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Journal of Hepatology Jun 2024Biliary complications are a major cause of morbidity and mortality in liver transplantation. Up to 25% of patients that develop biliary complications require additional...
BACKGROUND & AIMS
Biliary complications are a major cause of morbidity and mortality in liver transplantation. Up to 25% of patients that develop biliary complications require additional surgical procedures, re-transplantation or die in the absence of a suitable regraft. Here, we investigate the role of the primary cilium, a highly-specialised sensory organelle, in biliary injury leading to post-transplant biliary complications.
METHODS
Human biopsies were used to study the structure and function of primary cilia in liver transplant recipients that develop biliary complications (N=7) in comparison with recipients without biliary complications (N=12). To study the biological effects of the primary cilia during transplantation, we generated murine models that recapitulate liver procurement and cold storage, and assessed the elimination of the primary cilia in biliary epithelial cells in the K19CreERKif3a mouse model. To explore the molecular mechanisms responsible for the observed phenotypes we used in vitro models of ischemia, cellular senescence and primary cilia ablation. Finally, we used pharmacological and genetic approaches to target cellular senescence and the primary cilia, both in mouse models and discarded human donor livers.
RESULTS
Prolonged ischemic periods before transplantation result in ciliary shortening and cellular senescence, an irreversible cell cycle arrest that blocks regeneration. Our results indicate that primary cilia damage results in biliary injury and a loss of regenerative potential. Senescence negatively impacts primary cilia structure and triggers a negative feedback loop that further impairs regeneration. Finally, we explore how targeted interventions for cellular senescence and/or the stabilisation of the primary cilia improve biliary regeneration following ischemic injury.
CONCLUSIONS
Primary cilia play an essential role in biliary regeneration and we demonstrate that senolytics and cilia-stabilising treatments provide a potential therapeutic opportunity to reduce the rate of biliary complications and improve clinical outcomes in liver transplantation.
IMPACT AND IMPLICATIONS
Up to 25% of liver transplants result in biliary complications, leading to additional surgery, retransplants, or death. We found that the incidence of biliary complications is increased by damage to the primary cilium, an antenna that protrudes from the cell and is key to regeneration. Here, we show that treatments that preserve the primary cilia during the transplant process provide a potential solution to reduce the rates of biliary complications.
PubMed: 38879173
DOI: 10.1016/j.jhep.2024.06.002 -
Pathology, Research and Practice May 2024To explore the clinical, imaging, pathologic characteristics and differential diagnosis of solitary pulmonary capillary hemangioma (SPCH).
OBJECTIVE
To explore the clinical, imaging, pathologic characteristics and differential diagnosis of solitary pulmonary capillary hemangioma (SPCH).
METHODS
Thirty two cases of SPCH were collected and studied, with literature review.
RESULTS
This study included 13 males and 19 females, with a male-to-female ratio of 1:1.5. The age ranged from 26 to 70 years (median age of 43 years). All patients were asymptomatic at presentation. Lung nodules were incidentally discovered during chest computed tomography (CT). Imaging features included 21 cases with partial solid nodules (PSN), 7 cases with ground-glass nodules (GGN), and 4 cases with solid nodules (SN). Eleven cases were in the left lung lower basal segment, 11 cases in the right lung lower basal segment, 6 cases in the right lung upper anterior segment, and 4 cases in the right lung middle lateral segment. The lower basal segments of the lungs were involved in 22 (11 in each lung) cases (22/32, 68 %). The tumors ranged from 6 to 18 mm (average 10 mm). Macroscopically, 16 cases had clear boundaries, while 16 cases had unclear boundaries, and gray-red or dark brown on cut surfaces. Intraoperative frozen section was performed in 27 cases, with diagnosis of SPCH in 12 and pneumonia or inflammatory lesion in 15. Microscopically, the nodules were composed of densely proliferated and dilated capillaries. The capillary walls were lined with a single layer of flat endothelial cells, without atypical features. Collapsed alveolar septa were replaced by a large number of capillaries. All cases showed proliferating capillaries spreading into the walls of small veins/arteries and bronchi, with 3 cases showing dilated capillaries protruding into the bronchiolar lumens as polyp-like structures. Twenty-six cases (26/32, 81 %) showed proliferating capillaries passed over the interlobular septa. Twenty-six cases (26/32, 81 %) showed irregular intimal thickening of small muscular arteries in the peripheral areas of the lesions, with the thickened intima being cellular or fibrous. In twenty-seven cases (27/32, 84 %) the lesions were located in the subpleura, with 6 cases involving the pleura.
CONCLUSION
SPCH is a rare benign lung tumor that mostly occurs in the lung lower basal segments with predominance in females. It usually appears as a ground-glass nodule on CT and is very similar to early-stage lung cancer. Accurate diagnosis requires collaboration of radiologists, surgeons, and pathologists. SPCH should be regarded as an important differential diagnosis of small incidental lung nodules.
PubMed: 38878664
DOI: 10.1016/j.prp.2024.155372 -
International Journal of Surgery Case... Jul 2024Standard treatment for renal cell carcinomas (RCCs) is radical/partial nephrectomy and unlike upper urothelial carcinoma, complete ureteral removal is not necessary nor...
INTRODUCTION
Standard treatment for renal cell carcinomas (RCCs) is radical/partial nephrectomy and unlike upper urothelial carcinoma, complete ureteral removal is not necessary nor is advised in RCCs as tumor recurrence in ureteral remnant has scarcely been reported. Here, we present a rare case of chromophobe RCC (ChRCC) metastasis in remnant ureter following radical nephrectomy and perform a literature review in this regard.
CASE PRESENTATION
A 66-year-old man presented with a CT scan-as a surveillance protocol imaging- showing a mass in ipsilateral remnant ureter 9 months after radical nephrectomy due to ChRCC while being completely asymptomatic. Cystoscopy revealed a polypoid mass protruding from right ureterovesical junction and transurethral resection of tumor revealed it to be a ChRCC. Distal ureterectomy was performed confirming pathology without any lymph node involvement. 12 months after ureterectomy, he remained asymptomatic with no sign of metastasis or recurrence in his follow up CT scan.
DISCUSSION
RCC metastasis to distal ureter after radical nephrectomy has been rarely reported and only 2 cases of them were ChRCC. Gross hematuria has been the main presentation of such disease. However, our case was completely asymptomatic, highlighting necessity of surveillance imaging. No specific treatment guideline exists for such presentation but tumor resection has been the most common treatment modality.
CONCLUSION
Metachronous RCC metastasis may occur in remnant ureter which can be completely asymptomatic, highlighting necessity of surveillance imaging and reviewing them meticulously. Surgical resection of the metastasis by distal ureterectomy seems to be the best treatment option.
PubMed: 38875827
DOI: 10.1016/j.ijscr.2024.109907 -
Lumbar Spine Infected by Mycobacterium tuberculosis and Cryptococcus neoformans: a Rare Case Report.Clinical Laboratory Jun 2024In July 2023, our hospital confirmed one case of lumbar spine infected complicated by Mycobacterium tuberculosis and Cryptococcus neoformans. The patient was admitted...
BACKGROUND
In July 2023, our hospital confirmed one case of lumbar spine infected complicated by Mycobacterium tuberculosis and Cryptococcus neoformans. The patient was admitted due to lower back pain for 1 year and a hard lump for 3 months. Symptoms and signs: Dressing can be seen fixed on the lower back, with severe bleeding. When the dressing is removed, a hard and protruding lump with a size of 6 cm x 8 cm, a sinus tract can be seen near the mass, with a slightly red wound and a sinus depth of about 3 cm. Light red fluid can be seen flowing out. There are no symptoms such as redness, swelling, or heat in the rest of the lower back, and the patient has no other underlying diseases or surgical history.
METHODS
Lumbar magnetic resonance imaging and lumbar CT examination; Percutaneous puncture lumbar vertebral biopsy was performed, and the biopsy tissue was subjected to pathological examination, mNGS (metagenomic next-generation sequencing), and acid-fast staining; Extract pus from the lump for fungal culture and ink staining, and identify the fungi through MALDI-TOF MS.
RESULTS
Bone destruction and bone marrow edema in the L5 vertebral body, compression of the spinal canal at the L5 vertebral body level; The pathological results of the biopsy tissue indicate granulomatous lesions. The acid-fast staining of the tissue is positive, and the mNGS of the tissue indicates infection with Mycobacterium tuberculosis. A single fungus was cultured from pus and identified by MALDI-TOF MS as Cryptococcus neoformans. Clinically, isoniazid 0.3 g ivgtt + rifampicin 0.45 g qd po + ethambutol 0.25 g qd po + pyrazinamide 0.75 g qd po + fluconazole 0.3 g qd po was administered for treatment. After 11 days, there was slight pain at the incision site, and the original symptoms were significantly relieved. The wound dressing was fixed in place, dry and without obvious exudation. Improved and discharged, followed up for 3 months with no recurrence of the lesion.
CONCLUSIONS
mNGS is an effective identification technique that can be used to accurately diagnose suspected infection cases. MALDI-TOF MS has significant advantages over traditional detection methods in shortening detection time. This case achieved satisfactory treatment results for patients through a reasonable treatment plan, which is of great significance for exploring the diagnosis and treatment of similar disease infections.
Topics: Humans; Cryptococcus neoformans; Lumbar Vertebrae; Mycobacterium tuberculosis; Cryptococcosis; Male; Tuberculosis, Spinal; Magnetic Resonance Imaging; Antitubercular Agents; Middle Aged; Tomography, X-Ray Computed
PubMed: 38868894
DOI: 10.7754/Clin.Lab.2024.240118 -
Spine Surgery and Related Research May 2024The major symptoms of lumbar disc herniation (LDH) are low back pain, radiative lower extremity pain, and lower limb movement disorder. Patients with LDH suffer from... (Review)
Review
The major symptoms of lumbar disc herniation (LDH) are low back pain, radiative lower extremity pain, and lower limb movement disorder. Patients with LDH suffer from great distress in their daily life accompanied by severe economic hardship and difficulty in self-care, with an increasing tendency in the aging population. PubMed and the Cochrane Central Register of Controlled Trials were searched for relevant studies of spontaneous resorption or regression in LDH after conservative treatment and for other potential studies, which included those from inception to June 30, 2023. The objective of this narrative review is to summarize previous literatures about spontaneous resorption in LDH and to discuss the mechanisms and influencing factors in order to assess the probability of spontaneous resorption by conservative treatment. Spontaneous resorption without surgical treatment is influenced by the types and sizes of the LDH, inflammatory responses, and therapeutic factors. If the lumbar disc herniated tissue comprises a higher percentage of cartilage or modic changes have been shown on magnetic resonance imaging (MRI), resorption in LDH is prevented. The bull's eye sign on enhanced MRI, which is a ring enhancement around a protruding disc, is a vital indicator for easy reabsorption. In addition, the type of extrusion and sequestration in LDH could forecast the higher feasibility of natural reabsorption. Moreover, the higher the proportion of protrusion on the intervertebral disc tissue within the spinal canal, the greater the likelihood of reabsorption. Therefore, which illustrates the feasibility of conservative treatments for LDH. Nonsurgical management of LDH with clinical symptoms is recommended by the authors.
PubMed: 38868799
DOI: 10.22603/ssrr.2023-0152 -
British Journal of Biomedical Science 2024Colorectal cancer has a high prevalence and mortality rate in the United Kingdom. Cancerous colorectal lesions often bleed into the gastrointestinal lumen. The faecal...
Colorectal cancer has a high prevalence and mortality rate in the United Kingdom. Cancerous colorectal lesions often bleed into the gastrointestinal lumen. The faecal immunochemical test (FIT) detects haemoglobin (Hb) in the faeces of patients and is used as a first line test in the diagnosis of colorectal cancer. A retrospective audit of all FIT performed and all colorectal cancers diagnosed in the Hull and East Riding of Yorkshire counties of the United Kingdom (population approximately 609,300) between 2018 and 2022 was conducted. FIT were performed using a HM-JACKarc analyser from Kyowa medical. The predominant symptom suggestive of colorectal cancer which prompted the FIT was recorded. Colorectal cancer was diagnosed using the gold standard of histological biopsy following colonoscopy. Between 2018 and 2022, 56,202 FIT were performed on symptomatic patients. Follow on testing identified 1,511 with colorectal cancer. Of these people, only 450 people with a confirmed colorectal cancer had a FIT within the 12 months preceding their diagnosis. Of these 450 FIT results, 36 had a concentration of <10 μg/g and may be considered to be a false negative. The sensitivity of FIT in the patients identified was 92.00%. The most common reason stated by the clinician for a FIT being performed in patients with colorectal cancer was a change in bowel habits, followed by iron deficient anaemia. The number of patients diagnosed with colorectal cancer decreased in 2020, but increased significantly in 2021. This study shows that 8.00% of people diagnosed with colorectal cancer in the Hull and East Riding of Yorkshire regions had a negative FIT. This study also shows that the SARS-CoV-2 pandemic affected the number of people diagnosed with colorectal cancer, and therefore skews the prevalence and pre-test probability of a positive test. There are many reasons why a FIT could produce a false negative result, the most likely being biological factors affecting the stability of haemoglobin within the gastrointestinal tract, or pre-analytical factors influencing faecal sampling preventing the detection of haemoglobin. Some colorectal lesions do not protrude into the gastrointestinal lumen and are less likely to bleed. This is the first study showing data from outside of a structured clinical trial and provides the largest study to date showing the sensitivity of FIT in a routine clinical setting. This study also provides evidence for the impact COVID-19 had on the rate of colorectal cancer diagnosis.
Topics: Humans; Colorectal Neoplasms; Retrospective Studies; Occult Blood; United Kingdom; Female; Early Detection of Cancer; Male; Feces; Sensitivity and Specificity; Middle Aged; Hemoglobins; Aged; Immunochemistry; Colonoscopy
PubMed: 38868754
DOI: 10.3389/bjbs.2024.12862 -
International Journal of Surgery Case... Jul 2024The most common cancer among females worldwide and in Saudi Arabia is breast cancer. Lobular breast carcinoma is the second most common subtype of breast cancer. There...
INTRODUCTION AND IMPORTANCE
The most common cancer among females worldwide and in Saudi Arabia is breast cancer. Lobular breast carcinoma is the second most common subtype of breast cancer. There are different patterns of metastasis as ductal breast cancer spreads to the liver, lung, brain, and bone while the lobular subtype metastasizes to the gastrointestinal tract.
CASE PRESENTATION
A 69-year-old Indian pilgrim presented to the ER complaining of abdominal pain, vomiting, and abdominal distention admitted as a case of intestinal obstruction. CT scan demonstrated intestinal obstruction with transition zone at the terminal ileum. The patient underwent exploratory laparotomy where she was found to have a mass at the terminal ileum. Resection of around 8 cm of small bowel and primary anastomosis were done, histopathology revealed metastatic lobular breast carcinoma.
CLINICAL DISCUSSION
Patients with metastatic breast cancer to the gastrointestinal tract often present with nonspecific symptoms, while acute cases present with complications such as perforation. In a retrospective review of metastatic breast cancer, the majority metastasizes to the colon and rectum, while 19 % to the small bowel. Palliative surgery is considered the first-line treatment of complicated patients, while stable cases are referred to medical oncology.
CONCLUSION
Breast cancer is the second most common cancer leading to death and lobular subtype has more propensity to metastasize to the gastrointestinal tract compared to ductal breast cancer. Regarding patients presenting to the emergency bay, treating the emergency complaints is the standard management. For immigrant patients, we highly recommend creating a data system for sending histopathology reports to facilitate follow-up in their countries.
CASE PRESENTATION
A 69-year-old Indian pilgrim patient presented to the ER complaining of abdominal pain for 3 days associated with nausea and vomiting, not passing stool nor flatus was admitted as a case of intestinal obstruction. On examination patient was in pain with tachycardia, abdominal distended with generalized tenderness. Labs revealed metabolic alkalosis with hypokalemia. Abdomen X-ray showed signs of intestinal obstruction with multiple air-fluid levels and dilated small bowel loops. CT scan abdomen and pelvis with IV contrast reported (Figs. 1,2) distended ileum around 5 cm proximal to the transition zone at the terminal ileum with mild free fluid in the abdomen and pelvis. The patient underwent exploratory laparotomy where she was found to have a mass at the terminal ileum with the proximal loop dilated and distal loops collapsed, and further exploration showed enlarged mesenteric lymph nodes. Small bowel resection of around 8 cm and side to side anastomosis was done to relive the intestinal obstruction. Gross pathology showed a solid lesion protruding into the lumen measuring 1.5*1.5*1.5 cm, while the microscopic description consists of small cells with round ovoid nuclei which lack cohesion and appear individually dispersed through a fibrous connective tissue and arranged in single file linear cords that invade the stroma (Fig. 4) concluded as metastatic lobular carcinoma of the breast. Immunohistochemistry reported CK7 + ve, ER + ve, EMA + ve and CKAE1/AE3 + ve. The patient had an uneventful recovery, then she was discharged against medical advice and traveled to her country after two days before the histopathology result and she lost follow-up with us.
PubMed: 38865947
DOI: 10.1016/j.ijscr.2024.109855 -
Catheterization and Cardiovascular... Jun 2024Management of a protruding coronary stent into the aortic root in patients undergoing evaluation for transcatheter aortic valve replacement can be challenging. We...
Management of a protruding coronary stent into the aortic root in patients undergoing evaluation for transcatheter aortic valve replacement can be challenging. We describe a patient treated with stent trimming and surgical aortic valve replacement, highlighting the importance of a multidisciplinary evaluation and selection process in this complex scenario.
PubMed: 38860636
DOI: 10.1002/ccd.31120 -
American Journal of Medical Genetics.... Jun 2024Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and...
Dyggve-Melchior-Clausen dysplasia (DMC) and Smith-McCort dysplasia (SMC types 1 and 2) are rare spondylo-epi-metaphyseal dysplasias with identical radiological and clinical findings. DMC and SMC type 1 are allelic disorders caused by homozygous or compound heterozygous variants in DYM, while biallelic causative variants in RAB33B lead to SMC type 2. The terminology "skeletal golgipathies" has been recently used to describe these conditions, highlighting the pivotal role of these two genes in the organization and intracellular trafficking of the Golgi apparatus. In this study, we investigated 17 affected individuals (8 males, 9 females) from 10 unrelated consanguineous families, 10 diagnosed with DMC and seven with SMC type 2. The mean age at diagnosis was 9.61 ± 9.72 years, ranging from 20 months to 34 years, and the average height at diagnosis was 92.85 ± 15.50 cm. All patients exhibited variable degrees of short trunk with a barrel chest, protruding abdomen, hyperlordosis, and decreased joint mobility. A total of nine different biallelic variants were identified, with six being located in the DYM gene and the remaining three detected in RAB33B. Notably, five variants were classified as novel, four in the DYM gene and one in the RAB33B gene. This study aims to comprehensively assess clinical, radiological, and molecular findings along with the long-term follow-up findings in 17 patients with DMC and SMC type 2. Our results suggest that clinical symptoms of the disorder typically appear from infancy to early childhood. The central notches of the vertebral bodies were identified as early as 20 months and tended to become rectangular, particularly around 15 years of age. Pseudoepiphysis was observed in five patients; we believe this finding should be taken into consideration when evaluating hand radiographs in clinical assessments. Furthermore, our research contributes to an enhanced understanding of clinical and molecular aspects in these rare "skeletal golgipathies," expanding the mutational spectrum and offering insights into long-term disease outcomes.
PubMed: 38860472
DOI: 10.1002/ajmg.a.63785 -
The Journal of Craniofacial Surgery Jun 2024The paper presented the treatment procedure of a 2-year-old patient with unrepaired bilateral cleft lip and palate (BCLP). Complicated situation included severely...
The paper presented the treatment procedure of a 2-year-old patient with unrepaired bilateral cleft lip and palate (BCLP). Complicated situation included severely protruded premaxilla and constricted upper dental arch, possibly related to delayed treatment of cleft lip and palate. Orthodontic expansion lasted for 8 months, including using fan-type expander for 3 months. After that, premaxillary osteotomy was performed to reset the premaxilla, and 4 months later, simultaneous repair of cleft lip and palate was taken. Follow-up evaluation in 5.5 years revealed acceptable language development and craniofacial profile, and maxillary growth was satisfactory. The treatment procedure of this patient provided an exploratory protocol for those patients with unrepaired BCLP who suffered from deteriorated preaxillary protrusion and constricted upper arch.
PubMed: 38847541
DOI: 10.1097/SCS.0000000000010394