Palmitoylethanolamide and polydatin in pediatric irritable bowel syndrome: A multicentric randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the efficacy and safety of co-micronized palmitoylethanolamide (PEA)/polydatin (PD) in the treatment of abdominal pain symptoms in pediatric patients with irritable bowel syndrome (IBS). METHODS: This was a multicenter trial conducted at three Italian pediatric gastroenterology centers, employing a double-blind, placebo-controlled, parallel-arm design. Participants were ages 10 to 17 y and met Rome IV criteria for pediatric IBS. They were randomly allocated to receive either co-micronized PEA/PD or placebo, administered three times daily in a 1:1 ratio, over a 12-wk period. The study assessed baseline severity using the IBS-Severity Scoring System (IBS-SSS) at enrollment and after 4, 8, and 12 wk of treatment. Abdominal pain frequency was assessed on a scale from 1 to 7 d/wk, while stool consistency was classified using the Bristol Stool Scale (BSS) to categorize various IBS subtypes. The primary outcome was the percentage of patients who achieved complete remission, defined as IBS-SSS score <75 points after 12 wk of therapy. RESULTS: The study involved 70 children with IBS. Of the participants, 34 received co-micronized PEA/PD, and 36 received a placebo. As compared with the placebo group, the co-micronized therapy group had significantly more patients achieving complete remission after 12 wk (P = 0.015), with particular benefit in the IBS-diarrhea subtype (P = 0.01). The treatment group also experienced a significant reduction in abdominal pain intensity and frequency compared with the placebo group. No adverse events were recorded during the study period. CONCLUSIONS: Co-micronized PEA/PD is a safe and effective treatment to treat abdominal pain symptoms in pediatric IBS.

Sphaleron Rate of N_{f}=2+1 QCD.

We compute the sphaleron rate of N_{f}=2+1 QCD at the physical point for a range of temperatures 200 MeV≲T≲600 MeV. We adopt a strategy recently applied in the quenched case, based on the extraction of the rate via a modified version of the Backus-Gilbert method from finite-lattice-spacing and finite-smoothing-radius Euclidean topological charge density correlators. The physical sphaleron rate is finally computed by performing a continuum limit at fixed physical smoothing radius, followed by a zero-smoothing extrapolation. Dynamical fermions were discretized using the staggered formulation, which is known to yield large lattice artifacts for the topological susceptibility. However, we find them to be rather mild for the sphaleron rate.

Large and bleeding gastroduodenal artery aneurysm: Challenging diagnosis and treatment. A case report.

INTRODUCTION: Visceral artery aneurysms (VAA), including gastroduodenal artery aneurysms (GAA), are rare pathologies that can be challenging to diagnose due to their often-asymptomatic nature. VAA are usually correlated to atherosclerosis, fibro dysplasia, or hemodynamics changes, while pseudo aneurysms are mostly correlated to infection, inflammation, traumas, or iatrogenic lesions. PRESENTATION OF CASE: We report the case of an 82-years-old female presenting with abdominal pain and hematemesis. Upper gastrointestinal endoscopy retrieved a large duodenal mass and subsequent CT scans identified a large GAA with contrast extravasation. Endovascular procedure included selective arteriography, microcatheterization, and embolization. DISCUSSION: VAA are mostly located in the splenic and hepatic artery. Symptoms of VAA are related to pressure on neighboring organs. VAA rupture is associated with a high mortality risk (over 76 %) and presents with symptoms like acute abdominal pain, hematemesis, and hemodynamic shock. Diagnosis is often made through CT scans and angiography. Treatment options for VAAs and GAAs include both surgical and endovascular methods. Endovascular treatment is preferred, with a success rate of 89 %-98 %. CONCLUSION: This case provides an example of challenging diagnosis and treatment of a large and bleeding GAA.

Wandering spleen causing small bowel obstruction: Laparoscopic surgical treatment (with video).

INTRODUCTION: Wandering spleen (WS) is a clinical entity in which the spleen is not located in its normal anatomical site. Few cases have been reported, mainly in women of childbearing age. This condition can be congenital or acquired due to excessive elasticity of the spleen's suspensory ligaments. WS may cause acute complications requiring emergency surgery, especially related to the rotation of its vascular pedicle, leading to chronic or acute ischemia. The aim of the present case is to show a rare complication of WS, small bowel obstruction (SBO), and its management. PRESENTATION OF CASE: We report the case of a 40-year-old female presenting with abdominal pain, nausea, and vomiting. CT scan showed SBO caused by WS located in the pelvis with an enlarged spleen vascular pedicle (SVP). Laparoscopic exploration, splenectomy, small bowel resection and anastomosis were performed. DISCUSSION: WS may cause chronic or acute complications, mainly linked with enlargement and torsion of SVP, including acute ischemia and spleen necrosis, or compression of the near organs such as small intestine, stomach, pancreas. The diagnosis is based on physical examination, CT scan and blood exams. Generally, the WS's treatment is laparoscopic splenectomy or splenopexy. In case of vital spleen, splenopexy can be performed, in case of not vital spleen, splenectomy should be preferred. CONCLUSION: This case provides an excellent example of SBO related to WS. In the video, the management of this complex situation is shown. In these cases, splenectomy represents a valuable option.

Overall Survival Following Anastomotic Leakage After Surgery for Carcinoma of the Esophagus and Gastroesophageal Junction: A Systematic Review.

The effect of anastomotic leakage, in patients who underwent surgery for carcinoma of the esophagus and gastroesophageal junction, on overall survival (OS) is a debated and controversial topic. The aim of this systematic review was to clarify the impact of anastomotic leakage on long-term survival of patients with esophageal cancer undergoing esophagectomy. A systematic literature review was carried out from 2000 to 2022. We chose articles reporting data from patients who underwent surgery for carcinoma of the esophagus and gastroesophageal junction. Data regarding 1-, 3- and 5-year OS were analyzed. Twenty studies met the inclusion criteria, yielding a total of 9,279 patients. Analyzing data from selected studies, anastomotic leakage was found to be associated with decreased OS in 5,456 cases while in the remaining 3,823 it had no impact on long term survival (p<0.05). However, this result did not emerge from the other studies considered in the systematic review. Anastomotic leakage is a severe postoperative complication, which seems to have an impact on overall survival. However, the topic remains debated and not supported by all case series included in this systematic review.

Postoperative Pancreatic Fistula: Is Minimally Invasive Surgery Better than Open? A Systematic Review and Meta-analysis.

BACKGROUND/AIM: Minimally invasive pancreaticoduodenectomy (PD) is gaining popularity. The aim of this study was to compare the incidence of postoperative pancreatic fistula (POPF) after minimally invasive versus open procedures. MATERIALS AND METHODS: Following the PRISMA statement, literature research was conducted focusing on papers comparing the incidence of POPF after open pancreaticoduodenectomy (OPD) versus minimally invasive pancreaticoduodenectomy (MIPD). RESULTS: Twenty-one papers were included in this meta-analysis, for a total of 4,448 patients. A total of 2,456 patients (55.2%) underwent OPD, while 1,992 (44.8%) underwent MIPD. Age, ASA score III patients, incidence of pancreatic ductal adenocarcinoma and duct diameter were significantly lower in the MIPD group. No statistically significant differences were found between the OPD and MIPD regarding the incidence of major complications (15.6% vs. 17.0%, respectively, p=0.55), mortality (3.7% vs. 2.4%, p=0.81), and POPF rate (14.3% vs. 12.9%, p=0.25). CONCLUSION: MIPD and OPD had comparable rates of postoperative complications, postoperative mortality, and POPF.

The Role of Surgery in the Treatment of Metachronous Liver Metastasis from Gastric Cancer: A Systematic Review.

BACKGROUND: Few data are available regarding metachronous liver metastases from gastric cancer. We aimed to identify data regarding the survival of these patients, considering the chosen treatment, with particular attention to the role of surgery. MATERIALS AND METHODS: A systematic review was carried out from 2000 to 2020. We chose articles reporting data from patients with metachronous liver metastases after curative gastrectomy. Data regarding 1-, 3- and 5-year overall survival were analyzed. RESULTS: Survival was improved in patients eligible for surgery (absence of extrahepatic non-curative factors and feasible complete macroscopic removal of liver deposits, i.e., H1 and H2 liver involvement, metastases less than 5 cm in size) when curative liver resection was performed, with a median overall survival of 24 months (vs. 3.13 in patients treated with chemotherapy). N Status, extent and maximum size of liver metastases, and hepatic surgical treatment were identified as independent prognostic factors. CONCLUSION: Selected patients with metachronous liver metastases from gastric cancer may benefit from multimodal 'aggressive' treatment. When hepatic involvement is limited (H1 and H2) and the size of metastases less than 5 cm, surgery was shown to increase survival.

Distal Pancreatectomy with Celiac Axis Resection: Systematic Review and Meta-Analysis.

BACKGROUND: Major vascular invasion represents one of the most frequent reasons to consider pancreatic adenocarcinomas unresectable, although in the last decades, demolitive surgeries such as distal pancreatectomy with celiac axis resection (DP-CAR) have become a therapeutical option. METHODS: A meta-analysis of studies comparing DP-CAR and standard DP in patients with pancreatic adenocarcinoma was conducted. Moreover, a systematic review of studies analyzing oncological, postoperative and survival outcomes of DP-CAR was conducted. RESULTS: Twenty-four articles were selected for the systematic review, whereas eleven were selected for the meta-analysis, for a total of 1077 patients. Survival outcomes between the two groups were similar in terms of 1 year overall survival (OS) (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.34 to 1.31, p = 0.24). Patients who received DP-CAR were more likely to have T4 tumors (OR 28.45, 95% CI 10.46 to 77.37, p < 0.00001) and positive margins (R+) (OR 2.28, 95% CI 1.24 to 4.17, p = 0.008). Overall complications (OR, 1.72, 95% CI, 1.15 to 2.58, p = 0.008) were more frequent in the DP-CAR group, whereas rates of pancreatic fistula (OR 1.16, 95% CI 0.81 to 1.65, p = 0.41) were similar. CONCLUSIONS: DP-CAR was not associated with higher mortality compared to standard DP; however, overall morbidity was higher. Celiac axis involvement should no longer be considered a strict contraindication to surgery in patients with locally advanced pancreatic adenocarcinoma. Considering the different baseline tumor characteristics, DP-CAR may need to be compared with palliative therapies instead of standard DP.

Left-sided portal hypertension after pancreatoduodenectomy with resection of the portal/superior mesenteric vein confluence. Results of a systematic review.

BACKGROUND: Pancreatoduodenectomy with synchronous resection of the portal vein/superior mesenteric vein confluence may result in the development of left-sided portal hypertension. Left-sided portal hypertension presents with splenomegaly and varices and may cause severe gastrointestinal bleeding. The aim of the study is to review the incidence, treatment, and preventive strategies of left-sided portal hypertension. METHODS: A systematic literature search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement to identify all studies published up to September 30, 2019 reporting data on patients with left-sided portal hypertension after pancreatoduodenectomy with venous resection. RESULTS: Eight articles including 829 patients were retrieved. Left-sided portal hypertension occurred in 7.7% of patients who had splenic vein preservation and 29.4% of those having splenic vein ligation. Fourteen cases of gastrointestinal bleeding owing to left-sided portal hypertension were reported at a mean interval of 28 months from pancreatoduodenectomy. Related mortality at 1 month was 7.1%. Treatment of left-sided portal hypertension consisted of splenectomy in 3 cases (21%) and colectomy in 1 (7%) case, whereas radiologic, endoscopic procedures or conservative treatments were effective in the other cases (71%). CONCLUSION: Left-sided portal hypertension represents a potentially severe complication of pancreatoduodenectomy with venous resection occurring at greater incidence when the splenic vein is ligated and not reimplanted. Left-sided portal hypertension-related gastrointestinal bleeding although rare can be managed depending on the situation by endoscopic, radiologic procedures or operative intervention with low related mortality.

Impact of Anastomotic Leakage on Overall and Disease-free Survival After Surgery for Gastric Carcinoma: A Systematic Review.

BACKGROUND/AIM: Gastric cancer is the fifth most frequently diagnosed cancer and the second most common cause of cancer-related death. The only potentially curative treatment is surgical resection, which is associated with potentially severe complications, such as anastomotic leakage. The aim of this systematic review was to evaluate the relationship between anastomotic leakage and overall and disease-free survival after surgery for gastric cancer. MATERIALS AND METHODS: A systematic literature search was performed and 7 articles published between 2010 and 2019 were included, including a total of 7,167 patients. RESULTS: Among the included studies the frequency of anastomotic leakage ranged from 6 to 41%. Patients affected by anastomotic leakage had an overall survival ranging between 4.1 and 97.6 months, whereas patients who did not experience anastomotic leakage had an overall survival between 23 and 109.5 months. CONCLUSION: Closer follow-up or even more aggressive oncological therapy may be considered for patients affected by anastomotic leakage after surgery for gastric cancer.

In vivo Bioluminescence-Based Monitoring of Liver Metastases from Colorectal Cancer: An Experimental Model.

BACKGROUND: In this study we aimed to develop a new in vivo bioluminescence-based tool to monitor and to quantify colon cancer (CC) liver metastasis development. METHODS: HCT 116 cells were transducted with pLenti6/V5-DEST-fLuc for constitutive expression of firefly luciferase. Infection was monitored analyzing endogenous bioluminescence using the IVIS Lumina II In vivo Imaging System and a positive clone constitutively expressing luciferase (HCT 116-fLuc) was isolated. HCT 116-fLuc cells were left untreated or treated with 1 µM GDC-0449, a Hedgehog pharmacological inhibitor. Moreover, 1 x 106 HCT 116-fLuc cells were implanted via intra-splenic injection in nude mice. Bioluminescence was analyzed in these mice every 7 days for 5 weeks. After that, mice were sacrificed and bioluminescence was analyzed on explanted livers. RESULTS: We found that in vitro bioluminescence signal was significantly reduced when HCT 116-fLuc cells were treated with GDC-0449. Regarding in vivo data, bioluminescence sources consistent with hepatic anatomical localization were detected after 21 days from HCT 116-fLuc intrasplenic injection and progressively increased until the sacrifice. The presence of liver metastasis was further confirmed by ex-vivo bioluminescence analysis of explanted livers. CONCLUSIONS: Our in vitro results suggest that inhibition of Hedgehog pathway may hamper CC cell proliferation and impel for further studies. Regarding in vivo data, we set-up a strategy for liver metastasis visualization, that may allow follow-up and quantification of the entire metastatic process. This cost-effective technique would reduce experimental variability, as well as the number of sacrificed animals.

Recurrence Following Anastomotic Leakage After Surgery for Carcinoma of the Distal Esophagus and Gastroesophageal Junction: A Systematic Review.

BACKGROUND: Esophageal cancer is the ninth most common cancer. The only potentially curative treatment is surgical resection, which unfortunately is still associated with major complications, the most important being anastomotic leakage, currently with an overall rate of up to 26% morbidity. The aim of this systematic review was to evaluate the relationship between anastomotic leakage and recurrence of disease. MATERIALS AND METHODS: A literature search was systematically performed. Seven out of 312 articles dated between 2009 and 2018 fulfilled the selection for a total of 5,433 patients. RESULTS: The frequency of anastomotic leakage ranged from 7.2 to 11.2%. Patients affected by anastomotic leakage had a recurrence rate of 9-56%. CONCLUSION: Closer follow-up or even more aggressive oncological therapy should be considered for patients affected by anastomotic leakage after surgery for carcinoma of the distal esophagus and gastroesophageal junction.

An unusual cause of colic stenosis in a renal transplant recipient: primary colonic diffuse large B-cell lymphoma.

BACKGROUND: Primary colic lymphoma represents a rare disease accounting for the 0.2%-0.6% of all large-bowel malignancies. We here report a case of diffuse large B-cell lymphoma presenting as a left colic stenosis in a patient who had undergo renal transplant 23 years before. CASE REPORT: A 67-years old man presented with recurrent abdominal pain, distension, nausea and constipation since 3 weeks. His past medical history included hepatic and renal polykystose with renal transplant 23 years before. Colonoscopy revealed a non-surmountable inflammatory left colic stenosis at 55 cm from the anal verge. Biopsies demonstrated inflammatory colic mucosa without neoplastic cells. Non-enhanced CT scan and CT virtual colonoscopy were performed, showing a left colon circumferential thickening of 4 cm. Laparoscopic left colectomy was performed to treat the colic obstructive syndrome and to have complete specimen analysis. After Pathological analysis and Immunohistochemistry the diagnosis of diffuse large B cell lymphoma was established. The resection was R0. The postoperative course was uneventfully. CONCLUSION: Large B-cell lymphoma represents a rare case of bowel tumor. However it has to be considered in the differential diagnosis of colic stenosis in immunosuppressed patients as transplant recipients. KEY WORDS: Colorectal lymphoma, Diffuse large B-cell lymphoma, Immunosuppressed patients.

Cancer Rate of the Indeterminate Lesions at Low or High Risk According to Italian System for Reporting of Thyroid FNA.

Background: Italian consensus for the classification and reporting of thyroid cytology (ICCRTC) has been used in almost all Italian institutions since 2014. High reliability of ICCRTC in classifying low and high risk indeterminate nodules (Tir 3A and Tir 3B, respectively) was demonstrated. Here we reviewed our casuistry of thyroid indeterminate lesions to analyze the histologic outcome. Methods: All lesions undergone FNA and final histology at S. Andrea Hospital of Rome after a cytologic assessment of Tir 3A and Tir 3B, according to ICCRTC, were included in the study. Results: A number of 157 indeterminate FNA was found after the introduction of ICCRTC. Of these, 75 undergone surgery and were finally included for the study. At histology we found a 33.3% of cancers and a 67.7% of benign lesions. Out of the overall series, 25 were classified as Tir 3A and 50 as Tir 3B. Cancer rate observed in Tir 3A (1/25, 4%) was significantly (p = 0.0002) lower than that of Tir 3B (24/50, 48%). No significant difference was found in age and size between the two subcategories. Conclusions: We confirm in our series that Italian consensus for the classification and reporting of thyroid cytology allows to discriminate indeterminate lesions at low and high risk of malignancy.

Coupling between intra- and intermolecular motions in liquid water revealed by two-dimensional terahertz-infrared-visible spectroscopy.

The interaction between intramolecular and intermolecular degrees of freedom in liquid water underlies fundamental chemical and physical phenomena such as energy dissipation and proton transfer. Yet, it has been challenging to elucidate the coupling between these different types of modes. Here, we report on the direct observation and quantification of the coupling between intermolecular and intramolecular coordinates using two-dimensional, ultra-broadband, terahertz-infrared-visible (2D TIRV) spectroscopy and molecular dynamics calculations. Our study reveals strong coupling of the O-H stretch vibration, independent of the degree of delocalization of this high-frequency mode, to low-frequency intermolecular motions over a wide frequency range from 50 to 250 cm-1, corresponding to both the intermolecular hydrogen bond bending (≈ 60 cm-1) and stretching (≈ 180 cm-1) modes. Our results provide mechanistic insights into the coupling of the O-H stretch vibration to collective, delocalized intermolecular modes.

Video-assisted anal fistula treatment in the management of complex anal fistula: a single-center experience.

BACKGROUND: Video-assisted anal fistula treatment (VAAFT) is now a mature technique, supported by many short-term published case series. METHODS: We designed a monocentric, retrospective and observational study in order to evaluate early and long-term outcomes of VAAFT in the treatment of primary and recurrent complex anal fistula. Between November 2011 and March 2014, 224 consecutive patients affected by complex perianal fistula underwent Video Assisted Anal Fistula Treatment. Fifty-two were affected by primary and 172 by recurrent disease. We registered all intra and postoperative complications and healing rate. Median follow-up was 48 months (range 27-60 months). RESULTS: In the primary fistula group, 40 of the 52 patients were completely healed within 3 months after surgery (77%); at 12 months, considering also 12 patients (23%) treated with a second VAAFT due to recurrent disease, the overall healing rate was 92.3% In the second group with recurrent anal fistula (N.=172), primary healing was observed in 110 patients (64%; P=0.1) within 3 months after surgery and increases to 80.2%, after 12 months (P=0.06). Few patients required analgesics in the postoperative period (N.=33, 14.7%), the remaining did not require pain killers at all. All patients were able to resume daily activities within 7 days from surgery (range 2-12 days). Main limitation of our study was its retrospective and monocentric design. CONCLUSIONS: VAAFT seems to be a safe and effective technique for treating primary and recurrent perianal fistula, providing a very good healing rate without sphincters impairment and allowing a very quick return to normal activities.

Pancreatectomy combined with multivisceral resection for pancreatic malignancies: is it justified? Results of a systematic review.

BACKGROUND: Multivisceral resections combined with pancreatectomy have been proposed in selected patients with tumor invasion into adjacent organs, in order to allow complete tumor resection. Some authors have also reported multivisceral resection combined with metastasectomy in very selected cases. The utility of this practice is debated. The aim of the review is to compare the postoperative results and survival of pancreatectomies combined with multivisceral resections with those of standard pancreatectomies. METHODS: A systematic literature search was performed to identify all studies published up to February 2017 that analyzed data of patients undergoing multivisceral and standard pancreatectomies. Clinical effectiveness was synthetized through a narrative review with full tabulation of results. RESULTS: Three studies were retrieved, including 713 (80%) patients undergoing standard pancreatectomies and 176 (20%) undergoing multivisceral resections (MVR). Postoperative morbidity ranged from 37% to 50% after standard resections and from 56% to 69% after MVR. In-hospital mortality ranged from 4% after standard pancreatectomies to 10% after MVR. Median survival ranged from 20 to 23 months in standard resections and from 12 to 20 months after MVR, without significant differences. DISCUSSION: The current literature suggests that multivisceral pancreatectomies are feasible and may increase the number of completely resected patients. Morbidity and mortality are higher than after standard pancreatectomies, and these procedures should be reserved to selected patients in referral centers. Further studies on the role of neoadjuvant therapy in this setting are advisable.