Endoscopic ultrasound-guided neurolysis in advanced pancreatic cancer: current status.

Pancreatic cancer has a very poor prognosis with patients often presenting with locally advanced, inoperable or metastatic disease. A significant proportion of patients have visceral pain due to perineural infiltration or coeliac plexus involvement by the tumour. This pain is difficult to control and may become refractory to conventional pain management. Therefore, coeliac plexus neurolysis (CPN) has been proposed to ablate the neuronal transmission pathway of pain permanently. CPN is recommended for those who have uncontrolled pain, are experiencing unacceptable opioid adverse effects or are receiving escalating doses of analgesics. It is not known whether CPN performed at diagnosis as the first-line treatment ('early') would impact short-term and long-term pain control and quality of life. NICE has recommended (2018) a randomised trial comparing early endoscopic ultrasound-guided coeliac plexus neurolysis (EUS-CPN) with on-demand EUS-CPN in pancreatic cancer. In this context, we will review the current evidence on its clinical benefits.

Clinico-pathologic findings in patients with median arcuate ligament syndrome (celiac artery compression syndrome).

Median Arcuate Ligament Syndrome (MALS) is a rare entity characterized by severe post-prandial epigastric pain, nausea, vomiting, and/or weight loss. Symptoms have been attributed to vascular compression (celiac artery compression syndrome, CACS), but it remains controversial whether they could be secondary to neural compression. Literature review identified rare description of pathologic findings in surgery journals. The clinico-pathologic findings of four MALS patients who underwent robotic or laparoscopic surgery in our hospital are described. All our patients were female with a median age of 32.5 (range 25-55 years), and a median BMI of 23.5 kg/m2. They presented with chronic often post-prandial abdominal pain (4/4), nausea (3/4), emesis (2/4), anorexia (1/4), and weight loss (1/4). Two patients had a history of Crohn's disease. At intraoperative exploration, the celiac artery and adjacent nerves and ganglia were encased and partially compressed by fibrotic tissue in each patient. In each case laparoscopic excision of fibrotic tissue, celiac plexus and ligament division and was performed; celiac plexus nerve block was also performed in one patient. After surgical intervention, symptoms improved in three of the patients whose specimens show periganglionic and perineural fibrosis with proliferation of small nerve fibers. Our findings support neurogenic compression as a contributing factor in the development of pain and other MALS symptoms, and favor the use of MALS rather than CACS as diagnostic terminology. To further study the pathogenesis of this unusual syndrome, surgeons should submit all tissues excised during MALS procedures for histopathologic examination.

Non-invasive peripheral focused ultrasound neuromodulation of the celiac plexus ameliorates symptoms in a rat model of inflammatory bowel disease.

NEW FINDINGS: What is the central question of this study? Does peripheral non-invasive focused ultrasound targeted to the celiac plexus improve inflammatory bowel disease? What is the main finding and its importance? Peripheral non-invasive focused ultrasound targeted to the celiac plexus in a rat model of ulcerative colitis improved stool consistency and reduced stool bloodiness, which coincided with a longer and healthier colon than in animals without focused ultrasound treatment. The findings suggest that this novel neuromodulatory technology could serve as a plausible therapeutic approach for improving symptoms of inflammatory bowel disease. ABSTRACT: Individuals suffering from inflammatory bowel disease (IBD) experience significantly diminished quality of life. Here, we aim to stimulate the celiac plexus with non-invasive peripheral focused ultrasound (FUS) to modulate the enteric cholinergic anti-inflammatory pathway. This approach may have clinical utility as an efficacious IBD treatment given the non-invasive and targeted nature of this therapy. We employed the dextran sodium sulfate (DSS) model of colitis, administering lower (5%) and higher (7%) doses to rats in drinking water. FUS on the celiac plexus administered twice a day for 12 consecutive days to rats with severe IBD improved stool consistency scores from 2.2 ± 1 to 1.0 ± 0.0 with peak efficacy on day 5 and maximum reduction in gross bleeding scores from 1.8 ± 0.8 to 0.8 ± 0.8 on day 6. Similar improvements were seen in animals in the low dose DSS group, who received FUS only once daily for 12 days. Moreover, animals in the high dose DSS group receiving FUS twice daily maintained colon length (17.7 ± 2.5 cm), while rats drinking DSS without FUS exhibited marked damage and shortening of the colon (13.8 ± 0.6 cm) as expected. Inflammatory cytokines such as interleukin (IL)-1ß, IL-6, IL-17, tumour necrosis factor-α and interferon-γ were reduced with DSS but coincided with control levels after FUS, which is plausibly due to a loss of colon crypts in the former and healthier crypts in the latter. Lastly, overall, these results suggest non-invasive FUS of peripheral ganglion can deliver precision therapy to improve IBD symptomology.

Navigated magnetic resonance imaging-guided celiac plexus neurolysis using an open magnetic resonance system for pancreatic cancer patients with upper abdominal pain.

AIMS: The study aimed to evaluate the safety and efficacy of navigated magnetic resonance imaging (MRI)-guided celiac plexus neurolysis (CPN) using a 0.4 T open magnetic resonance system. MATERIALS AND METHODS: A retrospective analysis was performed on 23 patients with unresectable pancreatic cancer who underwent MRI-guided CPN between January 2013 and October 2017. Clinical outcomes were evaluated by recording the complications, the opioid intake, and questionnaire before the intervention and at the time point of 1 day, 1 month, and 3 months postprocedure using a numerical visual analog scale (VAS). RESULTS: Navigated MRI guidance allowed the precise placement of needle in the targeted area and the visualization of the injected neurolysis agents for all cases. The VAS scores decreased from 8.8 ± 1.0 to 2.9 ± 0.9, 4.2 ± 1.7, and 4.7 ± 1.8 at 1 day, 1 month, and 3 months postprocedure (P < 0.05). This intervention reduced the dosage of opioid consumption 1 month after the procedure (52.3 ± 10.4 mg before the treatment vs. 28.2 ± 4.9 mg after the treatment; P < 0.001). Treatment-related side effects included hematoma in one patient, short episodes of diarrhea in three patients, and hypotension in four patients. CONCLUSIONS: With the assistance of the navigation system, MRI-guided CPN is a safe and effective treatment approach for managing the upper abdominal pain in patients with unresectable pancreatic cancer.

Bilateral vs. unilateral endoscopic ultrasound-guided celiac plexus neurolysis for abdominal pain management in patients with pancreatic malignancy: a systematic review and meta-analysis.

CONTEXT: Endoscopic ultrasound-guided celiac plexus neurolysis (EUS-CPN) by bilateral or unilateral approach is widely used in palliative abdominal pain management in pancreatic cancer patients, but the analgesic effect and relative risks of the two different puncture routes remain controversial. OBJECTIVES: The aim of this systematic review was to evaluate the analgesic efficacy and safety of bilateral EUS-CPN compared with unilateral EUS-CPN. METHODS: An electronic database search was performed for randomized controlled trials comparing bilateral and unilateral approaches of EUS-CPN using the Pubmed, Cochrane Library, Web of Science, Google Scholar, and CNKI databases. Meta-analysis was performed using RevMan 5.3 after screening and methodological evaluation of the selected studies. Outcomes included pain relief, treatment response, analgesic reduction, complications, and quality of life (QOL). RESULTS: Six eligible studies involving 437 patients were included. No significant difference was found in short-term pain relief [SMD = 0.31, 95% CI (- 0.20, 0.81), P = 0.23] and response to treatment [RR = 0.99, 95% CI (0.77, 1.41), P = 0.97] between the bilateral and unilateral neurolysis groups. However, only the bilateral approach was associated with a statistically significant reduction in the postoperative use of analgesics [RR = 0.66, 95% CI (0.47, 0.94), P = 0.02] compared to the unilateral approach. A descriptive analysis was performed for complications and QOL. CONCLUSION: The short-term analgesic effect and general risk of bilateral EUS-CPN are comparable with those of unilateral EUS-CPN, but our evidence supports the conclusion that the bilateral approach significantly reduces postoperative analgesic use.

Primary malignant melanoma of the gallbladder with multiple metastases: A case report.

RATIONAL: Primary malignant melanoma of the gallbladder is an extremely rare tumor, with fewer than 40 cases reported in the literature worldwide. The majority of patients presented as a solitary lesion in the gallbladder. To our knowledge, only one case of primary malignant melanoma of the gallbladder with multiple metastases has been reported, which involved the stomach, duodenum, pancreas, jejunum and a mesenteric lymph node. PATIENT CONCERNS: We report a case of primary malignant melanoma of the gallbladder with metastases to the duodenal bulb, right adrenal and a celiac lymph node. DIAGNOSES: Primary malignant melanoma of the gallbladder with multiple metastases. INTERVENTIONS: Gastrojejunostomy, cholecystectomy, and biopsy of the three metastatic lesions were performed. Histopathologic examination revealed melanin pigments were within the tumor cells of the four lesions, however, junctional activity was noted only in the gallbladder, supporting that the gallbladder was the primary site. No pigmented lesions were detected on the skin or eyes. The postoperative recovery was uneventful, and subsequently, chemotherapy with paclitaxel and carboplatin was administered. OUTCOMES: The patient survived for 16 months due to tumor. progression. LESSONS: The current case was unique due to the adrenal involvement. For patients with multiple metastases of malignant melanoma, gallbladder origin should be considered in the differential diagnosis from cutaneous origin.

Phase-contrast MRI evaluation of haemodynamic changes induces by a coeliac axis stenosis in the gastroduodenal artery.

OBJECTIVE: To evaluate the correlation between the gastroduodenal artery (GDA) haemodynamic changes and the degree of coeliac axis (CA) stenosis using phase-contrast MRI. METHODS: The study was institutional review board approved, and written informed consent was obtained from patients included prospectively. A two-dimensional phase-contrast MRI was performed in 23 patients scheduled for a potential complex supramesocolic surgery, in a plane perpendicular to the GDA, during inspiration and expiration. The peak and mean velocities (Vp and Vm), mean flow rate (Qm) and flow direction at inspiration and at expiration have been correlated with the degree of CA stenosis evaluated by CT. RESULTS: 13 of 23 patients presented CA stenosis due to the median arcuate ligament (34-80% of stenosis), 4 of them had associated atheromatous calcifications. Vp, Vm and Qm of GDA presented a significant and linear relationship with the degree of CA stenosis, at inspiration as well as at expiration (r > 0.74, p < 0.001). Velocities and flow rates presented a different pattern depending on the degree of CA stenosis: <34% (n = 10), flow direction remained physiological with low velocities and flow rates; >60% of stenosis (n = 5), a reverse flow direction with increased velocities and flow rates were observed; variable patterns between 34% and 60%. CONCLUSION: Phase-contrast MRI permits the evaluation of haemodynamic changes in GDA induced by CA stenosis, including median arcuate ligament compression, and could be of great interest in therapeutic decision making in supramesocolic surgery, such as liver transplantation or duodenopancreatectomy, by detecting haemodynamically significant stenoses. Advances in knowledge: Physiological phase-contrast MRI detects haemodynamically significant stenoses of the CA by evaluating haemodynamic parameters in the GDA. Physiological phase-contrast MRI demonstrates that flow in the GDA can be a direct marker of the real haemodynamic impact of a CA stenosis on the hepatic vascularization and could thus participate in the pre-surgical work-up of duodenopancreatectomy or hepatic graft, whereas existing pre-operative imaging are only morphological.

MDCT Diagnosis of Perineural Invasion Involving the Celiac Plexus in Intrahepatic Cholangiocarcinoma: Preliminary Observations and Clinical Implications.

OBJECTIVE: The purpose of this study was to test the hypothesis that soft-tissue infiltration along the celiac plexus and delayed enhancement exceeding two-thirds of the tumor area on preoperative MDCT correlate with histologic evidence of perineural invasion in resected intrahepatic cholangiocarcinomas. MATERIALS AND METHODS: Two experienced abdominal radiologists retrospectively reviewed preoperative multiphasic MDCT scans of 20 patients who underwent resection of intrahepatic cholangiocarcinoma, identifying soft-tissue infiltration along the celiac plexus, delayed enhancement exceeding two-thirds of the tumor area, and maximum tumor diameter. Consensus findings were compared with intratumoral perineural invasion in resected intrahepatic cholangiocarcinomas using the Fisher exact test. RESULTS: Six patients had histologic intratumoral perineural invasion, five of whom had soft-tissue infiltration along the celiac plexus on preoperative MDCT, with corresponding 83.3% sensitivity and 92.9% specificity for perineural invasion and significant association between these MDCT and histologic findings (p = 0.002). No patients with histologic perineural invasion had enhancement exceeding two-thirds of the tumor area on MDCT; sensitivity was 0.0% for this finding. Tumor diameter on MDCT was not significantly associated with perineural invasion at histopathology (p = 0.530). CONCLUSION: Soft-tissue infiltration along the celiac plexus on MDCT is an indicator of perineural invasion in patients with intrahepatic cholangiocarcinoma. The data did not confirm an association between delayed enhancement exceeding two-thirds of the tumor area and perineural invasion. Because perineural invasion from intrahepatic cholangiocarcinoma is associated with a very poor prognosis and is generally a contraindication to surgery, the MDCT diagnosis of celiac plexus perineural invasion in patients with intrahepatic cholangiocarcinoma may have important implications for prognosis and treatment planning.

Detailed analysis of extra-pancreatic nerve plexus invasion in pancreatic body carcinoma analyzed by 50 consecutive series of distal pancreatectomy with en-bloc celiac axis resection.

BACKGROUND/AIMS: Advanced pancreatic body carcinoma frequently accompany extra-pancreatic nerve plexus (PL) invasion, one of the poor indicator of patient prognosis. The present study aimed to reveal the progress of the PL invasion from cancer of the pancreas body toward the root of the celiac artery (CA) and superior mesenteric artery (SMA) followed by investigation of the relevance of diagnostic accuracy. METHODOLOGY: Resected specimens from 50 consecutive patients who underwent distal pancreatectomy with en bloc celiac axis resection (DP-CAR) were pathologically analyzed for the direction of PL invasion. Diagnostic accuracy on CT imaging were also investigated. RESULTS: Thirty seven of the 50 patients (74%) were positive for PL invasion around the CHA, SPA, CA and SMA. In terms of the diagnostic accuracy, positive predictive values for the PL invasion were 35%, 36%, 43% and 81% for the SPA, CHA, CA and SMA, respectively. Among 21 patients and 23 patients with PL invasion around CHA and SPA, 13 and 6 patients also accompanied PL invasion around CA, respectively. CONCLUSIONS: Carcinoma of the pancreatic body is found to frequently accompany PL invasion around CA. Under the limitation of low diagnostic accuracy, DP-CAR might be feasible operation that increases the possibility of R0 resection.

MR-guided neurolytic celiac plexus ablation: an evaluation of effect and injection spread pattern in cancer patients with celiac tumor infiltration.

OBJECTIVE: The purpose of this study was to evaluate the feasibility, the initial accuracy, and the effects of the MR-guided neurolytic celiac plexus ablation as a method to treat cancer-induced chronic abdominal pain. METHODS: Thirteen celiac plexus ablations were performed for 12 patients. A 0.23-T open MRI scanner with optical navigation was used for procedural guidance. As an adjunct to the MR-guided needle positioning, the needle location was confirmed with saline injection and consequent MR imaging (STIR sequence). The spread of the ablative injection material (alcohol-lidocaine mix) was observed by repeating this sequence after the therapeutic injection. Pain scores from seven patients (eight ablations) were used to assess the therapy effect. RESULTS: MR guidance allowed adequate needle positioning and visualization of injection material in all cases. The rest pain scores significantly decreased from 4 (median) at baseline to 1 (median) at 2 weeks (p < 0.05). Average and worst pain experienced during the past week were significantly lower at the 2-week time point compared with the baseline (p < 0.05). However, the intervention did not result in reduction of opioid use at 2 weeks. CONCLUSIONS: MR guidance is an accurate and safe method for celiac plexus ablation with positive therapeutic effect.

Severe diarrhea following neurolytic coeliac plexus block: case report and literature review.

Diarrhea is one of the commonest complication following coeliac plexus ablative procedures. It is believed to occur due to inadvertent chemical sympathectomy by the block. For the majority of patients, complications are temporary and self limited. Unfortunately few cases of refractory diarrhea have been reported and some of them proved fatal. The mainstay of therapy is aggressive hydration to restore body fluids and early treatment with antidiarrheal agents. This includes the use of high fiber diet, opioids, anticholinergics, alpha 2 agonists and somatostatin analogues e.g., Octreotide in an attempt to inhibit gut motility and control the diarrhea. We would like to present a case of severe diarrhea following a neurolytic coeliac plexus block using alcohol 50% in a patient with cancer pancreas. Patient achieved a significant reduction in her pain scores but developed severe diarrhea and dehydration. Diarrhea was refractory to medical treatment and patient died few weeks later.

Interventional therapies for the management of cancer pain.

Timely interventional cancer pain therapies complement conventional pain management by reducing the need for high-dose opioid therapy and its associated toxicity. All patients with upper abdominal visceral pain should be considered for celiac plexus neurolysis soon after diagnosis. Intrathecal therapy should be considered in any patient with moderate-to-severe pain despite a reasonable therapeutic trial of opioid pharmacotherapy or in any patient intolerant of opioid therapy. Specific interventions for vertebral metastases and other sites of metastatic bone pain, including vertebroplasty, kyphoplasty, and image-guided tumor ablation, should be understood and considered. A collaborative model of care, including pain medicine specialists with expertise in interventional therapies, should be standard in all oncologic practices in order to optimize outcomes for patients with cancer throughout the course of their treatment.

Compression of the left renal artery and celiac trunk by diaphragmatic crura.

Symptomatic compression of the celiac trunk by crura of the diaphragm is a rare disorder. Even more infrequent external compression of renal arteries is found. Although the indication for surgical therapy is controversially discussed in the literature for celiac artery compression syndrome, it is unequivocally for renal artery entrapment. We present the case of a young woman who was assigned to our hospital with arterial hypertension and stenosis of the left renal artery. After percutaneous transluminal angioplasty was performed, immediate recoil occurred. Therefore, the suspicion of entrapment by diaphragmatic crura was expressed. Additionally performed diagnostic procedures including computed tomography (CT)-angiography verified our suspicion. Surgical decompression of both vessels was successfully performed.

Chemotherapy followed by surgery in patients with carcinoma of the distal esophagus and celiac lymph node involvement.

BACKGROUND: Patients with carcinoma of the distal esophagus and metastatic celiac lymph nodes (M1a) have a poor prognosis and are often denied surgery. In this study, we evaluated our treatment strategy of chemotherapy followed by surgery in patients with M1a disease. METHODS: Thirty-eight patients who received chemotherapy for carcinoma of the distal esophagus with celiac lymph node involvement between 2000 and 2007 were identified from a prospective database. Clinical and histopathological responses to chemotherapy were analyzed and follow-up comprised review of medical charts. RESULTS: Twelve non-responding patients were not eligible for surgery. Twenty-six patients with partial responses or stable disease were operated on. The resectability rate was 96% (25/26) and tumor-free resection margins (R0) were achieved in 68% (17/25). The overall survival of patients with M1a disease was 16 months. Patients who received chemotherapy alone had a median survival of 10 months; patients who underwent additional surgery had a median survival of 26 months (log-rank P < 0.001). CONCLUSION: The overall survival of patients with carcinoma of the distal esophagus and clinical celiac lymph node involvement is poor. Tumor-free resection margins (R0) in M1a patients with clinical response to chemotherapy are likely to be achieved and contributes to prolonged survival.

Surgery for patients with gastric cancer in the terminal stage of the illness - TNM stage IV.

PURPOSE: To assess any survival advantage in patients with incurable gastric cancer who had undergone resection, bypass or exploratory surgery. In nonresectable patients with pain, the effect of celiac plexus neurolysis was assessed. METHODS: We retrospectively analysed data of 330 patients, operated between 1992 and 2006. The patients were followed until death or last examination. Incurable gastric cancer was defined as TNM stage IV disease: locally advanced (LA), with solitary distant metastasis (SM) or with multiple metastases and/or peritoneal carcinomatosis (MMC). The patients were divided into these 3 groups. Their postoperative survival was calculated and compared in relation to the surgical technique used. Factors which influenced mortality and survival were identified. RESULTS: 131 patients (39.7%) had locally LA cancer, 98 (29.7%) SM, and 101 (30.6%) belonged to the MMC group. The surgical procedures included 138 (41.8%) exploratory laparotomies, 84 (25.5%) bypass procedures and 108 (32.7%) resections. Thirty-three (10%) unresectable patients with pain underwent celiac plexus neurolysis. The mean survival was 21.8 months after resections, 7 months after by-passes and 4.8 after exploratory laparotomies (p = 0.0001). It was 14.57 months (p=0.001) in the LA group, 12.53 (p = 0.005) in the SM group, and 5.2 in the MMC group. Survival was shorter in patients with preoperative weight loss of more than 20 kg (3.2 months, p <0.0001). Postoperative 30-day mortality was 23.2% after exploratory laparotomies, 23.8% after bypasses and 20.4% after resections. Increased mortality was observed in the MMC group (27.7%) and in multivisceral resections (41%, p > 0.05), while significantly increased mortality occurred in patients with weight loss of over 20 kg (32%, p=0.03). Celiac plexus neurolysis was immediately effective in 30 out of 33 (91%) patients (p=0.0001), while 3 months later it was still effective in 15 (45.5%) patients (p=0.08). CONCLUSION: Resections are suggested in the LA and SM groups, and neurolysis in all nonresected patients with pain.

Terapéutica paliativa guiada por ecoendoscopia en pacientes con cáncer de páncreas / No disponible

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The adult coeliac ganglion: a morphologic study.

The coeliac plexus is located on the sides of the coeliac trunk and nearby the origins of the superior mesenteric and renal arteries. Afferent branches get to this plexus from the vagus nerve, splanchnic nerves and the right phrenic nerve; efferents leave for viscera through periarterial plexuses and the retroportal nerves. The coeliac plexus ganglia - coeliac, superior mesenteric, aorticorenal - are prevertebral ganglia that receive the preganglionic sympathetic fibers brought by the splanchnic nerves from the thoracic spinal cord. For studying the adult coeliac ganglia dissections were performed then pieces were drawn for silver staining by the method of Bielschowsky on blocks and HE stains. The adult coeliac ganglia consist of well-defined ganglionic subunits, of a varying number of neurons with somata ranging from 14 to 48 microns and characteristically involved in extensive dendritic fields. Individual degrees of coalescence may justify the macroscopic appearance of the coeliac ganglion but its structure keeps distinctive subunits.

Diagnostic and therapeutic applications of endoscopic ultrasound-guided punctures.

Endoscopic ultrasound (EUS) has emerged as an excellent tool for the imaging of the gastrointestinal wall and surrounding structures. EUS-guided fine needle aspiration has broadened the applicability of this tool by allowing tissue sampling of a variety of lesions within or accessible from the gastrointestinal (GI) tract. In particular, EUS became the test of choice for evaluating pancreatic cysts and mass lesions, biliary strictures and masses, abnormal adenopathy accessible from the GI tract, and GI submucosal lesions. There appears to be an increasing role for EUS in the staging of lung cancer, evaluating adrenal lesions and GI mesenchymal tumors. More recently, EUS has acquired a new dimension in interventional applications. This includes, but is not limited to, celiac plexus block and celiac neurolysis for the management of pain associated with chronic pancreatitis and locally advanced pancreaticobiliary malignancies, respectively.