Peritoneal Lesions Research Articles

Targeting sphingosine kinase-1 with the low MW inhibitor SKI-5C suppresses the development of endometriotic lesions in mice.

Limited evidence suggests that the sphingosine-1-phosphate/sphingosine kinase 1 (S1P/SPHK1) signalling pathway is involved in the pathogenesis of endometriosis. Therefore, we analyzed in this study whether the inhibition of SPHK1 and, consequently, decreased levels of S1P affected the vascularization and growth of endometriotic lesions. Endometriotic lesions were surgically induced in the peritoneal cavity and the dorsal skinfold chamber of female BALB/c mice. The animals received a daily dose of the SPHK1 inhibitor SKI-5C or vehicle (control). Analyses involved the determination of lesion growth, cyst formation, microvessel density and cell proliferation within peritoneal endometriotic lesions by means of high-resolution ultrasound imaging, caliper measurement, histology and immunohistochemistry. In the dorsal skinfold chamber model the development of newly formed microvascular networks and their microhemodynamic parameters within endometriotic lesions were investigated by means of intravital fluorescence microscopy. SKI-5C significantly inhibited the development and vascularization of peritoneal endometriotic lesions, as indicated by a reduced growth and cyst formation, a lower microvessel density and a suppressed cell proliferation, when compared to vehicle-treated controls. Endometriotic lesions in dorsal skinfold chambers of SKI-5C-treated animals exhibited a significantly smaller lesion size, lower functional microvessel density, smaller microvessel diameters and a reduced blood perfusion of the newly developing microvascular networks. SPHK1/S1P signalling promotes the establishment and progression of endometriotic lesions. The inhibition of this pathway suppresses the development of endometriotic lesions, suggesting SPHK1 as a potential novel target for future endometriosis therapy.

Associations between body mass index and the surgical phenotype and location of endometriotic lesions

Research questionIs there a relationship between body mass index (BMI) and endometriotic lesions, specifically surgical phenotype and lesion location? DesignAn observational retrospective cohort study at the Royal Women's Hospital, Melbourne, Australia, including 471 histologically confirmed endometriosis patients. Statistical analyses included multivariate logistic regression and multivariate modelling, correcting for multiple testing. Outcomes were the presence or absence of surgically classified lesion phenotypes, as per revised American Society for Reproductive Medicine criteria including superficial or deep, peritoneal or ovarian, and adhesions (Study I); and lesions at specific anatomical locations (including pelvic side wall, uterosacral ligament, pouch of Douglas, ovarian, uterovesical fold, bladder, and pararectal endometriosis) (Study II). ResultsIn Study I, patients with higher BMI were more likely to have superficial peritoneal lesions (odds ratio [OR] 1.070, 95% confidence interval [CI] 1.004–1.144; P = 0.044), and less likely to have deep ovarian lesions (OR 0.928, 95% CI 0.864–0.993; P = 0.034). In Study II, patients with higher BMI were less likely to have uterovesical fold lesions (OR 0.927, 95% CI 0.867–0.985; P = 0.021) or anterior compartment lesions (OR 0.940, 95% CI 0.888–0.989; P = 0.023). After correcting for multiple testing, the relationship between BMI and lesion phenotypes did not persist (P > 0.01). ConclusionsThis analysis does not conclusively support an influence of BMI on endometriotic lesion phenotype based on surgical classification or location. Further investigation of the physiological disturbances underlying BMI and the promotion of endometriotic lesion phenotypes and their location is warranted, but any effect is likely to be small.

Comprehensive Analysis of Peritoneal Metastasis Sequencing Data to Identify LINC00924 as a Prognostic Biomarker in Gastric Cancer.

BackgroundGastric cancer peritoneal metastasis has high mortality. At present, there is no effective way to cure the patients diagnosed with gastric cancer peritoneal metastasis due to its indistinct molecular mechanism. Therefore, to understand the pathogenesis and help for further target therapy, we conduct comprehensive analysis of peritoneal metastasis by bioinformatics in gastric cancer.MethodsMicroarray sequencing was used to find differential mRNAs and long non-coding RNAs (lncRNAs) expression between primary foci and peritoneal metastases lesion in gastric cancer. RT-qPCR was used to verify the expression levels of lncRNAs in gastric cancer cells after co-culture with adipocytes. TCGA, Cytoscape, lnCAR, cBioPoratal and R packages (ggrisk, survival, survminer, timeROC, forestplot, immunedeconv, ggplot2, pheatmap and ggpubr) were applied in this work.ResultsAdipocytes co-culture model was used to mimic the peritoneal microenvironment and found that LINC01151 (NR_126348), FAM27B (NR_027422) and LINC00924 (NR_027133) were up-regulated in co-culture group. Increased LINC00924 expression was significantly associated with reduced overall survival and up-regulated percentage abundance of tumor-infiltrating CD8+ T, B, macrophage and NK immune cells; moreover, immune checkpoint blockers (ICBs) had a worse effect on the LINC00924 high expression group. Furthermore, through univariate and multivariate Cox regression analysis, we found that LINC00924-related PEX5L in CNC network was an independent prognostic factor in gastric cancer progression.ConclusionLINC00924 expression was associated with poor survival, immune infiltrations and worse response to ICBs. LINC00924 might be immunotherapeutic targets of advanced gastric cancer.

ASSOCIATION BETWEEN PELVIC EXENTERATION AND HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY FOR RECTAL CANCER

Colorectal cancer spreads via multiple pathways, the most commonly encountered ways being represented by the peritoneal and hematogenous ones as well as by direct contiguity. At this time significant benefits in terms of survival have been reported in cases presenting locally advanced lesions and for those presenting extended peritoneal lesions of peritoneal carcinomatosis especially if radical resection is achievable. In this respect, certain authors went further and investigated whether the association of the two surgical strategies – extended pelvic resections and cytoreductive surgery of the peritoneal metastases could improve survival in cases in which both patterns of spread are present. Meanwhile, the possibility of association of hyperthermic intraperitoneal chemotherapy (HIPEC) was also investigated. The aim of the current study is to review and analyze the most relevant studies conducted on this issue.

Diffuse peritoneal lymphomatosis or abdominal tuberculosis: a clinico-radiological conundrum

Primary extra nodal lymphoma occurs in approximately 25% to 40% of patients and is more common in patients with NHL. Diffuse large B-cell lymphoma (DLBCL) is the dominant histological subtype. A 60-year-old gentleman presented to our hospital with pain abdomen associated with abdominal distension since a month, few constitutional symptoms with bilateral axillary and inguinal lymphadenopathy. Blood investigations showed high total count with significantly high LDH levels. Provisional diagnosis of tubercular Abdomen/Malignant Ascites with Unknown primary was made. CT Abdomen showed large bowel wall thickening with parietal peritoneal lesions with omental cake. Excision biopsy of inguinal lymph node showed lymphoid follicles with poorly defined attenuated mantle zones having centrocytes and centroblasts. Immunohistochemistry was positive for markers, which confirmed the diagnosis of Stage 4B DLBCL, germinal center B-cell type. Sepsis and acute kidney injury occurred and the patient expired, 6 days after diagnosis. To conclude, Peritoneal lymphomatosis is an extremely rare condition. This case highlights the need to have a high index of suspicion for malignancy, when a given case is clinically diagnosed with tuberculosis as and when new findings appear during investigation.

The Gynecologic Surgeon's Approach to Evaluating a Patient With Suspected Endometriosis: A Systematic Review

Background: The objective of this review is to assess the most recent literature recommendations for how to approach a patient presenting with chronic pelvic pain (CPP), when a high clinical suspicion of endometriosis exists, to prevent the clinical and economic burden associated with delayed diagnosis. Methods: An online review of PubMed and Europe PubMed Central was conducted with a final total of 11 articles being reviewed. The search was limited to the preoperative management of these patients, excluding literature focused on the effectiveness of medical vs. surgical management of the disease. There is no main outcome measure. Results: A thorough history of patient symptomatology and physical exam are paramount to a timely diagnosis of endometriosis. Additionally, the literature supports the use of sonogram as the first-line imaging modality for diagnosis; however, its utility is limited to detection of the two less common forms of the disease, endometrioma and deep peritoneal lesions, with less reliable prediction of superficial implants. If a high clinical suspicion exists for either endometrioma or deep infiltrating disease, magnetic resonance imaging can reliably demonstrate these findings. The gold standard method of laparoscopy for definitive diagnosis is not controversial; however, the literature suggests that proper, sequential evaluation by history, physical and imaging may aid in accurate and timely diagnosis. Delay in the diagnosis of endometriosis creates a significant burden on patient well-being as well as an economic burden on the healthcare system. Conclusion: Further studies assessing biomarkers of endometriosis and specific features of the disease in time are needed to better understand the etiology and pathogenesis and to subsequently decrease disease burden. J Clin Gynecol Obstet. 2021;10(2):40-45 doi: https://doi.org/10.14740/jcgo742

Differences in growth and vascularization of ectopic menstrual and non-menstrual endometrial tissue in mouse models of endometriosis.

Is there a difference in the growth and vascularization between murine endometriotic lesions originating from menstrual or non-menstrual endometrial fragments? Endometriotic lesions developing from menstrual and non-menstrual tissue fragments share many similarities, but also exhibit distinct differences in growth and vascularization, particularly under exogenous estrogen stimulation. Mouse models are increasingly used in endometriosis research. For this purpose, menstrual or non-menstrual endometrial fragments serve for the induction of endometriotic lesions. So far, these two fragment types have never been directly compared under identical experimental conditions. This was a prospective experimental study in a murine peritoneal and dorsal skinfold chamber model of endometriosis. Endometrial tissue fragments from menstruated (n = 15) and non-menstruated (n = 21) C57BL/6 mice were simultaneously transplanted into the peritoneal cavity or dorsal skinfold chamber of non-ovariectomized (non-ovx, n = 17), ovariectomized (ovx, n = 17) and ovariectomized, estrogen-substituted (ovx+E2, n = 17) recipient animals and analyzed throughout an observation period of 28 and 14 days, respectively. The engraftment, growth and vascularization of the newly developing endometriotic lesions were analyzed by means of high-resolution ultrasound imaging, intravital fluorescence microscopy, histology and immunohistochemistry. Menstrual and non-menstrual tissue fragments developed into peritoneal endometriotic lesions without differences in growth, microvessel density and cell proliferation in non-ovx mice. Lesion formation out of both fragment types was markedly suppressed in ovx mice. In case of non-menstrual tissue fragments, this effect could be reversed by estrogen supplementation. In contrast, endometriotic lesions originating from menstrual tissue fragments exhibited a significantly smaller volume in ovx+E2 mice, which may be due to a reduced hormone sensitivity. Moreover, menstrual tissue fragments showed a delayed vascularization and a reduced blood perfusion after transplantation into dorsal skinfold chambers when compared to non-menstrual tissue fragments, indicating different vascularization modes of the two fragment types. To limit the role of chance, the experiments were conducted under standardized laboratory conditions. Statistical significance was accepted for a value of P < 0.05. N/A. Endometriotic lesions were induced by syngeneic tissue transplantation into recipient mice without the use of pathological endometriotic tissue of human nature. Therefore, the results obtained in this study may not fully relate to human patients with endometriosis. The present study significantly contributes to the characterization of common murine endometriosis models. These models represent important tools for studies focusing on the basic mechanisms of endometriosis and the development of novel therapeutic strategies for the treatment of this frequent gynecological disease. The presented findings indicate that the combination of different experimental models and approaches may be the most appropriate strategy to study the pathophysiology and drug sensitivity of a complex disease such as endometriosis under preclinical conditions. There was no specific funding of this study. The authors have no conflicts of interest to declare.

Anterior Lumbar Interbody Fusion (ALIF) L5-S1 with overpowering of posterior lumbosacral instrumentation and fusion mass: a reliable solution in revision spine surgery.

In cases of spine surgical revisions of patients affected by sagittal malalignment, the restoration of the ideal lumbar lordosis (LL) is mandatory. ALIF procedures represent a powerful and effective approach to improve the LL in case of hypolordosis. This study evaluates the feasibility of ALIF to overpower posterior lumbar instrumentation and fusion mass in revision spine surgery and secondarily to estimate complications, clinical and radiological outcomes. This is a single-center retrospective analysis of prospectively collected data on the use of ALIF overpowering in cases of lumbosacral instrumentation and/or fusion.Demographic, comorbidity, corrective strategy adopted, surgical data, clinical and radiological results, and intraoperative and postoperative complications were recorded. Twelve patients (3 male; 9 female) underwent overpowering ALIF L5-S1 were included in the study with a mean FU of 34.0 ± 13.4 months. In 10 cases, a posterior titanium instrumentation and fusion mass were present; in 2 patients, only a fusion mass was present. Indicators of pain and disability improved in all patients (p < 0.01). Sagittal realignment with the restoration of ideal spinopelvic parameters was obtained in all cases. One peritoneal lesion requiring intraoperative suture without sequelae, two cases of postoperative radiculopathy, and one posterior wound infection requiring surgical debridement and antibiotic therapy were reported. Anterior implant of lordotic and hyperlordotic cages with increasing segmental lordosis is possible in the presence of posterior instrumentation and/or solid fusion mass. The biomechanical strength of this corrective technique can overcome posterior instrumentation and bone fusion resistance, therefore allowing a single-staged surgery for sagittal realignment.

Regulation of Inflammatory and Proliferative Pathways by Fotemustine and Dexamethasone in Endometriosis.

Endometriosis is a common disease. Its pathogenesis still remains uncertain, but it is clear that cell proliferation, apoptosis and chronic inflammation play an important role in its development. This paper aimed to investigate the anti-proliferative and anti-inflammatory effects of a combined therapy with fotemustine and dexamethasone. Endometriosis was induced by intraperitoneal injections of uterine fragments from donor animals to recipient animals. Next, the pathology was allowed to develop for 7 days. On the seventh day, fotemustine was administered once and dexamethasone was administered daily for the next 7 days. On Day 14, the animals were sacrificed, and peritoneal fluids and lesions were explanted. In order to evaluate the gastrointestinal side effects of the drugs, stomachs were harvested as well. The combined therapy of fotemustine and dexamethasone reduced the proinflammatory mediator levels in the peritoneal fluid and reduced the lesions’ area and diameter. In particular, fotemustine and dexamethasone administration reduced the heterogeneous development of endometrial stroma and glands (histological analysis of lesions) and hyperproliferation of endometriotic cells (immunohistochemical analysis of Ki67 and Western blot analysis of PCNA) through the mitogen-activated protein kinase (MAPK) signaling pathway. Combined fotemustine and dexamethasone therapy showed anti-inflammatory effects by inducing the synthesis of anti-inflammatory mediators at the transcriptional and post-transcriptional levels (Western blot analysis of NFκB, COX-2 and PGE2 expression). Fotemustine and dexamethasone administration had anti-apoptotic activity, restoring the impaired mechanism (TUNEL assay and Western blot analysis of Bax and Bcl-2). Moreover, no gastric disfunction was detected (histological analysis of stomachs). Thus, our data showed that the combined therapy of fotemustine and dexamethasone reduced endometriosis-induced inflammation, hyperproliferation and apoptosis resistance.

Elagolix Sodium: Novel GnRH Antagonist for the Treatment of Endometriosis

Endometriosis is a category of lesions and fibroids which occur in the innermost lining of the uterus that is the endometrial layer and spreads to the other parts of the neighboring tissues. It is characterized by inflammation, pelvic pain, menstrual bleeding, and Dysmenorrhea. Endometriosis exists in 3 forms based on its spreadability. i.) superficial peritoneal lesions ii.) deep infiltrating lesion and iii.) cyst. Traditional treatments involve are NSAIDS, Oral contraceptives, Aromatase inhibitors, and GnRH agonists. Elagolix emerges out to be the latest potent drug that acts by inhibiting the GnRH receptor. Unlike other allopathy medicine, it is not an asymptomatic pain reliever but acts on the root cause of the disease. FDA has approved it for specific treatment of endometriosis in July 2018. It is believed that endometriosis occurs by an increase in the production of estrogen. Elagolix competitively binds to the GnRH receptors and prevents the binding of the Gonadotropin hormone flowing through blood capillaries from the Hypothalamus to the pituitary gland and thereby stops the formation of Oestrogen in the reproductive system which ultimately ceases in the proliferation of endometrial layers and tissue spread. In estrogen biosynthesis, the aromatase P450 enzyme plays a vital role. Elagolix belongs to BCS class III and available in the oral dosage form of 150, 200mg. It is rapidly absorbed and Cmax reaches within 1hour. The plasma protein binding is 80%. In this review, various aspects related to Elagolix sodium have been summarised, which include pathophysiology, Mode of Action, Structure-activity relationship, Pharmacokinetics, pharmacodynamics, and clinical studies with minimal side effects.

Safety of in-vitro fertilization in women with endometriosis.

Management of women with endometriosis in general is complex. It requires a multidisciplinary and tailored approach. The time of in-vitro fertilization (IVF) may be particularly complicated because women with the disease face peculiar additional risks. In particular, oocytes retrieval may be more difficult and women with endometriomas are exposed to a low but consistent risk of infection and ovarian abscess development. There are also concerns regarding progression of deep invasive peritoneal lesions and misdiagnosis of an occult early ovarian cancer. However, evidence on these latter points is more controversial. Taken together, this body evidence is generally reassuring and does not justify prophylactic surgery prior to IVF to shrink these risks. However, given the uncertainties, women with endometriosis must be informed in depth of these peculiar additional risks.

Correlation between surgical findings and magnetic resonance imaging of deep infiltrating endometriosis

In this review, images during surgical excision of Deep Infiltrating Endometriosis (DIE) were correlated to preoperative Magnetic Resonance Imaging (MRI) findings. MRI is known to be the best tool for mapping DIE, it displays a high accuracy in the diagnosis and the characterization of endometriosis lesions. Recent studies showed also that MRI findings can be correlated to the length of operating time, to the duration of hospital stay, and to the risk of voiding problems. In this article we emphasize on the importance of having an experienced radiologist that has the ability of detecting adhesions and superficial peritoneal lesions, a value that was underestimated in previous studies. DIE presents on MRI as an intermediate signal intensity on T1-weighted images, hypointense signal on T2-weighted images, and homo- or heterogeneous enhancement after intravenous gadolinium injection. Preoperative MRI findings help doctors to elaborate a tailored therapeutic plan for each patient depending on the clinical context (Fertility preservation, IVF, complete surgical excisions). Most importantly correct investigation and accurate description of small lesions enhance surgical planification and adequate information of the patients.

Tricky Diagnosis and Robot-laparoscopic Surgical Approach to Disseminated Peritoneal Leiomyomatosis

To show the challenging diagnosis of, and safe robotic surgical approach to, a rare case of disseminated peritoneal leiomyomatosis (DPL). A clinical case shown by a sequential demonstration of investigation, diagnosis, and surgical approach, with narrated video footage. DPL is a rare disease, with only a little more than 150 cases reported in the literature [1]. It is defined by subperitoneal proliferation of benign smooth muscle cell nodules, macroscopically mimicking peritoneal carcinomatosis [2]. The etiology remains unclear, but different hypotheses have been put forward, such as subperitoneal mesenchymal stem cell metaplasia and iatrogenic origin after myomectomy [3]. Despite its usual benign behavior, DPL can rarely present with malignant degeneration, and therefore a complete resection of multiple lesions is recommended [4]. This case involves a 45-year-old patient presenting with dysmenorrhea, abdominal pain, and major abnormal uterine bleeding, requiring previous blood transfusion and no response after 2 years of clinical treatment. She had a previous cesarean delivery, with no reproductive desire at present and no history of other pelvic surgeries. Pelvic examination showed an enlarged mobile uterus at the height of the pubic symphysis, and both ultrasonography and magnetic resonance imaging confirmed an enlarged uterus due to multiple myomas. (1) Diagnostic laparoscopy with implant biopsies and uterine curettage for investigation of DPL and its differential diagnoses, followed by robot-assisted laparoscopic approach, with key strategies for a safe performance. (2) Radical hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and wide pelvic peritoneal resection were performed. (3) For this complex procedure, the identification and preservation of important landmarks and pelvic anatomy were mandatory, as well as removal of all surgical specimens in monobloc. Final pathology report: disseminated leiomyomatosis with no evidence of malignancy. The patient had no complications after surgery and was discharged on the second postoperative day with mild abdominal pain. DPL diagnosis can be tricky owing to its macroscopic similarity to peritoneal carcinomatosis and the difficulty of identification in imaging examinations. Moreover, the robotic platform can be a helpful and safe tool for the surgical treatment of DPL and complete resection of all peritoneal lesions.

GIANT OVARIAN CYST PRESENTING AS EPIGASTRIC MASS-A CASE REPORT

Giant ovarian cysts (GOCs) are rare tumours of the ovary presenting with diameters greater than 10 cm. Ovarian cysts are generally asymptomatic at early stages causing symptoms only after reaching enormous dimensions, and consequently they are often diagnosed late. Majority of GOCs are benign and are generally treated by surgical excision either by cystectomy or salpingo-oophorectomy. Malignant ovarian cysts (MOC) constitute over 10% of GOCs and are treated by total abdominal hysterectomy with bilateral salpingo-oophorectomy ± omentectomy .We encountered a 65 years old female who presented with the history of progressively increasing distension of upper abdomen for last 6 months. Abdominal examination revealed a uniformly large cystic mass in the epigastrium with ill-dened lower border. There was uniform fullness in both the anks. Contrast enhanced Computed Tomography suggested large well dened intra peritoneal cystic lesion with few thin internal sepatations probably cystic lesion from the ovary. Laparotomy was done and there was a large cystic mass arising from the pelvis which was excised with membranes intact. Bilateral oophorectomy with appendectomy was done. Histologically it was found to be mucinous cystadenoma.

Clinical use of indocyanine green during nerve-sparing surgery for deep endometriosis

To describe the anatomic and technical highlights of a novel nerve-sparing surgery in deep endometriosis (DE) using near-infrared (NIR) fluorescence technology and indocyanine green (ICG). Stepwise demonstration of this method with narrated video footage. An urban general hospital. A 48-year-old woman was referred for severe chronic pelvic pain, dysmenorrhea, and pain on defecation, all of which were resistant to medication therapy. Magnetic resonance imaging revealed uterine adenomyosis and left ovarian endometrioma with DE involving the uterosacral ligament, posterior cervix, and surface of the rectum, with complete cul-de-sac obliteration. An intravenous injection of 0.25 mg/kg body weight of ICG for intraoperative NIR fluorescence imaging. Ethics approval was obtained from the institutional review board at our hospital (IRB No.: 985). Evaluation of blood perfusion of DE nodule and achieving better visualization of anatomic relationship to the pelvic autonomic nerves. The procedure was performed using the following eight steps with the da Vinci Xi surgical platform: Step 0, observing peritoneal endometriotic lesions; Step 1, adhesiolysis and adnexal surgery; Step 2, separation of the nerve plane; Step 3, dissection of the ureter; Step 4, reopening of the pouch of Douglas; Step 5, complete removal of DE lesions while avoiding injury to the nerve plane; Step 6, hysterectomy (if the patient desires nonfertility-sparing surgery); Step 7, checking for rectal injury using air leakage test and tissue perfusion; and Step 8, barrier agents for adhesion prevention. During surgery, we could easily identify ischemic nodules, which included DE and fibrosis under NIR fluorescence imaging, beyond the limits of macroscopic disease. Endometriosis or fibrosis was confirmed pathologically from all resected tissues, and resection margins of these tissues were negative for the disease. These results suggest that this technique might be feasible for objectively identifying the border between DE lesions and healthy tissue. Furthermore, the hypogastric nerve and inferior hypogastric plexus were strongly highlighted by ICG and objectively preserved with the assessment of perfusion. The patient developed no perioperative complications, including postoperative bladder or rectal dysfunction after surgery. To our knowledge, this is the first reported use of ICG during nerve-sparing surgery for gynecologic disease. Application of ICG with NIR fluorescence appears potentially useful, not only to remove DE, but also to improve nerve-sparing.

High CD8/CD33 ratio in peritoneal metastatic lesions is associated with favorable prognosis in gastric cancer.

BackgroundTumor‐infiltrating lymphocytes (TILs) and other immune cells have been reported as a prognostic factor in several tumors, including gastric cancer, and they play an important role in antitumor effect at the primary site. There were few reports on the immune status in peritoneal metastatic lesions for gastric cancer.AimsThe aims of this study were to assess the prognostic significance of TILs (CD4, CD8, CD19, regulatory T cells [Tregs]), and myeloid‐derived suppressor cells (MDSCs) in peritoneal metastatic lesions.MethodsWe retrospectively investigated 60 patients for gastric cancer with peritoneal metastasis who were treated between 2009 and 2016 in our institute. Immunohistochemistry for CD4, CD8, CD19, FOXP3, and CD33 was performed in the peritoneal metastatic lesions. The absolute numbers of immune cells and ratios were evaluated, and the relationship between immune‐related marker and overall survival (OS) was investigated.ResultsA high infiltration of CD8+ lymphocytes or high CD8/CD33 ratio was a better prognosis for OS in univariate analysis using all immunologic variables (P = .012, P = .001). In multivariate analysis for clinical and immunologic variables, high CD8/CD33 ratio was identified as an independent prognostic factor for OS (Hazard ratio: 0.291, 95% confidence interval: 0.126‐0.670, P = .004).ConclusionHigh CD8/CD33 ratio and high infiltration of CD8+ lymphocytes in peritoneal metastatic lesions were favorable prognoses for gastric cancer patients with peritoneal metastasis. It is necessary to modify the immune microenvironment result to increase the level of CD8+ lymphocytes in the peritoneal metastatic lesions.

Incidental encounter of intraperitoneal tuberculosis during renal surgeries: A surgeon's dilemma

Tuberculosis is a major healthcare burden in India, which accounts for the maximum number of cases worldwide. Due to its non-specific features, peritoneal tuberculosis has been dubbed as the great mimicker of various other abdominal pathologies. This case series highlights the importance of incidental intra operative detection of peritoneal tuberculosis in cases being operated for renal pathologies. Diagnostic and therapeutic dilemma is bound to occur when surgeon is faced with such an unexpected finding. Incidental peritoneal tuberculosis was defined as peritoneal tubercular lesions (ascites or tubercles) detected intraoperatively in patients being operated for non-tuberculosis related indications and no prior preoperative suspicion of abdominal tuberculosis. We here review 3 cases with different renal pathologies and no prior history or exposure to tuberculosis in which intraperitoneal tuberculosis was encountered incidentally at the time of surgery. Case 1 was a suspected case of right renal cell carcinoma and underwent right robotic nephron sparing surgery. Case 2 underwent robotic assisted lap simple nephrectomy for a right nonfunctioning kidney due to obstructive ureteric calculus. Case 3 was a suspected case of left upper tract urothelial carcinoma who underwent robotic nephroureterectomy with bladder cuff excision. In all 3 cases, on encountering the peritoneal lesions, an intraoperative decision to continue with the proposed surgery was made after frozen section biopsies from the multiple peritoneal and omental deposits revealed no malignant cells. Histopathology of these lesions in all 3 cases revealed caseating granulomas consistent with a diagnosis of disseminated peritoneal tuberculosis. None of the resected specimen had features suggestive of tuberculosis. ATT was started and on follow up the patients are doing well. Peritoneal tuberculosis although uncommon is not a rare presentation of active tuberculosis. Surgeons on encountering such lesions during non-related surgeries should always have a high suspicion of tuberculosis. Despite the existing literature favoring abandoning the procedure in such situations, we successfully completed the proposed surgeries.

The Design and Preclinical Evaluation of a Single-Label Bimodal Nanobody Tracer for Image-Guided Surgery.

Intraoperative guidance using targeted fluorescent tracers can potentially provide surgeons with real-time feedback on the presence of tumor tissue in resection margins. To overcome the limited depth penetration of fluorescent light, combining fluorescence with SPECT/CT imaging and/or gamma-ray tracing has been proposed. Here, we describe the design and preclinical validation of a novel bimodal nanobody-tracer, labeled using a “multifunctional single attachment point” (MSAP) label, integrating a Cy5 fluorophore and a diethylenetriaminepentaacetic acid (DTPA) chelator into a single structure. After conjugation of the bimodal MSAP to primary amines of the anti-HER2 nanobody 2Rs15d and 111In-labeling of DTPA, the tracer’s characteristics were evaluated in vitro. Subsequently, its biodistribution and tumor targeting were assessed by SPECT/CT and fluorescence imaging over 24 h. Finally, the tracer’s ability to identify small, disseminated tumor lesions was investigated in mice bearing HER2-overexpressing SKOV3.IP1 peritoneal lesions. [111In]In-MSAP.2Rs15d retained its affinity following conjugation and remained stable for 24 h. In vivo SPECT/CT and fluorescence images showed specific uptake in HER2-overexpressing tumors with low background. High tumor-to-muscle ratios were obtained at 1h p.i. and remained 19-fold on SPECT/CT and 3-fold on fluorescence images over 24 h. In the intraperitoneally disseminated model, the tracer allowed detection of larger lesions via nuclear imaging, while fluorescence enabled accurate removal of submillimeter lesions. Bimodal nuclear/fluorescent nanobody-tracers can thus be conveniently designed by conjugation of a single-molecule MSAP-reagent carrying a fluorophore and chelator for radioactive labeling. Such tracers hold promise for clinical applications.

Accuracy of whole-body diffusion-weighted MRI (WB-DWI/MRI) in diagnosis, staging and follow-up of gastric cancer, in comparison to CT: a pilot study

BackgroundAccurate staging of patients with gastric cancer is necessary for selection of the most appropriate and personalized therapy. Computed tomography (CT) is currently used as primary staging tool, being widely available with a relatively high accuracy for the detection of parenchymal metastases, but with low sensitivity for the detection of peritoneal metastases. Magnetic resonance imaging (MRI) with diffusion-weighted imaging (DWI) has a very high contrast resolution, suggesting a higher diagnostic performance in the detection of small peritoneal lesions. The aim of this study was to retrospectively evaluate the added value of whole-body diffusion-weighted MRI (WB-DWI/MRI) to CT for detection of peritoneal carcinomatosis (PC) and distant metastases in the preoperative staging of gastric cancer.MethodsThis retrospective study included thirty-two patients with a suspicion of gastric cancer/recurrence, who underwent WB-DWI/MRI at 1.5 T, in addition to CT of thorax and abdomen. Images were evaluated by two experienced abdominal radiologists in consensus. Histopathology, laparoscopy and/or 1-year follow-up were used as reference standard.ResultsFor overall tumour detection (n = 32), CT sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) was 83.3%, 100%, 100% and 82.4% respectively. For WB-DWI/MRI these values were 100%, 92.9%, 94.7% and 100%, respectively. For staging (n = 18) malignant lymph nodes and metastases, CT had a sensitivity, specificity/PPV/NPV of 50%/100%/100%/71.4%, and 15.4%/100%/100%/31.3% respectively. For WB-DWI/MRI, all values were 100%, for both malignant lymph nodes and metastases. WB-DWI/MRI was significantly better than CT in detecting tumour infiltration of the mesenteric root, serosal involvement of the small bowel and peritoneal metastases for which WB-DWI/MRI was correct in 100% of these cases, CT 0%.ConclusionsWB-DWI/MRI is highly accurate for diagnosis, staging and follow-up of patients with suspected gastric cancer.

Use of selective PGE2 receptor antagonists on human endometriotic stromal cells and peritoneal macrophages.

Non-hormonal therapeutic strategies for endometriosis are needed. The aim of this study was to characterize the effects of prostaglandin (PG)E2 receptor inhibitors to explore their potential as novel therapeutic strategies for endometriosis. The expression of PGE2 receptors (EP2 and EP4) in donated tissues from human ovarian endometriosis, adenomyosis and peritoneal endometriosis was examined using immunohistochemistry. Human endometriotic stromal cells (ESC) isolated from ovarian endometriotic tissue and peritoneal macrophages were treated with EP2 and EP4 antagonists. cAMP accumulation and the effect of EP antagonists were measured using cAMP assays. DNA synthesis in ESC was detected using bromodeoxyuridine incorporation analysis. Interleukin (IL)-6 and IL-8 protein levels in ESC supernatants were measured using ELISAs. mRNA expression level for aromatase by ESC, and selected cytokines by peritoneal macrophages was measured using RT–PCR. EP2 and EP4 receptors were expressed in cells derived from control and diseased tissue, ovarian endometriotic, adenomyotic and peritoneal lesions. A selective EP2 antagonist reduced DNA synthesis, cAMP accumulation and IL-1β-induced proinflammatory cytokine secretion and aromatase expression. A selective EP4 antagonist negated IL-1β-induced IL-6 secretion and aromatase expression. In peritoneal macrophages, EP expression was elevated in endometriosis samples but the EP4 antagonist reduced cAMP levels and expression of vascular endothelial growth factor, chemokine ligand 2 and chemokine ligand 3 mRNA. EP2 and EP4 are functioning in endometriosis lesions and peritoneal macrophages, and their selective antagonists can reduce EP-mediated actions, therefore, the EP antagonists are potential therapeutic agents for controlling endometriosis.