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Saddle pulmonary embolism (SPE) is a rare type of pulmonary embolism that can lead to hemodynamic compromise causing sudden deaths. Due to a dearth of large prospective studies in this area, little is known regarding the epidemiology, and prognosis and factors affecting the latter for COVID-19-associated SPE. We aimed to describe COVID-19-associated SPE and quantify and compare mortality and factors affecting mortality among the cases. We included a total of 25 publications with a total of 35 cases. The average age was 45 ± 16.3 years with 11 females and 24 males. Dyspnoea (82.5%), orthopnoea (43.5%), and cough (43.5%) were the most common symptoms, and obstructive shock was present in five (21.7%) patients. The average reported oxygen (O2) saturation was 85.8% ± 11.9 mm Hg. Hypertension (26.1%), diabetes (21.7%), and deep vein thrombosis (21.7%) were the most commonly reported comorbidities. Right heart strain was recognized in seven (30%) patients on electroencephalogram (S1QIIITIII) and 12 (52.2%) patients on echocardiogram. Anticoagulation, thrombolysis, and percutaneous intervention were tried in 21 (91.3%), 13 (56.5%), and 6 (26.1%) cases, respectively. Despite the aggressive management, 2 of 25 (8.7%) patients died in our smaller case report cohort. We conclude that despite aggressive management modalities, the mortality of SPE remains high in COVID-19.

Abstract Background Ancient schwannomas are degenerate peripheral nerve sheath tumors that very rarely occur in the retroperitoneum. They generally reach large proportions before producing symptoms due to mass effect. We describe three cases of retroperitoneal ancient schwannomas and discuss the diagnosis and management of these tumors. Case presentations Three female patients with retroperitoneal ancient schwannomas were reviewed. One patient presented with several weeks of upper abdominal pain and lower chest discomfort, whereas back pain and leg pain with associated weakness were predominant symptoms in the remaining two. Abdominal imaging findings demonstrated heterogeneous masses in the retroperitoneum with demarcated margins, concerning for malignancy. The patients successfully had radical excision of their tumors. Histological examination showed encapsulated tumors that displayed alternating areas of dense cellularity and areas of myxoid matrix consistent with a diagnosis of ancient schwannoma. Conclusion A diagnosis of ancient schwannoma should be entertained for any heterogeneous, well encapsulated mass in the retroperitoneum. In these cases less radical surgical resection should be considered as malignant transformation of these tumors is extremely rare and recurrence is uncommon following excision.

Intratumoral TLR9 agonists and anti-PD-1 produce clinical responses and broad immune activation. We conducted a single-arm study of neoadjuvant TLR9 agonist vidutolimod combined with anti-PD-1 nivolumab in high-risk resectable melanoma. In 31 evaluable patients, 55% major pathologic response (MPR) was observed, meeting primary endpoint. MPR was associated with necrosis, and melanophagocytosis with increased CD8 + tumor-infiltrating lymphocytes and plasmacytoid dendritic cells (pDCs) in the tumor microenvironment, and increased frequencies of Ki67 + CD8 + T cells peripherally. MPRs had an enriched pre-treatment gene signature of myeloid cells, and response to therapy was associated with gene signatures of immune cells, pDCs, phagocytosis, and macrophage activation. MPRs gut microbiota were enriched for Gram-negative bacteria belonging to the Bacteroidaceae and Enterobacteriaceae families and the small subgroup of Gram-negative Firmicutes. Our findings support that combined vidutolimod and nivolumab stimulates a broad anti-tumor immune response and is associated with distinct baseline myeloid gene signature and gut microbiota. ClinicalTrials.gov identifier: NCT03618641., Competing Interests: Declaration of interests D.D. reports grants/research support (NIH/NCI and Checkmate Pharmaceuticals) and consulting (Checkmate Pharmaceuticals) during the conduct of the study. D.D. also reports grants/research support (Arcus, Immunocore, Merck, Regeneron Pharmaceuticals Inc., Tesaro/GSK.), consulting (ACM Bio, Ascendis, Castle, Clinical Care Options [CCO], Gerson Lehrman Group [GLG], Immunitas, Medical Learning Group [MLG], Replimmune, Trisalus, Xilio Therapeutics), speakers’ bureau (Castle Biosciences), steering committee membership (Immunocore, Replimmune) and patents related to gut microbial signatures of response and toxicity to immune checkpoint blockade (US Patent 63/124,231 and US Patent 63/208,719) outside the submitted work. P.D. is currently employed by Nanostring Technologies and reports stock options. Y.G.N. reports grants/research support (Bristol-Myers Squibb, Merck Sharp & Dohme and Pfizer) and consulting (Checkmate Pharmaceuticals) outside the submitted work. J.J.L. reports grants/research support (multiple), membership on data safety monitoring boards (multiple), membership on scientific advisory boards with no stock ownership or stock options (multiple), membership on scientific advisory boards with stock for (multiple), consulting (multiple) and a provisional patent for cancer immunotherapy (PCT/US18/36052: Microbiome Biomarkers for anti-PD-1/PD-L1 responsiveness: diagnostic, prognostic and therapeutic uses thereof) all outside the submitted work. D.M. is currently employed by Codiak Biosciences and reports stock options. D.B., J.W. and A.K. were formerly employed by CheckMate and report stock options. M.G.F. is currently employed by Regeneron Pharmaceuticals Inc. and reports stock options. J.M.K. reports grants/research support (Bristol-Myers Squibb, Amgen Inc.) and consulting (Bristol-Myers Squibb, Checkmate Pharmaceuticals, Novartis, Amgen Inc., Checkmate, Castle Biosciences, Inc., Immunocore LLC, Iovance, Novartis.) outside the submitted work. J.M.T. reports grants and consulting from Bristol-Myers Squibb, Merck Sharp & Dohme, Astra Zeneca, and Compugen outside the submitted work. H.M.Z. reports grants/research support (NIH/NCI and Checkmate Pharmaceuticals) and consulting (Checkmate Pharmaceuticals) during the conduct of the study. H.M.Z. also reports grants/research support (NIH/NCI, Bristol-Myers Squibb and GlaxoSmithKline), personal fees (GlaxoSmithKline, Bayer, and Vedanta) and pending provisional patents related to gut microbial signatures of response and toxicity to immune checkpoint blockade (US Patent 63/124,231 and US Patent 63/208,719) outside the submitted work., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Atrioventricular block (AVB) is rare in hyperthyroidism (HTH). Little is known about the true prevalence, clinical course, optimal management, and outcomes of different types of AVBs in patients with HTH. To address these uncertainties, we aimed to conduct a systematic review by combining the available literature to provide more meaningful data regarding AVBs in HTH., Methods: We systematically searched PubMed, Scopus, Embase, and Google Scholar for articles reporting patients who developed AVB in the context of HTH. Data were analysed in STATA 16. The main outcomes included types of AVB, frequency of pacemaker insertion, and resolution of AVB. The systematic review is registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification number CRD42022335598., Results: A total of 56 studies (39 case reports, 12 case series, 3 conference abstracts, 1 retrospective study, and 1 prospective observational study) with 87 patients were included in the analysis, with a mean age of 39.1 ± 17.6 years. Females constituted 65.7% ( n  = 48) of the cohort. Complete heart block (CHB) was the most commonly reported AVB ( N  = 45, 51.7%), followed by first-degree AVB (16.1%) and second-degree AVB (14.9%). Overall, 21 patients underwent pacing. A permanent pacemaker was inserted in one patient with second-degree AVB and six patients with CHB. Mortality was reported in one patient with CHB. The clinical course and management of HTH and AVBs did not differ in patients with CHB or lower-degree blocks. Apart from lower rates of goitre and more use of carbimazole in those who underwent pacing, no differences were found when compared to the patients managed without pacing., Conclusion: Current data suggest that CHB is the most common type of AVB in patients with HTH. Most patients can be managed with anti-thyroid management alone. Additionally, whether pacemaker insertion alters the clinical outcomes needs further exploration.

Introduction: Insulin-like growth factor-2 (IGF-2)-mediated hypoglycemia is a rare yet clinically significant entity with considerable morbidity and mortality. Existing literature is limited and fails to offer a comprehensive understanding of its clinical trajectory, management and prognostication., Methods: Systematic review of English-language articles reporting primary patient data on IMH was searched using electronic databases (PubMed, Scopus and Embase) from any date up to 21 December 2022. Data were analysed in STATA-16., Results: The systematic review contains 172 studies, including 1 Randomised controlled trial, 1 prospective observational study, 5 retrospective observational studies, 150 case reports, 11 case series and 4 conference abstracts. A total of 233 patients were analysed, averaging 60.6 ± 17.1 years in age, with comparable proportions of males and females. The commonest tumours associated with Insulin-like Growth Factor-2-mediated hypoglycaemia were fibrous tumours (N = 124, 53.2%), followed by non-fibrous tumours originating from the liver (N = 21, 9%), hemangiopericytomas (N = 20, 8.5%) and mesotheliomas (N = 11, 4.7%). Hypoglycaemia was the presenting feature of NICT in 42% of cases. Predominant clinical features included loss of consciousness (26.7%) and confusion (21%). The mean IGF-2 and IGF-1 levels were 882.3 ± 630.6 ng/dL and 41.8 ± 47.8, respectively, with no significant correlation between these levels and patient outcomes. Surgical removal was the most employed treatment modality (47.2%), followed by medication therapy. The recovery rate was 77%, with chronic liver disease (CLD) significantly associated with a poor outcome (OR: 7.23, P: 0.03). Tumours originating from fibrous tissues were significantly associated with recovery (p < .001). In the logistic regression model, CLD remained a significant predictor of poor outcomes., Conclusion: This systematic review highlights that most non-islet-cell tumour-hypoglycaemia (NICTH) is due to fibrous tumours. NICTs demonstrate a variable prognosis, which is fair if originating from fibrous tissue. Management such as octreotide, corticosteroids, diazoxide, embolization, radiotherapy and surgical resection have disparate success rates., (© 2024 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

We assessed CD8 + T-cell density in 351 resected stage II to III colon cancers from 2011 to 2015 and correlated the findings with disease-free survival and survival effect of adjuvant chemotherapy. Most tumors (70%) had high/intermediate CD8 + T-cell density, and this was significantly associated with mismatch repair deficiency compared with tumors with low CD8 + T-cell density (28% vs. 13%, P =0.003). Fewer tumors with high/intermediate CD8 + T-cell density had adverse histologic features compared with tumors with low CD8 + T-cell density including high tumor budding (16% vs. 27%) and venous (22% vs. 35%), lymphatic (54% vs. 65%), and perineural (23% vs. 33%) invasion (all with P <0.05). In the stage III cohort, high/intermediate CD8 + T-cell density was an independent predictor of disease-free survival on multivariate analysis (hazard ratio: 0.39, 0.21 to 0.71 95% CI, P =0.002). For stage III patients with high/intermediate CD8 + T-cell density, adjuvant chemotherapy was significantly associated with improved disease-free survival (hazard ratio: 0.28, 0.11 to 0.74 95% CI, P =0.01) whereas stage III patients with low CD8 + T-cell density did not have improved survival with adjuvant chemotherapy. In conclusion, in stage III colon cancer, CD8 + T-cell density is an independent prognostic biomarker for disease-free survival and may help to identify patients who benefit from adjuvant chemotherapy., Competing Interests: R.K.P. is a consultant for Alimentiv, and this relationship is unrelated to the content of this manuscript. The remaining authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Introduction: Around 5% of the world's population is expected to have some degree and type of thalassaemia. Beta thalassaemia (BT) occurs due to a deficient production of the beta-globin chain of haemoglobin. Extramedullary haematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassaemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. We aim to pool the available data and provide cumulative evidence on the occurrence of EMH in BTM patients., Methods: This is a systematic review of case reports, series, and retrospective studies that presented data on the occurrence of EMH in BTM patients. Data were recorded and analyzed in Microsoft Excel 2016 and SPSS 26. The protocol has been registered in PROSPERO: CRD42021242943., Results: Data from 253 cases of EMH in BTM patients were extracted with a mean age of 35.3 years. Mean haemoglobin at presentation with EMH was 8.2 mg/dL. Lower limb weakness was the most common presenting feature ( N  = 23) (paraspinal EMH). Magnetic resonance imaging (MRI) was the most widely used diagnostic modality (226). Overall, blood transfusion was the commonest reported treatment (30), followed by radiotherapy (20), surgery (15), hydroxyurea (12), steroids (6), and exchange transfusion (2). An outcome was reported in 20% of patients, all recovered, except one who died as a result of nosocomial infection., Conclusion: EMH is rare in BTM and can occur in any organ system with varied clinical features. MRI can effectively diagnose EMH, and conservative management has similar results compared to invasive treatments. Larger studies, focussing on outcomes may enhance guidelines on preventive and therapeutic strategies for managing EMH in BTM.KEY MESSAGESExtramedullary haematopoiesis is a rare complication in beta thalassaemia. Although it is more common in non-transfusion dependent thalassaemia, increasingly reported cases suggest a higher prevalence of EMH in TDT than what is known before.There are no clear guidelines on the management of EMH in TDT, with reported patients showing similar outcomes with conservative invasive treatment modalities.More extensive and preferably prospectively designed studies are required focussing on the management of EMH and its outcomes in patients with TDT to formulate evidence-based guidelines.

Background: Vanishing bile duct syndrome (VBDS) is a serious cholestatic liver disease that can be a complication of drug-induced liver injury (DILI). While journals have published case reports of this condition, large studies on a cohort of these patients are lacking. We aimed to compile published case reports and case series of patients with VBDS and DILI to describe the clinical and laboratory characteristics of the disease and identify factors associated with good and poor outcomes., Methods: We included case reports and case series of VBDS secondary only to DILI. We extracted demographic, clinical, laboratory, treatment, and exposure data from each case report and categorized cases by outcome, good versus poor. We defined poor outcomes as cases with severe long-term complications or death. We analyzed risk factors for poor outcomes using logistic regression., Results: We identified a total of 59 eligible cases. Of those, 39 (59%) were female, the median age was 36 (IQR:12-58), and 18 (31%) were pediatric cases (≤18 years). The most common offending drug class was antibiotics, especially beta-lactams. Patients with increased total bilirubin (OR=4.69; 95% CI=1.55-15.49; p = 0.008), increased direct bilirubin (OR=6.50; 95% CI=1.34-48.91; p = 0.034), lower liver synthetic activity (OR=0.11; 95% CI=0.02-0.55; p = 0.013), and older age (OR=3.31; 95% CI=1.15-10.04; p = 0.029) were more likely to develop poor outcomes., Conclusions: In patients with VBDS and DILI, antibiotics were the most common offending agents. Higher total and direct bilirubin levels were associated with poor outcomes., Competing Interests: Declaration of interests The authors declare no financial or personal conflicts of interest., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Background: Despite its high prevalence, migraine remains underdiagnosed worldwide. A significant reason is the knowledge gap in physicians regarding diagnostic criteria, clinical features, and other clinical aspects of migraine., Aim: To measure the knowledge deficit in physicians and medical students and to assess the prevalence of migraine in the same population., Methods: An online questionnaire was developed and distributed among physicians and final year medical students on duty in various medical and surgical specialties of Allied and DHQ Hospitals, Faisalabad, between October 2018 and October 2019. Inclusion criteria were public practicing physicians who experience headaches, while those who never experienced headaches were excluded. Different questions assessed respondents on their knowledge of triggers, diagnosis, management, and prophylaxis of the migraine headache. They were asked to diagnose themselves using embedded ICHD-3 diagnostic criteria for different types of migraine. Graphs, tables, and figures were made using Microsoft Office 2016 and Microsoft Visio, and data analysis was done in R Studio 1.4., Results: We had 213 respondents and 175 fulfilled inclusion criteria, with 99 (52%), 58 (30%) and 12 (6.3%) belonging to specialties of medicine, surgery, and others, respectively. Both genders were symmetrically represented (88 male and 87 female). Fifty-two (24.4%) of our 213 respondents were diagnosed with migraine, with 26 (50%) being aware of it. Females had higher prevalence among study participants ( n = 28, 32.2%) compared to males ( n = 20, 22.7%, P = 0.19). A majority (62%) of subjects never consulted any doctor for their headache. Similarly, a majority (62%) either never heard or did not remember the diagnostic criteria of migraine. Around 38% falsely believed that having any type of aura is essential for diagnosing migraine. The consultation rate was 37% ( n = 65), and migraineurs were significantly more likely to have consulted a doctor, and a neurologist in particular ( P < 0.001). Consulters and migraineurs fared better in the knowledge of diagnostic aspects of the disease than their counterparts. There was no significant difference in other knowledge aspects between consulters versus non-consulters and migraineurs versus non-migraineurs., Conclusion: Critical knowledge gaps exist between physicians and medical students, potentially contributing to misdiagnosis and mismanagement of migraine., Competing Interests: Conflict-of-interest statement: All authors report no relevant conflict of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Introduction: The central location, size, and instability of saddle pulmonary embolism (SPE) have raised significant concerns regarding its clinical, hemodynamic effects as well as optimal management. Pulmonary embolism (PE) guidelines barely address such concerns. We aimed to pool the available data on the clinical behavior and outcomes of SPE and study the effects of various treatment modalities on mortality outcomes., Methods: PubMed, Scopus, and Google Scholar were searched for articles (any date up to February 28, 2022) reporting patients with SPE. Data on SPE demographics, clinical characteristics, management, and outcomes were extracted and analyzed., Results: Results from all SPE cases: A total of 5251 patients from 194 studies were included in the review. Dyspnea (57 %) was the most prevalent symptom. Massive and submassive PE comprised 9.7 % and 45.8% of cases, respectively. Thrombolytic therapy (TT) was administered in 18.1 %, and thrombectomy was performed in 16 % of cases. SPE-related mortality was observed in 4.6 %, late decompensation in 9.5 %, and PE recurrence in 4.5 % of cases. Female sex (61.5 % vs. 41.3 %, p = 0.019), hypoxemia (90 % vs. 59.2 %, p < 0.001), massive PE features (89.7 % vs. 30.1 %, p < 0.001), associated chronic kidney disease (CKD) (10.3 % vs. 1.4 %, p = 0.002), and the need for mechanical ventilation (28.2 % vs. 13.1 %, p = 0.02) were significantly associated with increased mortality. The use of TT was significantly associated with increased survival (27.1 % vs. 12.5 %, p < 0.001). In a multivariate logistic regression model, massive PE features significantly increased the odds of death (OR: 29.3, CI: 4.86-181.81, p < 0.001), whereas, treatment with anticoagulation (AC) alone (OR: 0.1, CI: 0.027-0.356, p < 0.001), TT (OR: 0.065, CI: 0.019-0.26, p < 0.001), surgical thrombectomy (ST) (OR: 0.047, CI: (0.010-0.23), p < 0.001), or percutaneous thrombectomy (PT) (OR: 0.12, CI: 0.020-0.84, p = 0.032) significantly decreased odds of death. Results from a meta-analysis of observational studies: Meta-analysis of the included 17 observational studies revealed an overall 10 % (95 % CI: 4.56-16.89) SPE prevalence among all PE cases. The overall SPE-related mortality rate was 8 % (95 % CI: 5.26-10.96). Massive PE was observed in 13.3 % (95 % CI: 5.56-23.70), PE recurrence in 5.1 % (95 % CI: 2.22-9.05), and late decompensation in 11 % (95 % CI: 3.43-22.34) of patients., Conclusions: SPE comprises 10 % of all PE cases. Despite its ominous radiologic appearance, the clinical, hemodynamic, and mortality outcomes of SPE seem comparable to that of other PE types in general. The presence of massive PE features is the main predictor of mortality in SPE patients. AC, TT, ST, and PT are all associated with decreased odds of death from SPE., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: Severe acute respiratory syndrome-coronavirus 2 (SARSCoV2) pandemic has been an unceasing plight with a wide range of clinical presentations. The direct effects of the virus, increased use of medications, and lifestyle changes have contributed to the vulnerability to co-infections. Fungal and bacterial co-infections led to increased morbidity and mortality during the pandemic. Similarly, the surge of skin signs in conjunction with herpes zoster (HZ) manifestations has been reported. In this study, we pooled the data on the clinical characteristics of SARS-CoV-2 patients co-infected with HZ., Methodology: Electronic databases including PubMed, Scopus, and Google Scholar were extensively searched to identify the relevant studies on HZ infection among the SARS-CoV-2 patients., Results: A total of 79 patients (from case reports, series, and retrospective studies) were included in the analysis. Fever was the most common constitutional symptom recorded, followed by cough and dyspnea. A systemic rash was reported in 78.5% of cases with mild symptoms of HZ and SARS-CoV-2 in 87% and 76%, respectively. Only 19% of the cases presented during the prodrome period of SARS-CoV-2. HZV polymerase chain reaction (PCR) was positive in 8.9% of the cases, and the remaining were diagnosed clinically. SARS-CoV-2 PCR was reported positive in 65 cases (82.3%). Leukopenia was observed in 7 cases (8.9%) and lymphopenia in 25 (31.6%). All patients recovered through conservative treatment., Conclusion: SARS-CoV-2 escalated the incidence of HZ reactivation. Most of the patients were seen with older individuals either simultaneously or a few days after the SARS-CoV-2 infection, but a few cases were reported during the asymptomatic prodrome period of SARS-CoV-2., (© 2021 Thada, Ata, Ali, Affas, Bhandari, Sarwar, Ahmed, Choudry, licensee HBKU Press.)

We evaluated 368 consecutively resected rectal cancers with neoadjuvant therapy for DNA mismatch repair (MMR) protein status, tumor response to neoadjuvant therapy, histopathologic features, and patient survival. Nine (2.4%) rectal cancers were mismatch repair-deficient (MMRD): 8 (89%) Lynch syndrome-associated tumors and 1 (11%) sporadic MLH1-deficient tumor. Of the 9 MMRD rectal cancers, 89% (8/9) had a tumor regression score 3 (poor response) compared with 23% (81/359) of MMR proficient rectal cancers ( P <0.001). Patients with MMRD rectal cancer less often had downstaging after neoadjuvant therapy compared with patients with MMR proficient rectal cancer (11% vs. 57%, P =0.007). In the multivariable logistic regression analysis, MMRD in rectal cancer was associated with a 25.11-fold increased risk of poor response to neoadjuvant therapy (tumor regression score 3) (95% confidence interval [CI]: 3.08-44.63, P =0.003). In the multivariable Cox regression analysis, the only variables significantly associated with disease-free survival were pathologic stage III disease (hazard ratio [HR]=2.46, 95% CI: 1.54-3.93, P <0.001), College of American Pathologists (CAP) tumor regression score 2 to 3 (HR=3.44, 95% CI: 1.76-6.73, P <0.001), and positive margins (HR=2.86, 95% CI: 1.56-5.25, P =0.001). In conclusion, we demonstrated that MMRD in rectal cancer is an independent predictor of poor response to neoadjuvant therapy and infrequently results in pathologic downstaging following neoadjuvant therapy. We also confirmed that MMRD in rectal cancer is strongly associated with a diagnosis of Lynch syndrome. Our results suggest that MMR status may help to provide a more patient-centered approach when selecting neoadjuvant treatment regimens and may help predict tumor response to neoadjuvant therapy., Competing Interests: Conflicts of Interest and Source of Funding: R.K.P. is a consultant for Alimentiv, and this relationship is unrelated to the content of this manuscript. For the remaining authors none were declared., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Pulmonary hypertension (PHTN) may occur in thyroid disorders, especially in hypothyroidism. However, there is increasing evidence of PHTN in hyperthyroidism (HTH). The etiology, clinical course, management, and factors associated with outcomes of PHTN in the setting of HTH are unascertained. This systematic review consolidates available evidence on patients with HTH who developed PHTN., Methods: We conducted a systematic review on English articles from PubMed, Scopus, and Google Scholar reporting PHTN in patients with hyperthyroidism. Data were analyzed and reported in Microsoft Excel 2020, SPSS version 26, and Jamovi version 1.2., Results: We identified 589 patients with PHTN in the setting of HTH. Etiologies included Grave disease 66.7%), toxic multinodular goiter (TMNG) (16.8%), drug-induced HTH (0.3%), thyroiditis(0.8%), and toxic adenoma(0.1%). Most patients did not receive any specific management for PHTN and were managed by antithyroid treatment (97.4%). Outcomes of PHTN were reported in 181 patients, with a 94% recovery rate. Pulmonary artery pressures (PAP) before and after HTH management ranged from 22.5 to 75 mm Hg and from 24 to 50 mm Hg, respectively. Outcome analysis performed on data from case reports and series with individually identifiable data revealed a 67.6% female preponderance. An estimated 73.5% of the patients had PHTN at the initial presentation of HTH, which was associated with a better resolution rate of PHTN(OR: 12, P-value: 0.048). TRAB was positive in 47% patients with no clinical difference in outcomes. antiTG AB was reported positive in 29.4%, all of whom had an improvement, compared to an 83.3% improvement rate in those with negative antiTG AB. Various etiologies and treatments did not have any significant differences in the outcome of PHTN., Conclusions: PHTN can be present at the initial diagnosis of HTH, which is associated with better outcomes of PHTN. There is a clear female preponderance in the development of PHTN. However, resolution rates seem to be better in males. Although TRAB is associated with the development of PHTN, it does not seem to affect the outcomes. PHTN in patients with HTH does not need any specific management, with >90% resolution with antithyroid therapy. Whether any specific antithyroid therapy has a better outcome in PHTN needs to be explored prospectively., Competing Interests: Declaration: This manuscript is original work and has not been submitted or is not under consideration for publication elsewhere. All the authors have reviewed the manuscript and approved it before submission. None of the authors have any conflict of interest in publishing this work. The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Free-floating right-heart thrombus (FFRHT) in the context of a pulmonary embolism (PE) is a rare but serious encounter with no guidelines addressing its management. We performed a systematic review and meta-analysis addressing prevalence, clinical behavior, and outcomes of FFRHT associated with PE. Among the included 397 patients with FFRHT and PE, dyspnea was the main presenting symptom (73.3%). Obstructive shock was documented in 48.9% of cases. Treatment with thrombolytic therapy, surgical thrombectomy, and percutaneous thrombectomy was documented in 43.8%, 32.7%, and 6.5% of patients, respectively. The overall mortality rate was 20.4%. Syncope ( p : 0.027), chest pain ( p : 0.006), and obstructive shock ( p : 0.037) were significantly associated with mortality. Use of thrombolytic therapy was significantly associated with survival ( p : 0.008). A multivariate logistic regression model to determine mortality predictors revealed that syncope (OR: 1.97, 95% CI: 1.06-3.65, p : 0.03), and obstructive shock (OR: 2.23, 95% CI: 1.20-4.14, p : 0.01) were associated with increased death odds. Treatment with thrombolytic therapy (OR: 0.22, 95% CI: 0.086-0.57, p : 0.002) or surgical thrombectomy (OR: 0.35, 95% CI: 0.137-0.9, p : 0.03) were associated with reduced death odds. Meta-analysis of observational studies revealed a pooled prevalence of FFRHT among all PE cases of 8.1%, and overall mortality of 23%. Although uncommon, the presence of FFRHT in the context of PE is associated with high obstructive shock and mortality rates. Favorable survival odds are observed with thrombolytic therapy and surgical thrombectomy. Data are derived from case reports and observational studies. Clinical trials elucidating these findings are needed.

Background and Aims: Thalassemia is one of the most common hemoglobinopathies, with around 5% of the world's population expected to have some degree and type of thalassemia. Beta thalassemia (BT) occurs due to a deficient production of the beta-globin chain of hemoglobin. Extramedullary hematopoiesis (EMH) is one of the complications of BT, mainly observed in minor/intermedia subtypes. EMH is the production of blood cells outside the marrow as a compensatory response to longstanding hypoxia. Due to chronic transfusions, it is not expected in patients with beta-thalassemia major (BTM). However, there are increasingly reported cases of EMH in BTM. The incidence of EMH in BTM is thought to be <1%. However, it seems that the true incidence is much higher than expected. This review aims to pool the available data and provide cumulative evidence on the reports of EMH in BTM patients., Methods: We aim to conduct a systematic review via searching multiple electronic databases (PubMed, Scopus, Google Scholar) to identify eligible articles from any date up to December 2020. Eligible studies should report extramedullary hematopoiesis in BTM. Case reports, case series, observational studies with cross-sectional or prospective research design, case-control studies, and experimental studies will be included if found relevant. Two reviewers (FA and ES) will individually analyze the study quality using the statistical methodology and categories guided by the Cochrane Collaboration Handbook, PRISMA guidelines, and Joanna Briggs Institute checklist for case reports and series., Results: This study will analyze and incorporate the available evidence on EMH in BTM concerning patient demographics, sites of EMH, management, and clinical outcomes of EMH., Conclusion: By summarizing and statistically analyzing the data about EMH in BTM, this study will generate extensive knowledge on the topic for a better understanding of atypical presentations in BTM, a common hemoglobinopathy., Competing Interests: The authors declare that they have no competing interests., (© 2021 The Authors. Health Science Reports published by Wiley Periodicals LLC.)

Background: Peritoneal metastases portend poor prognosis in the setting of standard chemotherapy. Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) improves outcomes, but relapse is common. We report a phase II trial evaluating the safety and efficacy of adjuvant αDC1 vaccination with chemokine modulation (CKM) after CRS/HIPEC., Methods: Patients undergoing CRS/HIPEC for appendiceal cancer, colorectal cancer, or peritoneal mesothelioma were enrolled. In addition to standard adjuvant chemotherapy, patients received intranodal and intradermal injections of autologous tumor-loaded αDC1 vaccine. After each vaccine booster, patients received CKM over 4 days, consisting of celecoxib, interferon (IFN)-α, and rintatolimod., Results: Forty-six patients underwent CRS/HIPEC followed by αDC1 treatment, including 24 appendiceal primaries, 20 colorectal, and 2 mesotheliomas. DC maturation was successful, with 97% expressing HLA-DR and CD86. Tumor cell recovery from peritoneal tumors was challenging, resulting in only 17% of patients receiving the target dose of αDC1. The αDC1 and CKM regimen was well tolerated. CKM successfully modulated serum inflammatory cytokine and chemokine levels. Median progression-free survival (PFS) for appendiceal primaries was 50.4, 34.2, and 8.9 months for grade 1, 2, and 3 tumors, respectively, while median PFS for colorectal cancer was 20.5 and 8.9 months for moderately and poorly differentiated tumors, respectively., Conclusions: Adjuvant autologous tumor antigen-loaded αDC1 vaccine and CKM is well tolerated. The mucinous nature of peritoneal metastases limits the feasibility of obtaining adequate autologous tumor cells. The improvement in median PFS did not meet our predefined thresholds, leading us to conclude that αDC1 vaccination is not appropriate for patients undergoing CRS/HIPEC for peritoneal metastases.

Background: Sickle cell disease (SCD) is commonly encountered in Africa and Middle Eastern countries. The causative mutation in the gene encoding the hemoglobin subunit β (HBB) leads to various genotypic variants of the disease. This results in varied phenotypes, with a spectrum of complications, from benign to fatal. Hemoglobin SS (HBSS) genotype is associated with most of these complications; hence, it is a severe form of SCD. On the other hand, rare genotypes such as hemoglobin SE (HBSE) are considered benign. There is limited literature about the clinical manifestations and characteristics of patients with HBSE. We pooled all available data describing the phenotypic manifestations of HBSE heterozygote worldwide to perform a systematic review., Methods: We performed a systematic review according to PRISMA guidelines using PubMed, SCOPUS, and Google Scholar databases. Two independent reviewers (FA and IK) evaluated studies for eligibility and extracted data. We synthesized data on demographics, manifestations, and management of HBSE disease. PROSPERO Registration Number: CRD42021229877., Results: We found 68 HBSE patients reported in the literature. 24 cases were extracted from case reports whereas 44 cases from case series and retrospective studies. Turkey reported the highest number of patients (n = 22). 32 (47%) of the patients were males. The mean age was 20.9 ± 18.26 years. The mean HBS and HBE percentages were 61.1% ± 7.25% and 32.3% ± 5.06%, respectively, whereas the mean hemoglobin was 11.64 ± 1.73 g/dl. Reported manifestations of HBSE disease included acute vaso-occlusive pain crisis (n = 22, 32.3%), splenomegaly (n = 11, 16.1%), hemolytic anemia (n = 10, 14.7%), infections (n = 8. 11.7%), bone infarction (n = 4, 5.8%), gallstones (n = 3, 4.4%), venous thromboembolism (VTE) (n = 2, 2.9%) and stroke (n = 2, 2.9%), and hematuria (n = 2, 2.9%). Death due to HBSE complications was reported in three patients., Conclusion: HBSE is a rare genotypic variant of SCD. It has been considered a benign form; however, there are multiple reports of severe complications. Severe complications observed in HBSE disease include vaso-occlusive crisis, acute chest syndrome, stroke, bone marrow embolism, and death.

Introduction: Vitamin B12 (VitB12) deficiency rarely manifests with visual symptoms. Optic nerve damage in VitB12 deficiency is thought to be via degeneration. However, optic neuritis, though infrequent, has been reported secondary to VitB12 deficiency., Material and Methods: We conducted a systematic review of all the reported cases of VitB12 deficiency with optic nerve involvement in Pubmed, Cochrane, and Google Scholar any date up to September 6, 2020. We have discussed the findings and compiled the available information on ophthalmological manifestations of VitB12 deficiency. We aim to provide a unified knowledge about the evidence related to types of optic neuropathies reported to date secondary to VitB12 deficiency. We also present a case of bilateral optic neuritis secondary to VitB12 deficiency., Presentation of Case: We present a 29-year-old previously healthy male with progressive, painful, bilateral, but asymmetric visual deterioration for forty-five days. A detailed history, examination, and laboratory workup were carried out. He was diagnosed as having optic neuritis secondary to VitB12 deficiency. He showed partial improvement with the replacement of VitB12., Conclusion: We suggest promptly identifying and replacing VitB12 in patients with optic neuritis with proven VitB12 deficiency to prevent permanent damage to the optic nerve. Patients with VitB12 deficiency should have a baseline fundoscopic exam to rule out subclinical optic nerve damage. Moreover, patients who present with visual disturbances should be screened for VitB12 deficiency, especially the vegan population., (© 2020 The Author(s).)

Aims: Peritoneal spread is the most common route of metastasis in appendiceal goblet cell adenocarcinoma. The aim of this study was to assess the prognostic significance of the World Health Organization (WHO) 5th edition grading criteria in peritoneal metastases of goblet cell adenocarcinoma., Methods and Results: We evaluated the clinicopathological features and survival of 63 patients with peritoneal metastasis of goblet cell adenocarcinoma who underwent cytoreductive surgery with hyperthermic intraperitoneal chemoperfusion (CRS-HIPEC), stratified according to the WHO 5th edition and the Tang et al. grading schemes. The patients were also compared with 120 patients with peritoneal metastasis of appendiceal mucinous neoplasia. Most (73%) peritoneal metastases of goblet cell adenocarcinoma were WHO Grade 3 (G3), there being fewer cases of Grade 2 (G2) (16%) and Grade 1 (G1) (11%) disease. No significant differences in overall survival were observed between WHO G1 and G2 tumours or between the three Tang grades. In the multivariable model of survival, WHO G3 [hazard ratio (HR) 2.81, 95% confidence interval (CI) 1.02-7.70] and the presence of >50% extracellular mucin (HR 2.30, 95% CI 1.09-4.88) were associated with reduced overall survival for patients with goblet cell adenocarcinoma. As compared with patients with peritoneal metastasis of mucinous neoplasia, patients with goblet cell adenocarcinoma had significantly reduced survival (median overall survival of 37 months versus 102 months, P < 0.001), which was attributed to the reduced survival of patients with G1/G2 goblet cell adenocarcinoma as compared with patients with G1 mucinous neoplasia (median survival of 98 months versus 204 months, P < 0.001)., Conclusions: Grade of peritoneal goblet cell adenocarcinoma determined according to the WHO 5th edition criteria is a clinically relevant measure that independently predicts survival in patients treated with CRS-HIPEC., (© 2020 John Wiley & Sons Ltd.)

Background: Disaccharides such as lactose and sucrose are sugars commonly found in human diet. They are broken down by mucosal disaccharidases in the duodenum. Previous small studies found no associations between gastrointestinal (GI) symptoms and combined low disaccharidase activity. We aim to explore the associations of low activity of disaccharidase and combinations of low activity of different disaccharidases with general GI symptom presentations in a large cohort of pediatric patients., Methods: We examined a cohort (0-21 yrs.) who have undergone esophagogastroduodenoscopy and received disaccharidase activity assay from duodenal biopsy in the time period 2010 to 2012. Disaccharidase assays tested for activity of lactase, sucrase, maltase, and palatinase. GI symptoms were grouped into four categories, abdominal pain, diarrhea, weight loss, and gastroesophageal reflux., Results: Of the 347 subjects, we found an association between low lactase activity and abdominal pain (OR = 1.78; 95% CI = 1.07-2.97; p < 0.05). Subjects with a lactase/sucrase ratio < 0.2 were found to be associated with abdominal pain (OR = 2.25; 95% CI = 1.25-4.04; p < 0.05), Subjects with low pandisaccharidase may be correlated with abdominal pain and have a unique frequency of GI symptoms due to low frequency of diarrhea and weight loss, but they were not statistically significant., Conclusions: Low activities of certain disaccharidase combinations may be associated with GI symptoms in subjects; a prospective study may be needed to investigate further.

Despite their association with DNA mismatch repair (MMR) protein deficiency, colonic adenocarcinomas with mucinous, signet ring cell, or medullary differentiation have not been associated with improved survival compared with conventional adenocarcinomas in most studies. Recent studies indicate that increased T-cell infiltration in the tumor microenvironment has a favorable prognostic effect in colonic adenocarcinoma. However, the prognostic effect of tumor-associated T cells has not been evaluated in histologic subtypes of colonic adenocarcinoma. We evaluated CD8-positive T-cell density in 259 patients with colonic adenocarcinoma, including 113 patients with tumors demonstrating mucinous, signet ring cell, or medullary differentiation, using a validated automated quantitative digital image analysis platform and correlated CD8-positive T-cell density with histopathologic variables, MMR status, molecular alterations, and survival. CD8-positive T-cell densities were significantly higher for MMR protein-deficient tumors (P<0.001), BRAF V600E mutant tumors (P=0.004), and tumors with medullary differentiation (P<0.001) but did not correlate with mucinous or signet ring cell histology (P>0.05 for both). In the multivariable model of factors predicting disease-free survival, increased CD8-positive T-cell density was associated with improved survival both in the entire cohort (hazard ratio=0.34, 95% confidence interval, 0.15-0.75, P=0.008) and in an analysis of patients with tumors with mucinous, signet ring cell, or medullary differentiation (hazard ratio=0.06, 95% confidence interval, 0.01-0.54, P=0.01). The prognostic effect of CD8-positive T-cell density was independent of tumor stage, MMR status, KRAS mutation, and BRAF mutation. Venous invasion was the only other variable independently associated with survival in both the entire cohort and in patients with tumors with mucinous, signet ring cell, or medullary differentiation. In summary, our results indicate that the prognostic value of MMR protein deficiency is most likely attributed to increased tumor-associated CD8-positive T cells and that automated quantitative CD8 T-cell analysis is a better biomarker of patient survival, particularly in patients with tumors demonstrating mucinous, signet ring cell, or medullary differentiation.

Aim: To explore and to analyze the patterns in decision-making by pediatric gastroenterologists in managing a child with a suspected diagnosis of functional gallbladder disorder (FGBD)., Methods: The questionnaire survey included a case history with right upper quadrant pain and was sent to pediatric gastroenterologists worldwide via an internet list server called the PEDGI Bulletin Board., Results: Differences in decision-making among respondents in managing this case were observed at each level of investigations and management. Cholecystokinin-scintigraphy scan (CCK-CS) was the most common investigation followed by an endoscopy. A proton pump inhibitor was most commonly prescribed treating the condition. The majority of respondents considered a referral for a surgical evaluation when CCK-CS showed a decreased gallbladder ejection fraction (GBEF) value with biliary-type pain during CCK injection., Conclusion: CCK infusion rate in CCK-CS-CS and GBEF cut-off limits were inconsistent throughout practices. The criteria for a referral to a surgeon were not uniform from one practitioner to another. A multidisciplinary team approach with pediatric gastroenterologists and surgeons is required guide the decision-making managing a child with suspected FGBD. ​., Competing Interests: Conflict-of-interest statement: No potential conflicts of interest relevant to this article were reported.

Peritoneal metastasis in colorectal carcinoma is associated with a dismal prognosis; however, features that correlate with patterns of metastatic spread are not well characterized. We analyzed the clinicopathologic and molecular features of 166 patients with colorectal carcinomas stratified by metastases to the peritoneum or liver. Mucinous and signet ring cell differentiation were more frequently observed in colorectal carcinoma with peritoneal dissemination compared to colorectal carcinoma with liver metastasis (mucinous differentiation: 62% vs 23%, P < .001; signet ring cell differentiation: 21% vs 0%, P < .0001). The significant association of mucinous differentiation with peritoneal dissemination compared with liver metastasis was identified in patients with both synchronous and metachronous development of metastasis ( P < .01). In contrast, colorectal carcinomas with liver metastasis were more frequently low-grade (90% vs 72%, P = .005) and associated with dirty necrosis (81% vs 56%, P = .001) compared with colorectal carcinomas with peritoneal dissemination. No significant differences were identified between colorectal carcinoma with peritoneal metastasis versus liver metastasis with respect to KRAS mutations, BRAF mutation, or high levels of microsatellite instability. Patients with tumors involving the peritoneum had a significantly worse overall survival in comparison to patients with liver metastasis lacking peritoneal involvement ( P = .02). When including only those patients with peritoneal metastasis, the presence of any mucinous or signet ring cell differentiation was associated with a significantly worse overall survival ( P = .006). Our findings indicate that mucinous and signet ring cell differentiation may be histologic features that are associated with an increased risk of peritoneal dissemination and poor overall survival in patients with peritoneal metastasis.

Purpose: The current study examined prospective relationships between preoperative depressive symptoms and short-term (30-day morbidity and readmission) and long-term (overall survival) outcomes after hyperthermic intraperitoneal chemotherapy with cytoreductive surgery (HIPEC + CS)., Methods: Ninety-eight patients scheduled for HIPEC + CS completed the Center for Epidemiologic Studies-Depression (CES-D) scale before surgery. Demographic and disease-specific factors and information about morbidity and readmission within 30 days after discharge were gathered from medical records. Survival was measured from date of surgery to death., Results: Twenty-eight percent of patients had CES-D scores indicative of clinically significant depressive symptoms. Thirty-day morbidity occurred in 31.9% of patients and readmission in 22.2%. At the time of analysis (median follow-up of 49 months), 71.6% of patients were deceased, with median survival time of 11 months for those who died. After adjusting for relevant preoperative demographic and disease-specific factors, depressive symptoms were associated with greater odds of 30-day morbidity (n = 68; odds ratio, 5.50; 95% CI, 1.23 to 24.73; P = .03) and greater likelihood of 30-day readmission (n = 72; odds ratio, 5.92; 95% CI, 1.27 to 27.64; P = .02). Depressive symptoms were associated with shorter survival after adjustment for preoperative demographic and disease-specific factors (n = 87; hazard ratio, 1.88; 95% CI, 1.07 to 3.31; P = .03). This association was no longer significant when intraoperative/postoperative prognostic variables were added to the statistical model (n = 87; hazard ratio, 1.31; 95% CI, 0.72 to 2.37; P = .37)., Conclusion: Patients with clinically significant levels of preoperative depressive symptoms are at risk for poor clinical outcomes after HIPEC + CS, including greater risk of 30-day morbidity and readmission. Further research is warranted to determine biobehavioral mechanisms and examine whether effective interventions targeting preoperative depressive symptoms can reduce postoperative risk in this patient population., (© 2016 by American Society of Clinical Oncology.)

Background: Cytoreductive surgery (CRS) and heated intraperitoneal chemotherapy (HIPEC) are used to treat peritoneal carcinomatosis from a variety of primary tumor sites. Little is known about the in vivo effects of CRS and HIPEC., Methods: We examined tumor and non-neoplastic peritoneal tissue samples from 38 patients undergoing CRS and HIPEC for appendiceal or colorectal carcinomatosis, using conventional histologic analysis and immunohistochemical analysis for markers of early DNA damage (phosphorylated H2AX, γH2AX) and early necrosis (extracellular HMGB1). Findings were correlated with clinicopathologic features and oncologic outcome., Results: Histologic findings corresponding with CRS and HIPEC included extensive submesothelial inflammatory infiltrate, endothelial activation, mesothelial karyolysis and surface fibrin deposition. Endothelial activation in submesothelial vessels exhibited high specificity for samples obtained following HIPEC relative to samples obtained following CRS but prior to HIPEC. Mesothelial nuclear γH2AX staining and submesothelial extracellular HMGB1 staining increased progressively following CRS and HIPEC, consistent with DNA damage and necrosis. No significant increase in tumor staining for markers was seen with CRS or HIPEC. Submesothelial HMGB1 staining was associated with increased progression-free survival on univariate analysis., Conclusions: The immediate histologic effects of CRS and HIPEC are defined and provide evidence that DNA damage and early steps of necrosis are underway in mesothelial tissues at the conclusion of the procedure. Further research will be necessary to investigate the impact of these findings on long-term oncologic outcome, and may provide insight into the downstream effects of CRS and HIPEC that could facilitate refinement of regional therapeutic regimens for carcinomatosis.

Drug-induced hepatotoxicity most commonly manifests as an acute hepatitis syndrome and remains the leading cause of drug-induced death/mortality and the primary reason for withdrawal of drugs from the pharmaceutical market. We report a case of acute liver injury in a 12-year-old Hispanic boy, who received a series of five antibiotics (amoxicillin, ceftriaxone, vancomycin, ampicillin/sulbactam, and clindamycin) for cervical lymphadenitis/retropharyngeal cellulitis. Histopathology of the liver biopsy specimen revealed acute cholestatic hepatitis. All known causes of acute liver injury were appropriately excluded and (only) drug-induced liver injury was left as a cause of his cholestasis. Liver-specific causality assessment scales such as Council for the International Organization of Medical Sciences/Roussel Uclaf Causality Assessment Method scoring system (CIOMS/RUCAM), Maria and Victorino scale, and Digestive Disease Week-Japan were applied to seek the most likely offending drug. Although clindamycin is the most likely cause by clinical diagnosis, none of causality assessment scales aid in the diagnosis.

We evaluated a consecutive series of signet ring cell colorectal carcinomas in an attempt to correlate the histopathologic pattern of infiltration with molecular alterations and prognosis. Of the 4760 primary colorectal carcinomas surgically resected between the years 2002 and 2012, 53 (1%) were composed of >50% signet ring cells. Of the 53 signet ring cell carcinomas, 40 (75%) were composed of >50% extracellular mucin with signet ring cells floating within pools of mucin and were subclassified as mucin-rich signet ring cell carcinomas. Thirteen (25%) carcinomas were characterized by diffusely infiltrating carcinomas with minimal to no extracellular mucin and were subclassified as mucin-poor signet ring cell carcinomas. All 13 mucin-poor signet ring cell carcinomas were either stage III or IV, whereas many cases of mucin-rich signet ring cell carcinoma were stage I or II (17 cases) (P=0.005). Compared with mucin-rich tumors, mucin-poor signet ring cell carcinomas more frequently demonstrated adverse histologic features such as lymphatic invasion (13/13, 100% vs. 22/40, 55%; P=0.002), venous invasion (6/13, 46% vs. 3/40, 8%; P=0.004), and perineural invasion (11/13, 85% vs. 9/40, 23%; P=0.0001). Twenty-three of 53 (43%) signet ring cell carcinomas demonstrated high levels of microsatellite instability (MSI-H). Twenty-two of 23 (96%) MSI-H signet ring cell carcinomas were mucin rich; only 1 MSI-H signet ring carcinoma was mucin poor (P=0.0033). Mucin-poor signet ring cell carcinoma had significantly reduced overall and recurrence-free survival compared with mucin-rich signet ring cell carcinomas (P=0.0035 and 0.0001, respectively), even when adjusting for tumor stage. Mucin-poor signet ring cell carcinoma had a higher propensity for peritoneal dissemination (5/13, 38%) compared with mucin-rich signet ring cell carcinoma (5/40, 12.5%), although this was not statistically significant (P=0.052). Finally, MSI-H and microsatellite-stable signet ring cell carcinomas had similar overall and recurrence-free survival (P=0.2266 and 0.1055, respectively), even when adjusting for tumor stage. In conclusion, we identified a unique subset of signet ring cell colorectal carcinoma with diffuse infiltration and minimal to no extracellular mucin (mucin-poor signet ring cell carcinoma), which lacks MSI-H and has a dismal prognosis with an aggressive clinical course often with peritoneal dissemination. Further, our results confirm that MSI does not affect survival in colorectal signet ring cell carcinomas.

Importance: Multicenter studies indicate that outcomes of open (ODP) and minimally invasive distal pancreatectomy (MIDP) are equivalent for benign lesions. However, data for pancreatic carcinoma are limited., Objective: To compare outcomes of ODP and MIDP for early-stage pancreatic ductal carcinoma to determine relative safety and oncologic efficacy., Design: Retrospective analysis of 62 consecutive patients undergoing ODP or MIDP for pancreatic ductal carcinoma by intention to treat with propensity scoring to correct for selection bias., Setting: A high-volume university center for pancreatic surgery., Participants: Sixty-two patients at a single institution., Interventions: Patients underwent ODP or MIDP., Main Outcome Measures: Perioperative mortality, morbidity, readmission, postoperative complications, disease progression, and overall survival., Results: Thirty-four patients underwent ODP, and 28 underwent MIDP with 5 conversions to ODP. No significant differences in age, body mass index, performance status, tumor size, or radiographic stage were identified. High rates of margin-negative resection (ODP, 88%; MIDP, 86%) and median lymph node clearance (ODP, 12; MIDP, 11) were achieved in both groups with equal rates and severity of postoperative complications (ODP, 50%; MIDP, 39%) and pancreatic fistula (ODP, 29%; MIDP, 21%). Despite conversions, intended MIDP was associated with reduced blood loss (P = .006) and length of stay (P = .04). Conversion was associated with a poor histologic grade and positive nodes. Median overall survival for the entire cohort was 19 (95% CI, 14-47) months. Minimally invasive distal pancreatectomy was performed increasingly in later study years and for patients with a higher Charlson-Age Comorbidity Index. Overall survival after ODP or intended MIDP was equivalent after adjusting for comorbidity and year of surgery (relative hazard, 1.11 [95% CI, 0.47-2.62])., Conclusions and Relevance: We detected no evidence that MIDP was inferior to ODP based on postoperative outcomes or overall survival. This conclusion was verified by propensity score analysis with adjustment for factors affecting selection of operative technique.

Background: Laparoscopic distal pancreatectomy (LDP) reduces postoperative morbidity, hospital stay, and recovery as compared with open distal pancreatectomy. Technical limitations of laparoscopic surgery may limit patient eligibility and require conversion to open or hand-assisted surgery to maintain patient safety. We hypothesized that robot-assisted distal pancreatectomy (RADP) was superior to LDP as a result of improved surgical manipulation and visualization, potentially expanding the indications for minimally invasive pancreatectomy., Methods: We performed a retrospective analysis of all minimally invasive distal pancreatectomies at University of Pittsburgh Medical Center between January 2004 and February 2011. We compared the perioperative outcomes, 90-day morbidity and mortality of our first 30 RADPs to 94 consecutive historical control LDPs., Results: Patients undergoing RADP and LDP demonstrated equivalent age, sex, race, American Society of Anesthesiologists' score, and tumor size. Postoperative length of hospital stay and rates of pancreatic fistula, blood transfusion, and readmission were not statistically different. Patients in the RADP group did not require conversion to open surgery unlike the LDP group (16%, P < 0.05) and had reduced risk of excessive blood loss. There were more pancreatic ductal adenocarcinomas approached robotically (43%) than laparoscopically (15%) (P < 0.05). Oncological outcomes in these cases were superior for the robotic-assisted group with higher rates of margin negative resection and improved lymph node yield for both benign and malignant lesions (P < 0.0001)., Conclusions: RADPs were equivalent to LDPs in nearly all measures of outcome and safety but significantly reduced the risk of conversion to open resection, despite a statistically greater probability of malignancy in the robotic cohort. We concluded that robotic assistance may broaden indications for minimally invasive pancreatectomy.

Background: To prospectively review the clinicopathologic pattern and out come in 15 patients with adolescent ovarian tumours in Military Hospital Rawalpindi between Jan 2004 to Sep 2007., Methods: All cases of adolescent ovarian tumours reporting to the gynaecology department of Military Hospital Rawalpindi during the period of enrolment. Out of 15 cases 12 were managed surgically. Data was recorded regarding clinical presentation, patient's age, size of tumour, bilaterality, histopathology, staging if tumour was malignant and sites of extra ovarian involvement. All patients were followed up for one year., Results: Majority of patients fell in the subgroup 14-16 year age. Majority harboring ovarian malignancy belonged to subgroup 17-19 years. Clinical presentation in the majority was mass abdomen and abdominal distension. Approach was transcutaneous in 3 (20%), laparoscopic in 2(20%), and open laparotomy in 10 (60%). Frozen section was performed in 3 cases. Histopathology was benign in 11 cases and malignant in 4. In 3 cases cyst fluid was negative for malignancy. In 2 cyst wall biopsy and one patient where entire cyst was removed histopathology revealed benign serous cyst adenoma/luteal cyst (26%). There were 5 cases of dermoid cysts (33.3%), one patient had bilateral dermoids, one malignant and one benign. All 4 malignancies were found to be to non-epithelial on histopathology. One case had surgery twice. Unilateral oopherectomy followed by recurrence and total abdominal hysterectomy and contralateral salpingo-oopherectomy after 2 years., Conclusion: This study shows the preponderance of non-epithelial tumours and high percentages of malignant germ cell tumours in adolescents. The incidence of malignant tumours in adolescents is higher than in adults. Early correct diagnosis could be reached by careful physical examination, imaging and tumour markers Surgery should as much as is safely possible be fertility preserving.

Purpose: Invasion of the superior mesenteric vein (SMV) or superior mesenteric-portal vein (SMPV) confluence, in pancreatic adenocarcinoma of the head and uncinate process, is the most common unexpected finding at the time of pancreaticoduodenectomy. Resection of the SMV or SMPV with reconstruction using autologous and synthetic conduits is well established. We describe the use of the left renal vein as a practical, easy, and durable alternative as an interposition graft after pancreaticoduodenectomy with en bloc segmental resection of the SMV., Methods and Results: Involvement of the SMV by a pancreatic mass is resected en bloc with a standard pancreaticoduodenectomy. The left renal vein is then harvested from the junction with the IVC and proximal to the adrenal vein. This is then used as a vein graft for the resected portion of the SMV., Discussion: Complete pancreatic cancer resection with grossly tumor-free margins provides the only chance for long-term cure. Isolated tumor involvement of the SMV or SMPV confluence is not associated with histopathological variables predictive of a poor prognosis and appears to be a function of tumor location rather than an indicator of biological aggressiveness. Recurrence and long-term survival following pancreaticoduodenectomy with and without vein resection are equivalent, provided grossly negative margins are achieved. We describe the use of the left renal vein as a technically feasible, easy, and durable conduit for SMV reconstruction in pancreaticoduodenectomy. After resection of the left renal vein, significant increase in postoperative serum creatinine has not been reported; collateral flow has been confirmed by radiological methods and severe renal dysfunction perioperatively, postoperatively, and during long-term follow-up has not been observed.

Objective: Decision making in cases of acute appendicitis poses a clinical challenge specially in developing countries where advanced radiological investigations do not appear cost effective and so clinical parameters remain the mainstay of diagnosis. The aim of our study was to devise a scoring system from our local database and test its accuracy in the preoperative diagnosis of acute appendicitis., Methods: Clinical data from 401 patients having undergone appendectomy were collected to identify predictive factors that distinguished those with appendicitis from those who had a negative appendectomy. Ten such factors were identified and using Bayesian probability a weight was assigned to each and the results summated to get an overall score. A cut-off point was identified to separate patients for surgery and those for observation. The scoring system was then retrospectively applied to a second population of 99 patients in order to compare suggested actions (derived from the scoring system) to those actually taken by surgeons. The sensitivity, specificity and accuracy for the level of decision was then calculated., Results: Of the 99 patients, the method suggested immediate surgery for 65 patients, 63 of whom had acute appendicitis (3.1% diagnostic error rate). Of the 33 patients in whom the score suggested active observation, 18 had appendicitis. The accuracy of our scoring system was 82%. The method had a sensitivity of 78%, specificity 89% and a positive predictive value of 97%. The negative appendectomy rate determined by our study was 7% and the perforation rate 13%., Conclusion: Scoring system developed from a local database can work effectively in routine practice as an adjunct to surgical decision making in questionable cases of appendicitis.