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Frontiers in Pharmacology 2024Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of...
Systemic chemotherapy is typically administered following radical gastrectomy for advanced stage. To attenuate systemic side effects, we evaluated the effectiveness of regional chemotherapy using paclitaxel, albumin-paclitaxel, and liposome-encapsulated albumin-paclitaxel via subserosal injection in rat models employing nuclear medicine and molecular imaging technology. Nine Sprague Dawley rats were divided into three groups: paclitaxel ( = 3), albumin-paclitaxel nano-particles (APNs; = 3), and liposome-encapsulated APNs ( = 3). [I]Iodo-paclitaxel ([I]I-paclitaxel) was synthesized by conventional electrophilic radioiodination using -butylstannyl substituted paclitaxel as the precursor. Albumin-[I]iodo-paclitaxel nanoparticles ([I]APNs) were prepared using a desolvation technique. Liposome-encapsulated APNs (L-[I]APNs) were prepared by thin-film hydration using DSPE-PEG2000, HSPC, and cholesterol. The rats in each group were injected with each test drug into the subserosa of the stomach antrum. After predetermined times (30 min, 2, 4, 8 h, and 24 h), molecular images of nuclear medicine were acquired using single-photon emission computed tomography/computed tomography. Paclitaxel, APNs, and L-APNs showed a high cumulative distribution in the stomach, with L-APNs showing the largest area under the curve. Most drugs administered via the gastric subserosal route are distributed in the stomach and intestines, with a low uptake of less than 1% in other major organs. The time to reach the maximum concentration in the intestine for L-APNs, paclitaxel, and APNs was 6.67, 5.33, and 4.00 h, respectively. These preliminary results imply that L-APNs have the potential to serve as a novel paclitaxel preparation method for the regional treatment of gastric cancer.
PubMed: 38904000
DOI: 10.3389/fphar.2024.1381406 -
Scientific Reports Jun 2024Fibrosis is an important complication in inflammatory bowel diseases. Previous studies suggest an important role of matrix Gla protein (MGP) and thrombospondin 2 (THBS2)...
Fibrosis is an important complication in inflammatory bowel diseases. Previous studies suggest an important role of matrix Gla protein (MGP) and thrombospondin 2 (THBS2) in fibrosis in various organs. Our aim was to analyse their expression together with regulatory miRNAs in submucosal and subserosal fibroblasts in ulcerative colitis (UC) and Crohn's disease (CD) using immunohistochemistry and qPCR. Digital pathology was used to compare collagen fibre characteristics of submucosal and subserosal fibrosis. Immunohistochemistry showed expression of MGP, but not THBS2 in submucosa in UC and CD. In the subserosa, there was strong staining for both proteins in CD but not in UC. qPCR showed significant upregulation of THBS2 and MGP genes in CD subserosa compared to the submucosa. Digital pathology analysis revealed higher proportion of larger and thicker fibres that were more tortuous and reticulated in subserosal fibrosis compared to submucosal fibrosis. These results suggest distinct fibroblast populations in fibrostenosing CD, and are further supported by image analysis showing significant differences in the morphology and architecture of collagen fibres in submucosal fibrosis in comparison to subserosal fibrosis. Our study is the first to describe differences in submucosal and subserosal fibroblast populations, contributing to understanding of the pathogenesis of fibrostenosis in CD.
Topics: Crohn Disease; Humans; Fibroblasts; Extracellular Matrix Proteins; Calcium-Binding Proteins; Fibrosis; Thrombospondins; Male; Matrix Gla Protein; Female; Adult; Middle Aged; Colitis, Ulcerative; MicroRNAs; Intestinal Mucosa; Aged; Immunohistochemistry
PubMed: 38877292
DOI: 10.1038/s41598-024-64672-7 -
Cureus May 2024The presence of a supernumerary subserosal muscle layer of the bowel is an extremely unusual congenital development. The following is a report of diffuse involvement of...
The presence of a supernumerary subserosal muscle layer of the bowel is an extremely unusual congenital development. The following is a report of diffuse involvement of the intestine with a supernumerary subserosal muscle coat. The current patient, a 29-year-old male, was evaluated in January 2022 for a long-standing history of subacute intestinal obstruction (SAIO). A preoperative CT scan of the abdomen and pelvis suggested mild dilatation and clumping of ileal loops in the right iliac fossa, with a subtle wall thickening of up to 5 mm. Intraoperatively, dense adhesions were noted between clumped bowel loops and the anterior abdominal wall. Following adhesiolysis, ileocecal resection with ileocolic anastomosis was done. The histopathological examination of the resected bowel segment showed irregular hypertrophy of circular and longitudinal muscle layers with the presence of an additional smooth muscle coat outer to the outer longitudinal layer that was seen in the ileum as well as the appendix. No evidence of vacuolar degeneration was noted, and ganglion cells were seen to be adequately present. The presence of additional smooth muscle bundles in the subserosa was confirmed with positive actin immunostaining. Additionally, CD117 staining was done that revealed a normal network of interstitial cells of Cajal. No evidence of active inflammation was noted in the resected bowel segment. Findings from the current case bring to light an extremely rare malformation of the muscularis propria of the intestine, namely a supernumerary subserosal muscle coat.
PubMed: 38860074
DOI: 10.7759/cureus.60096 -
Endocrine Pathology Jun 2024Appendiceal neuroendocrine tumors (NETs) are common and often are identified as incidental lesions at the time of appendectomy. The guidelines for management are based...
Appendiceal neuroendocrine tumors (NETs) are common and often are identified as incidental lesions at the time of appendectomy. The guidelines for management are based on tumor size, degree of invasion, and the Ki67 proliferation index. Most small bowel NETs are composed of serotonin-producing EC-cells, but there are multiple other neuroendocrine cell types. In the rectum, there are L-cell tumors that express peptide YY (PYY), glucagon-like peptides (GLPs), and pancreatic polypeptide (PP); they are thought to have a better prognosis than serotonin-producing tumors. We investigated whether the appendix has distinct neuroendocrine tumor types based on cell type and whether that distinction has clinical significance. We collected 135 appendiceal NETs from the pathology archives of UHN Toronto and UHCMC (Cleveland). We analyzed the expression of biomarkers including CDX2, SATB2, PSAP, serotonin, glucagon (that detects GLPs), PYY, and pancreatic polypeptide (PP) and correlated the results with clinicopathologic parameters. Immunohistochemistry identified three types of appendiceal NETs. There were 75 (56%) classified as EC-cell tumors and 37 (27%) classified as L-cell tumors; the remaining 23 (17%) expressed serotonin and one of the L-cell biomarkers and were classified as mixed. EC-cell tumors were significantly larger with more extensive invasion involving the muscularis propria, subserosa, and mesoappendix compared with L-cell tumors. Mixed tumors were intermediate in all of these parameters. Both EC-cell and mixed tumors had lymphatic and/or vascular invasion while L-cell tumors had none. Unlike EC-cell NETs, L-cell tumors were not associated with lymph node metastasis. Tumor type correlated with pT stage and the only patient with distant metastatic disease in this series had an EC-cell tumor. Our study confirms that appendiceal NETs are not a homogeneous tumor population. There are at least three types of appendiceal NET, including EC-cell, L-cell, and mixed tumors. This information is important for surveillance of patients, as monitoring urinary 5HIAA levels is only appropriate for patients with serotonin-producing tumors, whereas measurement of GLPs and/or PP is more appropriate for patients with L-cell tumors. Our data also show that tumor type is of significance with EC-cell tumors exhibiting the most aggressive behavior.
Topics: Humans; Appendiceal Neoplasms; Neuroendocrine Tumors; Female; Male; Middle Aged; Adult; Aged; Biomarkers, Tumor; Aged, 80 and over; Young Adult; Immunohistochemistry
PubMed: 38833137
DOI: 10.1007/s12022-024-09813-4 -
Revista Espanola de Enfermedades... May 2024A 70-year-old male was admitted with severe haematochezia and lipothymia. His medical history was relevant for coronary artery disease and radiation proctopathy. During...
A 70-year-old male was admitted with severe haematochezia and lipothymia. His medical history was relevant for coronary artery disease and radiation proctopathy. During hospitalization, was hemodynamically stable with persistent haematochezia. Laboratory examination revealed continuous haemoglobin fall, despite erythrocyte reposition, with administration of 11 units since admission. Colonoscopy showed an 8mm fibrinous lesion with an adherent clot, at 40cm from the anal verge. During exploration, a heavy spurting haemorrhage developed, with haemostasis being achieved with 4 clips, followed by site tattoo. Considering the risk of severe bleeding relapse in a high-risk patient, the patient underwent emergent Hartmann type colectomy. Histopathology report revealed a vascular lesion with arterial and venous vessels, protruding through the submucosa, muscular and subserosa, with a focal mucosal erosion, without neoplastic disease, compatible with an arteriovenous malformation (AVM).
PubMed: 38767028
DOI: 10.17235/reed.2024.10419/2024 -
Surgical Case Reports May 2024Colorectal cancer (CRC) often metastasizes to the liver, lungs, lymph nodes, and peritoneum but rarely to the bladder, small intestine, and skin. We here report the rare...
BACKGROUND
Colorectal cancer (CRC) often metastasizes to the liver, lungs, lymph nodes, and peritoneum but rarely to the bladder, small intestine, and skin. We here report the rare metastasis of anal cancer in the left bladder wall, followed by metastases to the small intestine and skin, after abdominoperineal resection and left lateral lymph node dissection with chemotherapy in a patient with clinician Stage IVa disease.
CASE PRESENTATION
A 66-year-old man presented with 1-month history of bloody stool and anal pain and diagnosed with clinical Stage IVa anal cancer with lymph node and liver metastases (cT3, N3 [#263L], M1a [H1]). Systemic chemotherapy led to clinical complete response (CR) for the liver metastasis and clinical near-CR for the primary tumor. Robot-assisted laparoscopic perineal rectal resection and left-sided lymph node dissection were performed. Computed tomography during 18-month postoperative follow-up identified a mass in the left bladder wall, which was biopsied with transurethral resection, was confirmed as recurrent anal cancer by histopathologic evaluation. After two cycles of systemic chemotherapy, partial resection of the small intestine was performed due to bowel obstruction not responding to conservative therapy. The histopathologic evaluation revealed lymphogenous invasion of the muscularis mucosa and subserosa of all sections. Ten months after the first surgery for bowel obstruction and two months before another surgery for obstruction of the small intestine, skin nodules extending from the lower abdomen to the thighs were observed. The histopathologic evaluation of the skin biopsy specimen collected at the time of surgery for small bowel obstructions led to the diagnosis of skin metastasis of anal cancer. Although panitumumab was administered after surgery, the patient died seven months after the diagnosis of skin metastasis.
CONCLUSIONS
This case illustrates the rare presentation of clinical Stage IVa anal cancer metastasizing to the bladder wall, small intestine, and skin several years after CR to chemotherapy.
PubMed: 38714637
DOI: 10.1186/s40792-024-01913-x -
Intestinal Research May 2024Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor...
BACKGROUND/AIMS
Poorly differentiated adenocarcinoma, signet-ring cell carcinoma, and mucinous adenocarcinoma (por/sig/muc), which are considered to be histologic subtypes with a poor prognosis, occur more frequently with colitis-associated cancer than with sporadic tumors. However, their invasiveness and manifestations are unclear. This study aimed to determine the prevalence of the por/sig/muc component in ulcerative colitis-associated neoplasms (UCANs) and its association with invasiveness and to clarify its clinicohistologic and endoscopic features.
METHODS
This retrospective observational study included patients diagnosed with ulcerative colitis-associated high-grade dysplasia or adenocarcinoma from 1997 to 2022 who were divided according to the presence or absence of a por/sig/muc component.
RESULTS
Thirty-five patients had UCAN with a por/sig/muc component and 66 had UCAN without this component. The 5-year survival rate was significantly lower in the por/sig/muc group than in the tub group (67% vs. 96%, P= 0.001), which was attributed to disease above stage III and depth to below the subserosa. Biopsy-based diagnosis before resection detected a por/sig/muc component in only 40% of lesions (14/35). Lesions with a por/sig/muc component were prevalent even in the early stages: stage 0 (4/36, 11%), I (8/20, 40%), II (7/12, 58%), III (10/14, 71%), and IV (6/8, 75%).
CONCLUSIONS
This is the first investigation that shows UCANs with a por/sig/muc component tended to be deeply invasive and were often not recognized preoperatively. Endoscopists should be aware that UCAN often has a por/sig/muc component that is not always recognized on biopsy, and the optimal treatment strategy needs to be carefully considered.
PubMed: 38712359
DOI: 10.5217/ir.2024.00006 -
Cureus Mar 2024Multiple primary tumors are rare but their incidence is increasing nowadays with advancements in diagnostic methods and the extended survival of individuals previously...
Multiple primary tumors are rare but their incidence is increasing nowadays with advancements in diagnostic methods and the extended survival of individuals previously treated for malignancies. However, synchronous occurrence of gastric cancer (GC) and colonic cancer (CC) is a rare entity. A 41-year-old male came with complaints of epigastric pain associated with anorexia, rapid weight loss, and occasional constipation. Contrast-enhanced computed tomography (CECT) of the abdomen and pelvis reported mucosal thickening in the antrum, likely GC with circumferential wall thickening of the transverse colon with pericolic fat stranding suggestive of CC. Upper gastrointestinal endoscopy and colonoscopy were also done and a biopsy was taken from representative sites, which confirmed malignancy. He completed three cycles of chemotherapy preoperatively and underwent subtotal gastrectomy, D2 lymphadenectomy, gastrojejunostomy, jejunojejunostomy, and transverse colectomy simultaneously. Histopathological examination confirmed moderately differentiated gastric adenocarcinoma penetrating into the subserosa and well-differentiated colonic adenocarcinoma invading the muscularis propria. Immunohistochemical analysis of mismatch repair (MMR) proteins was done to determine the association with hereditary nonpolyposis colorectal cancer syndrome (HNPCC) or Lynch syndrome. The patient underwent postoperative chemotherapy along with immunotherapy. To conclude, synchronous occurrence of primary GC and primary CC with similar MMR protein expression in immunohistochemistry is an uncommon entity.
PubMed: 38646233
DOI: 10.7759/cureus.56607 -
The American Journal of Case Reports Mar 2024BACKGROUND Diffuse intestinal lipomatosis is a rare condition that infiltrates mature fatty tissue into the intestinal submucosa and subserosa of the small or large...
BACKGROUND Diffuse intestinal lipomatosis is a rare condition that infiltrates mature fatty tissue into the intestinal submucosa and subserosa of the small or large intestine and can present with intestinal obstruction or torsion. This report is of the case of a 58-year-old woman who had acute torsion of the small bowel due to diffuse small intestinal lipomatosis. CASE REPORT A 58-year-old woman, who was otherwise in good health, arrived at our Emergency Department experiencing sudden, intense pain in the lower abdomen. She also reported abdominal swelling, feelings of nausea, vomiting, and reduced ability to defecate for at least 2 days. The next morning, contrast-enhanced abdominal computed tomography (CT) scan was performed, showing diffuse thickening of the small intestinal wall with hypodensity, fatty density, lumen narrowing, and wall thinning. The small intestine demonstrated a whirlpool-like distribution in the lower right abdomen and localized thickening of the small intestinal wall, suggesting acute intestinal torsion. An hour later, an emergency operation was performed to remove part of the small intestine. Three days later, pathological results showed a thin intestinal wall, expansion of the mucosal layer and submucosa, and hyperplasia of adipose tissue. CONCLUSIONS This report presents a rare case of torsion and small bowel obstruction caused by diffuse intestinal lipomatosis and focuses on the abdominal enhanced CT scan, which showed diffuse thickening of the small intestine, with multiple areas of fat density and torsion of the small intestine in the right lower abdomen. Histopathology is also presented, with the result showing intestinal lipomatosis.
Topics: Female; Humans; Middle Aged; Intestine, Small; Abdomen; Intestinal Obstruction; Tomography, X-Ray Computed; Lipomatosis
PubMed: 38519985
DOI: 10.12659/AJCR.942527 -
Indian Journal of Pathology &... Apr 2024Well-differentiated neuroendocrine tumors of the appendix (A-WDNET) are the most common neoplasms of the appendix but are rare and incidental. INSM1 is a novel...
Evaluation of immunohistochemical expression of novel neuroendocrine marker INSM1 and histological tumor growth pattern in well-differentiated neuroendocrine tumors of the appendix: 15-year single tertiary center experience.
INTRODUCTION
Well-differentiated neuroendocrine tumors of the appendix (A-WDNET) are the most common neoplasms of the appendix but are rare and incidental. INSM1 is a novel transcription factor marker with high sensitivity and specificity for neuroendocrine differentiation. It may display architecturally diverse tumor growth patterns including solid, nest, insular trabecular, and acinar.
AIMS
The aim of this study was to determine the staining expression of INSM1 in A-WDNETs and detail the morphological tumor growth patterns.
MATERIALS AND METHODS
INSM1 immunohistochemistry was performed on 35 A-WDNET patients. Tumors were histologically classified according to their growth patterns.
RESULTS
Thirty-five patients, 60% of whom were male, had a mean age of 30 years at diagnosis and a mean tumor size of 0.9 cm. Eight percent of the tumors invaded the mucosa/submucosa, 34.3% showed invasion into the muscularis propria, 57.1% showed invasion into the subserosa or mesoappendix, LN metastasis was observed in two patients, lymph-vascular invasion in two patients, and perineural invasion in five patients. Ninety-four percent of the tumors were grade 1, the mitotic rate was >2% in two cases, and Ki-67 PI was >3% in two cases. INSM1 was positive in all cases (100%), 1+ 8.6%, 2+ 5.7%, 3+ 17.1%, 4+ 68.6%, weak staining in 11.4%, moderate staining in 22.9%, and strong staining in 67.7%. Type A histological growth pattern was observed in 54.3%, type B in 31.4%, and type C in 14.3% architecturally.
CONCLUSIONS
INSM1 was positive in all A-WDNET morphological patterns and was 100% sensitive. INSM1 IHC can be used as an alternative to traditional neuroendocrine markers or in combination with the diagnosis of neuroendocrine tumors.
Topics: Humans; Male; Neuroendocrine Tumors; Female; Adult; Repressor Proteins; Immunohistochemistry; Biomarkers, Tumor; Middle Aged; Appendiceal Neoplasms; Young Adult; Adolescent; Tertiary Care Centers; Appendix; Aged
PubMed: 38427752
DOI: 10.4103/ijpm.ijpm_514_23