Perimuscular Connective Tissue Research Articles

NCDB analysis of the 8th ajcc gallbladder staging system: validating the T2 subclassification change

Background: In 2018, T-staging for cancers involving the gallbladder were updated to stratify T2 cancers by invasion through the perimuscular connective tissue on the peritoneal side (T2a) versus the liver side (T2b). A multicenter retrospective study from Shindoh et al established the prognostic power of tumor location after curative resection of T2 gallbladder cancer, but this update has yet to be validated with larger scale national data. The newest NCDB dataset offers the opportunity to evaluate survival for T2a and T2b cancers from hospital registry data. In this study, we sought to determine if a difference in survival exists between T2a and T2b tumors.

The relationship between clinical examination measures and ultrasound measures of fascia thickness surrounding trunk muscles or lumbar multifidus fatty infiltrations: An exploratory study.

Patients with chronic low back pain (CLBP) exhibit remodelling of the lumbar soft tissues such as muscle fatty infiltrations (MFI) and fibrosis of the lumbar multifidus (LuM) muscles, thickness changes of the thoracolumbar fascia (TLF) and perimuscular connective tissues (PMCT) surrounding the abdominal lateral wall muscles. Rehabilitative ultrasound imaging (RUSI) parameters such as thickness and echogenicity are sensitive to this remodelling. This experimental laboratory study aimed to explore whether these RUSI parameters (LuM echogenicity and fascia thicknesses), hereafter called dependent variables (DV) were linked to independent variables (IV) such as (1) other RUSI parameters (trunk muscle thickness and activation) and (2) physical and psychological measures. RUSI measures, as well as a clinical examination comprising physical tests and psychological questionnaires, were collected from 70 participants with LBP. The following RUSI dependent variables (RUSI-DV), measures of passive tissues were performed bilaterally: (1) LuM echogenicity (MFI/fibrosis) at three vertebral levels (L3/L4, L4/L5 and L5/S1); (2) TLF posterior layer thickness, and (3) PMCT thickness of the fasciae between subcutaneous tissue thickness (STT) and external oblique (PMCTSTT/EO ), between external and internal oblique (PMCTEO/IO ), between IO and transversus abdominis (PMCTIO/TrA ) and between TrA and intra-abdominal content (PMCTTrA/IA ). RUSI measures of trunk muscle's function (thickness and activation), also called measures of active muscle tissues, were considered as independent variables (RUSI-IV), along with physical tests related to lumbar stability (n=6), motor control deficits (n=7), trunk muscle endurance (n=4), physical performance (n=4), lumbar posture (n=2), and range of motion (ROM) tests (n=6). Psychosocial measures included pain catastrophizing, fear-avoidance beliefs, psychological distress, illness perceptions and concepts related to adherence to a home-based exercise programme (physical activity level, self-efficacy, social support, outcome expectations). Six multivariate regression models (forward stepwise selection) were generated, using RUSI-DV measures as dependent variables and RUSI-IV/physical/psychosocial measures as independent variables (predictors). The six multivariate models included three to five predictors, explaining 63% of total LuM echogenicity variance, between 41% and 46% of trunk superficial fasciae variance (TLF, PMCTSTT/EO ) and between 28% and 37% of deeper abdominal wall fasciae variance (PMCTEO/IO , PMCTIO/TrA and PMCTTrA/IA ). These variables were from RUSI-IV (LuM thickness at rest, activation of IO and TrA), body composition (percent fat) and clinical physical examination (lumbar and pelvis flexion ROM, aberrant movements, passive and active straight-leg raise, loaded-reach test) from the biological domain, as well as from the lifestyle (physical activity level during sports), psychological (psychological distress-cognitive subscale, fear-avoidance beliefs during physical activities, self-efficacy to exercise) and social (family support to exercise) domains. Biological, psychological, social and lifestyle factors each accounted for substantial variance in RUSI-passive parameters. These findings are in keeping with a conceptual link between tissue remodelling and factors such as local and systemic inflammation. Possible explanations are discussed, in keeping with the hypothesis-generating nature of this study (exploratory). However, to impact clinical practice, further research is needed to determine if the most plausible predictors of trunk fasciae thickness and LuM fatty infiltrations have an effect on these parameters.

Adenomatous Hyperplasia Mimicking Adenocarcinoma of the Gallbladder – Diagnostic Dilemma Resolved with Immunohistochemistry: A Case Report with Review of Literature

Adenomatous hyperplasia (AH) of the gallbladder is an uncommon and unique entity. AH is commonly confused with malignant GB neoplasms in the setting of chronic cholecystitis, gallstones or cholesterolosis. We herein report a case of AH with deep seated RA sinuses mimicking gallbladder cancer in a middle-aged female in the setting of symptomatic cholecystitis with cholelithiasis and cholesterolosis. In our case microscopy showed diffuse villous type of mucosal hyperplasia with proliferative, bland looking densely packed glands with numerous closely opposed R-A sinuses extending upto the peri muscular connective tissue. The whole microscopic picture closely simulating a well differentiated gall bladder carcinoma (GBC), hence warranted use of IHC to resolve the dilemma and to reach a definitive diagnosis. A literature search yields minimal information on these benign entities, thus suggesting the infrequency of its reporting, hence the need for this case report.

Simple cholecystectomy is an adequate treatment for grade I T1bN0M0 gallbladder carcinoma: Evidence from 528 patients

BACKGROUNDT1b gallbladder carcinoma (GBC) is defined as a tumor that invades the perimuscular connective tissue without extension beyond the serosa or into the liver. However, controversy still exists over whether patients with T1b GBC should undergo cholecystectomy alone or radical GBC resection.AIMTo explore the optimal surgical approach in patients with T1b gallbladder cancer of different pathological grades.METHODSPatients with T1bN0M0 GBC who underwent surgical treatment between 2000 and 2017 were included in the Surveillance, Epidemiology, and End Results database. The Kaplan-Meier method and log-rank test were used to analyze the overall survival (OS) and disease-specific survival (DSS) of patients with T1b GBC of different pathological grades. Cox regression analysis was used to identify independent predictors of mortality and explore the selection of surgical methods in patients with T1b GBC of different pathological grades and their relationship with prognosis.RESULTSOf the 528 patients diagnosed with T1bN0M0 GBC, 346 underwent simple cholecystectomy (SC) (65.5%), 131 underwent SC with lymph node resection (SC + LN) (24.8%), and 51 underwent radical cholecystectomy (RC) (9.7%). Without considering the pathological grade, both the OS (P < 0.001) and DSS (P = 0.003) of T1b GBC patients who underwent SC (10-year OS: 27.8%, 10-year DSS: 55.1%) alone were significantly lower than those of patients who underwent SC + LN (10-year OS: 35.5%, 10-year DSS: 66.3%) or RC (10-year OS: 50.3%, 10-year DSS: 75.9%). Analysis of T1b GBC according to pathological classification revealed no significant difference in OS and DSS between different types of procedures in patients with grade I T1b GBC. In patients with grade II T1b GBC, obvious survival improvement was observed in the OS (P = 0.002) and DSS (P = 0.039) of those who underwent SC + LN (10-year OS: 34.6%, 10-year DSS: 61.3%) or RC (10-year OS: 50.5%, 10-year DSS: 78.8%) compared with those who received SC (10-year OS: 28.1%, 10-year DSS: 58.3%). Among patients with grade III or IV T1b GBC, SC + LN (10-year OS: 48.5%, 10-year DSS: 72.2%), and RC (10-year OS: 80%, 10-year DSS: 80%) benefited OS (P = 0.005) and DSS (P = 0.009) far more than SC (10-year OS: 20.1%, 10-year DSS: 38.1%) alone.CONCLUSIONSimple cholecystectomy may be an adequate treatment for grade I T1b GBC, whereas more extensive surgery is optimal for grades II-IV T1b GBC.

Incidental Gallbladder Carcinoma: An Eastern Indian Experience and Necessity of Routine Histopathological Examination after All Cholecystectomy

Introduction: The carcinoma of gallbladder is the most common malignancy of the biliary tract. The incidence of this carcinoma varies geographically. Incidental gallbladder carcinoma is diagnosed during histopathological examination after cholecystectomy due to other reasons. Histopathological examination of all cholecystectomy specimens are very essential to rule out these incidental gallbladder carcinomas. Aim: To this study to estimate the frequency of incidental gallbladder carcinoma in patients undergoing routine cholecystectomy and also to evaluate the necessity of routine histopathological examination after all cholecystectomy. Materials and Methods: A retrospective observational study was conducted in Department of Pathology, Midnapore Medical College and Hospital, West Bengal, India between January 2014 to December 2019 (six years) covering 650 patients who underwent laparoscopic and open cholecystectomy. Patients' demographic data, pathologic results, macroscopic appearance of the specimen, cancer staging were recorded and frequency of incidental gallbladder carcinoma were calculated. Result: Total 650 cholecystectomy specimens due to benign gallbladder disease were received in pathology department. Histopathological examination revealed 18 cases of incidental gallbladder carcinoma which comprised 2.8% of all the cholecystectomies. Among them 13 were female and five were in male with male: female ratio of 1:2.6 and the age ranges from 35 to 68 years. Among 18 cases 10 cases showed invasion upto lamina propria (stage T1a), five) cases had invasion in muscular layer (stage T1b) and three cases showed perimuscular connective tissue invasion (stage T2a). Conclution: The present study observed that the incidence of incidental gallbladder carcinoma in cholecystectomy specimen was little higher range in East Indian population and so routine histopathological examination of all cholecystectomy specimens are recommended.

Intermittent pain in patients with chronic low back pain is associated with abnormalities in muscles and fascia.

We investigated the relationship between paravertebral muscles and perimuscular connective tissues of the thoracolumbar fascia region and the four types of pain in patients suffering from chronic low back pain. A total of 17 patients with chronic low back pain participated in this study. Ultrasound imaging method was used to measure the thickness and echogenicity of the paravertebral muscles and perimuscular connective tissues. The measurement site considered in this study was located lateral to the midpoint between L2-3 and L4-5 spines. In addition, age, gender, BMI, numerical rating scale and the short-form McGill pain questionnaire 2 (includes questions with respect to continuous pain, intermittent pain, neuropathic pain and affective descriptors) were used for assessment. Statistical analysis was performed using correlation analysis and multiple regression analysis. A significant association was observed between paravertebral muscle echogenicity at L2-3 and the numerical rating scale (r = 0.499), between paravertebral muscle echogenicity at L4-5 with numerical rating scale (r = 0.538) and intermittent pain (r = 0.594), and between perimuscular connective tissue thickness at L2-3 and numerical rating scale (r = 0.762). We observed that the factor influencing perimuscular connective tissue thickness at L2-3 and L4-5 was intermittent pain (β = 0.513, β = 0.597, respectively). It was also observed that some of the imaging findings were associated with age and BMI. In conclusion, we observed that paravertebral muscle echogenicity and perimuscular connective tissue thickness in patients with chronic low back pain were associated with pain, especially intermittent pain.

Structural remodeling of the lumbar multifidus, thoracolumbar fascia and lateral abdominal wall perimuscular connective tissues: Medium-term test-retest reliability of ultrasound measures

IntroductionGrowing interest is being paid to the lumbar multifidus (LM) intramuscular fatty infiltrations and fibrosis that are secondary to low back pain as well to the remodeling of perimuscular connective tissues (fasciae) such as the thoracolumbar fascia and fascia sheets separating the abdominal wall muscles. Magnetic resonance imaging and computed tomography have traditionally been used but rehabilitative ultrasound imaging (RUSI) is much more affordable and practical, which can accelerate research and clinical applications on this topic. The aim of this study was to test the medium-term (8 weeks) test-retest reliability of the corresponding RUSI measures. MethodsThirty-four participants with non-acute LBP and 30 healthy controls performed a RUSI assessment before and after an 8-week time interval. LM echogenicity was quantified to assess fatty infiltrations and fibrosis while fasciae were quantified with thickness measures. Relative and absolute reliability were estimated using the generalizability theory as a framework, allowing to partition the different sources of error. ResultsOverall, the reliability findings were quite acceptable, with negligible systematic effects. Excellent relative reliability was reached in half of the investigated RUSI measures, particularly when averaging measures across trials. However, neither relative, nor absolute reliability results support the use of these RUSI measurements on an individual basis (e.g. clinical applications) but they are useful on a group basis (e.g. research applications). DiscussionThe different sources of error were distributed unequally across RUSI measures, pointing to different measurement strategies to mitigate the underlying errors. ConclusionsThe use of the generalizability theory allowed identifying the sources of error of the different RUSI measures. For each category of measure, depending of the distribution of errors, it was possible to recommend specific measurement strategies to mitigate them.

Intra-rater reliability of measurement of abdominal perimuscular connective tissue thickness on ultrasound images.

[Purpose] The thickness of the perimuscular connective tissue (PMCT) reflects muscular atrophy and decreased flexibility that may cause low back pain. However, few studies have used ultrasound imaging to measure PMCT thickness. We aimed to examine and confirm the reliability of ultrasound in measuring the thickness of the PMCT of the abdominal wall muscle. [Participants and Methods] The participants were 38 healthy adult males without chronic back pain. The images were acquired in B mode with the participants in the supine position and the PMCT thickness of the abdominal wall muscle was measured on the images. The intraclass correlation coefficient (ICC) was used to confirm reliability. [Results] The ICC for both within-day and between-day PMCT measurements by ultrasound were 0.7–0.9. The 95% confidence interval ranged from 0.5–0.9. The standard error of measurement (SEM) was 0.02–0.1 mm in the abdominal wall muscle and 0.5 mm in the interrecti distance (IRD). The 95% confidence interval (95% CI) of the minimum detectable change (MDC95) was 0.1–0.3 mm in the abdominal wall muscle and 1.3–1.4 mm in the IRD. [Conclusion] We conducted a study to confirm the reliability of ultrasound-based measurement of PMCT thickness of the abdominal wall muscle, and the ICC results established reliability. However, since the values measured were small (0.02–1.4 mm) and there is a limit to visual observation, it was necessary to measure using computer software.

Unusual cause of abdominal pain in a young adult: The clinical pitfalls of adenocarcinoma of the gallbladder with liver invasion

Gallbladder (GB) cancer is a rare cause of abdominal pain in young adults. It is difficult to confirm an immediate and correct diagnosis based on the presentation of an acute episode of abdominal pain. We report a 36-year-old man who was referred to our hospital because of right upper abdominal pain that had persisted for 1 month. The tentative diagnosis was gallstone-induced acute on chronic cholecystitis according to the clinical symptoms/signs and imaging studies. Laparoscopic cholecystectomy (LC) was performed after admission. Histological examination revealed adenocarcinoma of the GB that was moderately differentiated and invading the perimuscular connective tissue. Magnetic resonance imaging was performed after the surgery, showing negativity for the invasion to other organs. Laparoscopic bisegmentectomy of the liver (seg. 4b + 5) and lymph node dissection was performed following LC. Adjuvant chemotherapy was administered, and the patient is currently alive without recurrence for 6 months. The uncommon etiology of cholecystitis in young adults is discussed.

Structural remodeling of the lumbar multifidus, thoracolumbar fascia and lateral abdominal wall perimuscular connective tissues: A search for its potential determinants.

Recently remodeling of lumbar soft tissues has received increased research attention. However, the major determinants that influence remodeling need to be elucidated in order to understand the impact of different rehabilitation modalities on tissue remodeling. The main aim of this study was to explore the between-subject variance of different measures of lumbar soft tissues quantified with rehabilitative ultrasound imaging (RUSI). RUSI measures (n=8) were collected from 30 subjects without and 34 patients with LBP: (1) lumbar multifidus (LM) echogenicity (fatty infiltration/fibrosis) at three vertebral levels (L3/L4, L4/L5 and L5/S1) (n=3); (2) posterior layer thickness of the thoracolumbar fascia (n=1); and (3) thickness of the fasciae surrounding the external oblique (EO), internal oblique (IO), and transversus abdominis (TrA) (n=4). Forward stepwise multivariate regression modeling was conducted with these RUSI measures as dependent variables, using the following independent variables as potential determinants: age, sex, the presence of LBP, body size/composition characteristics (height, weight, trunk length, subcutaneous tissue thickness over the abdominal, and LM muscles), trunk muscle function (or activation) as determined with the percent thickness change of LM, EO, IO, and TrA muscles during a standardized effort (RUSI measures), and physical activity level during sport and leisure activities as estimated with a self-report questionnaire. Two or three statistically significant predictors (or determinants) were selected in the regression model of each RUSI measure (n=8 models), accounting for 26-64% of their total variance. The subcutaneous tissue thickness on the back accounted for 15-30% variance of LM echogenicity measures and thoracolumbar fascia thickness while the subcutaneous tissue thickness over the abdominals accounted for up to 42% variance of the fascia separating the subcutaneous adipose tissues and the EO muscle. The thickness of IO at rest accounted for 13-21% variance of all investigated abdominal fasciae except the fascia separating the subcutaneous adipose tissue and EO. Pain status accounted for 13-18% variance of the anterior and posterior fasciae of the TrA. Age accounted for 11-14% variance of LM echogenicity at all investigated vertebral levels while sex accounted for 15-21% variance of LM echogenicity at L3/L4 and fascia separating subcutaneous adipose tissue and EO muscle. The function (or activation) of EO and LM at L3/L4 accounted for 8-11% variance of the thoracolumbar fascia and fascia separating TrA and intra-abdominal content (TrA posterior fascia), respectively. Finally, the physical activity level during sport activities accounted for 7% variance of the fascia separating the subcutaneous adipose tissues and the EO muscle. These findings suggest that determinants other than body size characteristics may impact the remodeling of lumbar soft tissues, more importantly the subcutaneous adipose tissue deposits (thickness RUSI measures), which are associated with ectopic fat deposition in the LM and in the fasciae that are more closely positioned to the surface. While age, sex, and pain status explain some variability, modifiable factors such as physical activity level as well as trunk muscle thickness and function were involved. Overall, these results suggest that rehabilitation can potentially impact tissue remodeling, particularly in terms of intramuscular and perimuscular adipose tissues.

S1601 Malignant Melanoma of the Gallbladder Masquerading as Cholangitis and Cholecystitis

INTRODUCTION: Metastatic Malignant melanoma is reported in the stomach, intestine and colon. The involvement of the gallbladder and the bile duct are extremely rare. CASE DESCRIPTION/METHODS: A 61-year-old male presented with abdominal pain, nausea, vomiting, fever, chills, and 10lb weight loss. Physical examination was notable for right upper quadrant abdominal tenderness with a positive Murphy’s sign and minimal jaundice. Lab data showed no leukocytosis and normal hemoglobin. Elevated liver tests with Alk Phos 435U/L, ALT 546U/L, AST 474U/L, and Tbili 3.1mg/dl prompted an abdominal ultrasound which showed intrahepatic and extrahepatic bile duct dilatation (common bile duct (CBD) 11mm). A diffusely abnormal thick-walled gall bladder filled with debris was seen. This was concerning for cholecystitis and cholangitis. He was started on piperacillin/tazobactam. An endoscopic ultrasound (EUS) revealed hyperechoic material suggestive of thick sludge versus tissue within gallbladder lumen extending into the CBD (Figure 1a). Endoscopic retrograde cholangio-pancreatography (ERCP) revealed irregular filling defects within CBD close to cystic duct takeoff (Figure 1b). After sphincterotomy, balloon sweeps evacuated pigmented tissue debris (Figure 1c) which was retrieved and sent for pathology. Unusual EUS/ ERCP findings prompted an MRI which showed high T1 signal within periportal nodes and gallbladder suggesting hemorrhage. Surgical consultation was obtained and patient underwent laparoscopic cholecystectomy, but frozen section indicated malignancy, therefore, an open liver resection and lymphadenectomy was completed. The gross pathology showed a 2.5 × 1.6 × 1.5cm mass arising from the gallbladder (Figure 2a) with invasion into the peri muscular connective tissue on the hepatic side but with no direct extension. An immunostain on the tumor and the prior biliary tissue debris showed positive staining for Vimentin, and S100 and a diagnosis of melanoma was confirmed (Figures 2b and 2c). Surgical staging was pT2bN1. Skin and ocular examination did not reveal any lesions. DISCUSSION: Melanoma involving the gastrointestinal tract is usually metastatic from known cutaneous melanoma; however primary melanoma of the GI tract have been reported. Within the GI tract, primary gallbladder melanoma is extremely rare with less than 40 cases reported in the literature. Clinical course is typically aggressive; our patient developed metastatic disease to brain soon after gallbladder resection.Figure 1.: EUS and ERCP image.Figure 2.: Pathology image.

Structural remodelling of the lumbar multifidus, thoracolumbar fascia and lateral abdominal wall perimuscular connective tissues: A cross-sectional and comparative ultrasound study

IntroductionWith low back pain (LBP), remodelling of the lumbar soft tissues involves both trunk muscles and neighbouring passive connective tissues. The aim of the present study was to compare three quantitative measures of these tissues, using ultrasound imaging (USI), among healthy controls and individuals with LBP. MethodsUSI measures from 30 healthy subjects and 34 patients with non-acute LBP were compared between groups and sexes. The measures employed were (1) lumbar multifidus echogenicity (fatty/fibrosis infiltration) at three vertebral levels; (2) posterior layer thickness of the thoracolumbar fascia, and (3) thickness of the perimuscular tissues surrounding the external oblique, internal oblique and transversus abdominis (TrA). ResultsUSI measures of (1) multifidus echogenicity showed statistically significant changes between vertebral levels and sexes (females > males; p = 0.02); (2) differences in thoracolumbar fascia thickness approached statistical significance between groups (LBP > controls; p = 0.09) and sexes (females < males; p = 0.07); and (3) perimuscular tissue surrounding the TrA was significantly thinner (p ≤ 0.001) in patients with LBP compared to controls. DiscussionThe thinner perimuscular tissues surrounding the TrA in patients with LBP is a new finding, concurring with previous findings with regard to the lower activation of this deep muscle as well as more recent findings on other perimuscular tissue. ConclusionOverall, USI measures were sensitive to different potential changes (pain status, sex, vertebral level), and this is useful in studying the remodelling of various soft tissues of the trunk.

Haemocholecyst related to gallbladder malignancy

A haemocholecyst is a clot-filled gallbladder caused by bleeding into its lumen. It is a rare entity with fewer than 50 cases reported in the English literature. Preoperative diagnosis is often not possible even with good quality cross-sectional imaging. Here, we present a case of a gallbladder mass, whose nature was only made clear at operation, where a hugely enlarged gallbladder was found filled with blood clots. There was neither liver infiltration nor regional lymphadenopathy. The clinical status of the patient demanded simple cholecystectomy. Histopathological examination, however, revealed a gallbladder adenocarcinoma, infiltrating the perimuscular connective tissue. Thus, more radical surgery was performed eight weeks later. At the 21-month follow-up, the patient was found to be well.

Is postural control during unstable sitting a proxy measure for determinants associated with lumbar stability?

The aim of this study was to test whether determinants associated with lumbar stability can predict performance during unstable sitting (trunk postural control - TPC). If confirmed, unstable sitting could be viewed as a proxy measure for these determinants.Wobbling chair motion was measured in 58 subjects with an inertial sensor, and six outcomes were computed (mean frequency and velocity, frequency dispersion, two variables from the sway density analysis and Lyapunov exponent - short interval) to represent TPC performance. Subjects also performed five other trunk neuromuscular tests to quantify the thickness of back and abdominal muscles and connective tissues, lumbar proprioception, lumbar stiffness, feedforward and feedback control mechanisms, and trunk/muscle coordination.Four to five predictors explained between 36 and 47% of TPC outcomes variance, as determined with multivariate analyses. These predictors were mainly related to (1) angular kinematic parameters of the pelvis or lumbar spine following rapid arm movement, (2) lumbar intrinsic stiffness, (3) thickness of perimuscular connective tissues surrounding specific abdominal muscles, (4) activation onsets of specific trunk muscles (IO/TrA and iliocostalis lumborum) before rapid arm movement, and (5) percent thickness change of internal oblique (IO) and transversus abdominis (TrA) muscles. Lumbar proprioception and reflex responses were not predictive, possibly due to the lack of appropriate measurements.These findings support the use of TPC in unstable sitting as a proxy measure for determinants associated with lumbar stability. This might be useful in research and clinical settings, considering time and equipment constraints associated with measuring these determinants individually.

Mixed Neuroendocrine-Nonneuroendocrine Carcinoma Arising in the Gallbladder: A Rare Case of a Three-Component Composite Neoplasm

Abstract Introduction Neuroendocrine gallbladder neoplasms are rare, comprising 0.5% of all neuroendocrine cancers and about 2% of gallbladder cancers. Interestingly, those neoplasms can also be observed along with other malignant components of epithelial origin, mostly adenocarcinomas. Herein we report an unusual case of a patient with a gallbladder neoplasm composed of a neuroendocrine carcinoma, a squamous cell carcinoma, and an adenocarcinoma. Methods The patient was a 62-year-old woman who presented with right upper quadrant abdominal pain with a positive Murphy’s sign on physical examination. She was clinically diagnosed with acute cholecystitis and underwent cholecystectomy. Gross examination showed a 5-cm exophytic mass at the gallbladder fundus. Histopathologic examination of the mass showed an infiltrating squamous cell carcinoma and an adjacent high-grade neuroendocrine carcinoma; each of these two components composed more than 30% of the neoplasm and infiltrated into the perimuscular connective tissue with no serosal involvement. Additionally, a superficial adenocarcinoma component was also seen composing 10% of the neoplasm. The squamous cell carcinoma showed moderate differentiation with areas of keratinization; it was positive for Ck7, p40, and p63. The neuroendocrine carcinoma showed areas of geographic necrosis, and the cells had inconspicuous nucleoli and granular chromatin, with numerous mitotic figures; it was positive for synaptophysin and chromogranin. The adenocarcinoma showed gland formation with mucicarmine stain, highlighting the mucin within the neoplastic cells; it was positive for Ck7 but negative for p40. Subsequently, the patient underwent resection of the liver bed, which was negative for metastasis, and was then referred for chemotherapy. Conclusion Our review of the literature revealed seven documented cases of three-component gallbladder neuroendocrine neoplasms. Generally, patients with these tumors have a poor prognosis, and due to their rarity, no specific treatment guidelines have yet been established. It has been suggested that a multipotent common stem cell is the origin of these tumors.

Ultrasonography features of abdominal perimuscular connective tissue in elite and amateur basketball players: an observational study.

The purpose of this study was to assess and compare with rehabilitative ultrasound imaging (RUSI) the perimuscular connective tissue (PMCT) and interrecti distance (IRD) between elite and amateur basketball players. A sample of 22 healthy basketball players was included and divided into two groups: elite basketball players from Spanish 1st division (n = 11) and amateur basketball players from an entertainment Spanish division (n = 11). Ultrasound images of the external oblique (EO), internal oblique (IO), transversus abdominis (TrAb), rectus anterior (RA) and IRD PMCT were measured and analysed by the ImageJ software. Measurements of abdominal wall muscles PMCT present statistically differences (P < .05) for an increase of perimuscular connective tissue of external oblique (PMCTEO), perimuscular connective tissue of transversus abdominis (PMCTTA) of the left side and an increase of PMCTEO on the right side in favor of the elite group. Rather, the study showed statistically differences (P < .05) for a decrease of perimuscular connective tissue between the internal oblique and transversus abdominis (PMCTIO-TA), and a decrease in PMCT total summation of the left side with elite group in respect to amateur group. This study reported an increase of left PMCTEO, left PMCTTAA, right PMCTEO as well as a decrease of left PMCTIO-TA and in PMCT total summation on the left side.

A 0.8-cm clear cell neuroendocrine tumor G1 of the gallbladder with lymph node metastasis: a case report

BackgroundNeuroendocrine tumors (NETs) of the gallbladder are rare and generally considered low-grade malignancies. We herein describe a case of a patient with a 0.8-cm clear cell NET G1 of the gallbladder with nodal involvement.Case presentationA 65-year-old man with no medical history indicative of von Hippel-Lindau (VHL) disease underwent laparoscopic cholecystectomy for cholecystolithiasis. There was a 0.8-cm tumor in the neck of the gallbladder. Histologic examination revealed nests or trabecular growth of clear cells with small round-to-oval nuclei. Immunohistochemically, tumor cells showed positivity for chromogranin A and synaptophysin; Ki-67 index was < 1.0%. Based on the World Health Organization 2010 classification, we made a diagnosis of clear cell variant of NET G1 without VHL disease. The tumor invaded the muscular layer and had no extension to the perimuscular connective tissue but had metastasized to a cystic duct node. A radical second resection with regional lymphadenectomy of the gallbladder was performed, and there was no metastasis on histology. After the definitive surgery, he was followed up for 10 months without adjuvant therapy and is alive and well with no evidence of recurrence.ConclusionsOur experience suggests that, even when smaller than 1 cm, NET G1 of the gallbladder can metastasize. When NET G1 is incidentally identified in the gallbladder of a surgical specimen, detailed pathologic examination of the cystic duct node, when found, should be performed to guide whether a radical second resection with regional lymphadenectomy is appropriate.

Evaluation of Surgical Procedures for T2 Gallbladder Cancer in Terms of Recurrence and Prognosis.

T2 (tumor invades perimuscular connective tissue; no extension beyond serosa or into liver) gallbladder cancer has generally been treated by S4aS5 subsegmentectomy (S4aS5 HR). We investigated the therapeutic effect of full-thickness cholecystectomy (FC) and gallbladder bed resection (GBR), in terms of tumor location and resection margin (distance from the tumor). At our department we employ the following protocol to determine the extent of resection needed to achieve R0 status: (1) A tumor located in the gallbladder fundus (Gf) or body (Gb) and only on the free peritoneal side was classified as P-type, for which full-thickness cholecystectomy and regional lymph node dissection were performed. (2) A tumor located in Gf or Gb and in contact with the liver bed was classified as H-type, for which gallbladder bed resection and regional lymph node dissection were performed. (3) A tumor located in the gallbladder neck (Gn) was classified as N-type, for which gallbladder bed resection, bile duct resection, and regional lymph node dissection were performed. Twenty-two patients admitted to our department between January 2000 and December 2014 with pT2gallbladder cancers were included in our study. Surgical procedures performed were compared with those specified in our protocol, and patients in whom the extent of resection was greater than that specified in our strategy were evaluated clinicopathologically and in terms of recurrence and the prognosis. Six (27.2%), 7 (31.8%), and 9 (40.9%) patients underwent limited, standard, and extended surgery, respectively. Ten (66.7%) of 15 patients with tumors close to the liver bed underwent cholecystectomy or extended surgery, 7 (85.7%) of 8 patients with tumors close to the bile duct underwent bile duct resection, and 16 (72.7%) of 22 patients underwent regional lymph node dissection. Recurrence at the bile duct resection margin, para-aortic lymph node metastasis, and hepatic metastasis occurred in 2, 1, and 3 patients, respectively. The 3-year survival rates (for patients including those dying of noncancer causes) were 50, 100, and 75% after limited, standard, and extended surgery, respectively. There was a significant difference in the survival rate of patients who underwent standard or extended surgery (P=0.0273). Favorable results were obtained in T2 gallbladder cancer patients without performing S4aS5 subsegmentectomy. Depending on the tumor location, neither full-thickness cholecystectomy nor gallbladder bed resection appeared to pose problems regarding recurrence or prognosis. In conclusion, surgical treatment based on our protocol, which aims to achieve the condition of R0, may result in a sufficient therapeutic effect.

Readability and histological biocompatibility of microchip transponders in horses

Identification of horses by microchip transponder is mandatory within the European Union with only a few exceptions. In this study, the readability of such microchips in 428 horses with three different scanners (A, B and C) and the histological changes at the implantation site in 16 animals were assessed. Identification of microchips differed between scanners (P<0.001), and with ‘side of neck’ (P<0.001). Scanners A, B and C identified 93.5%, 89.7% and 100% of microchips, respectively, on the ‘chip-bearing’ side of the neck. From the contralateral side, scanners A, B and C identified 21.5%, 26.9% and 89.5% of transponders, respectively. Microchip readability was affected by age (P<0.001), but not by breed of horse.At necropsy, transponders were found in the subcutaneous fat (n=3), inter- or peri-muscular connective tissue (n=8), or musculature (n=5), where they were surrounded by a fibrous capsule ranging in thickness from 12.7 to 289.5μm in 15 animals. In two animals, immature granulation tissue with attendant granulomatous inflammation, and a granulomatous myositis, surrounding the microchip were identified, respectively. Severe (n=1), moderate (n=1), and mild (n=3) lymphohistiocytic inflammation was noted within the fibrous capsule. Microchip transponders were found to be a highly reliable and biocompatible method of horse identification.

Rokitansky-Aschoff Sinuses Mimicking Adenocarcinoma of the Gallbladder

We describe 8 cases of cholecystectomy specimens (6 laparoscopic and 2 open cholecystectomies) with Rokitansky-Aschoff (R-A) sinuses that were misinterpreted as adenocarcinomas. They were compared with 8 examples of classical R-A sinuses and 6 cases of R-A sinuses containing foci of adenocarcinoma. Five cases misinterpreted as adenocarcinomas consisted of densely packed, closely opposed R-A sinuses with little intervening stroma or surrounded by a desmoplastic stroma. They were lined by a single layer of cuboidal or columnar cells. There were also pseudostratified columnar cells with mucin-containing cytoplasm and hyperchromatic or vesicular nuclei but without mitotic figures. In 2 cases, the columnar cells had subnuclear vacuoles. Small papillary projections into R-A sinuses were seen in 4 cases, and in 3 others collections of metaplastic pyloric glands, some connected to the epithelium of the sinuses, were recognized. There was focal reactive atypia in both the epithelium of the surface and that of the sinuses. The R-A sinuses resembling gland-like structures had a laminar distribution rather than a disorderly haphazard distribution seen in well-differentiated adenocarcinoma. The remaining 3 cases misinterpreted as adenocarcinomas consisted of numerous deeply penetrating long and short R-A sinuses that branched in different directions and which reach the subserosal or perimuscular connective tissue mimicking invasion. The sinuses were surrounded by hyperplastic smooth muscle bundles and lined by pseudostratified columnar cells mixed with a few goblet cells showing reactive atypia and no mitotic figures. There was focal reactive atypia in both the epithelium of the surface and that of the sinuses. The 2 types of R-A sinuses did not label with carcinoembryonic antigen or p53 and had very low proliferative activity as measured by the MIB1-labeling index. All patients are alive and disease free from 8 months to 17 years (mean follow-up 7 y). In contrast, the foci of invasive adenocarcinoma that arose in R-A sinuses consisted of glands lined by atypical cuboidal or columnar cells with loss of polarity, large hyperchromatic or vesicular nuclei, prominent nucleoli, and mitotic figures, quite different from the cells lining the R-A sinuses. Because of increasing number of laparoscopic cholecystectomies performed annually in the United States, pathologists should become familiar with these gallbladder lesions that are usually incidental findings but can simulate malignant epithelial neoplasms.