-
Cancer Immunology, Immunotherapy : CII Jul 2023Immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of cancer treatment. However, only a few patients respond to ICI treatment. Thus, uncovering...
BACKGROUND
Immune checkpoint inhibitors (ICIs) have dramatically changed the landscape of cancer treatment. However, only a few patients respond to ICI treatment. Thus, uncovering clinically accessible ICI biomarkers would help identify which patients will respond well to ICI treatment. A comprehensive objective response rate (ORR) data of anti-PD-1/PD-L1 monotherapy in pan-cancer would offer the original data to explore the new biomarkers for ICIs.
METHODS
We systematically searched PubMed, Cochrane, and Embase for clinical trials on July 1, 2021, limited to the years 2017-2021, from which we obtained studies centering around anti-PD-1/PD-L1 monotherapy. Finally, 121 out of 3099 publications and 143 ORR data were included. All of the 31 tumor types/subtypes can be found in the TCGA database. The gene expression profiles and mutation data were downloaded from TCGA. A comprehensive genome-wide screening of ORR highly correlated mutations among 31 cancers was conducted by Pearson correlation analysis based on the TCGA database.
RESULTS
According to the ORR, we classified 31 types of cancer into high, medium, and low response types. Further analysis uncovered that "high response" cancers had more T cell infiltration, more neoantigens, and less M2 macrophage infiltration. A panel of 28 biomarkers reviewed from recent articles were investigated with ORR. We also found the TMB as a traditional biomarker had a high correlation coefficient with ORR in pan-cancer, however, the correlation between ITH and ORR was low across pan-cancer. Moreover, we primarily identified 1044 ORR highly correlated mutations through a comprehensive screening of TCGA data, among which USH2A, ZFHX4 and PLCO mutations were found to be highly correlated to strengthened tumor immunogenicity and inflamed antitumor immunity, as well as improved outcomes for ICIs treatment among multiple immunotherapy cohorts.
CONCLUSION
Our study provides comprehensive data on ORR of anti-PD-1/PD-L1 monotherapy across 31 tumor types/subtypes and an essential reference of ORR to explore new biomarkers. We also screened out a list of 1044 immune response related genes and we showed that USH2A, ZFHX4 and PLCO mutations may act as good biomarkers for predicting patient response to anti-PD-1/PD-L1 ICIs.
Topics: Humans; B7-H1 Antigen; Biomarkers, Tumor; Neoplasms; Antigens, Neoplasm; Programmed Cell Death 1 Receptor
PubMed: 37022474
DOI: 10.1007/s00262-023-03441-3 -
Surgery Jun 2023We conducted a systematic review of randomized clinical trials on treating low anterior resection syndrome to help inform current practice. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
We conducted a systematic review of randomized clinical trials on treating low anterior resection syndrome to help inform current practice.
METHODS
This Preferred Reporting Items for Systematic Reviews and Meta-Analyses-compliant systematic review of randomized clinical trials involved different treatments for low anterior resection syndrome. The risk of bias 2 tool was used to assess the risk of bias. The main outcomes were improvement in low anterior resection syndrome after treatment assessed by change in low anterior resection syndrome, fecal incontinence scores, and adverse treatment effects.
RESULTS
After an initial screening of 1,286 studies, 7 randomized clinical trials were included. Sample sizes ranged between 12 to 104 patients. Posterior tibial nerve stimulation was the most frequently assessed treatment in 3 randomized clinical trials. The weighted mean difference between posterior tibial nerve stimulation and medical treatment or sham therapy in follow-up low anterior resection syndrome score (-3.31, P = .157) was insignificant. Transanal irrigation reduced major low anterior resection syndrome symptoms by 61.5% compared with 28.6% after posterior tibial nerve stimulation with a significantly lower 6-month follow-up low anterior resection syndrome score. Pelvic floor training achieved better improvement in low anterior resection syndrome than standard care (47.8% vs 21.3%) at 6 months, but this was not maintained at 12 months (40.0% vs 34.9%). Ramosetron was associated with a greater short-term improvement in major low anterior resection syndrome (23% vs 8%) and a lower low anterior resection syndrome score (29.5 vs 34.6) at 4-weeks follow-up than Kegels or Sitz baths. No significant improvement in bowel function was noted after probiotics use as probiotics and placebo had similar follow-up low anterior resection syndrome scores (33.3 vs 36).
CONCLUSION
Transanal irrigation was associated with improvement in low anterior resection syndrome according to 2 trials, and ramosetron showed promising short-term results in one trial. Posterior tibial nerve stimulation had a marginal benefit compared with standard care. In contrast, pelvic floor training was associated with short-term symptomatic improvement, and probiotics showed no tangible improvement in low anterior resection syndrome symptoms. Firm conclusions cannot be drawn due to the small number of trials published.
Topics: Humans; Low Anterior Resection Syndrome; Postoperative Complications; Rectal Neoplasms; Randomized Controlled Trials as Topic
PubMed: 37012144
DOI: 10.1016/j.surg.2023.02.010 -
Urology Jun 2023To systematically aggregate and summarize existing data on fistula prevalence among patients with a history of pelvic radiotherapy for prostate cancer. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To systematically aggregate and summarize existing data on fistula prevalence among patients with a history of pelvic radiotherapy for prostate cancer.
MATERIALS AND METHODS
We queried PubMed, Embase, and Web of Science on October 7, 2020 for peer-reviewed publications pertaining to radiation-induced fistulas in the pelvis. For meta-analysis, we used the random-effects model. We used the I statistic to quantify heterogeneity and the Newcastle-Ottawa Scale to assess risk of bias.
RESULTS
Our final meta-analysis included 6 cohort studies with a total of 7665 patients exposed to pelvic radiotherapy between 1967 and 2013. Median follow-up time was 35.5 months (IQR 33.5-57.5). Pooled prevalence of radiation-induced fistula across all 6 cohort studies was 0.2% (95% CI: 0.1-0.4, I = 0.000%, P < .608). In subgroup analysis, we did not detect significant heterogeneity in fistula prevalence in patients who were re-irradiated (0.3%, 95% CI: 0.1-0.4; P = .762) or patients on concurrent chemotherapy (0.4%, 95% CI: -0.3 -1.2; P = .664) compared to those receiving their first course of radiotherapy alone. No randomized controlled trials met inclusion criteria due to ambiguous and inconsistent reporting language for fistula occurrence.
CONCLUSION
There is limited published literature reporting fistula as an adverse event of prostate cancer radiotherapy, especially in the medium and long-term period. Patients undergoing pelvic radiotherapy for prostate cancer appear at low short-term risk for developing fistulas. Adverse event reporting in randomized controlled trials merits greater granularity where fistulas should be reported with specificity rather than aggregating into broad categories of genitourinary or gastrointestinal adverse events.
Topics: Male; Humans; Pelvis; Prostatic Neoplasms; Cohort Studies
PubMed: 36963666
DOI: 10.1016/j.urology.2023.03.015 -
International Journal of Gynecological... Jun 2023In endometrial carcinoma patients, sentinel lymph node bilateral mapping fails in 20-25% of cases, with several factors affecting the likelihood of detection. However,... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
In endometrial carcinoma patients, sentinel lymph node bilateral mapping fails in 20-25% of cases, with several factors affecting the likelihood of detection. However, pooled data about predictive factors of failure are lacking. The aim of this systematic review and meta-analysis was to assess the predictive factors of sentinel lymph node failed mapping in endometrial cancer patients undergoing sentinel lymph node biopsy.
METHODS
A systematic review and a meta-analysis was performed searching all studies assessing predictive factors of sentinel lymph node failed mapping in apparent uterine-confined endometrial cancer patients undergoing sentinel lymph node biopsy through the cervical injection of indocyanine green. The associations between sentinel lymph node failed mapping and predictive factors of failure were assessed, calculating the odds ratio (OR) with 95% confidence intervals.
RESULTS
Six studies with a total of 1345 patients were included. Compared with patients with sentinel lymph node bilateral successful mapping, patients with sentinel lymph node failed mapping showed: OR 1.39 (p=0.41) for body mass index >30 kg/m; OR 1.72 (p=0.24) for menopausal status; OR 1.19 (p=0.74) for adenomyosis; OR 0.86 (p=0.55) for prior pelvic surgery; OR 2.38 (p=0.26) for prior cervical surgery; OR 0.96 (p=0.89) for prior Cesarean section; OR 1.39 (p=0.70) for lysis of adhesions during surgery before sentinel lymph node biopsy; OR 1.77 (p=0.02) for indocyanine green dose <3 mL; OR 1.28 (p=0.31) for deep myometrial invasion; OR 1.21 (p=0.42) for International Federation of Gynecology and Obstetrics (FIGO) grade 3; OR 1.89 (p=0.01) for FIGO stages III-IV; OR 1.62 (p=0.07) for non-endometrioid histotype; OR 1.29 (p=0.25) for lymph-vascular space invasion; OR 4.11 (p<0.0001) for enlarged lymph nodes; and OR 1.71 (p=0.022) for lymph node involvement.
CONCLUSION
Indocyanine green dose <3 mL, FIGO stage III-IV, enlarged lymph nodes, and lymph node involvement are predictive factors of sentinel lymph node failed mapping in endometrial cancer patients.
Topics: Pregnancy; Humans; Female; Sentinel Lymph Node; Indocyanine Green; Lymph Node Excision; Cesarean Section; Sentinel Lymph Node Biopsy; Lymph Nodes; Endometrial Neoplasms; Lymphadenopathy; Coloring Agents
PubMed: 36914172
DOI: 10.1136/ijgc-2022-004014 -
World Journal of Surgical Oncology Mar 2023The purpose of this network meta-analysis was to compare the effectiveness and adverse effects of limited, standard, extended, and super-extended pelvic lymph node... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The purpose of this network meta-analysis was to compare the effectiveness and adverse effects of limited, standard, extended, and super-extended pelvic lymph node dissection (PLND) following radical prostatectomy.
METHODS
This study followed the PRISMA 2020 statement. Clinical trials were searched from three electronic databases, including PubMed, the Cochrane Library, and Embase from the database's inception to April 5, 2022. The lymph node-positive rate, biochemical recurrence-free rate, lymphocele rate, thromboembolic rate, and overall complication rate were compared by meta-analysis. Data analyses were performed using R software based on the Bayesian framework.
RESULTS
Sixteen studies involving 15,269 patients were included. All 16 studies compared the lymph node-positive rate; 5 studies compared the biochemical recurrence-free rate; 10 studies compared the lymphocele rate; 6 studies compared the thromboembolic rate, and 9 studies compared the overall complication rate. According to Bayesian analysis, the lymph node-positive rate, lymphocele rate, and overall complication rate were significantly associated with the extension of the PLND range. The limited, extended, and super-extended PLND templates showed a similar but lower biochemical recurrence-free rate and a higher thromboembolic rate than the standard template.
CONCLUSIONS
The extension of the PLND range is associated with an elevated lymph node-positive rate; however, it does not improve the biochemical recurrence-free rate and correlates with an increased risk of complications, especially lymphocele. The selection of the PLND range in clinical practice should consider the oncological risk and adverse effects.
TRIAL REGISTRATION
PROSPERO (CRD42022301759).
Topics: Male; Humans; Network Meta-Analysis; Bayes Theorem; Lymphocele; Prostatic Neoplasms; Prostatectomy; Lymph Node Excision
PubMed: 36872312
DOI: 10.1186/s12957-023-02932-y -
International Journal of Colorectal... Feb 2023The optimal surgical approach for removal of colorectal endometrial deposits is unclear. Shaving and discoid excision of colorectal deposits allow organ preservation but... (Meta-Analysis)
Meta-Analysis
PURPOSE
The optimal surgical approach for removal of colorectal endometrial deposits is unclear. Shaving and discoid excision of colorectal deposits allow organ preservation but risk recurrence with associated functional issues and re-operation. Formal resection risks potential higher complications but may be associated with lower recurrence rates. This meta-analysis compares peri-operative and long-term outcomes between conservative surgery (shaving and disc excision) versus formal colorectal resection.
METHODS
The study was registered with PROSPERO. A systematic search was performed on PubMed and EMBASE databases. All comparative studies examining surgical outcomes in patients that underwent conservative surgery versus colorectal resection for rectal endometrial deposits were included. The two main groups (conservative versus resection) were compared in three main blocks of variables including group comparability, operative outcomes and long-term outcomes.
RESULTS
Seventeen studies including 2861 patients were analysed with patients subdivided by procedure: colorectal resection (n = 1389), shaving (n = 703) and discoid excision (n = 742). When formal colorectal resection was compared to conservative surgery there was lower risk of recurrence (p = 0.002), comparable functional outcomes (minor LARS, p = 0.30, major LARS, p = 0.54), similar rates of postoperative leaks (p = 0.22), pelvic abscesses (p = 0.18) and rectovaginal fistula (p = 0.92). On subgroup analysis, shaving had the highest recurrence rate (p = 0.0007), however a lower rate of stoma formation (p < 0.00001) and rectal stenosis (p = 0.01). Discoid excision and formal resection were comparable.
CONCLUSION
Colorectal resection has a significantly lower recurrence rate compared to shaving. There is no difference in complications or functional outcomes between discoid excision and formal resection and both have similar recurrence rates.
Topics: Female; Humans; Endometriosis; Reoperation; Rectovaginal Fistula; Abdominal Abscess; Colorectal Neoplasms
PubMed: 36847868
DOI: 10.1007/s00384-023-04352-6 -
Medicina (Kaunas, Lithuania) Jan 2023The standard treatment approach in locally advanced cervical cancer (LACC) is exclusive concurrent chemoradiation therapy (RTCT). The risk of local residual disease... (Review)
Review
The standard treatment approach in locally advanced cervical cancer (LACC) is exclusive concurrent chemoradiation therapy (RTCT). The risk of local residual disease after six months from RTCT is about 20-30%. It is directly related to relapse risk and poor survival, such as in patients with recurrent cervical cancer. This systematic review aims to describe studies investigating salvage surgery's role in persistent/recurrent disease in LACC patients who underwent definitive RTCT. Studies were eligible for inclusion when patients had LACC with radiologically suspected or histologically confirmed residual disease after definitive RTCT, diagnosed with post-treatment radiological workup or biopsy. Information on complications after salvage surgery and survival outcomes had to be reported. The methodological quality of the articles was independently assessed by two researchers with the Newcastle-Ottawa scale. Following the recommendations in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement, we systematically searched the PubMed, Scopus, Cochrane, Medline, and Medscape databases in May 2022. We applied no language or geographical restrictions but considered only English studies. We included studies containing data about postoperative complications and survival outcomes. Eleven studies fulfilled the inclusion criteria and all were retrospective observational studies. A total of 601 patients were analyzed concerning the salvage surgery in LACC patients for persistent/recurrent disease after RTCT treatment. Overall, 369 (61.4%) and 232 (38.6%) patients underwent a salvage hysterectomy (extrafascial or radical) and pelvic exenteration (anterior, posterior, or total), respectively. Four hundred and thirty-nine (73%) patients had histologically confirmed the residual disease in the salvage surgical specimen, and 109 patients had positive margins (overall range 0-43% of the patients). The risk of severe (grade ≥ 3) postoperative complications after salvage surgery is 29.8% (range 5-57.5%). After a median follow-up of 38 months, the overall RR was about 32% with an overall death rate of 40% after hysterectomy or pelvic exenteration with or without lymphadenectomy. There is heterogeneity between the studies both in their design and results, therefore the effect of salvage surgery on survival and recurrence cannot be adequately estimated. Future homogeneous studies with an appropriately selected population are needed to analyze the safety and efficacy of salvage hysterectomy or pelvic exenteration in patients with residual tumors after definitive RTCT.
Topics: Female; Humans; Uterine Cervical Neoplasms; Retrospective Studies; Neoplasm Recurrence, Local; Hysterectomy; Chemoradiotherapy; Postoperative Complications
PubMed: 36837394
DOI: 10.3390/medicina59020192 -
Polski Przeglad Chirurgiczny May 2022<b> Aim: </b> The study was conducted to analyse the recent peer-reviewed literature related to symptomatic spilled gallstones after Laparoscopic...
<b> Aim: </b> The study was conducted to analyse the recent peer-reviewed literature related to symptomatic spilled gallstones after Laparoscopic Cholecystectomy (LC). </br></br> <b>Materials and methods:</b> Articles published in the peer-reviewed journals of repute from 20122022 were evaluated for nine variables including: [I] age of the patient, [II] gender, [III] interval since index LC, [IV] index LC if emergent/difficult or elective/straightforward, [V] clinical presentation, [VI] spilled gallstones if detected by imaging, [VII] management, [VIII] approach to management, [IX] number of spilled gallstones. </br></br> <b>Results:</b> There were a total of 71 cases (37 males and 34 females) with a mean age of 63.7 years. The time of onset of symptoms from spilled gallstones, after index LC, ranged from 2 days to 15 years and 57 patients (80.3%) presented within 6 years. Forty (56.3%) patients were unaware of the fact that gallstone spillage had occurred during index LC. The retained gallstones were detected by imaging in 47 (66.1%) cases and they were multiple in 51 (71.8%). In 52 patients (73.2%), the stones manifested as abdominal abscess/foreign body granuloma; the other presentations being pelvic pain/fistula, intestinal obstruction, abdominal lump simulating malignancy, incidental finding of metastatic lesions and generalized peritonitis. The major approaches adopted to retrieve the retained stones included open surgery, laparoscopy and percutaneous drainage. There were two deaths (2.9%) due to spilled gallstones. </br></br> <b>Conclusion:</b> Retained gallstones represent a complication of laparoscopic cholecystectomy (LC) that has a potential to create morbidity and diagnostic difficulties, even after a substantial delay. There is a need to spread awareness about the adverse effects of spilled stones so that they are actively looked for and retrieved if gallbladder perforates during cholecystectomy. Whenever such a complication occurs, the patient should be properly informed and the details should be very clearly mentioned in the operation notes.
Topics: Female; Male; Humans; Middle Aged; Gallstones; Cholecystectomy, Laparoscopic; Cholecystectomy; Laparoscopy; Abdominal Abscess; Abdominal Neoplasms
PubMed: 36805307
DOI: 10.5604/01.3001.0015.8571 -
International Journal of Gynecological... Apr 2023The predicament of achieving optimal surgical intervention faced by surgeons in treating ovarian cancer has driven research into improving intra-operative detection of...
BACKGROUND
The predicament of achieving optimal surgical intervention faced by surgeons in treating ovarian cancer has driven research into improving intra-operative detection of cancer using fluorescent materials.
OBJECTIVE
To provide a literature overview on the clinical use of intra-operative fluorescence-guided surgery for ovarian cancer, either for cytoreductive surgery or sentinel lymph node (SLN) biopsy.
METHODS
The systematic review included studies from June 2002 until October 2021 from PubMed, Web of Science, and Scopus as well as those from a search of related literature. Studies were included if they investigated the use of fluorescence-guided surgery in patients with a diagnosis of ovarian cancer. Authors charted variables related to study characteristics, patient demographics, baseline clinical characteristics, fluorescence-guided surgery material, and treatment details, and surgical, oncological, and survival outcome variables. After screening 2817 potential studies, 24 studies were included.
RESULTS
Studies investigating the role of fluorescence-guided surgery to visualize tumor deposits or SLN biopsy included the data of 410 and 118 patients, respectively. Six studies used indocyanine green tracer with a mean SLN detection rate of 92.3% with a pelvic and para-aortic detection rate of 94.8% and 96.7%, respectively. The sensitivity, specificity, and positive predictive value for micrometastases detection of OTL38 and 5-aminolevulinc acid at time of cytoreduction were 92.2% vs 79.8%, 67.3% vs 94.8%, and 55.8% vs 95.8%, respectively.
CONCLUSION
Fluorescence -guided surgery is a technique that may improve the detection rate of micrometastases and SLN identification in ovarian cancer. Further research is needed to establish whether this will lead to improved patient outcomes.
Topics: Humans; Female; Sentinel Lymph Node; Neoplasm Micrometastasis; Sentinel Lymph Node Biopsy; Coloring Agents; Indocyanine Green; Ovarian Neoplasms; Lymph Nodes; Lymph Node Excision
PubMed: 36707085
DOI: 10.1136/ijgc-2022-003846 -
Journal of Robotic Surgery Aug 2023Lateral pelvic lymph node dissection (LPLND) in rectal cancer has gained increasing traction worldwide. Robotic LPLND is an emerging technique. Utilising the IDEAL... (Review)
Review
Lateral pelvic lymph node dissection (LPLND) in rectal cancer has gained increasing traction worldwide. Robotic LPLND is an emerging technique. Utilising the IDEAL (idea, development, exploration, assessment and long-term follow-up) framework for surgical innovation, robotic LPLND is currently at the IDEAL 2A stage (development) mainly limited to case reports, case series and videos. A systematic literature review was performed for videographic robotic LPLND. Pubmed, Ovid and Web of Science were searched with a predefined search strategy. The LapVEGAS score for peer review of video surgery was adapted for the robotic approach (RoVEGAS) and applied to measure video quality. Two reviewers independently reviewed videos and consensus reached on technical steps and learning points. Data are presented as a narrative synthesis of results. The IDEAL 2A framework was applied to videos to assess their content at the present stage of innovation. A total of 83 abstracts were identified. In accordance with the PRISMA statement, nine videos were analysed. Adherence to the complete IDEAL 2a framework was low. All videos demonstrated LPLND; however, reporting of clinical outcomes was heterogeneous and completed in six of nine videos. Histopathology was reported in six videos, with other outcomes variably reported. No videos presented patient-reported outcome measures. Two videos reported presence or absence of recurrence on follow-up. Video articles provide a valuable educational resource in dissemination and adoption of robotic techniques. Standardisation of reporting objectives are needed. Complete reporting of pathology and oncologic outcomes is required in videographic procedural-based publications to meet the IDEAL 2A framework criteria.
Topics: Humans; Robotic Surgical Procedures; Laparoscopy; Lymph Node Excision; Robotics; Rectal Neoplasms
PubMed: 36689077
DOI: 10.1007/s11701-023-01526-w