Impact of grade on workup of rectal neuroendocrine tumors: a retrospective cohort study : Grade impact on workup of rectal NETs.

BACKGROUND: Rectal neuroendocrine tumors (RNETs) are often discovered on screening colonoscopy. Indications for staging and definitive resection are inconsistent in current guidelines. We evaluated the role of grade in guiding staging and procedural decision-making. METHODS: Patients with biopsy confirmed RNETs between 2004 and 2015 were reviewed. Baseline characteristics, staging investigations (biochemical and imaging), and endoscopic/surgical treatment were recorded. Associations between grade, preoperative staging, interventions, and survival were determined using Fisher-Freeman-Halton Exact, log-rank, and Kaplan-Meier analysis. RESULTS: Amongst 139 patients with RNETs, 9% were aged ≥ 75 years and 44% female. Tumor grade was: 73% grade 1 (G1), 18%, grade 2 (G2) and 9% grade 3 (G3). Staging investigations were performed in 52% of patients. All serum chromogranin A and 97% of 24-hour urine 5-hydroxyindoleacetic acid tests were normal. The large majority of staging computed tomography (CT) scans were negative (76%) with subgroup analysis showing no G1 patients with CT identified distant disease compared with 38% of G2 and 50% of G3 patients (p < 0.001). G1 patients were more likely to achieve R0/R1 resections compared to G2 (95% vs. 50%, p < 0.001) and G1 patients had significantly better 5-year overall survival (G1: 98%, G2: 67%, G3: 10%, p < 0.001). CONCLUSION: Tumor grade is important in preoperative workup and surgical decision-making. Biochemical staging may be omitted but staging CT should be considered for patients with grade ≥ 2 lesions. Anatomic resections should be considered for patients with grade 2 disease.

Screening for asymptomatic nephrolithiasis in primary hyperparathyroidism patients is warranted.

BACKGROUND: We aimed to investigate the prevalence, characteristics, and management of nephrolithiasis in primary hyperparathyroidism (PHPT) patients. METHODS: Medical records of patients who underwent parathyroidectomy at a tertiary care hospital in British Columbia from January 2016 to April 2023 were retrospectively reviewed. Demographic data, laboratory results, imaging reports, and urologic consultations were examined. Descriptive statistics and relevant statistical tests, including logistic regressions, were utilized for data analysis. RESULT: Of the 413 PHPT patients included in the study population, 41.9% harbored renal stones, and nearly half (48.6%) required urological interventions. Male sex, elevated preoperative serum ionized calcium (iCa) and 24-h urinary calcium (24 â€‹h urine Ca) levels were independent risk factors for stone formation. Additionally, male sex, younger age, and lower preoperative serum 25-hydroxyvitamin D (25(OH)D) level were associated with higher odds of requiring urological intervention for stones. CONCLUSIONS: This study identified significant prevalence of asymptomatic renal calcifications in PHPT patients, with a substantial proportion necessitating urological intervention. These findings emphasize the importance of incorporating screening and treatment of renal stones into the management of PHPT patients.

Sclerosing encapsulating peritonitis causing fatal bowel obstruction.

Sclerosing encapsulating peritonitis (SEP) is a rare condition characterised by a fibrotic peritoneal membrane encasing loops of bowel often resulting in obstruction. We present a case of SEP complicated by non-resolving small bowel obstruction in the context of prior malignancies and surgical complications. A literature review on SEP was performed to outline potential aetiologies, diagnostic investigations and treatment strategies that may be considered in the management of this disease.

Synoptic operative reporting in cancer surgery: A scoping review.

BACKGROUND: Narrative operative reports (NOR) are important for cancer management but often lack key information. This review investigated the efficacy of synoptic operative reports (SORs) for cancer operations compared to NORs. METHODS: A database search included published studies up to October 31, 2021. Overall report completeness and reporting frequencies of cancer elements were descriptively compared between NORs and SORs. RESULTS: Among 4353 studies, 32 were included. 47% of studies compared NORs to SORs. Overall completeness favored SORs (80 ± 19%) over NORs (47 ± 18%, p < 0.001). Essential cancer operative report elements including tumor location (NOR: 51 ± 28%, SOR: 89 ± 11%, p < 0.001), presence of metastases (NOR: 36 ± 33%, SOR: 96 ± 5%, p < 0.001), and final resection margins (NOR: 39 ± 30%, SOR: 87 ± 17%, p < 0.001) demonstrated higher mean reporting frequencies in SORs. CONCLUSION: Overall completeness and reporting of cancer elements were superior in SORs. Although standardization of SORs requires further research, transition from NORs to SORs may improve the quality of postoperative cancer care.

Association between surveillance imaging and survival outcomes in small bowel neuroendocrine tumors.

BACKGROUND: Surveillance guidelines following the resection of small bowel neuroendocrine tumors (SB-NETs) are inconsistent. We evaluated the impact of surveillance imaging on SB-NET recurrence and overall survival (OS). METHODS: Patients with completely resected SB-NETs referred to a provincial cancer center (2004-2015) were reviewed. Associations between imaging frequency, recurrence, post-recurrence treatment, and OS were determined using univariate and Cox-regression analyses. RESULTS: Among 195 completely resected SB-NET patients, 31% were ≥70 years, 43% were female, and 80% had grade 1 disease. Imaging frequency was predictive of recurrence (hazard ratio 2.52, 95% confidence interval 1.84-3.46, p < 0.001). 72% underwent interventions for recurrent disease. Patients who were treated for the recurrent disease had comparable OS to those who did not recur (median 152 vs. 164 months; p = 0.25). Imaging frequency was not associated with OS in those with treated recurrent disease (p = 0.65). Patients who recurred underwent more computerized tomography (CT) scans than those who did not recur (CT: 1.47 ± 0.89 vs. 1.02 ± 0.81 scans/year, p < 0.001). Detection of disease recurrence was 5%-7% per year during the first 6 years of surveillance and peaked at 17% in Year 9. CONCLUSION: Less frequent imaging over a longer duration should be emphasized to capture clinically relevant recurrences that can be treated to improve OS.

Risk of lymph node metastasis in early gastric cancer for a Western population.

INTRODUCTION: Endoscopic resection (ER) of early gastric cancer (EGC) is increasingly used in Eastern countries due to their low rates of lymph node metastasis (LNM); however, there is a paucity of evidence in Western countries. We investigated LNM and its effect on overall survival (OS) in Western patients with EGC. METHODS: Patients diagnosed with T1 gastric cancer between 2000 and 2017 were retrospectively evaluated. Univariate Kaplan-Meier, multivariate logistic and Cox-regression models were used to assess the associations between clinical characteristics, LNM, and OS. RESULTS: Among 86 patients, median age was 68 years and 72% were male. Node positivity was 30%. Two percent of patients met the classical guidelines for ER and all were node-negative, while 16% met expanded criteria of which 14% were node-positive. T1b disease (odds ratio [OR] 41.2 [95% confidence interval [CI] 1.62-1048], p = 0.02) and lymphovascular/perineural invasion (OR 18.0 [95% CI 2.41-134], p = 0.01) were predictive of node positivity. The 5-year OS for node-negative and node-positive patients was 84% and 53% (p = 0.004), respectively. CONCLUSIONS: The risk of LNM in Western patients with EGC is higher; therefore, generalizability of the expanded criteria for ER should be interpreted with caution.

Intraoperative frozen section analysis of margin status as a quality indicator in gastric cancer surgery.

INTRODUCTION: Positive pathologic margins following gastric cancer (GC) resection carries a poor prognosis. We evaluated intraoperative frozen section (IFS) analysis of resection margins (RMs) as a quality indicator in GC surgery. METHODS: Patients referred to a provincial cancer agency with surgically resected non-metastatic GC between 2004 and 2012 were included. Associations between IFS analysis, other baseline characteristics, RMs, and overall survival (OS) were assessed using logistic regression, Kaplan-Meier analyses, and Cox proportional hazards modeling. RESULTS: Among 377 patients, median age was 67 years, 68% were male, and 16% had +RMs. Thirty-four percent of patients underwent IFS analysis, which protected against +RMs (odds ratio [OR]: 0.34, 95% confidence interval [CI]: 0.16-0.73, p = 0.006) and improved OS (hazards ratio [HR]: 0.72, 95% CI: 0.54-0.98, p = 0.037). OS following re-resection of IFS positive patients was similar to IFS negative patients (69 vs. 54 months, p = 0.317). Stage III disease (OR: 12.8, 95% CI: 3.00-55.0, p = 0.001) and gastroesophageal junction tumors (OR: 2.25, 95% CI: 1.05-4.78, p = 0.036) predicted +RMs. Stage III disease led to worse OS (HR: 2.89, 95% CI: 1.92-4.34, p < 0.001) while intestinal histology improved OS (HR: 0.67, 95% CI: 0.50-0.90, p = 0.007). CONCLUSIONS: IFS analysis reduce +RMs and improve OS and should be incorporated in curative intent GC surgery for patients with locally advanced GC.

Lymph node mapping in gastric cancer: a pilot study in Western patients.

In East Asia, the role of lymph node (LN) mapping in assisting surgical lymphadenectomy, which is integral to the management of gastric cancer, has been explored. We sought to evaluate its safety and utility in Western patients. Thirteen patients with nonmetastatic gastric adenocarcinoma received endoscopic, peritumoural, submucosal indocyanine green fluorescence (ICG) injections before surgery, and ICG was assessed intraoperatively using a laparoscopic detection system. All patients underwent a laparoscopic subtotal gastrectomy, and 10 of them received D2 lymphadenectomies. ICG-mapped LNs fell outside the D1 distribution in all cases, outside the D1+ distribution in 54%, and within the D2 distribution in all cases. There were no ICG-related allergies, procedural complications, or perioperative deaths. We conclude that ICG LN mapping is safe and feasible in assisting LN dissections and localizing the primary tumour in Western patients. D2 dissections should be performed in patients with advanced gastric cancer, as LNs drained outside the D1/D1+ distributions in most cases.

Malignant tumor is the greatest risk factor for pulmonary embolism in hospitalized patients: a single-center study.

BACKGROUND: This study aimed to investigate the background of patients who presented with pulmonary embolism (PE) on contrast-enhanced chest computed tomography (CT) and to explore the risk factors for PE. METHODS: This study included a review of the medical records of all 50,621 patients who were admitted to one community hospital between January 1, 2013 and December 31, 2017. Data on sex, age, risk factors related to blood flow stagnation (obesity, long-term bed rest, cardiopulmonary disease, cast fixation, long-term sitting), risk factors related to vascular endothelial disorder (surgery, trauma/fracture, central venous catheterization, catheter tests/treatments, vasculitis, antiphospholipid antibody syndrome, history of venous thromboembolism (VTE)), and risk factors related to hypercoagulability (malignant tumor, use of oral contraceptives/low-dose estrogen progestin/steroids, infection, inflammatory enteric disease, polycythemia, protein C or protein S deficiency, dehydration) were evaluated. RESULTS: Of all inpatients, 179(0.35%) out of 50,621 were diagnosed with PE after contrast-enhanced chest CT examination, in which 74 patients were symptomatic and 105 patients had no symptom. Among asymptomatic 105 patients, 71 patients got CT scans for other reasons including cancer screening and searching infection focus, and 34 patients got CT scans for searching PE due to either apparent or suspicious DVT. The rate of discovering PE was significantly greater in women (0.46%, 90/19,409) than men (0.29%, 89/31,212) (P = 0.008). Of the 179 patients with PE, 164 (92%) had some type of risk factor. For both men and women, the most frequent risk factor was a malignant tumor, followed by obesity, long-term bed rest and infection for men and long-term bed rest, obesity and infection for women. The most common malignant tumor was lung cancer. Although taking antipsychotic agent is not advocated as a risk factor, there is a possibility of involvement. CONCLUSIONS: The risk factors for PE were identified in this single-center, retrospective study.

Tumour grade and primary site predict patterns of recurrence and survival in patients with resected gastroenteropancreatic neuroendocrine tumors.

BACKGROUND: Patterns of recurrence help to inform surveillance of patients with resected gastroenteropancreatic neuroendocrine tumors (GEP-NETs). METHODS: Patients with GEP-NETs in British Columbia, Canada (2004-2015) were reviewed. Associations between tumor characteristics, recurrence and survival were analyzed. RESULTS: Among 759 patients, 41%, 25%, and 17% had grade 1, 2, and 3 disease, respectively. 387 patients had R0/R1 resections, of which 30% recurred (median 25 months). 5-year incidence of recurrence was 22% (grade 1), 46% (grade 2), and 59% (grade 3) (p < 0.001). Grade predicted distant recurrence (Grade 2 HR 1.89, 95% CI 1.16-3.07; p = 0.011; Grade 3 HR 3.29, 95% CI 1.81-5.99; p < 0.001). Compared to small bowel NETs, pancreas NETs had less peritoneal recurrence (OR 0.15, 95% CI 0.03-0.68, p = 0.014). No patients had isolated pulmonary recurrences. CONCLUSION: Higher grade tumors and pancreatic NETs require more frequent surveillance. Evidence is limited for pulmonary surveillance.

An Evolutionarily Primitive and Distinct Auxin Metabolism in the Lycophyte Selaginella moellendorffii.

Auxin is a key regulator of plant growth and development. Indole-3-acetic acid (IAA), a plant auxin, is mainly produced from tryptophan via indole-3-pyruvate (IPA) in both bryophytes and angiosperms. Angiosperms have multiple, well-documented IAA inactivation pathways, involving conjugation to IAA-aspartate (IAA-Asp)/glutamate by the GH3 auxin-amido synthetases, and oxidation to 2-oxindole-3-acetic acid (oxIAA) by the DAO proteins. However, IAA biosynthesis and inactivation processes remain elusive in lycophytes, an early lineage of spore-producing vascular plants. In this article, we studied IAA biosynthesis and inactivation in the lycophyte Selaginella moellendorffii. We demonstrate that S. moellendorffii mainly produces IAA from the IPA pathway for the regulation of root growth and response to high temperature, similar to the angiosperm Arabidopsis. However, S. moellendorffii exhibits a unique IAA metabolite profile with high IAA-Asp and low oxIAA levels, distinct from Arabidopsis and the bryophyte Marchantia polymorpha, suggesting that the GH3 family is integral for IAA homeostasis in the lycophytes. The DAO homologs in S. moellendorffii share only limited similarity to the well-characterized rice and Arabidopsis DAO proteins. We therefore suggest that these enzymes may have a limited role in IAA homeostasis in S. moellendorffii compared to angiosperms. We provide new insights into the functional diversification of auxin metabolic genes in the evolution of land plants.

Integrin-Linked Kinase Mediates Therapeutic Resistance of Quiescent CML Stem Cells to Tyrosine Kinase Inhibitors.

Patients with chronic myeloid leukemia (CML) often require lifelong therapy with ABL1 tyrosine kinase inhibitors (TKIs) due to a persisting TKI-resistant population of leukemic stem cells (LSCs). From transcriptome profiling, we show integrin-linked kinase (ILK), a key constituent of focal adhesions, is highly expressed in TKI-nonresponsive patient cells and their LSCs. Genetic and pharmacological inhibition of ILK impaired the survival of nonresponder patient cells, sensitizing them to TKIs, even in the presence of protective niche cells. Furthermore, ILK inhibition eliminated TKI-refractory LSCs from patients, but not normal HSCs, in vitro and in vivo. RNA-sequencing and functional validation studies implicated an important role of ILK in maintaining a requisite level of mitochondrial oxidative metabolism in highly purified, quiescent LSCs. Thus, these findings point to ILK as a critical survival mediator to TKIs and quiescent stem cells, offering an attractive therapeutic target and model for curative combination therapies in stem-cell-driven cancers.

Bowen's Disease of the Nipple.

Bowen's disease is a type of intraepidermal squamous cell carcinoma that commonly develops in areas of the skin exposed to sunlight, such as the scalp, trunk, and limbs. Although development of Bowen's disease in other sites, such as the nipple, is extremely rare, we herein report our experience with one such case. A 76-year-old female presented to our hospital with complaints of right nipple pruritus. We diagnosed Bowen's disease via nipple skin biopsy, and the patient underwent right nipple resection. The deep tissue margin was positive for malignancy; therefore, the patient subsequently underwent right partial mastectomy. Histopathology revealed tumor cells inside the lactiferous ducts, but the resection margin was negative for malignancy. Bowen's disease of the nipple may progress from the skin to the lactiferous ducts. Clinical findings can be used to evaluate lesion progression and determine the necessary extent of skin and mammary gland resection.

Association of baseline patient characteristics with adjuvant chemotherapy toxicities in stage III colorectal cancer patients.

Toxicities can affect cancer patients' quality of life resulting in poor adherence to adjuvant chemotherapy (AC). While previous studies have explored the prevalence of toxicities following AC, few have examined the associations of baseline characteristics, such as age, sex, and performance status, with toxicity outcomes. In this study, we reviewed a cohort of 371 colorectal cancer patients treated with adjuvant monotherapy (capecitabine ) or combination therapy (FOLFOX or CAPOX) within 12 weeks of curative resection, and determined the associations between baseline characteristics and toxicity outcomes. Median age was 65 years, 52% were men, and 41% received monotherapy. A number of toxicities appeared to decrease with successive AC cycles. For monotherapy, univariate analyses found that age, sex, performance status, and pre-treatment anemia were associated with hematological toxicities whereas tumor location was associated with gastrointestinal (GI) toxicities (all P < 0.05). On multivariate analyses, hematological toxicities were predicted by advanced age (≥ 70) (OR 3.30; 95% CI 1.17-9.37; P = 0.025) and pre-treatment anemia (OR 23.18; 95% CI 6.36-84.48; P < 0.001), while GI toxicities were less likely to occur among tumors at or distal to the splenic flexure (OR 0.38; 95% CI 0.15-0.99; P = 0.047). For combination therapy, sex and pre-treatment anemia were associated with hematological toxicities (all P < 0.05), but only female sex was predictive on multivariate analyses (OR 5.13; 95% CI 2.08-12.68; P < 0.001). In conclusion, few baseline characteristics were associated with treatment toxicities. These findings may better inform discussions with patients and caregivers during AC decision-making and underscore to clinicians the need for close monitoring of patients during treatment.

Phosphorylation of NEUROG3 Links Endocrine Differentiation to the Cell Cycle in Pancreatic Progenitors.

During pancreatic development, proliferating pancreatic progenitors activate the proendocrine transcription factor neurogenin 3 (NEUROG3), exit the cell cycle, and differentiate into islet cells. The mechanisms that direct robust NEUROG3 expression within a subset of progenitor cells control the size of the endocrine population. Here we demonstrate that NEUROG3 is phosphorylated within the nucleus on serine 183, which catalyzes its hyperphosphorylation and proteosomal degradation. During progression through the progenitor cell cycle, NEUROG3 phosphorylation is driven by the actions of cyclin-dependent kinases 2 and 4/6 at G1/S cell-cycle checkpoint. Using models of mouse and human pancreas development, we show that lengthening of the G1 phase of the pancreatic progenitor cell cycle is essential for proper induction of NEUROG3 and initiation of endocrine cell differentiation. In sum, these studies demonstrate that progenitor cell-cycle G1 lengthening, through its actions on stabilization of NEUROG3, is an essential variable in normal endocrine cell genesis.