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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 -
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 -
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 -
Endoscopy International Open Jun 2024Colorectal endoscopic submucosal dissection (ESD) is increasingly used for treating early-stage colorectal cancer, including large, protruded lesions (LPL). However,...
Colorectal endoscopic submucosal dissection (ESD) is increasingly used for treating early-stage colorectal cancer, including large, protruded lesions (LPL). However, the challenges posed by LPLs, especially those accompanied by severe fibrosis or muscle-retracting sign (MRS), remain unclear. This study aims to investigate ESD outcomes for LPL, focusing on factors such as tumor size and, submucosal fibrosis. In a multicenter retrospective study (June 2012 to May 2023), data from 526 patients with 542 LPL lesions (≥ 2 cm) were analyzed. Parameters included lesion size, procedure time, dissection speed, physician experience, submucosal fibrosis, and adverse events. The tunnel method, including the double tunnel method, was used for cases with severe fibrosis or MRS. Multivariate analysis assessed factors affecting procedure difficulty, particularly LPLs ≥ 4 cm. The study revealed an impressive en bloc resection rate of 97.8% and a curative resection rate of 78.6% for LPLs. Notably, fibrosis and MRS were present in 25% and 18% of 4-cm LPLs, respectively, and their frequency tended to increase as the tumor diameter increased. One treatment strategy for LPLs was the tunneling method, which was used most frequently (41 cases, 7.6%). Factors affecting dissection speed included larger tumor size, submucosal fibrosis, MRS, and physician experience. Treating LPLs through colorectal ESD presents significant challenges, especially in patients with fibrosis and MRS. This study highlights the importance of recognizing these complexities, and that more reliable resection strategy must be established for accurate pathological evaluation.
PubMed: 38847018
DOI: 10.1055/a-2316-7755 -
Clinical Case Reports Jun 2024Vaginal cuff dehiscence post-hysterectomy is rare yet significant. Early recognition and prompt surgical intervention are crucial to prevent complications like bowel...
KEY CLINICAL MESSAGE
Vaginal cuff dehiscence post-hysterectomy is rare yet significant. Early recognition and prompt surgical intervention are crucial to prevent complications like bowel infarction. Consider second-look laparotomy in cases of uncertain bowel viability.
ABSTRACT
Vaginal cuff dehiscence (VCD) is a rare but potentially life-threatening complication following a hysterectomy characterized by the separation of the vaginal vault. This condition, which may result in vaginal evisceration (VE), presents a significant risk of pelvic contents, particularly the small bowel, protruding into the vagina. Early diagnosis and prompt surgical intervention are paramount to prevent severe complications, including bowel infarction, obstruction, and peritonitis. Although VCD and VE are rare, they require urgent surgical management to avoid adverse outcomes. We reported a case of small bowel evisceration in a woman with a history of total abdominal hysterectomy 6 months ago. VCD and VE are very rare but life-threatening complications of hysterectomy. Discussing the symptoms with patients who have multiple risk factors is crucial to avoid severe sequels following hysterectomy. Based on our experience, performing a second-look laparotomy is a reliable approach to ensure the viability of the intestinal loop. However, it will likely increase the risk of infection.
PubMed: 38827941
DOI: 10.1002/ccr3.8910 -
Frontiers in Genetics 2024Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder. A retrospective analysis predicted that the live birth prevalence of SRS in Estonia...
Silver-Russell syndrome (SRS) is a clinically and genetically heterogeneous disorder. A retrospective analysis predicted that the live birth prevalence of SRS in Estonia is 1:15,886 [Yakoreva et al., Eur J Hum Genet, 2019, 27(11), 1649-1658]. The most common causative genetic mechanism in the proband is loss of paternal methylation in the imprinted control region 1 (ICR1) at 11p15.5 chromosome. A few studies suggested that inherited or loss-of-function alterations of the gene, including the whole-gene deletion and intragenic pathogenic variants, could cause a rare type of SRS. To date, less than 20 unrelated -related SRS cases have been reported, and the clinical information about these cases is limited. We report the first prenatal case of SRS with 8q12 deletion (including the gene). The fetus presented with intrauterine growth retardation, small for gestational age, relative macrocephaly at birth, and a protruding forehead. Unlike classical SRS cases, the fetus had micrognathia and did not show body asymmetry. We hope that the literature review in this study provides new insights into genotype-phenotype relationships of -related SRS.
PubMed: 38826801
DOI: 10.3389/fgene.2024.1387649 -
Cureus Apr 2024Caesarean scar ectopic pregnancy is the rarest form of ectopic pregnancy. Nowadays, with the rise in caesarean deliveries, along with better awareness and improvement...
Caesarean scar ectopic pregnancy is the rarest form of ectopic pregnancy. Nowadays, with the rise in caesarean deliveries, along with better awareness and improvement in ultrasound diagnosis, there is an increase in the number and detection of caesarean scar ectopic pregnancy. A 28-year-old female patient with one previous caesarean delivery and a spontaneous abortion at three months visited the obstetrics emergency department due to three months of amenorrhea, abdominal pain, and vaginal bleeding on and off for two days. The patient was noticed to have severe anemia. After stabilizing the patient with blood transfusion, a laparotomy was performed with the presentation of hemoperitoneum and caesarean scar rupture. Fetus and soft vascular mass seen protruding from the previous scar were extracted. The caesarean scar site was repaired in layers.
PubMed: 38826599
DOI: 10.7759/cureus.59422 -
Research Square May 2024Stereocilia are unidirectional F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells and function as biological mechanosensors of sound and...
Live-cell single-molecule fluorescence microscopy for protruding organelles reveals regulatory mechanisms of MYO7A-driven cargo transport in stereocilia of inner ear hair cells.
Stereocilia are unidirectional F-actin-based cylindrical protrusions on the apical surface of inner ear hair cells and function as biological mechanosensors of sound and acceleration. Development of functional stereocilia requires motor activities of unconventional myosins to transport proteins necessary for elongating the F-actin cores and to assemble the mechanoelectrical transduction (MET) channel complex. However, how each myosin localizes in stereocilia using the energy from ATP hydrolysis is only partially understood. In this study, we develop a methodology for live-cell single-molecule fluorescence microscopy of organelles protruding from the apical surface using a dual-view light-sheet microscope, diSPIM. We demonstrate that MYO7A, a component of the MET machinery, traffics as a dimer in stereocilia. Movements of MYO7A are restricted when scaffolded by the plasma membrane and F-actin as mediated by MYO7A's interacting partners. Here, we discuss the technical details of our methodology and its future applications including analyses of cargo transportation in various organelles.
PubMed: 38826223
DOI: 10.21203/rs.3.rs-4369958/v1