Pathologic significance of peribiliary capillary plexus in gallbladder neoplasm.

AIMS: Significance of peribiliary capillary plexus (PCP) in gallbladder neoplasms remains unclear. Aims are to characterize high-grade biliary intraepithelial neoplasm (BilIN), pyloric gland adenoma (PGA), and intracholecystic papillary neoplasm (ICPN), precursors of gallbladder carcinoma, and to differentiate invasive carcinoma from pseudo-invasive lesions in gallbladder walls, referring to PCP. MATERIALS AND METHODS: High-grade BilIN (38 cases), PGA (5 cases), and ICPN (25 cases) were examined using capillary immunostaining. Non-neoplastic gallbladders were used as controls. RESULTS: In non-neoplastic gallbladders, a single layer of regularly dotted capillaries (PCP) was located beneath lining epithelia and around non-neoplastic glands (NNGs), including Rokitansky-Aschoff sinus (RAS), presenting a two-layer of lining epithelia and PCP. Intra-luminal components of all cases of high-grade BilIN and PGA and one-third of ICPNs presented a two-layer pattern. In the remaining ICPNs, capillaries were irregular and sparse in intraluminal neoplastic components presenting irregular and complicated lesions. Neoplastic glands in gallbladder walls of high-grade BilIN and ICPN were classifiable into 2 types: glands that were underlain by densely dotted capillaries and those that were not, with the latter suggestive of invasive carcinoma, while the former suggestive of non-invasive neoplasms involving NNGs intraepithelially and/or showing an expanding growth into gallbladder wall (pseudo-invasion). CONCLUSION: A two-layer pattern of lining epithelia and underlining capillaries were preserved in all cases of high-grade BilIN and PGA and one-third of ICPN cases. Presence or absence of dotted capillaries around neoplastic glands may be able to be added as a new pathologic feature to differentiate invasive carcinomas from pseudo-invasion in gallbladder wall.

The Accuracy of Point-of-Care Ultrasound in the Diagnosis of Acute Cholecystitis.

PURPOSE: Acute cholecystitis (AC) affects 50-200 000 patients per year. Early surgery is the treatment of choice for AC. Therefore, timely diagnosis is important to begin proper management. Recently, emergency departments have adopted point-of-care ultrasound (POCUS) for the initial evaluation of AC. The accuracy of POCUS for AC has not been well studied. METHODS: Patients receiving POCUS for evaluation of AC in the emergency department at our tertiary care institution for 2 years were considered. Patients with previous biliary diagnoses were excluded. Patients were deemed to have AC from a recorded POCUS result or 2/3 of the following POCUS findings: pericholecystic fluid, gallbladder wall hyperemia, and sonographic Murphy's sign. Formal ultrasound and final diagnosis from surgical and pathology reports were used as gold standards for comparison. RESULTS: In total, 147 patients met inclusion criteria. POCUS had a sensitivity and specificity of .4 (95% CI: .1216-.7376) and .99 (.9483-.9982), respectively, when compared to a final diagnosis and .33 (.0749-.7007) and .94 (.8134-.9932) when compared to formal US. The modified Tokyo guidelines for suspicion of AC had a sensitivity of .2 (.0252-.5561) and specificity of .88 (.8173-.931) compared to the final diagnosis. CONCLUSION: Point-of-care ultrasound was not a better screening test than the modified Tokyo guidelines. We recommend a simplified screening approach for AC using clinical findings and laboratory data, followed by confirmatory formal imaging. This strategy could prevent unnecessary delays in surgical management and use of physician resources.

Vascular evaluation using transabdominal ultrasound for gallbladder polyps.

Ultrasound (US) is a cost-effective and noninvasive procedure without radiation exposure, with real-time evaluation and high spatial resolution. Although it is useful for the detection of gallbladder (GB) polyps, including gallbladder cancer, adenoma, and benign polyps, conventional US is insufficient for differential diagnosis because it is not capable of evaluating hemodynamic information, unlike computed tomography or magnetic resonance imaging. With recent technological advances in US equipment and contrast agents, Doppler imaging and contrast-enhanced ultrasonography (CEUS) are being used to characterize GB polyps, and several reports on evaluation of the vascularity of GB polyp have been published. In this review, we aimed to report the latest developments in the hemodynamic diagnosis of GB polyps based on previous reports, with an emphasis on CEUS, and to evaluate the efficacy for differential diagnosis. The information in this article is expected to enable early diagnosis and prompt surgical treatment for gallbladder cancer.

Patch-based classification of gallbladder wall vascularity from laparoscopic images using deep learning.

PURPOSE: In this study, we propose a deep learning approach for assessment of gallbladder (GB) wall vascularity from images of laparoscopic cholecystectomy (LC). Difficulty in the visualization of GB wall vessels may be the result of fatty infiltration or increased thickening of the GB wall, potentially as a result of cholecystitis or other diseases. METHODS: The dataset included 800 patches and 181 region outlines of the GB wall extracted from 53 operations of the Cholec80 video collection. The GB regions and patches were annotated by two expert surgeons using two labeling schemes: 3 classes (low, medium and high vascularity) and 2 classes (low vs. high). Two convolutional neural network (CNN) architectures were investigated. Preprocessing (vessel enhancement) and post-processing (late fusion of CNN output) techniques were applied. RESULTS: The best model yielded accuracy 94.48% and 83.77% for patch classification into 2 and 3 classes, respectively. For the GB wall regions, the best model yielded accuracy 91.16% (2 classes) and 80.66% (3 classes). The inter-observer agreement was 91.71% (2 classes) and 78.45% (3 classes). Late fusion analysis allowed the computation of spatial probability maps, which provided a visual representation of the probability for each vascularity class across the GB wall region. CONCLUSIONS: This study is the first significant step forward to assess the vascularity of the GB wall from intraoperative images based on computer vision and deep learning techniques. The classification performance of the CNNs was comparable to the agreement of two expert surgeons. The approach may be used for various applications such as for classification of LC operations and context-aware assistance in surgical education and practice.

Transarterial Yttrium-90 Radioembolization of Hepatocellular Carcinoma Perfused by the Cystic Artery: Multi-institutional Feasibility Study.

PURPOSE: To assess the safety and efficacy of transarterial yttrium-90 radioembolization via the cystic artery for patients with hepatocellular carcinoma (HCC) adjacent to the gallbladder with cystic artery supply. MATERIALS AND METHODS: This retrospective study included 17 patients treated at 4 institutions. Patients with HCC perfused by the cystic artery who received ablative-dose radioembolization were included. Median tumor size was 3.8 cm (range, 2.0-8.8 cm). Fourteen patients (82%) had Child-Pugh class A cirrhosis and 3 (18%) had class B cirrhosis. Adverse events, tumor response, and time to progression were analyzed. RESULTS: Median dose to the tissue perfused by the cystic artery was 340 Gy (range, 200-720 Gy). There were no occurrences of acute cholecystitis warranting invasive intervention. Four patients (24%) experienced transient right upper quadrant pain, with symptom resolution within 3 mo. Six patients (35%) exhibited gallbladder wall edema on follow-up imaging. Two (12%) and 0 grade 3/4 increases in alkaline phosphatase and bilirubin were observed, respectively. Follow-up imaging demonstrated complete response in 13 target tumors (76%) and partial response in 4 (24%). There were no cases of target tumor progression during a median follow-up of 9 mo (range, 3-72 mo). CONCLUSIONS: Direct infusion of 90Y microspheres via the cystic artery appears to have an acceptable safety profile, without resulting in acute cholecystitis warranting invasive intervention. In selected patients with HCC in whom other treatments may be contraindicated and the tumor is supplied via the cystic artery, treatment with selective ablative radioembolization can be considered.

Intussusceptive Angiogenesis and Peg-Socket Junctions between Endothelial Cells and Smooth Muscle Cells in Early Arterial Intimal Thickening.

Angiogenesis in arterial intimal thickening (AIT) has been considered mainly in late AIT stages and only refers to sprouting angiogenesis. We assess angiogenesis during early AIT development and the occurrence of the intussusceptive type. For this purpose, we studied AIT development in (a) human arteries with vasculitis in gallbladders with acute cholecystitis and urgent (n = 25) or delayed (n = 20) cholecystectomy, using immunohistochemical techniques and (b) experimentally occluded arterial segments (n = 56), using semithin and ultrathin sections and electron microscopy. The results showed transitory angiogenic phenomena, with formation of an important microvasculature, followed by vessel regression. In addition to the sequential description of angiogenic and regressive findings, we mainly contribute (a) formation of intravascular pillars (hallmarks of intussusception) during angiogenesis and vessel regression and (b) morphological interrelation between endothelial cells (ECs) in the arterial wall and vascular smooth muscle cells (VSMCs), which adopt a pericytic arrangement and establish peg-and-socket junctions with ECs. In conclusion, angiogenesis and vessel regression play an important role in AIT development in the conditions studied, with participation of intussusceptive angiogenesis during the formation and regression of a provisional microvasculature and with morphologic interrelation between ECs and VSMCs.

Histopathological findings in a COVID-19 patient affected by ischemic gangrenous cholecystitis.

BACKGROUND: Since its first documentation, a novel coronavirus (SARS-CoV-2) infection has emerged worldwide, with the consequent declaration of a pandemic disease (COVID-19). Severe forms of acute respiratory failure can develop. In addition, SARS-CoV-2 may affect organs other than the lung, such as the liver, with frequent onset of late cholestasis. We here report the histological findings of a COVID-19 patient, affected by a tardive complication of acute ischemic and gangrenous cholecystitis with a perforated and relaxed gallbladder needing urgent surgery. CASE PRESENTATION: A 59-year-old Caucasian male, affected by acute respiratory failure secondary to SARS-CoV-2 infection was admitted to our intensive care unit (ICU). Due to the severity of the disease, invasive mechanical ventilation was instituted and SARS-CoV-2 treatment (azithromycin 250 mg once-daily and hydroxychloroquine 200 mg trice-daily) started. Enoxaparin 8000 IU twice-daily was also administered subcutaneously. At day 8 of ICU admission, the clinical condition improved and patient was extubated. At day 32, patient revealed abdominal pain without signs of peritonism at examination, with increased inflammatory and cholestasis indexes at blood tests. At a first abdominal CT scan, perihepatic effusion and a relaxed gallbladder with dense content were detected. The surgeon decided to wait and see the evolution of clinical conditions. The day after, conditions further worsened and a laparotomic cholecystectomy was performed. A relaxed and perforated ischemic gangrenous gallbladder, with a local tissue inflammation and perihepatic fluid, was intraoperatively met. The gallbladder and a sample of omentum, adherent to the gallbladder, were also sent for histological examination. Hematoxylin-eosin-stained slides display inflammatory infiltration and endoluminal obliteration of vessels, with wall breakthrough, hemorrhagic infarction, and nerve hypertrophy of the gallbladder. The mucosa of the gallbladder appears also atrophic. Omentum vessels also appear largely thrombosed. Immunohistochemistry demonstrates an endothelial overexpression of medium-size vessels (anti-CD31), while not in micro-vessels, with a remarkable activity of macrophages (anti-CD68) and T helper lymphocytes (anti-CD4) against gallbladder vessels. All these findings define a histological diagnosis of vasculitis of the gallbladder. CONCLUSIONS: Ischemic gangrenous cholecystitis can be a tardive complication of COVID-19, and it is characterized by a dysregulated host inflammatory response and thrombosis of medium-size vessels.

Hallazgos y propuesta de sistematización de las variaciones quirúrgicamente importantes de la arteria cística en un estudio in vivo en 2000 colecistectomías laparoscópicas ambulatorias / Findings and proposal for systematization of surgically important variations of the cystic artery based on an in vivo study of 2000 outpatient laparoscopic cholecystectomies

Realizar un estudio anatómico in vivo con la especial y pequeña disección quirúrgica durante una colecistectomía laparoscópica sobre las variaciones de la arteria cística. Estudio prospectivo de 38 meses, en 2000 pacientes consecutivos sometidos a colecistectomía laparoscópica programada, sin signos de inflamación aguda, ni alteración que impida disección y correcta evaluación del triángulo hepatocístico. Se disecó quirúrgicamente identificándose la arteria cística y posible duplicación, eran clínicamente importantes aquellas con diámetro mayor a 1,5 mm, requerían maniobra hemostática. Se anotaron los hallazgos en planilla especial a los fines del presente estudio. En 1831 casos había arteria única en medio del triángulo hepatocístico. Hubo 169 variaciones (8,45 %). En 97 casos: doble vascularización, con una arteria en situación normal y otra ubicada lateralmente al triangulo hepatocístico. En 44 pacientes había una arteria única lateralmente al conducto cístico que no lo cruzaba nunca. En 22 casos existía una arteria cruzando el colédoco y el cístico entrando en el triángulo. En 6 oportunidades una doble arteria, una en el triángulo hepatocístico y otra lateralmente que no cruzaba el cístico ni colédoco. En una oportunidad se observó una sola arteria importante que salía directamente de la placa cística entre segmento 4 y 5, y en otro caso solo pequeñas arterias proveniente de la placa cística. Podemos dividirlas en arterias únicas o dobles, en base exclusiva a la necesidad de maniobra hemostática. Podemos decir que las variaciones estarán presentes en aproximadamente 1/12 casos y necesitará una maniobra hemostática especial en 1/20 casos.

This is an anatomical study with the special and small dissection of a laparoscopic cholecystectomy on the surgically important variations of the cystic artery. A prospective, 19-month study was conducted in 2000, including consecutive patients undergoing programmed laparoscopic cholecystectomy, without signs of acute inflammation, or alteration, that would prevent dissection and correct evaluation of the cystohepatic triangle. It was surgically dissected, identifying the main cystic artery and its possible collateral arteries. Those with a diameter greater than 1.5 mm being considered as clinically important, requiring haemostatic maneuver (clipping and / or electrocoagulation). The findings were recorded on a special form for the purposes of this study. The classic, single-artery arrangement in the middle of the cystohepatic triangle was found in 1831 cases. The variations found were 169 (8.45 %). In 97 cases there was double vascularization, with one artery in normal position and another outside the cystic duct. In 44 patients, a single artery that did not cross the cystic was observed. In 22 cases an artery outside the cystic but crossing it before the duct. In 6 cases a double artery, one in the cystohepatic triangle and another outside the triangle, did not cross the cystic or the bile duct. In one instance, a single major artery was seen emerging directly from the cystic plaque between segments four and five. These can be divided into single or double arteries, based exclusively on the need for hemostatic maneuver. Knowledge of anatomical variations of the cystic artery is important for the surgeon. The variation presents in 1 of 12 cases, and requires a special hemostatic maneuver in 1 of 20 cases.

Liver transplantation as a rescue surgery after failure of embolization of a giant hepatic artery pseudoaneurysm.

We present the case of a male diagnosed with a giant hepatic artery aneurysm, which first presented with pain and hemorrhage due to a partial rupture of the aneurysm. After discarding treatment with a stent or surgery due to the wide extension, we chose to embolize the hepatic artery with coils. However, the progress was unfavorable after the procedure, with the appearance of liver failure that was resolved by an urgent liver transplantation. Giant hepatic artery pseudoaneurysms are an infrequent entity and their management is a great challenge. The diagnosis is usually delayed due to non-specific clinical signs and the life of the patient may be threatened in the case of rupture. Thus, endovascular or surgical treatment is recommended. Aneurysm embolization or ligation has been described in the literature as a valid treatment option in cases where revascularization by stent or bypass is not possible, as it preserves the viability of the liver due to the portal flow and collateral arteries. However, in the case of the failure of these treatments, liver transplantation is a rescue option.

Bleeding from gallbladder varices in a patient with an unknown liver cirrhosis. An exceptional entity.

Liver cirrhosis is a disease related to numerous severe complications such as portal hypertension or collateral circulation. Varices that are located outside the gastroesophageal region (ectopic varices) such as the anorectal region, colon, ileum or gallbladder are unusual. In many cases, they are related to the existence of portal vein thrombosis. We report the case of a patient with a severe hemorrhage of gallbladder varices due to alcohol-related cirrhosis.

Cholecystic Venous Anatomy: A Cadaveric Study with Implications for Portal Venous Interruption Procedure.

The techniques of portal vein embolization (PVE) or ligation (PVL) have the goals of combining an induced atrophy of metastatic segments with the rapid relative compensatory hypertrophy of the postresection future liver remnant (FLR). Our study examines the anatomy of right-left hepatic lobar venous connections in the adult cadaver using corrosion cast analysis in an effort to define some of the inherent anatomical reasons why both PVL and PVE may be technically unsuccessful. Corrosion cast models of 215 cadaveric liver specimens were evaluated for hepatopetal venous blood flow, with a particular emphasis on cholecystic venous drainage patterns, including 57 cases prepared after lobar portal venous ligation. In 88.8 per cent of corrosion casts, there was a segmental venous communication between the gallbladder and all segments of the liver, except segment II. There was cystic vein drainage directly into a main lobar branch or directly into the portal vein itself in 11.2 per cent of cases. In all 57 cases, after portal lobar venous division, in situ cystic veins allowed persistent venous communication between lobes. Our cadaveric corrosion cast study has suggested that there is extensive intrahepatic cholecystic venous drainage to many segments of the liver. Perfusion from the gallbladder may potentially contribute to a limited response to procedures which interrupt the portal venous flow and could affect their capacity to induce an adequate FLR which would permit a wider hepatectomy.

Anatomy of rodent and human livers: What are the differences?

The size of the liver of terrestrial mammals obeys the allometric scaling law over a weight range of >3 ∗ 106. Since scaling reflects adaptive changes in size or scale among otherwise similar animals, we can expect to observe more similarities than differences between rodent and human livers. Obvious differences, such as the presence (rodents) or absence (humans) of lobation and the presence (mice, humans) or absence (rats) of a gallbladder, suggest qualitative differences between the livers of these species. After review, however, we conclude that these dissimilarities represent relatively small quantitative differences. The microarchitecture of the liver is very similar among mammalian species and best represented by the lobular concept, with the biggest difference present in the degree of connective tissue development in the portal tracts. Although larger mammals have larger lobules, increasing size of the liver is mainly accomplished by increasing the number of lobules. The increasing role of the hepatic artery in lobular perfusion of larger species is, perhaps, the most important and least known difference between small and large livers, because it profoundly affects not only interventions like liver transplantations, but also calculations of liver function.

Hemobilia due to cystic artery pseudoaneurysm following cholecystectomy: diagnosis and management, a case report.

Hemobilia is an unusal cause of upper gastrointestinal bleeding and may be the result of the formation of an hepatic vessel pseudoaneurysm. This is a rare occurence after laparoscopic or open cholecistectomy. The most importants factor for pathogenesis are direct or indirect iatrogenic injuries during intervention and hepatic trauma. Clinical presentation may also be late and includes more frequently upper gastrointestinal bleeding due to pseudoaneurysm rupture, abdominal pain and jaundice secondary to bile duct compression. Therapies includes trans arterial embolization of feeding artery and percutaneous ingjection of embolic devices into the aneurysm. Surgery must be reserved for cathether based therapy failure. We report a case of a 66 year old man, presenting a month after cholecystectomy, complaining abdominal pain in the upper right quadrant and hematemesis. An EGDS exam showed hemobilia and computed tomography (CT) revealed a cistic artery pseudoaneurysm (PSA) wich have been successfully treated with hyperselective arterial embolization. Although this is a rare complication the surgeon must be aware of related symptoms and signs in order to sospect pseudoaneurysm as prompt recognition and treatment are essential. Untreated haemobilia may determine an immediate threat to life leading to acute haemodynamic instability We describe both diagnostic features and therapeutic strategies in comparison to the most recent literature. (www.actabiomedica.it).

Gallbladder varices in a pediatric patient after roux-en-Y gastric bypass.

This is a case with associated radiologic images for a pediatric patient who developed portomesenteric and splenic vein thrombosis (PMSVT) after Roux-en-Y gastric bypass with subsequent development of portal cavernoma and gallbladder varices (GBV). This case highlights both the importance of post-operative prophylactic anti-coagulation after gastric bypass and detailed imaging following a diagnosis of PMSVT. This case is relevant for pediatric surgeons as they are performing this operation more frequently with the increase in pediatric obesity.

[Cavernoma complicated with biliopatia secondary to type 1 Gaucher disease: report of a Peruvian case]. / Cavernoma portal complicada con biliopatía secundario a enfermedad de Gaucher tipo 1: reporte de un caso peruano.

Gaucher disease is an autosomal recessive lysosomal storage disorder characterized by deficiency of beta-glucosidase that would lead to the accumulation of glucosylceramide mainly in cells of the mononuclear phagocytic system causing systemic effectations. We present a patient of twenty years who is suffering from chronic pain in the left hypochondrium with episodes of bleeding for 3 years and sensation of thermal rise, physical examination revealed jaundice and massive splenomegaly, without neurological involvement. Severe osteoporosis, pancytopenia, and the presence of portal vein thrombosis with cavernomatous transformation complicated by portal biliopathy simulating a klatskin tumor, marrow and enzymatic studies were compatible with Gaucher disease, were shown as unexpected findings. he received treatment with imiglucerase, following up. It is a rare case, of great interest, heterogeneity in its clinical manifestations and unpublished by its complication, constituting a challenge to reach its diagnosis of this orphan disease.

An unusual presentation of gall bladder papillomatosis in association with metachromatic leukodystrophy.

A 5-year-old boy with metachromatic leukodystrophy, debilitated by spastic quadriparesis presented to us with massive ascites and respiratory distress. A subtotal cholecystectomy was performed on him from another centre for a gall bladder mass a year before he came to us. Imaging revealed a polypoidal frond-like mass arising from the gall bladder fossa which was supplied by a hypertrophied branch of the right hepatic artery. A decision was made to offer surgical resection preceded by embolisation of the feeding vessel. At surgery, a polypoidal frond-like mass in communication with the peritoneal cavity was seen arising from the remnant gall bladder bed with over 4 L of mucoid ascites. The mass along with the remnant gall bladder was removed. Biopsy revealed villous papilloma of the gall bladder. The child is well and asymptomatic at 5-month follow-up.