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Strahlentherapie Und Onkologie : Organ... Aug 2023Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose...
PURPOSE
Primary radiochemotherapy (RCT) constitutes the standard of care for early- and advanced-stage anal carcinoma. This retrospective study investigates the impact of dose escalation on colostomy-free survival (CFS), overall survival (OS), locoregional control (LRC), progression-free survival (PFS), and acute and late toxicities in patients with squamous cell anal cancer.
METHODS
Considered were the outcomes of 87 patients with anal cancer treated with radiation/RCT between May 2004 and January 2020 at our institution. Toxicities were evaluated according to the Common Terminology Criteria for Adverse Events (CTCAE version 5.0).
RESULTS
The 87 patients received treatment with a median boost of 63 Gy to the primary tumor. With a median follow-up of 32 months, the 3‑year CFS, OS, LRC, and PFS were 79.5%, 71.4%, 83.9%, and 78.5%, respectively. Tumor relapse occurred in 13 patients (14.9%). Dose escalation to > 63 Gy (maximum 66.6 Gy) to the primary tumor in 38/87 patients revealed a nonsignificant trend for improved 3‑year CFS (82.4% vs. 97%, P = 0.092), a significantly improved CFS for T2/T3 tumors (72.6% vs. 100%, P = 0.008), and a significantly improved 3‑year PFS for T1/T2 tumors (76.7% vs. 100%, P = 0.035). While acute toxicities did not differ, dose escalation > 63 Gy led to a higher rate of chronic skin toxicities (43.8% vs. 69%, P = 0.042). Treatment with intensity-modulated radiotherapy (IMRT) showed a significant improvement in 3‑year OS (75.4% vs. 53.8%, P = 0.048). In multivariate analysis, significant improvements for T1/T2 tumors (CFS, OS, LRC, PFS), G1/2 tumors (PFS), and IMRT (OS) were shown. The nonsignificant trend for CFS improvement with dose escalation > 63 Gy was also apparent in multivariate analysis (P = 0.067).
CONCLUSION
Dose escalation > 63 Gy (maximum 66.6 Gy) may improve CFS and PFS for certain subgroups, with a concomitant increase in chronic skin toxicities. Modern IMRT seems to be associated with an improvement in OS.
Topics: Humans; Neoplasm Recurrence, Local; Treatment Outcome; Radiotherapy, Intensity-Modulated; Chemoradiotherapy; Carcinoma, Squamous Cell; Anus Neoplasms; Epithelial Cells; Retrospective Studies
PubMed: 36862155
DOI: 10.1007/s00066-023-02056-y -
MBio Jun 2024Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital...
Human papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States and are a major etiological agent of cancers in the anogenital tract and oral cavity. Growing evidence suggests changes in the host microbiome are associated with the natural history and ultimate outcome of HPV infection. We sought to define changes in the host cervicovaginal microbiome during papillomavirus infection, persistence, and pathogenesis using the murine papillomavirus (MmuPV1) cervicovaginal infection model. Cervicovaginal lavages were performed over a time course of MmuPV1 infection in immunocompetent female mice and extracted DNA was analyzed by qPCR to track MmuPV1 viral copy number. 16S ribosomal RNA (rRNA) gene sequencing was used to determine the composition and diversity of microbial communities throughout this time course. We also sought to determine whether specific microbial communities exist across the spectrum of MmuPV1-induced neoplastic disease. We, therefore, performed laser-capture microdissection to isolate regions of disease representing all stages of neoplastic disease progression (normal, low- and high-grade dysplasia, and cancer) from female reproductive tract tissue sections from MmuPV1-infected mice and performed 16S rRNA sequencing. Consistent with other studies, we found that the natural murine cervicovaginal microbiome is highly variable across different experiments. Despite these differences in initial microbiome composition between experiments, we observed that MmuPV1 persistence, viral load, and severity of disease influenced the composition of the cervicovaginal microbiome. These studies demonstrate that papillomavirus infection can alter the cervicovaginal microbiome.IMPORTANCEHuman papillomaviruses (HPVs) are the most common sexually transmitted infection in the United States. A subset of HPVs that infect the anogenital tract (cervix, vagina, anus) and oral cavity cause at least 5% of cancers worldwide. Recent evidence indicates that the community of microbial organisms present in the human cervix and vagina, known as the cervicovaginal microbiome, plays a role in HPV-induced cervical cancer. However, the mechanisms underlying this interplay are not well-defined. In this study, we infected the female reproductive tract of mice with a murine papillomavirus (MmuPV1) and found that key aspects of papillomavirus infection and disease influence the host cervicovaginal microbiome. This is the first study to define changes in the host microbiome associated with MmuPV1 infection in a preclinical animal model of HPV-induced cervical cancer. These results pave the way for using MmuPV1 infection models to further investigate the interactions between papillomaviruses and the host microbiome.
Topics: Female; Animals; Papillomavirus Infections; Microbiota; Vagina; Mice; Disease Models, Animal; Cervix Uteri; RNA, Ribosomal, 16S; Papillomaviridae; Viral Load
PubMed: 38742830
DOI: 10.1128/mbio.00933-24 -
International Journal of Surgery Case... Mar 2024Intestinal atresia is a congenital anomaly commonly happening in the small bowel and rarely in the colon. Colonic atresia can manifest as intestinal obstruction with...
INTRODUCTION AND IMPORTANCE
Intestinal atresia is a congenital anomaly commonly happening in the small bowel and rarely in the colon. Colonic atresia can manifest as intestinal obstruction with abdominal distention and bilious vomiting.
CASE PRESENTATION
A 3-day-old male new-born who was referred from a rural hospital, full term, product of normal vaginal delivery, with a weight of 2400 g. The patient had a complaint of bilious vomiting, inability to pass meconium, and abdominal distension for three days. On clinical examination the patient had visible bowel loops and yellowish aspiration from the orogastric tube. An erect abdominal radiograph showed distended bowel loops and sharp air-fluid levels. Administration of contrast enema revealed resistance to pass the rectal tube and stopping of contrast pas the rectosigmoid region with contrast spillage from the anus.
CLINICAL DISCUSSION
Sigmoid atresia is a rare congenital anomaly that occurs in approximately 1 in 20,000 live births. The most common presentation is bilious vomiting and abdominal distension in the first 24 h of life. Diagnosis is confirmed with abdominal X-ray and contrast enema. Treatment is surgical, with primary repair being the most common approach. He underwent two stages of repair with an end colostomy and mucous fistula, then closure of the colostomy after four months of the first stage.
CONCLUSION
This presentation requires clinical suspicion with prompt care, as this condition can mimic Hirschsprung's disease. In our case, the patient has a classical presentation of sigmoid atresia that had an early diagnosis, which resulted in a better outcome.
PubMed: 38401322
DOI: 10.1016/j.ijscr.2024.109434 -
Discover Oncology Dec 2023Machine learning techniques have been widely used in predicting disease prognosis, including cancer prognosis. One of the major challenges in cancer prognosis is to...
Machine learning techniques have been widely used in predicting disease prognosis, including cancer prognosis. One of the major challenges in cancer prognosis is to accurately classify cancer types and stages to optimize early screening and detection, and machine learning techniques have proven to be very useful in this regard. In this study, we aimed at identifying critical genes for diagnosis and outcomes of hepatocellular carcinoma (HCC) patients using machine learning. The HCC expression dataset was downloaded from GSE65372 datasets and TCGA datasets. Differentially expressed genes (DEGs) were identified between 39 HCC and 15 normal samples. For the purpose of locating potential biomarkers, the LASSO and the SVM-RFE assays were performed. The ssGSEA method was used to analyze the TCGA to determine whether there was an association between SPINK1 and tumor immune infiltrates. RT-PCR was applied to examine the expression of SPINK1 in HCC specimens and cells. A series of functional assays were applied to examine the function of SPINK1 knockdown on the proliferation of HCC cells. In this study, 103 DEGs were obtained. Based on LASSO and SVM-RFE analysis, we identified nine critical diagnostic genes, including C10orf113, SPINK1, CNTLN, NRG3, HIST1H2AI, GPRIN3, SCTR, C2orf40 and PITX1. Importantly, we confirmed SPINK1 as a prognostic gene in HCC. Multivariate analysis confirmed that SPINK1 was an independent prognostic factor for overall survivals of HCC patients. We also found that SPINK1 level was positively associated with Macrophages, B cells, TFH, T cells, Th2 cells, iDC, NK CD56bright cells, Th1 cells, aDC, while negatively associated with Tcm and Eosinophils. Finally, we demonstrated that SPINK1 expression was distinctly increased in HCC specimens and cells. Functionally, silence of SPINK1 distinctly suppressed the proliferation of HCC cells via regulating Wnt/β-catenin pathway. The evidence provided suggested that SPINK1 may possess oncogenic properties by inducing dysregulated immune infiltration in HCC. Additionally, SPINK1 was identified as a novel biomarker and therapeutic target for HCC.
PubMed: 38093163
DOI: 10.1007/s12672-023-00849-2 -
Updates in Surgery Sep 2023This study aimed to report a multicentric national experience about the outcomes of pediatric endoscopic pilonidal sinus treatment (PEPSiT). The medical records of all...
This study aimed to report a multicentric national experience about the outcomes of pediatric endoscopic pilonidal sinus treatment (PEPSiT). The medical records of all pediatric patients, aged up to 18 years, who underwent PEPSiT in the period 2019-2021, were retrospectively reviewed. Patients' demographics, operative details, and post-operative outcomes were assessed. A total of 294 patients (182 boys), with median age of 14 years (range 10-18), receiving PEPSiT in the study period, were enrolled. Pilonidal sinus disease (PSD) was primary in 258 (87.8%) and recurrent in 36 (12.2%). The median operative time was 36 min (range 11-120). The median VAS pain score was 0.86 (range 0-3) and the median duration of analgesic use was 27 h (range 12-60). The overall success rate was 95.2% (280/294) and the median time to full healing was 23.4 days (range 19-50). Six/294 (2.0%) patients developed Clavien 2 post-operative complications. The recurrence rate was 4.8% (14/294) and all recurrences were re-operated using PEPSiT. Redo-surgery for wound debridement was performed in one (0.3%) patient with late healing. On multivariate analysis, hirsutism and typology of sinus (pits ≥ 2, paramedian and more proximal to the anus) were predictors of PSD recurrence (p = 0.001). To date, this is the largest series of PEPSiT published in the pediatric population. The outcomes reported after a 3 years experience confirm that PEPSiT is a safe, effective, and real minimally invasive procedure to treat adolescents with PSD. It provides patients quick and painless recovery, satisfactory success, and high quality of life.
Topics: Male; Adolescent; Humans; Child; Aged; Pilonidal Sinus; Treatment Outcome; Retrospective Studies; Quality of Life; Neoplasm Recurrence, Local; Pain, Postoperative; Recurrence
PubMed: 37145226
DOI: 10.1007/s13304-023-01508-5 -
European Journal of Surgical Oncology :... Oct 2023Chemoradiotherapy is the primary treatment for anal cancer. 15-33% of patients will have persistent or recurrent disease after treatment requiring salvage surgery....
BACKGROUND
Chemoradiotherapy is the primary treatment for anal cancer. 15-33% of patients will have persistent or recurrent disease after treatment requiring salvage surgery. Relapse after surgery, postoperative complications, and mortality as well as possible risk factors are not fully understood due to the rareness of the disease. The aim of the study was to report outcomes after salvage surgery as well as evaluate risk factors for postoperative complications, cancer relapse and survival.
METHODS
Data were retrospectively collected from electronical patients charts and pathology reports from all patients undergoing salvage surgery from July 1st 2011 to July 1st 2021 at the Department of Surgery, Aarhus University Hospital, Denmark.
RESULTS
A total of 98 patients were included in the study. The 5-year overall survival was 61.8%. Relapse after surgery occurred in 36.7% of patients and was significantly associated with R1-resection (HR = 4.4) and preoperative nodal metastases (HR = 4.5). Negative prognostic factors for survival were found to be R1-resection (HR = 3.2), preoperative nodal metastases (HR = 2.9), and male gender (HR = 0.5). There was no association found between complications and survival (HR 1.2). None of the possible risk factors were associated with major postoperative complications.
CONCLUSIONS
An acceptable overall survival after surgery was found. Survival and relapse-free survival was negatively associated with R1 resections and positive preoperative lymph nodes. Complications did not influence long-term survival.
PubMed: 37657174
DOI: 10.1016/j.ejso.2023.107050 -
Cureus Dec 2023Background Natural orifice specimen extraction (NOSE) involves the removal of specimens through a naturally occurring orifice, such as the anus, rather than...
Background Natural orifice specimen extraction (NOSE) involves the removal of specimens through a naturally occurring orifice, such as the anus, rather than trans-abdominal extraction. NOSE procedures have been shown to significantly reduce postoperative complications and improve healing. Objective The purpose of this case series is to report the outcomes of 27 patients undergoing sigmoidectomies through natural orifice specimen extraction. Materials and methods We carefully recorded demographic data on age and BMI, as well as operative data on surgical indication, and length of stay. We also collected data on postoperative complications, including infection, hernia, wound dehiscence, urinary tract infections (UTIs), or anastomotic leaks. Results Our patients were majority female ( = 21, 77.8%) with a median age of 53.5 (range: 25-79) and median BMI of 33.2 kg/m (range: 16.7 - 48.3 kg/m). Thirteen patients (48.1%) were obese (BMI > 30.0 kg/m). The majority of these patients underwent sigmoidectomies for benign conditions such as recurrent diverticulitis ( = 9, 33.3%), rectal prolapse ( = 8, 29.6%), perforated diverticulitis ( = 3, 11.1%), colovesical fistula ( = 3, 11.1%), and abdominal abscess ( = 3, 11.1%) (Table 1). One patient was receiving treatment for sigmoid cancer. The average estimated blood loss was 63.26 mL. The average hospital stay was 3.61 days. Three patients (11.1%) developed a fever postoperatively (temperature >= 100.4 F), which resolved the day after. One patient completed a post-operative hospital stay of 19 days for dialysis and rehab placement. No patients (0.0%) experienced any postoperative complications, including wound infection, hernia, dehiscence, UTIs, or anastomotic leakages. There was no postoperative mortality. Conclusions Our study demonstrates the practicality and safety of NOSE procedures for sigmoidectomies as an alternative to transabdominal approaches to treat benign colon diseases.
PubMed: 38174165
DOI: 10.7759/cureus.49902 -
Techniques in Coloproctology Dec 2023Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive...
BACKGROUND
Anal intraepithelial neoplasia (AIN) appears in three different stages. AIN 1 and AIN 2 (p16 negative) are defined as low risk and unlikely to progress to invasive anal cancer. AIN 2 (p16 positive) and AIN 3 are of high risk and should be treated because progression rates to anal cancer are around 10% and treatment significantly reduces this risk. The correct treatment is still a matter of debate. Human papilloma virus (HPV) plays a role in the development of AIN. Our aim was to assess anal endoscopic dissection (aESD) as an intervention for AIN3.
METHODS
We retrospectively evaluated patients who underwent aESD for AIN 3 between December 2017 and March 2023. The interventional technique itself (duration, complications, size of specimen) and patient outcomes (recurrence, progression to anal cancer, re-intervention) were analyzed.
RESULTS
Fifteen patients with a median age of 52 years (23-78) underwent aESD for AIN 3. All tested specimens were positive for HPV. Median duration of intervention was 56.1 min, one delayed postinterventional bleeding occurred, and specimen size was 12.05 cm. Median follow-up was 11.17 months. Three recurrences (20%) appeared: one was resected via biopsy and two were again treated with aESD. There was no progression to invasive anal cancer in the follow-up period.
CONCLUSIONS
Anal endoscopic submucosal dissection seems to be a safe and feasible treatment for AIN. Recurrences are seldom and can be treated again with the same method. Nevertheless, indications for resection in comparison to radiofrequency ablation, pharmacological therapy, and watch-and-wait strategy are still unclear.
TRIAL REGISTRATION
Ethics commission of Salzburg, Austria, EK-Nr. 1056/2023. Keywords: Endoscopic submucosal dissection, anal intraepithelial neoplasia, anal cancer.
Topics: Humans; Young Adult; Adult; Middle Aged; Aged; Endoscopic Mucosal Resection; Papillomavirus Infections; Retrospective Studies; Feasibility Studies; Carcinoma in Situ; Anus Neoplasms
PubMed: 38102514
DOI: 10.1007/s10151-023-02896-x -
European Radiology May 2024The incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence....
OBJECTIVES
The incidence of anal squamous cell carcinoma (ASCC) is increasing worldwide, with a significant proportion of patients treated with curative intent having recurrence. The ability to accurately predict progression-free survival (PFS) and overall survival (OS) would allow for development of personalised treatment strategies. The aim of the study was to train and external test radiomic/clinical feature derived time-to-event prediction models.
METHODS
Consecutive patients with ASCC treated with curative intent at two large tertiary referral centres with baseline FDG PET-CT were included. Radiomic feature extraction was performed using LIFEx software on the pre-treatment PET-CT. Two distinct predictive models for PFS and OS were trained and tuned at each of the centres, with the best performing models externally tested on the other centres' patient cohort.
RESULTS
A total of 187 patients were included from centre 1 (mean age 61.6 ± 11.5 years, median follow up 30 months, PFS events = 57/187, OS events = 46/187) and 257 patients were included from centre 2 (mean age 62.6 ± 12.3 years, median follow up 35 months, PFS events = 70/257, OS events = 54/257). The best performing model for PFS and OS was achieved using a Cox regression model based on age and metabolic tumour volume (MTV) with a training c-index of 0.7 and an external testing c-index of 0.7 (standard error = 0.4).
CONCLUSIONS
A combination of patient age and MTV has been demonstrated using external validation to have the potential to predict OS and PFS in ASCC patients.
CLINICAL RELEVANCE STATEMENT
A Cox regression model using patients' age and metabolic tumour volume showed good predictive potential for progression-free survival in external testing. The benefits of a previous radiomics model published by our group could not be confirmed on external testing.
KEY POINTS
• A predictive model based on patient age and metabolic tumour volume showed potential to predict overall survival and progression-free survival and was validated on an external test cohort. • The methodology used to create a predictive model from age and metabolic tumour volume was repeatable using external cohort data. • The predictive ability of positron emission tomography-computed tomography-derived radiomic features diminished when the influence of metabolic tumour volume was accounted for.
Topics: Humans; Positron Emission Tomography Computed Tomography; Middle Aged; Anus Neoplasms; Male; Female; Fluorodeoxyglucose F18; Carcinoma, Squamous Cell; Radiopharmaceuticals; Aged; Retrospective Studies; Prognosis
PubMed: 37924344
DOI: 10.1007/s00330-023-10340-9 -
Scientific Reports Oct 2023Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A...
Natural course of perianal abscess (PA) in infancy remains obscure. This study aimed to investigate the natural course of infants with PA after conservative treatment. A retrospective cohort study was conducted in infants with PA who were treated conservatively (due to the parents' refusal of surgery), for more than 2 months between 2014 and 2020 at a single tertiary center. 153 patients (149 boys and 4 girls) were identified. The median follow-up was 5.3 years (range 3-8.2 years). Initially, 119 patients (77.8%) were completely cured by conservative treatment, and 34 (22.2%) failed. Among the 34 patients, 23 continued conservative treatment (20 cure, 3 fistula formation) and 11 underwent surgery. After conservative treatment, the rate of fistula formation, abscess recurrence, and new-onset abscess were 15.0%, 4.6%, and 6.5%, respectively. Overall, 139 patients (90.8%) were cured conservatively without surgery, and 11 (7.2%) underwent surgical management. In addition, 3 (2.0%) patients developed fistula-in-ano (under observation). PA in infants may be a time-limited and self-limited condition. Conservative management should be the first choice of treatment in most cases. Longer periods of conservative treatment may achieve better clinical outcomes in selected cases. There will be a percentage of patients (about 10%) that would require surgical treatment.
Topics: Male; Female; Humans; Infant; Retrospective Studies; Abscess; Treatment Outcome; Drainage; Anus Diseases; Rectal Fistula
PubMed: 37891236
DOI: 10.1038/s41598-023-45751-7