Stage 3C Research Articles

Assessing para-aortic nodal status in high-grade endometrial cancer patients with negative pelvic sentinel lymph node biopsy.

To determine the accuracy of pelvic sentinel lymph node biopsy (SLN) in detecting positive para-aortic (PA) lymph nodes in high-grade uterine cancer, and to determine the recurrence rate in patients with high-grade uterine cancers who did not receive adjuvant chemotherapy based on negative pelvic SLNs. This was a retrospective cohort study of patients with newly diagnosed, high-grade endometrial cancer who underwent surgery, including pelvic SLNs with or without PA node dissection, at a tertiary care institution between 2015 and 2020. Baseline demographics, surgical management, pathology data, and outcomes were analyzed using descriptive statistics, and survival analysis. Postoperative histology of the 110 patients meeting inclusion criteria was 45.5% grade 3 endometrioid, 36.4% serous, 10.9% clear cell, and 7.3% carcinosarcoma. On final pathology, 63.7% were stage 1, and 23.6% were stage 3C with positive nodes. A total of 63 patients (57.3%) had a PA lymph node dissection (56 bilateral, 7 unilateral) in addition to the pelvic SLN. Among this group, 5.8% (95% confidence interval 1.2%-16.0%) had a positive PA node despite a negative pelvic SLN. Among those with a negative pelvic SLN and no adjuvant chemotherapy (n = 75), the rate of distant recurrence was 14.7%, and 3-year recurrence-free survival was 71.9%. The rate of isolated PA node metastasis in high-grade endometrial cancers despite a negative pelvic SLN may be significantly higher than the accepted rate of isolated PA node metastasis in low-grade endometrial cancer. This supports adjuvant treatment decisions continuing to incorporate primary tumor pathology and molecular classification.

Stage 3C.

Stage 3C.

Pembrolizumab related perforated appendicitis.

Pembrolizumab is a humanized monoclonal antibody IgG4 programmed cell death protein 1 antagonist, and its use in oncology has been increasing in recent years, providing durable and favorable responses and tolerable toxicity profiles in various types of cancer. We describe a case of pembrolizumab related perforated appendicitis in a patient with stage 3C malignant melanoma (MM). A 70-year-old male patient who had no known disease was diagnosed with MM as a result of the excision of the mass on his right shoulder. The disease stage was stage 3C (pT4aN1bM0). Subsequently, adjuvant pembrolizumab treatment was started. A few days after the fourth maintenance course, he presented to the emergency department complaining of abdominal pain, nausea and vomiting. Emergency abdominal tomography showed a significant increase in the diameter of the appendix vermiformis, peritoneal thickening and appendiceal wall defects that could be significant in terms of perforation. The mentioned finding and given the clinical presentation, was attributed to a perporating of the appendix, so the patient was hospitalized in the Department of Surgery and the patient underwent emergency appendectomy. Histological findings were consistent with appendicitis. After a day in the hospital, the abdominal pain subsided, C-reactive protein tended to decrease and the patient was discharged. In patients who develop acute abdominal pain with or without diarrhea during immunotherapy, urgent imaging, endoscopic and clinical evaluation should be performed, and bowel perforation, although rare, should be considered as a potential complication of any immunotherapy.

MIRRORS ICG: Perfusion Assessment Using Indocyanine Green (ICG) Peritoneal Angiography during Robotic Interval Cytoreductive Surgery for Advanced Ovarian Cancer.

Indocyanine green (ICG) is a fluorescent dye used for sentinel lymph node assessment and the assessment of perfusion in skin flaps and bowel anastomoses. ICG binds serum proteins and behaves as a macromolecule in the circulation. Tumour tissue has increased vascular permeability and reduced drainage, causing macromolecules to accumulate within it. MIRRORS ICG is designed to determine whether indocyanine green (ICG) helped identify metastatic deposits in women undergoing robotic interval cytoreductive surgery for advanced-stage (3c+) ovarian cancer. Peritoneal surfaces of the abdominal and pelvic cavity were inspected under white light and near-infrared light (da Vinci Si and Xi Firefly Fluorescence imaging, Intuitive Surgical Inc.) following intravenous injection of 20 mg ICG in sterile water. Visibly abnormal areas were excised and sent to histopathology, noting IGC positivity. In total, 102 biopsies were assessed using ICG. Intravenous ICG assessment following neoadjuvant chemotherapy had a sensitivity of 91.1% (95% CI [82.6-96.4%]), a specificity of 13.0% (95% CI [2.8-33.6%]), a positive predictive value of 78.3% (95% CI [68.4-86.2%]), and a negative predictive value of 30.0% (95% CI [6.7-65.2%]) False-positive samples were seen in 9/20 patients. Psammoma bodies were noted in the histopathology reports of seven of nine of these patients with false-positive results, indicating that a tumour had been present (chemotherapy-treated disease). This study demonstrates the appearance of metastatic peritoneal deposits during robotic cytoreductive surgery following the intravenous administration of ICG in women who have undergone neoadjuvant chemotherapy for stage 3c+ advanced ovarian cancer. A perfusion assessment using indocyanine green (ICG) peritoneal angiography during robotic interval cytoreductive surgery for advanced ovarian cancer did not clinically improve metastatic disease identification in patients with high-volume disease. The use of ICG in patients with excellent response to chemotherapy where few tumour deposits remained shows some promise. The potential of molecular imaging to enhance precision surgery and improve disease identification using the robotic platform is a novel avenue for future research.

HIPEC in Ovarian Cancer: When and to Whom?

To evaluate the optimal candidates for hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CRS) in ovarian cancer. Descriptive study. Place and Duration of the Study: Health Sciences University, Dr. Abdurrahman YurtasianAnkara Oncology Training and Research Hospital, Ankara, Turkey, between 2013 and 2021. Ovarian cancer patients who underwent HIPEC and CRS for peritoneal involvement were included in this study. Thermosolutions were prepared as a closed system by using HT 2000 hyperthermic perfusion device. Then, cisplatin was applied at 100 mg/m2 at 42-42.5 °C for 60 minutes after CRS. A total of 47 patients were enrolled. The median age was 54 years (27-80) at the time of diagnosis. Forty (85.1%) patients had high grade serous carcinoma and 22 (46.7%) patients had clinical stage 3C disease. The median peritoneal cancer index (PCI) was 13 (3-24) in the whole population. HIPEC was applied as first-line treatment in 25 (51%) patients. Eleven (23.4%) patients had HIPEC in the post-neoadjuvant interval whereas 10 (21.3%) patients had it in platinum sensitive relapse. Median progression free survival (PFS) was 31(95% CI:11-50), 33 (95% CI:1-67), and 18 (95% CI:8-27) months in the primary, post-neoadjuvant interval, and platinum-sensitive relapse HIPEC groups, respectively. The patients with lower PCI (PCI<13) had significantly better OS than others with higher PCI (PCI>13, 145 months versus 42 months, p=0.034). HIPEC with CRS should be considered in selected serous carcinoma patients with peritoneal involvement, especially for the patients with primary ovarian cancer with lower PCI (PCI<13). Ovarian cancer, HIPEC, Peritoneal cancer index.

The application of pringle manoeuvre, type three liver mobilisation, full thickness diaphragmatic resection with primary closure technique and peritonectomy in the management of advanced ovarian malignancy.

We present an educational technique for the safe completion of complete cytoreduction of diaphragmatic disease for the management of advanced ovarian malignancy. We demonstrated these steps with attention to anatomical landmarks and surgical approaches, considering intraoperative and postoperative morbidity and mortality. We present the case of a 49-year-old female patient diagnosed with suspected stage 3C ovarian malignancy following diagnostic laparoscopy. We demonstrate the surgical application of the Pringle maneuver, type 3 liver mobilization, and full-thickness diaphragmatic resection. This was completed with a primary closure technique, with integrity ensured through the performance of an air test and Valsalva maneuver. Final histology confirmed a serous borderline tumor with invasive implants within a port site nodule (stage 4A). This technique affirms the essential skills in gynecological oncology training and details a challenging case requiring advanced surgical skills and knowledge, with specific consideration for intraoperative multidisciplinary decision-making.

Using chemotherapy response by KELIM score to predict response to first line maintenance PARP inhibitor therapy in non-BRCA mutant/homologous recombination deficiency (HRD) unknown high grade serous ovarian cancer (HGSOC).

e17547 Background: Maintenance PARP inhibitor therapy after response to first line chemotherapy is now standard of care in advanced HGSOC. Niraparib is available to all patients based on the PRIMA trial data; however, the progression free survival (PFS) benefit for patients without BRCA mutations or homologous recombination deficiency (HRD) is limited. Funded HRD testing is not accessible in many countries. Patient selection for PARPi therapy in non-BRCA mutant HGSOC is challenging. The calculated CA-125 ELIMination of Rate Constant K (KELIM) score is a mathematical model developed to evaluate CA-125 kinetics during chemotherapy. KELIM has been shown to correlate with chemosensitivity, with scores ≥1 associated with better clinical outcomes. This project aims to use real-world patient data to assess if surrogate markers, such as KELIM score and/or pathological chemotherapy response score, can predict response to 1st line maintenance PARPi in the absence of funded HRD testing. Methods: A retrospective review of non-BRCA mutant HGSOC cases on first line maintenance PARPi therapy at BC Cancer, Canada between April 2020 and June 2022. Only cases confirmed to be non-BRCA mutant (by both germline and tumour testing) were included in the study. Data collection was through electronic medical records and included patient demographics, chemotherapy intent (neoadjuvant vs. adjuvant), pathological (p) chemotherapy response score (CRS), progression-free survival (PFS) defined as start of niraparib to radiological evidence of disease progression. PFS analysis was performed in all patients provided 1 full cycle had been completed. The rate of not progressing at 12 months (PFS12) was calculated. KELIM score was calculated from at least 3 CA125 values taken within 100 days from the chemotherapy start date and using a validated calculation software. Results: 70 patients met the full eligibility criteria for analysis. All patients received niraparib as PARPi therapy. Mean age was 67 years and 40 patients (57%) were ≥ 65 years. Most patients were FIGO stage 3C at presentation (56%). Median number of niraparib cycles was 10 (range 1-28). 35/70 patients (50%) had disease progression at time of data analysis with a median follow-up of 13.2 months. 59 patients had evaluable KELIM scores. pCRS was not associated with any statistically significant differences in PFS. Patients with KELIM scores ≥1 had a trend to greater PFS from niraparib vs. those with KELIM &lt;1 with median PFS of 15 months vs. 8.3 months respectively ( p=0.06). PFS12 rate was higher at 64% with KELIM scores ≥1 vs. 43% with KELIM &lt;1; ( p=0.18). Conclusions: We show that KELIM score could be a useful tool to predict PARP inhibitor response and aid clinical decision-making by oncologists and patients in the real world setting where HRD testing is unfunded.

Abstract 4402: Survival impact of post-operative immunotherapy in resected stage III cutaneous melanomas in the checkpoint era

Abstract Introduction: Since 2015, immune checkpoint inhibitors have been approved as post-operative therapy for resected stage 3 cutaneous melanoma. This approval was a result of studies which demonstrated improved recurrence free survival. However, overall survival (OS) benefit has yet to be observed. We examine the OS of postoperative immunotherapy in stage 3 melanoma using real world data from the National Cancer Database (NCDB). Methods: Data was collected from the 2020 NCDB Participant Use File (October 2022 release). Patients were staged by both the 7th and 8th version of American Joint Committee on Cancers (AJCC). Those who underwent definitive surgery since 2016 and had sufficient pathologic data for staging were included. Patients who received systemic therapy prior to surgery were excluded. Patients were then sorted by the type of postoperative therapy started within 12 weeks from definitive surgery and classified into the no post-operative systemic therapy (NP) or postoperative immunotherapy (PI) groups. Survival time was calculated from the time of definitive surgery to last contact or death. OS was estimated by Kaplan-Meier method and compared by log-rank method. Results: 18,167 patients underwent surgery for stage 3 disease between 2016-2020. By AJCC v8 staging, 4,256 had Stage 3A disease, 3,752 stage 3B disease, 9,251 stage 3C disease, and 908 stage 3D disease. Median OS was not met in any stage 3 PI groups. The 36 - month landmark survival of all stage 3 subgroups is shown in Table 1. Only 13.3% of patient received PI in 2016. PI use increased to 24.8% in 2017, 43.8% in 2018, 46.8% in 2019, and 50.8% in 2020. Discussion: Using a large real-world database, we found that patients receiving post-operative immunotherapy in the checkpoint era have a significant survival benefit compared to those who did not. The benefit was significant in stage IIIB-C in AJCC v7 and Stage IIIC-D in AJCC v8. However, the benefit was not significant in stage 3A melanoma. Table 1. 36-month Landmark survival reported with 95% confidence interval for both AJCC versions No Post-Operative Immunotherapy Post-Operative Immunotherapy Given Stage Total Patients (n) n (%) 36- month survival % (95% CI) n (%) 36- month survival % (95% CI) p-value AJCC v 7 Stage 3 15272 Stage 3A 3818 2539 (66.5) 90 (89-91) 1141 (29.9) 91 (90-92) p=0.737 Stage 3B 4572 2990 (65.4) 78 (77-79) 1461 (32.0) 83 (82-94) p=0.001 Stage 3C 6882 4021 (58.4) 64 (63-65) 2637 (38.3) 73 (72-74) p&amp;lt;0.001 AJCC v 8 Stage 3 18167 Stage 3A 4256 2981 (70.0) 91 (90-92) 1145 (26.9) 93 (92-94) p=0.354 Stage 3B 3752 2255 (60.1) 84 (83-85) 1379 (36.8) 87 (86-88) p=0.057 Stage 3C 9251 5592 (60.4) 65 (64-66) 3372(36.5) 76 (75-77) p&amp;lt;0.001 Stage 3D 908 550 (60.6) 44 (42-46) 316 (34.8) 59 (56-62) p&amp;lt;0.001 Citation Format: Garo G. Hagopian, Christopher Grant, Danielle Brazel, Priyanka Kumar, Maki Yamamoto, James Jakowatz, Warren Chow, Thuy Tran, Justin Moyers. Survival impact of post-operative immunotherapy in resected stage III cutaneous melanomas in the checkpoint era. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4402.

Wide arthroscopic dorsal capsuloligamentous repair in patients with severe scapholunate instability.

A conventional arthroscopic capsuloligamentous repair is a reliable surgical solution in most patients with scapholunate instability. However, this repair does not seem to be sufficient for more advanced injuries. The aim of this study was to evaluate the functional results of a wide arthroscopic dorsal capsuloligamentous repair (WADCLR) in the management of severe scapholunate instability. This was a prospective single-centre study undertaken between March 2019 and May 2021. The primary outcome was the evaluation of the reduction of the radiological deformity and the functional outcomes after WADCLR. A secondary outcome was the evaluation of the effectiveness of this technique in patients with the most severe instability (European Wrist Arthroscopy Society (EWAS) stage 5). The patients were reviewed postoperatively at three, six, and 12 months. The study included 112 patients (70 male and 42 female). Their mean age was 31.6 years (16 to 55). A total of three patients had EWAS stage 3A injuries, 12 had stage 3B injuries, 29 had stage 3C injuries, 56 had stage 4 injuries, and 12 had stage 5 injuries. There was a significant improvement of the radiological signs in all patients with a return to normal values. There was also a significant improvement in all aspects of function except for flexion, in which the mean increase was negligible (0.18° on average). There was also a significant improvement in all criteria for patients with a stage 5 injury, except for some limitation of extension, flexion, and radial and ulnar deviation, although these showed a trend towards improvement (except for flexion). WADCLR is a minimally invasive, easy, and reproducible technique with few complications, offering a clear improvement in function and a reduction in the radiological deformity at one year postoperatively.

Long-term outcomes of transcutaneous retrobulbar amphotericin B in COVID-19-associated mucormycosis.

To describe the long-term outcomes of transcutaneous retrobulbar amphotericin B (TRAMB) in COVID-19-associated mucormycosis. In total, 18 cases of COVID-19-associated mucormycosis were reviewed. In addition to the recommended treatment protocol, all patients were to be given 3.5 mg/ml/day of TRAMB for five days. Of the 18 patients, 2 presented with stage 3a disease, 13 had stage 3c disease, and 3 patients had central nervous system (CNS) involvement (stage 4a and 4c). In addition to planned retrobulbar doses, five patients were given more while two patients received fewer injections (i.e., <5). At the last mean follow-up of 34.67 (±8.88) weeks, 11 patients were in radiological regression and 4 had stable disease while 2 patients had to undergo exenteration; one mortality was observed because of disease progression. Clinical regression in terms of visual and ptosis improvement was seen in seven and nine patients, respectively. Rhino-orbito-cerebral mucormycosis is a serious condition which warrants an aggressive treatment strategy. In unprecedented situations witnessed recently, TRAMB turned out to be an effective and economical alternative. Though large randomized studies are needed to establish its efficacy, TRAMB still manages to halt progression and salvage the globe in significant number of patients, and hence its use should be encouraged on a case-to-case basis especially in developing countries with limited resources.

Rhino-orbito-cerebral mucormycosis in a pregnant woman

Mucormycosis is an uncommon, rapidly progressive, angioinvasive fungal infection characterized by large areas of tissue necrosis. We report a case of a 25-year-old primigravida of gestational age 25 weeks with clinically and radiologically proven COVID-19-related rhino-orbito-cerebral mucormycosis (ROCM) stage 3c with gestational diabetes. She was treated with injection liposomal amphotericin B, but her condition rapidly progressed with impending intracranial extension. She was subjected to total exenteration of the left eye with extensive endoscopic sinus surgery and continued on systemic antifungals along with supportive therapy for four weeks after surgery.

Prevalence of Ophthalmic Manifestations in COVID-19 Positive Indoor Patients during Second Wave at Rural Tertiary Care Hospital of Gujarat: A Prospective Observational Study

Introduction: Coronavirus Disease-2019 (COVID-19) can affect multiple system of body including eye. In eye, it can cause mild conjunctivitis, posterior segment involvement, neurosensory involvement and lethal opportunistic infection like mucormycosis. Associated co-morbidities, severity of COVID19 infection and corticosteroids used in its management can affect ophthalmic involvement. Aim: To determine the frequency and various types of ophthalmic manifestation of patients with COVID-19. Materials and Methods: This prospective observational study was conducted on indoor patients of Shree Krishna Hospital, a rural, tertiary care hospital affiliated with Pramukh Swami Medical College, Karansad, Gujarat, India, from 1st May 2021 to 1st January 2022. Second wave of COVID-19 was from 13th March 2021 to 19th June 2021. Patients’ demographic data, details of COVID-19 infection severity score, oxygen requirement, use of corticosteroids, history of various co-morbidities and stages of Rhino-Orbital-Cerebral Mucormycosis (ROCM) (if present) were noted. Bedside ophthalmic examination was done with torch light, fluorescent strip, cobalt blue light of direct ophthalmoscope and fundus examination with indirect ophthalmoscopy under institutional COVID-19 guidelines. Descriptive Statistics {Mean, (SD), Frequency, (%)} were used for analysis of the collected data. Results: Out of 649 COVID-19 patients, 368 were male and 281 were female with mean age of 52.58 (±15.38) years. All over prevalence of ophthalmic manifestations was 9.86% (n=64 out of 649 patients). A total of 63 patients (9.71%) did not require any oxygen supplement, 352 patients (54.24%) required nasal prongs, 201 patients (30.97%) required non invasive ventilator support and 33 patients (5.08%) required mechanical ventilation. The 378 patients (58.24%) received cortico-steroids in oral or intravenous form. A total of 325 patients (50.1%) had diabetes,267 patients (41.1%) had hypertension, 29 patients (4.5%) had chronic kidney disease and 15 patients (2.3%) had thyroid disease. A total of 52 patients (8.01%) had conjunctivitis. Mean age of patients with conjunctivitis was 50.04 (±15.28) with male preponderance (n=30, 57.7%). Most common systemic presentation was fever (n=29,55.8%). Patients with conjunctivitis had high D-dimer (&gt;500 ng/mL) (n=42;80.8%) and C-Reactive Protein (CRP) values (&gt;3 mg/L) (n=39;75%). A total of 144 patients (22.2%) were vaccinated with COVID-19 vaccine first dose while ten patients (19.23%) out of 52 patients having conjunctivitis were vaccinated. Out of 649 patients, prevalence of ROCM was 1.85% (n=12) with mean age 58.58 years (±9.71 years) and male preponderance (n=8, 66.66%). Nine out of twelve patients had high blood sugar levels (mean level 340 mg/ dL) at the time of admission. Out of twelve, eight patients had received corticosteroids for management of COVID-19 infection. Six patients of ROCM (50%) did not require any oxygen support while two patient (16.7%) required nasal prongs for mean 7.50 days and four patient (33.3%) required non invasive ventilator support for mean 7.33 days (±2.5 days). One patient had stage 2C disease, one had stage 3B, five patients had stage 3C while five patients had stage 4C disease. Conclusion: Ocular manifestations of COVID-19 range from conjunctivitis to ROCM. Conjunctivitis has mild and self-limited course while ROCM is sight threatening and life-threatening condition, if not treated appropriately.

The Role of Retrobulbar Injection of Amphotericin B in the Management of Orbital Mucormycosis in a Tertiary Care Centre—Prospective Analytical Study

Aim: To study the role of retrobulbar (intraorbital) injection of amphotericin-B in the management of orbital mucormycosis. Materials and Methods: Patients with nasal diagnostic endoscopy or imaging confirmed, orbital mucormycosis were given 3 doses of 3.5 mg/ml of retrobulbar injection amphotericin-B for 3 alternate days and followed up for 72 hours for progression of symptoms. Results: Out of total 696 in-patients, 464 were males (66%) and 232 were females (34%), 612 were diabetic (88%), 490 were covid positive (71%), 308 patients have taken steroid (45%), 205 patients were given oxygen (30%). Out of 696 in-patients, 312 (45%) were started on retrobulbar injection of amphotericin. Dose wise-out of 312 retrobulbar injections, less than 3 doses is given for 69 patients (22%), 3 doses completed for 243 patients (78%). Outcomes-out of 243 three dose completed patients,49 (20%) patients has shown improvement in terms of vision and symptoms, 172 (71%) patients were stable without progression, 64 (26%) patients have shown deterioration out of which 35 patients progressed rapidly and undergone exenteration and remaining 29 are under observation. Conclusion: Retrobulbar injection of amphotericin-B along with iv amphotericin and sinus debridement through FESS have shown improvement and also halted the progression. Patients in stage 3a and 3b have shown better outcome with retrobulbar injection of amphotericin-b than in stage 3c and 3d.

Forensic age estimation in males by MRI based on the medial epiphysis of the clavicle

Increasing cross-border migration has brought forensic age assessment into focus in recent decades. Forensic age estimation is based on the three pillars: physical and medical constitution, bone age, and tooth age. Part of the bone age examination includes the assessment of the medial end of the clavicles when the hand bones are already fully developed and a minority must be excluded. Recent research has brought MRI to the forefront as a radiation-free alternative for age assessment. However, there exits only a few studies with large sample size regarding the clavicles and with controversies about staging, motion artifacts, and exclusion based on anatomic norm variants. In the current prospective study, 338 central European male individuals between 13 and 24 years of age underwent MRI examination of the sternoclavicular region. Development was assessed by three blinded raters according to the staging system described by Schmeling et al. and Kellinghaus et al. and related to age by descriptive statistics and transition analyses with a cumulative probit model. In addition, reliability calculations were performed. No statistically significant developmental difference was found between the left and right clavicles. Inter-rater agreement was only moderate, but intra-rater agreement, on the other hand, was good. Stage 3c had a minimum age of 19.36 years and appears to be a good indicator of proof of majority. The minimum age of stage 4 was lower compared with other studies, 20.18 years, and therefore seems not to be an indicator of age of 21 years. In conclusion, we confirmed the value of clavicular MRI in the age estimation process. The transition analysis model is a good approach to circumvent the problems of age mimicry and samples that are not fully equilibrated. Given the moderate agreement between raters, a consensus reading is recommended.

Heterogeneous early illness courses of Korean patients with bipolar disorders: replication of the staging model

BackgroundClinical staging of bipolar disorder (BD) requires application of real-world data, as the next step in hypothesis. This study used the staging model to analyze the long-term course of BD in Korean patients based on clinical features and treatment responses to map the progression of bipolar illness from its early phase after the onset of illness.MethodsA total of 136 patients diagnosed with BD-I (n = 62) or BD-II (n = 74) were recruited. Their progressive stages were retrospectively evaluated. A multi-state model was used to calculate the probability of progression to each stage. Hazard ratios of covariates expected to influence different courses of BD were calculated. Using the Alda score, long-term responses to mood stabilizers depending on the current stage were compared.ResultsSeveral sub-populations showed varied courses during the first five years after the onset of illness, with 41.5% remaining in stage 2 and 53% progressing to higher stages with shortened time for transition. Profiles of patients with BD-I and BD-II were different, suggesting biologically distinct groups. Comorbid psychiatric disorders, such as obsessive-compulsive disorder (OCD) and bulimia nervosa (BN) were associated with a recurrent course (stage 3a or 3b) or a malignant course (stage 3c or 4). Early age of onset, shorter duration of illness, older age at the start of medication, and poor response to lithium affected the illness progression.ConclusionWe were able to apply the stage model based on episode recurrence patterns in early illness courses of Korean patients with BD. The stage progression pattern differed from the early phase in BD-I and BD-II patients. Psychotic comorbidity, age at onset, age at starting psychiatric treatment showed associations with the illness progression.

The Accuracy of MRI in the Local Staging of Endometrial Cancer: An Experience From a Tertiary Care Oncology Institute in Pakistan.

Objective Our objective is to assess the diagnostic accuracy of contrast-enhanced magnetic resonance imaging (MRI) in identifying the depth of myometrial invasion and cervical stromal involvement in endometrial carcinoma (EC) along with nodal status and its correlation with surgical and histopathological (HP) findings. Materials and methods We performed a retrospective study on female patients at Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. Patients with endometrial carcinoma (CA) were searched from the electronic record system, and a total of 188 patients fulfilling the study criteria were selected. All the patients were evaluated using a 1.5T MRI and underwent a hysterectomy. The outcome of preoperative MRI was correlated withhistopathology results, keeping pathologyas the gold standard. Results A total of 188 patients were included in the study, with a mean age of 56.67 ± 12.47 years. Of the patients, 72 (38.3%)were diagnosed with stage 1a. The second common stage was1b, seen in 43 (22.9%) patients. It was found that the staging of endometrial CA on MRI and HP were significantly correlated for myometrial invasion (stage 1a and 1b), cervical stromal involvement (stage 2b), serosal and adnexal (stage 3a), vaginal(stage 3b), and nodal (stage 3c) involvement as shown by their p-values of <0.01. However, in cases of parametrial invasion (stage 3b), bladderinvolvement, and rectal involvement (stage 4), MRI showed decreased sensitivity as shown by their p-values of 0.833, 0.87, and 0.9, respectively. Conclusion Preoperative MRI can predict local disease and low-risk patients accurately, thereby helping in proper surgical planning and avoiding more extensive surgery such as lymphadenectomy in these patients.

CELIAC DISEASE IN SUBJECTS WITH TYPE 1 DIABETES MELLITUS AND ITS EFFECT ON GLYCEMIC CONTRO

Objective: To observe celiac disease incidence in patients with diabetes mellitus 1 and its effect on glycemic control.&#x0D; Methods: Type 1 diabetic patients presenting in the Sughra Diabetic clinic in Benazir Bhutto Hospital from 22 August 2011 till 22 February 2012 were included in this study. Medical history, including age of the patient at diagnosis of diabetes, duration of disease and daily insulin requirements was taken. Subjects with positive tTGAb levels had biopsy of 2nd part of duodenum to confirm CD according to Marsh criteria on histopathological examination.&#x0D; Results: The study included 125 patients with type 1 diabetes mellitus. The mean age was 30.08±8.9 years. 42 (33.6%) were males and 83 (66.4%) females. 5 (4%) of type 1 diabetics had celiac disease. All 5 had both a positive anti-tissue transglutaminase antibodies (&gt;24 U/ml) and all 5 also had histopathological changes confirming celiac disease. 4 had Marsh stage 3 (2 had stage 3b and 2 had stage 3c) and 1 had Marsh stage 4 changes on histopathology. All 5 CD-positive patients (100%) had poorly controlled diabetes whereas among CD-negative patients only 26 (21.6%) had well controlled diabetes; this difference was p = 0.242.&#x0D; However, mean HbA1c level CD-positive patients was significantly higher than HbA1c of CD-negative patients; p = 0.015. The mean daily insulin requirement of CD-positive patients was significantly lower than CD-negative patients; p = 0.000.&#x0D; Conclusions: The incidence of celiac disease in type 1 diabetics increases as compared to general population. Because most diabetics are asymptomatic, it is better to screen all. Moreover, CD is associated with lesser daily insulin requirement and poorer diabetes control.

Illness progression in older-age bipolar disorder: Exploring the applicability, dispersion, concordance, and associated clinical markers of two staging models for bipolar disorder in an older population.

The validity and applicability of two existing staging models reflecting illness progression have been studied in bipolar disorder (BD) in adults, but not in older adult populations. Staging model A is primarily defined by the number and recurrence of mood episodes, model B is defined by the level of inter-episodic functioning. This study aimed to explore the applicability, dispersion, and concordance of, and associations with clinical markers in these two staging models in older-age bipolar disorder (OABD). Using cross-sectional data from the Dutch Older Bipolars study, OABD outpatients (N=126, ≥50years) were staged using models A and B. Dispersion over the stages and concordance between the models were assessed. Associations were explored between model stages and clinical markers (familial loading, childhood abuse, illness duration, episode density, treatment resistance, Mini-Mental State Examination, and composite cognitive score). Ninety subjects could be assigned to model A, 111 to model B, 80 cases to both. The majority (61%) had multiple relapses (model A, stage 3C) but were living independently (model B, stage I-III). Concordance between models was low. For model A, the markers childhood abuse, illness duration, and episode density significantly increased over subsequent stages. Model B was not associated with a significant change in any marker. Assigning stages to OABD subjects was possible for both models, with age-related adjustments for model B. Model B as currently operationalized may be less suitable for OABD or may measure different aspects of illness progression, reflected by its low correspondence with model A and lack of associated clinical markers.

Retrobulbar Amphotericin B Injection in Curbing the Progression of COVID Associated Rhino-orbital Cerebral Mucormycosis: A Retrospective Case Series.

Purpose To assess whether transcutaneous retrobulbar Amphotericin B (TRAMB) injection can halt disease progression and reduce the requirement of exenteration in post-COVID 19 Rhino-orbital cerebral Mucormycosis (ROCM)) with limited orbital disease. Methods Retrospective series from a single center included 22 patients with KOH proved post-COVID 19 ROCM with radiographic evidence of limited orbital involvement were evaluated from May 2021 to October 2021. TRAMB was given along with systemic intravenous Amphotericin B injection and sinus debridement. Demographic profile, clinical data, operative notes, blood and radiological investigations were evaluated. The primary outcome was to assess the halt in the progression of orbital disease. The primary outcome measure was to assess the halt of the disease progression and the secondary outcome was improvement in the clinical signs and symptoms. Results The mean age was 50.36 ± 9.72 years and 77.3% were men. The Stagewise distribution was twelve (54.5%) patients in stage 3a, four (18.2%) patients in stage 3b, four (18.2%) in stage 3c, one (4.5%) patient in stage 3d and one (4.5%) had stage 4 disease. Improvement in lid edema and conjunctival chemosis were noticed and it was statistically significant (p value < 0.01), similarly visual acuity and ocular motility showed significant improvements (p value 0.04 and < 0.01 respectively). 1 patient died and 1 patient required exenteration later. Twenty patients showed halting of orbital disease after TRAMB injection. Conclusion TRAMB can be an alternative adjuvant therapeutic option to preserve the globe in patients with limited orbital disease but not at all replacement for exenteration.

What are the problems with the current staging of discontinuous tumour nodules (DTNs) in colorectal carcinoma? Is there a better way?

Discontinuous extramural tumour nodules (DTNs) are deposits of metastatic carcinoma in soft tissue not associated with lymph nodes. Although they are established as an adverse prognostic factor in colorectal carcinoma (CRC), under the AJCC eighth edition staging system their presence does not upstage patients who also have lymph node metastases. Counterintuitively, in some situations the presence of lymph node metastases may in effect downstage a patient with DTNs from pN1c to pN1a/b. Therefore, we sought to critically assess the significance of DTNs in a large unselected single institution cohort of patients undergoing surgical resection for CRC. Of 3822 CRC patients undergoing surgical resection from 2005 to 2021, DTNs were present in 686 (18.0%). In univariate (HR=2.687, 95CI 2.355-3.065; p<0.001) and multivariate analysis (HR=1.805, 95CI 1.529-2.132; p<0.001) in a model including age, gender, stage, grade, location, lymph node ratio and apical lymph node status, DTNs were associated with worse overall survival (OS). N1c patients (DTN present but no nodal metastasis) demonstrated worse OS compared to the current pN1a group (p<0.001) and were least different to the current pN2a group (p=0.571). Within the current N1a (p=0.013), N1b (p=0.004) and N2a (p=0.002) groups, patients who also had DTNs had worse OS. DTNs were associated with worse OS for all stage III CRCs combined (p<0.001), and for stage IIIB (p<0.001) and stage IIIC (p=0.007) individually. We conclude that DTNs are an independent adverse prognostic factor that should be considered in the staging system in a way that is additional to (rather than integrated with) the number of involved lymph nodes. We then assess a simple suggestion for how this could be achieved by increasing the overall stage by one group in the presence of DTNs (requiring the creation of a new stage IIID).