underwent neurolytic splanchnic nerve block (NSNB) via transintervertebral disc approach for intractable cancer pain at five tertiary hospitals in Japan from April 2005 to October 2020. The primary outcome was the clinical success ratio of NSNB, and the secondary outcome was the incidence ratio of NSNB-related adverse events. Results: In total, 103 patients were included in the analysis. Of these, 77 patients met the definition of clinical success, with a ratio of 74.8%. The incidence ratio of NSNB-related adverse events was 40.8% (hypotension, 21.4%; alcohol intoxication, 13.6%; diarrhea, 11.7%; and vascular puncture, 3.9%; duplicates were present). All adverse events improved with observation and symptomatic treatment only. No patient had infection or serious adverse events such as organ or nerve damage. Conclusions: The clinical success ratio of this technique was 74.8%. Although the incidence of adverse events was 40.8%, all events were mild and no serious adverse events were observed. The findings demonstrate the efficacy and safety of our NSNB in patients with intractable cancer pain. Plain Language Summary: In patients with intractable pain from abdominal cancer, fluoroscopy-guided neurolytic splanchnic nerve block via transintervertebral disc approach is an effective and safe procedure. It can be completed with a single needle puncture, and is anatomically less likely to cause organ or nerve damage compared with other approaches. The analgesia produced by this technique, along with conventional pharmacotherapy for cancer pain, may reduce opioid dose and its side effects and improve patients' quality of life. [ABSTRACT FROM AUTHOR]

An unidentified cause of functional dyspepsia (FD) is closely associated with medication resistance. Acid suppression is a traditional and preferential method for the treatment of FD, but the efficacy of this treatment varies between epigastric pain syndrome (EPS) and postprandial syndrome (PDS): it is efficient in the former but not much in the latter. Transepithelial electrical resistance (TEER), a surrogate of mucosal barrier function, was measured under pH 3 and pH 5 acidic conditions using duodenal biopsy specimens obtained from the patients with EPS and PDS and asymptomatic healthy controls. The infiltration of inflammatory cells to the duodenal mucosa was accessed by immunohistochemical analysis. The duodenal mucosal TEER in EPS patients was decreased by exposure to the acidic solution compared to that of the controls and the PDS patients. The decrease in TEER of the EPS patients was observed even under pH 5 weak acidic condition and was correlated to degree of the epigastric pain. Moreover, the duodenal mucosa of EPS patients presented an increase in mast cells and plasma cells that expressed Ig-E. Duodenal mucosal vulnerability to acid is likely to develop EPS. [ABSTRACT FROM AUTHOR]

Here, we report that pancreatic cancer-derived extracellular vesicles (EVs) carry adipocyte-targeting integrins and induce lipolysis, constituting the underlying mechanism of cancer-associated cachexia (CAC). GLO:F2H7/01nov22:ctm21089-fig-0003.jpg PHOTO (COLOR): 3 Panc-1 cell-derived extracellular vesicles (EVs) preferably distribute to adipose and lung tissues via ITGB1 and ITGA6. EVs derived from normal cells induce lipolysis only slightly because these EVs are rarely captured by adipocytes. After 4 h, more Panc-1-derived EVs were taken up by EV-treated adipocytes compared with Capan-2 EVs (Figure S3C). [Extracted from the article]

Head and neck cancer etiology and architecture is quite diverse and complex, impeding the prediction whether a patient could respond to a particular cancer immunotherapy or combination treatment. A concomitantly arising caveat is obviously the translation from pre-clinical, cell based in vitro systems as well as syngeneic murine tumor models towards the heterogeneous architecture of the human tumor ecosystems. To bridge this gap, we have established and employed a patient-derived HNSCC (head and neck squamous cell carcinoma) slice culturing system to assess immunomodulatory effects as well as permissivity and oncolytic virus (OV) action. The heterogeneous contexture of the human tumor ecosystem including tumor cells, cancer-associated fibroblasts and immune cells was preserved in our HNSCC slice culturing approach. Importantly, the immune cell compartment remained to be functional and cytotoxic T-cells could be activated by immunostimulatory antibodies. In addition, we uncovered that a high proportion of the patient-derived HNSCC slice cultures were susceptible to the OV VSV-GP. More specifically, VSV-GP infects a broad spectrum of tumor-associated lineages including epithelial and stromal cells and can induce apoptosis. In sum, this human tumor ex vivo platform might complement pre-clinical studies to eventually propel cancer immune-related drug discovery and ease the translation to the clinics. [ABSTRACT FROM AUTHOR]

A non-ampullary duodenal mixed adenoneuroendocrine carcinoma (MANEC), consisting of a conventional adenocarcinoma and a neuroendocrine carcinoma (NEC), is exceedingly rare. Moreover, mismatch repair (MMR) deficient tumors have recently attracted attention. The patient, a 75-year-old woman with epigastric pain and nausea, was found to have a type 2 tumor of the duodenum, which was diagnosed on biopsy as a poorly differentiated carcinoma. A pancreaticoduodenectomy specimen showed a well-defined 50 × 48 mm tumor in the duodenal bulb, which was morphologically composed of glandular, sheet-like, and pleomorphic components. The glandular component was a tubular adenocarcinoma, showing a MUC5AC-positive gastric type. The sheet-like component consisted of homogenous tumor cells, with chromogranin A and synaptophysin diffusely positive, and a Ki-67 index of 72.8%. The pleomorphic component was diverse and prominent atypical tumor cells proliferated, focally positive for chromogranin A, diffusely positive for synaptophysin, and the Ki-67 index was 67.1%. The sheet-like and pleomorphic components were considered NEC, showing aberrant expression of p53, retinoblastoma, and p16. Notably, all three components were deficient in MLH1 and PMS2. We diagnosed a non-ampullary duodenal MANEC with MMR deficiency. This tumor has a unique morphology and immunohistochemical profile, and is valuable for clarifying the tumorigenesis mechanism of a non-ampullary duodenal MANEC. [ABSTRACT FROM AUTHOR]

The guinea pig is the only small animal model for congenital cytomegalovirus (CMV) but requires species-specific guinea pig cytomegalovirus (GPCMV). Infection of epithelial cells and trophoblasts by GPCMV requires the viral glycoprotein pentamer complex (PC) and endocytic entry because of the absence of platelet-derived growth factor receptor alpha (PDGFRA). Endothelial cells represent an important cell type for infection, dissemination in the host, and disease but have been poorly evaluated for GPCMV. Novel endothelial cell lines were established from animal vascular systems, including aorta (EndoC) and placental umbilical cord vein (GPUVEC). Cell lines were characterized for endothelial cell protein markers (PECAM1, vWF, and FLI1) and evaluated for GPCMV infection. Only PC-positive virus was capable of infecting endothelial cells. Individual knockout mutants for unique PC components (GP129, GP131, and GP133) were unable to infect endothelial cells without impacting fibroblast infection. Ectopic expression of PDGFRA in EndoC cells enabled GPCMV(PC2) infection via direct cell entry independent of the PC. Neutralizing antibodies to the essential viral gB glycoprotein were insufficient to prevent endothelial cell infection, which also required antibodies to gH/gL and the PC. Endothelial cell infection was also dependent upon viral tegument pp65 protein (GP83) to counteract the IFI16/cGAS-STING innate immune pathway, similar to epithelial cell infection. GPCMV endothelial cells were lytically (EndoC) or persistently (GPUVEC) infected dependent on tissue origin. The ability to establish a persistent infection in the umbilical cord could potentially enable sustained and more significant infection of the fetus in utero. Overall, results demonstrate the importance of this translationally relevant model for CMV research. [ABSTRACT FROM AUTHOR]

In addition to the poor prognosis, excruciating abdominal pain is a major challenge in pancreatic cancer. Neurotropism appears to be the underlying mechanism leading to neuronal invasion. However, there is a lack of animal models suitable for translationally bridging in vitro findings with clinical trials. We characterized KPC (KrasG12D/+; Trp53R172H/+; P48-Cre) and KPPC (KrasG12D/+; Trp53R172H/R172H; P48-Cre) mice with genetically determined pancreatic ductal adenocarcinoma (PDAC) and compared them with an orthotopic pancreatic cancer mouse model, healthy littermates and human tissue. We analyzed behavioral correlates of cancer-associated pain and well-being, and studied neuronal remodeling and cytokine expression. Histologically, we found similarities between KPC and KPPC tissue with human samples. Compared to healthy littermates, we detect nerve fiber hypertrophy, which was not restricted to a certain fiber type. Interestingly, while KPPC mice showed significantly reduced well-being, KPC mice emerged to be better suited for studying long-lasting cancer pain that emerges over a slow course of tumor progression. To address the neuroinflammatory correlate of loss of well-being, we studied cytokine levels in KPPC mice and observed a significant upregulation of CXCL16, TNFRSF5, CCL24, CXCL1, CCL22, CLL20 and CX2CL1. In summary, we demonstrate that the KPC mouse model is best suited to studying cancer pain, whereas the KPPC model can be employed to study cancer-associated reduction in well-being. [ABSTRACT FROM AUTHOR]

NICIs ESTABLISH A NEW ATHEROSCLEROSIS DISEASE PARADIGM Our recent data in experimental mice and human cardiovascular tissues1,2 have provided information on a series of unexpected mechanistic insights into the pathogenesis of atherosclerosis.3-5 This body of evidence suggests a new disease paradigm of atherosclerosis progression. 35 These approaches could lead to vaccination strategies, antibody (B cell-based) treatment strategies and T cell therapies by engineering T cell receptors that specifically recognise disease-causing peptide sequences in bona fide atherosclerosis-specific autoantigens with the help of CRISPR-CAS9-gene engineered cells. However, since the NS uses the adventitia of all arteries as its main conduit to reach distant targets and indeed all parenchymal cells, we speculated that PNS axons may crosstalk to adventitia immune cells. [Extracted from the article]

Although celiac plexus block (CPB) is a well known technique that has been performed for years, only in the last 30 years controlled studies, demonstrated its efficacy and safety. A historical pathway of literature regarding CPB and a critical analysis may help understand some points which remain still controversial, for a better interpretation of data. [ABSTRACT FROM AUTHOR]

We determined that the Tp53 stain is wild-type and the Smad4 stain is intact in both regions. gl Our identification of a microscopic, intraparenchymal pancreatic cancer metastasis highlights one mechanism for tumour recurrence in the remnant pancreas after apparently curative surgery. Using CODA, a technique for three-dimensional reconstruction of large tissues, Kiemen et al. report observation of a microscopic focus of pancreatic cancer found in the vasculature of grossly normal human pancreas tissue resected adjacent to a large tumour. Gain of tumour protein I Tp53 i is found in approximately 85% of pancreatic cancers, while loss of I Smad4 i is found in approximately 55% of pancreatic cancers.[5] We found that both foci had wild-type labelling for I Tp53 i and intact I Smad4 i expression (Figure 2). [Extracted from the article]

Background: Refractory epigastric/midback pain is associated with locally advanced abdominal malignancies, especially pancreatic cancer. The pain is caused by tumor infiltration of the celiac plexus, a nerve network attached to the abdominal aorta. Contemporary palliative approaches are often inadequate. We hypothesized that ablative radiation targeted to the celiac plexus would alleviate this pain.Methods and Materials: We performed a single-arm prospective clinical trial (ClinicalTrials.gov identifier: NCT02356406). Eligible and evaluable patients had celiac pain of at least 5 out of 10 on the Numerical Rating Scale, completed treatment per protocol, and had at least 1 posttreatment visit. The entire retroperitoneal celiac plexus was irradiated with a single 25-Gy fraction. The primary endpoint was change in the Numerical Rating Scale 3 weeks posttreatment. Toxic effects and pain interference (as measured with the Brief Pain Inventory) were secondary endpoints.Results: For our study, 31 patients signed consent, and, of these, 18 patients were treated and evaluable. Median age was 68 years (range, 51-79); 89% of the patients had pancreatic cancer; the median Eastern Cooperative Oncology Group performance status was 1; and the median interval from initial diagnosis to treatment was 9 months (range, 1-36), and, in this interval, patients received a median of 1 systemic treatment line (range, 0-3). Acute toxicity was limited to grade 1 to 2. Three weeks after treatment, 16 patients (84%) reported decreased celiac pain, with median pain level falling from 6 out of 10 (interquartile range [IQR], 5.0-7.5) at baseline to 3 out of 10 (IQR, 1.0-4.3); six weeks after treatment, the Numerical Rating Scale number fell further to 2.8 out of 10 (IQR, 0-3.3; both P < .005 vs baseline), including 4 patients who reported complete eradication of their celiac pain. Total daily morphine milligram equivalents decreased from 59 pretreatment to 50 at 3 weeks, and from 50 to 45 at 6 weeks. Significant improvement was seen in pain-interference scores.Conclusions: Celiac plexus radiosurgery appears to alleviate cancer-related pain. An international multicenter phase 2 trial is currently accruing. [ABSTRACT FROM AUTHOR]

Endoscopic ultrasound (EUS) gained wide acceptance as the diagnostic and minimally invasive therapeutic approach for intra-luminal and extraluminal gastrointestinal, as well as various non-gastrointestinal lesions. Since its introduction, EUS has undergone substantial technological advances. This multi-centric study is a retrospective analysis of a prospectively maintained database of patients who underwent EUS for the evaluation of lesions located within the gastrointestinal tract and the proximal organs. It aimed to extensively assess in dynamic the dual-center EUS experience over the course of the past 20 years. Hence, we performed a population study and an overall assessment of the EUS procedures. The performance of EUS-FNA/FNB in diagnosing pancreatic neoplasms was evaluated. We also investigated the contribution of associating contrast-enhanced ultrasound imaging (CE-EUS) with EUS-FNA/FNB for differentiating solid pancreatic lesions or cystic pancreatic lesions. A total of 2935 patients undergoing EUS between 2002–2021 were included, out of which 1880 were diagnostic EUS and 1052 EUS-FNA/FNB (80% FNA and 20% FNB). Therapeutic procedures performed included endoscopic transmural drainage of pancreatic fluid collections, celiac plexus block and neurolysis, while diagnostic EUS-like CE-EUS (20%) and real-time elastography (12%) were also conducted. Most complications occurred during the first 7 days after EUS-FNA/FNB or pseudocyst drainage. EUS and the additional tools have high technical success rates and low rates of complications. The EUS methods are safe, cost effective and indispensable for the diagnostic or therapeutic management in gastroenterological everyday practice. [ABSTRACT FROM AUTHOR]

Objectives: This study evaluated the efficacy of endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) in combination with EUS-guided celiac ganglia neurolysis (EUS-CGN) for pancreatic cancer-associated pain. Methods: This multicenter prospective trial was registered in the University Hospital Medical Information Network (UMIN000031228). Fifty-one consecutive patients with pancreatic cancer-associated pain who presented at one of five Japanese referral centers between February 2018 and March 2021 were enrolled. EUS-CGN was added in cases of visible celiac ganglia. The primary endpoint was effectiveness, defined as a decrease in the numerical rating scale (NRS) by ≥ 3 points. NRS data were prospectively acquired at 1 week after the procedure to evaluate its effectiveness and the extent of pain relief. Results: The technical success rates of EUS-CPN and EUS-CGN were 100% and 80.4%, respectively. The overall efficacy rate was 82.4% [90% confidence interval (CI) 71.2–90.5, P < 0.0001]. The complete pain relief rate was 27.4%. The adverse events rate was 15.7%. The average pain relief period was 72 days. The efficacy rate was higher in the EUS-CPN plus EUS-CGN group than in the EUS-CPN alone group. EUS-CPN plus EUS-CGN was superior to EUS-CPN alone for achieving complete pain relief (P = 0.045). EUS-CGN did not improve the average length of the pain relief period. Conclusions: EUS-CPN combined with EUS-CGN is safe, feasible, and effective for pain relief in patients with pancreatic cancer. The patients who received additional EUS-CGN had a better short-term response. Clinical trial number: UMIN000031228. [ABSTRACT FROM AUTHOR]

Structural variations (SVs) are the greatest source of variations in the genome and can lead to oncogenesis. However, the identification and interpretation of SVs in human cancer remain technologically challenging. Here, long‐read sequencing is first employed to depict the signatures of structural variations in carcinogenesis of human pancreatic ductal epithelium. Then widespread reprogramming of the 3D chromatin architecture is revealed by an in situ Hi‐C technique. Integrative analyses indicate that the distribution pattern of SVs among the 3D genome is highly cell‐type specific and the bulk remodeling effects of SVs in the chromatin organization partly depend on intercellular genomic heterogeneity. Meanwhile, contact domains tend to minimize these disrupting effects of SVs within local adjacent genomic regions to maintain overall stability. Notably, complex genomic rearrangements involving two key driver genes CDKN2A and SMAD4 are identified, and their influence on the expression of oncogenes MIR31HG, MYO5B, etc., are further elucidated from both a linear view and 3D perspective. Overall, this work provides a genome‐wide resource and highlights the impact, complexity, and dynamicity of the interplay between structural variations and high‐order chromatin organization, which expands the current understanding of the pathogenesis of SVs in human cancer. [ABSTRACT FROM AUTHOR]

Obesity is a worldwide epidemic. Complication rates after body contouring surgeries in massive weight loss patients were quite high, with seroma development being the second most common complication, reported rates averaging 15%–40%, Methods described to reduce the annoying high rate of seroma did not have a statistically significant difference in reducing seromas. Our aim was to find a universal solution that could be used with any body-contouring surgery to manage seromas. We tried this novel technique initially on thigh lifts. Instead of wading in the jungle of methods aiming at preventing seromas, we contemplated a drainage channel that would continuously drain any fluid accumulation. The idea was borrowed from the hypothesis of Thompson on lymphoedema management. By excising an area of deep fascia overlying the Vastus Medialis muscle, the muscle would be directly exposed to any seroma fluid and would imbibe it as blotting paper. Furthermore, this technique would open new drainage channels between the superficial and deep lymphatics. This technique was tried in 20 patients, with the excision of deep fascia carried only in one limb. The other limb was left as a control. Rates of seroma formation were noted and duration before it dried up. This technique significantly reduced the incidence of detected seromas and the amount of seroma fluid. This technique reduced the incidence of seroma formation, and is recommended for routine use during all thigh lift surgeries. [ABSTRACT FROM AUTHOR]

Les pertes de substances de la racine de la cuisse après exérèse carcinologique des sarcomes peuvent être complexes et compromettre l'arbre vasculaire du membre inférieur. Nous rapportons le cas d'une patiente présentant un sarcome récidivant de la cuisse droite. Après de multiples exérèses, le fémur et l'articulation coxo-fémorale sont exposés. Les vaisseaux fémoraux superficiels et profonds ont été pris dans la pièce d'exérèse. La couverture est réalisée par un lambeau de grand dorsal libre musculocutané, anastomosé aux vaisseaux épigastriques inférieurs profonds controlatéraux. Les vaisseaux épigastriques inférieurs profonds ont une longueur suffisante pour rejoindre l'hémi-abdomen controlatéral après dissection avec un calibre permettant des anastomoses microchirurgicales. Ils peuvent servir de vaisseaux receveurs à un lambeau en couverture de la cuisse controlatérale. Thigh loss cover after carcinologic resection of sarcomas can be complex and compromise the vascular tree of the lower limb. We report a case of a patient with recurrent sarcoma of the right thigh. After multiple resections, the femur and hip joint are exposed. The superficial and deep femoral vessels are taken in the excisional piece. The reconstruction is performed by a free musculocutaneous latissimus dorsi flap, anastomosed to the deep inferior controlateral epigastric vessels. The deep inferior epigastric vessels are of sufficient length to join the contralateral hemiabdomen after dissection with a gauge allowing microsurgical anastomoses. They can serve as recipient vessels for a flap covering the contralateral thigh. [ABSTRACT FROM AUTHOR]

Pancreatic cancer has the poorest prognosis among digestive cancers. During the 1990s, the 5-year survival rate of surgical patients with pancreatic cancer was 14% in Japan. However, survival rates have increased to 40% in the 2020s due to the refinement of surgical procedures and the introduction of perioperative chemotherapy. Several pivotal randomized controlled trials have played an indispensable role to establish each standard treatment strategy. Resectability of pancreatic cancer can be classified into resectable, borderline resectable, and unresectable based on the anatomic configuration, and multidisciplinary treatment strategies for each classification have been revised rapidly. Investigation of superior perioperative adjuvant treatments for resectable and borderline resectable pancreatic cancer and the establishment of optimal conversion surgery for unresectable pancreatic cancer are the progressive subjects. [ABSTRACT FROM AUTHOR]

EUS-guided WON and pancreatic pseudocyst drainage In recent years, the WON concept has been established: EUS-guided drainage has become the first-line treatment. Endoscopic ultrasound (EUS) was first applied clinically in the early 1980s. EUS-guided pancreatic duct drainage (EUS-PD) Regarding EUS-pancreatic duct drainage (PD), it is no exaggeration to say that the report of EUS-guided pancreatography by Koito I et al i .7 in 1995 paved the way for EUS-PD today. In 2012, "EUS-guided transmural drainage" was listed for health insurance coverage in Japan, after which EUS-guided drainage became established for walled-off necrosis (WON) and infectious pancreatic pseudocysts, as well as obstructive jaundice. [Extracted from the article]

EUS-guided pancreatic duct drainage (EUS-PD) Regarding EUS-pancreatic duct drainage (PD), it is no exaggeration to say that the report of EUS-guided pancreatography by Koito I et al i .7 in 1995 paved the way for EUS-PD today. EUS-guided WON and pancreatic pseudocyst drainage In recent years, the WON concept has been established: EUS-guided drainage has become the first-line treatment. Endoscopic ultrasound (EUS) was first applied clinically in the early 1980s. In 2012, "EUS-guided transmural drainage" was listed for health insurance coverage in Japan, after which EUS-guided drainage became established for walled-off necrosis (WON) and infectious pancreatic pseudocysts, as well as obstructive jaundice. [Extracted from the article]

Background: Selectively replicating herpes simplex virus-2 (HSV-2) vector is a promising treatment for cancer therapy. The insertion of multiple transgenes into the viral genome has been performed to improve its oncolytic activity. Methods: Herein, we simultaneously constructed five "armed" oncolytic viruses (OVs), designated oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19. These OVs delete the ICP34.5 and ICP47 genes with the insertion of transgenes into the deleted ICP34.5 locus. The anti-tumor efficacy in vivo was tested in the syngeneic 4T1 and CT26 tumor-bearing mice model. Results: The OVs showed comparable oncolytic capability in vitro. The combination therapy of oHSV2-IL12, -IL15, GM-CSF, -PD1v, and IL7 × CCL19 exhibited the highest tumor inhibition efficacy compared with the treatment of single OV or two OVs combination. Conclusions: The OVs armed with different transgenes combination therapy also named 5-valent oHSV2 (also called cocktail therapy) might be an effective therapeutic strategy for solid tumors. [ABSTRACT FROM AUTHOR]

Background: Celiac disease is an autoimmune enteropathy driven by dietary intake of gluten proteins. Typical histopathologic features are villous flattening, crypt hyperplasia and infiltration of inflammatory cells in the intestinal epithelium and lamina propria. The disease is hallmarked by the gluten-dependent production of autoantibodies targeting the enzyme transglutaminase 2 (TG2). While these antibodies are specific and sensitive diagnostic markers of the disease, a role in the development of the enteropathy has never been established. Methods: We addressed this question by injecting murine antibodies harboring the variable domains of a prototypic celiac anti-TG2 immunoglobulin into TG2-sufficient and TG2-deficient mice evaluating for celiac enteropathy. Results: We found no histopathologic abnormalities nor clinical signs of disease related to the injection of anti-TG2 IgG or IgA. Conclusions: Our findings do not support a direct role for secreted anti-TG2 antibodies in the development of the celiac enteropathy. [ABSTRACT FROM AUTHOR]

Pancreatic carcinoma incidence showed a significant increase in men over the last few years and the prognosis remains poor. Patients are treated with different pharmacological plans with no evidence about gender-specific adverse effects. We aimed to investigate differences in the incidence of chemotherapy side effects in the treatment of pancreatic cancer, to provide insights toward a personalized assistance based in individual needs. The sample population is composed of 207 patients. Regression model highlighted the predictive role of female gender for alopecia, constipation, hand-foot syndrome, and epigastric pain. Also, considering single therapeutic schemes, gender differences have been reported. Moreover, evaluating the effect of age, a general reduced risk of toxicity has been reported in younger patients. To personalize chemotherapy and increase patient survival rate and life quality during the therapy, gender medicine and pharmacology studies are recommended. [ABSTRACT FROM AUTHOR]

Background: Neurolytic celiac plexus block (NCPB) is a typical treatment for severe epigastric cancer pain, but the therapeutic effect is often affected by the variation of local anatomical structures induced by the tumor. Greater and lesser splanchnic nerve neurolysis (SNN) had similar effects to the NCPB, and was recently performed with a paravertebral approach under the image guidance, or with the transdiscal approach under the guidance of computed tomography. This study observed the feasibility and safety of SNN via a transdiscal approach under fluoroscopic guidance. Methods: The follow-up records of 34 patients with epigastric cancer pain who underwent the splanchnic nerve block via the T11-12 transdiscal approach under fluoroscopic guidance were investigated retrospectively. The numerical rating scale (NRS), the patient satisfaction scale (PSS) and quality of life (QOL) of the patient, the dose of morphine consumed, and the occurrence and severity of adverse events were recorded preoperatively and 1 day, 1 week, 1 month, and 2 months after surgery. Results: Compared with the preoperative scores, the NRS scores and daily morphine consumption decreased and the QOL and PSS scores increased at each postoperative time point (P < 0.001). No patients experienced serious complications. Conclusions: SNN via the transdiscal approach under flouroscopic guidance was an effective, safe, and easy operation for epigastric cancer pain, with fewer complications. [ABSTRACT FROM AUTHOR]

Objective: Unusual or unexpected effect of treatment Background: Acute pancreatitis is the leading gastrointestinal cause of hospitalization in the United States. The associated pain, for which opioids are commonly prescribed, can result in complications of respiratory dysfunction secondary to impaired abdominal wall movement. Paravertebral nerve blockade has shown substantial efficacy in treatment of abdominal and thoracic pain, but its utility for pancreatitis pain and role in reducing hospital length of stay and narcotic use has not been well studied. Case Report: A 41-year-old woman with longstanding history of recurrent pancreatitis controlled with celiac plexus blocks and oxycodone was admitted for severe left upper quadrant abdominal pain. The patient was admitted, made NPO, and started on IV morphine. She underwent a left-sided T12-L1 paravertebral single shot injection and catheter placement, and experienced immediate relief. A Marcaine infusion was continued for 3 days and the patient required no additional narcotics while the catheter was in place. On hospital day 6, the catheter was removed and the patient was discharged. Conclusions: Our case illustrates the successful use of continuous thoracic paravertebral nerve blockade in a patient with pancreatitis. This intervention resulted in a significant reduction in narcotic requirements. As the number of hospitalizations and mean cost for acute pancreatitis has increased over the years despite an in-house mortality decrease, targeting cost reduction via length of stay reductions is key. Optimizing pain management in these patients is one way in which we can reduce LOS and thereby cost. We believe paravertebral nerve blockade is a viable analgesic option worth exploring in this patient population. [ABSTRACT FROM AUTHOR]

Background: Prior studies have reported that 40%-90% of the patients with celiac plexus-mediated visceral pain benefit from the neurolytic celiac plexus block (NCPB), but the predictive factors of response to NCPB have not been evaluated extensively. This study aimed to identify the factors associated with the immediate analgesic effectiveness of NCPB in patients with intractable upper abdominal cancer-related pain. Methods: A retrospective review was performed of 513 patients who underwent NCPB for upper abdominal cancer-related pain. Response to the procedure was defined as (1) a decrease of ≥ 50% or ≥ 4 points on the numerical rating scale (NRS) in pain intensity from the baseline without an increase in opioid requirement, or (2) a decrease of ≥ 30% or ≥ 2 points on the NRS from the baseline with simultaneously reduced opioid consumption after NCPB. Logistic regression analysis was performed to determine the factors associated with successful responses to NCPB. Results: Among the 513 patients included in the analysis, 255 (49.8%) and 258 (50.2%) patients were in the non-responder and responder group after NCPB, respectively. Multivariable logistic regression analysis showed that diabetes (odds ratio [OR] = 0.644, P = 0.035), history of upper abdominal surgery (OR = 0.691, P = 0.040), and celiac metastasis (OR = 1.496, P = 0.039) were the independent factors associated with response to NCPB. Conclusions: Celiac plexus metastases, absence of diabetes, and absence of prior upper abdominal surgery may be independently associated with better response to NCPB for upper abdominal cancer-related pain. [ABSTRACT FROM AUTHOR]