Search

An increasing proportion of elderly patients (EP) are undergoing Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (CRS/HIPEC). They have increased comorbidities and perioperative risk. Current literature is deficient in describing the outcomes of EP undergoing CRS/HIPEC.A retrospective review of our prospectively maintained CRS/HIPEC database analyzed perioperative and oncological outcomes of EP (70 y) compared to younger patients (YP) (60 y).Of 500 CRS/HIPEC patients, 62 EP and 210 YP were included. Median age was 73 y in EP and 46 y in YP. Demographic, clinical, operative, and perioperative outcomes were similar between groups. American Society of Anesthesiologists 3 was more prevalent in the EP with 88.2% versus 54.8% in the YP (P 0.001). Comorbidities were higher in the EP with 87.1% versus 39.0% in the YP (P 0.001). Peritoneal Cancer Index score was similar with a median of 9. All postoperative and severe complications were similar with 55.2% and 17.1% in the YP and 64.5% and 21.0% in the EP (P = 0.242; P = 0.448). Postoperative mortality was similar with 1.5% in the YP and 5.0% in the EP (P = 0.134). In colorectal primary patients, median overall and disease-free survival was 61.8 and 12.9 mo in the YP and 64.6 and 11.3 mo in the EP (P = 0.363; P = 0.845).Despite a significant age difference, increased comorbidities, worse American Society of Anesthesiologists, and similar Peritoneal Cancer Index burden, we found no significant differences in perioperative complications or oncological benefit in elderly CRS/HIPEC patients. EP appear to have similar perioperative and oncological outcomes as YP.

Peritoneal Cancer Index (PCI) and complete cytoreduction are the best outcome predictors following cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC). Lesions in critical areas, regardless of PCI, complicate surgery and impact oncological outcomes. We prospectively defined "Critical lesions" (CL) as penetrating the hepatic hilum, diaphragm at hepatic outflow, major blood vessels, pancreas, or urinary tract.Retrospective analysis of a prospective database of 352 CRS + HIPEC patients from 2015 to 2019. Excluded patients with aborted/redo operation (n = 112), or incomplete data (n = 19). Patients categorized by CL status and compared: operative time, estimated blood loss (EBL), PCI, transfusions, hospital stay, post-operative complications and mortality, overall survival (OS) and disease-free survival (DFS).Included 221 patients (78 CL; 143 no-CL). No difference in patients' characteristics: age, BMI, gender or co-morbidities noted. Operative time longer (5.3 h vs 4.3 h, p 0.01), EBL higher (769 ml vs 405 ml, p 0.01), transfusions higher (1.9 vs 0.7 Units, p 0.001) and PCI higher (15.5 vs 9.5, p 0.01) in CL. No difference in major complications. Postoperative complications, CL, OR-time and transfusions were predictive of OS in univariate analysis, while only complications remained on multivariate analysis. Median follow up of 21.4 months, 3-year DFS/OS was 22% vs 30% (p 0.037) and 73% vs 87% (p 0.014) in CL and non-CL, respectively. Despite CL complete resection, 17/38 patients (44.7%) that recurred had recurrence at previous CL site.Critical lesions complicate surgery and may be associated with poor oncological outcomes with high local recurrence rate, despite no significant difference in complications. Utilizing adjuvant or intra-operative radiation may be beneficial.

Pathological response of colorectal peritoneal metastasis (CRPM) may affect prognosis. We investigated the relationship between oncological outcomes and pathological response to chemotherapy of CRPM following cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). We conducted a retrospective analysis of a prospectively maintained Peritoneal Surface Malignancies database between 2015 and 2020. Analysis included patients with CRPM who underwent a CRS/HIPEC procedure (n = 178). The cohort was divided into three groups according to the response ratio (ratio of tumor-positive specimens to the total number of specimens resected): Group A, complete response; Group B, high response ratio, and Group C, low response ratio. The group demographics were similar, but the overall complication rate was higher in Group C (65.2%) compared with Groups A (55%) and B (42.8%) [p = 0.03]. Survival correlated to response ratio; the estimated median disease-free survival of Group C was 9.1 months (5.97–12.23), 14.9 months (4.72–25.08) for Group B, and was not reached in Group A (p = 0.001). The estimated median overall survival in Group C was 35 months (26.69–43.31), and was not reached in Groups A and B (p = 0.001). The pathological response ratio to systemic therapy correlates with survival in patients undergoing CRS/HIPEC. This study supports the utilization of preoperative therapy for better patient selection, with a potential impact on survival.

Small-bowel obstruction (SBO) after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS/HIPEC) is a common complication associated with re-admission that may alter patients' outcomes. Our aim was to characterize and investigate the impact of bowel obstruction on patients' prognosis.This was a retrospective analysis of patients with SBO after CRS/HIPEC (n = 392). We analyzed patients' demographics, operative and perioperative details, SBO re-admission data, and long-term oncological outcomes.Out of 366 patients, 73 (19.9%) were re-admitted with SBO. The cause was adhesive in 42 (57.5%) and malignant (MBO) in 31 (42.5%). The median time to obstruction was 7.7 months (range, 0.5-60.9). Surgical intervention was required in 21/73 (28.7%) patients. Obstruction eventually resolved (spontaneous or by surgical intervention) in 56/73 (76.7%) patients. Univariant analysis identified intraperitoneal chemotherapy agents: mitomycin C (MMC) (HR 3.2, p = 0.003), cisplatin (HR 0.3, p = 0.03), and doxorubicin (HR 0.25, p = 0.018) to be associated with obstruction-free survival (OFS). Postoperative complications such as surgical site infection (SSI), (HR 2.2, p = 0.001) and collection (HR 2.07, p = 0.015) were associated with worse OFS. Multivariate analysis maintained MMC (HR 2.9, p = 0.006), SSI (HR 1.19, p = 0.001), and intra-abdominal collection (HR 2.19, p = 0.009) as independently associated with OFS. While disease-free survival was similar between the groups, overall survival (OS) was better in the non-obstruction group compared with the obstruction group (p = 0.03).SBO after CRS/HIPEC is common and complex in management. Although conservative management was successful in most patients, surgery was required more frequently in patients with MBO. Patients with SBO demonstrate decreased survival.

The incidence of colorectal cancer (CRC) among young adults has been dramatically rising, with guidelines for screening recently adjusted to start at age 45. However, knowledge of the precursor lesions is limited. We recently reported that 83% of CRC diagnosed under age 50 are left sided. Our aim was to analyze the location and histology of benign colorectal lesions found in a cohort of patients younger than 50, documenting the presence of advanced histology. We used the database in the Department of Pathology to retrospectively review the location and histology of all benign colorectal neoplasms in patients under age 50 submitted to pathology examination during 2006–2016. A total of 8364 lesions were examined from 4773 patients, and 3534 (65.5%) of the patients had only one polyp and the rest had multiple. Mean age was 41.9 years (range 16–49) while 3843 (72.8%) of the patients were between the ages of 40 and 49. In total, 4570/8364 lesions (54.6%) were distal to the splenic flexure. The most common pathology was tubular adenoma (63.7%), then hyperplastic polyps (16.6%), sessile serrated lesions (SSLs) (13.1%), and tubulovillous adenomas (6.3%). Tubulovillous adenomas, villous lesions, advanced adenomas, and adenomas with high-grade dysplasia were all predominantly left sided (left colon and rectum = 77.6%, 85%, 78.3%, and 87.6% respectively). Of the SSLs, 71.5% were in the right colon while 16.6% of hyperplastic lesions were right sided. High-risk advanced adenomas are predominantly left sided. This focuses attention on the rectum and left colon where carcinogenesis is strong in the young.

Although elective laparoscopic cholecystectomy is the accepted strategy after endoscopic retrograde cholangiopancreatography (ERCP), papillotomy, and common bile duct (CBD) clearance, the decision to perform a cholecystectomy in high-risk elderly comorbid patients remains subjective and is controversial. The aim of this study was to examine the outcome of elderly patients with cholecystectomy deferral after successful initial endoscopic removal of CBD stones. The study examined a retrospective patient database, which included all patients aged >60 years who underwent an ERCP for CBD stones at the Chaim Sheba Medical Center. The study cohort was divided according to whether a subsequent cholecystectomy was performed and also by age 60 to 80 or >80 years. All biliary-related complications were recorded. The primary outcome measures were biliary complications, perioperative and periprocedural mortality, CBD stone recurrence, and the need for future surgical intervention. There were 111 patients (mean age 79.4 ± 9.1 years) who underwent ERCP with follow-up. After excluding 11 patients, 100 patients were left for analysis, 46 of whom underwent a cholecystectomy and 54 were observed without operation. There were significant longer term biliary complications in five of the operated patients (10.9%) and in four of the unoperated cases (7.4%). All biliary-related complications were managed successfully by conservative means except for one fatality in the nonoperated group. Biliary-related complications after successful ERCP for CBD stones were unaffected by surgery but were more commonly observed in older cases. A watch and wait policy may be justified in elderly comorbid patients.

Metastatic spread of malignant melanoma to the abdomen presents a therapeutic challenge. Targeted and Immune-therapies dramatically improve patients' survival, yet some patients may still benefit from surgical intervention. This study investigates the outcomes of surgical treatment of abdominal metastatic melanoma in the era of modern therapy.This is a retrospective study of all patients who underwent surgical resection for abdominal metastatic melanoma between the years 2009-2021 (n = 80). We examined the clinical, operative, perioperative, and oncological outcomes of these patients.The cohort included a therapeutic group (T, n = 43) and palliative group (P, n = 37). The rate of overall post-operative complications was lower in the T group (n = 3, 9.3%) compared to the P group (n = 10, 27.1%) (p = 0.04), but no difference in major complications rate (p = 0.41). The median follow-up was 13.4 months (range, 0.5-107), with an estimated 2- and 5-years survival of 66.5% and 45.3% respectively. The estimated 2- and 5-years survival of the T group was 76.61% and 69.65%, and 49.01% and 28.01% in the P group (p = 0.005). Univariate analysis identified Therapeutic resection (HR 3.2, p = 0.008), isolated lesions (HR 1.47, p = 0.033) and major complication score (HR 1.8, p=0.001) to be correlated with survival. On multivariate analysis, Therapeutic resection (HR 2.53, p = 0.042) and major complication score (HR 1.62, p = 0.004) remained significant independent factors correlated with survival. In patients who progressed on treatment, and their progression was treated with surgical resection 46.1% where able to be maintained on the same preoperative treatment strategy.We have demonstrated that abdominal metastesectomy is a safe and oncologically efficacious therapy in selected patients. Especially in the era of modern therapeutics, patients with isolated disease site, limited resectable progression on therapy, or patients with symptomatic metastases should be considered for surgical resection.

Bariatric surgery (BS) is effective in treating obesity and its associated comorbidities. However, there is a paucity of data on the effect of BS on thyroid function in hypothyroid patients, specifically in those treated with thyroid hormone replacement therapy (THR). The aim of this study was to assess the effect of BS on thyroid function and on THR dosage in patients with hypothyroidism. A retrospective analysis of prospectively collected data of all hypothyroid patients who underwent BS between 2010 and 2014 was performed. Data collected included demographic and anthropometric measurements, as well as changes in thyroid hormone levels and THR dosage up to a year from surgery. During the study period, 93 hypothyroid patients (85 females, 91%), 83 of which treated with replacement thyroid hormone, underwent BS. Laparoscopic sleeve gastrectomy was performed in 77 (82.8%) and Roux-en-Y gastric bypass in 16 patients. Average age and body mass index (BMI) were 46.6 ± 11.2 years and 43.7 ± 6.4 kg/m2, respectively. Mean BMI and thyroid-stimulating hormone (TSH) significantly deceased after 6 and 12 months following surgery whereas mean free T4 levels remained stable. TSH decrease was directly correlated to baseline TSH but not to BMI reduction. One year after surgery, 11 patients (13.2%) did not require THR, while the rest required a significantly lower average dose (P

Schizophrenia is a common neuropsychiatric disorder that has a strong genetic component. MicroRNAs (miRNAs) have been implicated in neurodevelopmental and psychiatric disorders including schizophrenia, as indicated by their dysregulation in post-mortem brain tissues and in peripheral blood of schizophrenia patients. The olfactory epithelium (OE) is one of the few accessible neural tissues that contain neurons and their stem cells. Previous studies showed that OE-derived tissues and cells can be safely and easily collected from live human subjects and may provide a "window" into neuronal processes involved in disorders such as schizophrenia, while avoiding the limitations of using postmortem brain samples or non-neuronal tissues. In this study, we found that the brain-enriched miR-382 (miR-382-5p) expression was elevated in in vitro cultured olfactory cells, in a cohort of seven schizophrenia patients compared with seven non-schizophrenic controls. MiR-382 elevation was further confirmed in laser-capture microdissected OE neuronal tissue (LCM-OE), enriched for mature olfactory neurons, in a cohort of 18 schizophrenia patients and 18 non-schizophrenic controls. In sharp contrast, miR-382 expression could not be detected in lymphoblastoid cell lines generated from schizophrenic or non-schizophrenic individuals. We further found that miR-382 directly regulates the expression of two genes, FGFR1 and SPRY4, which are downregulated in both the cultured olfactory cells and LCM-OE derived from schizophrenia patients. These genes are involved in the fibroblast growth factor (FGF) signaling pathway, while impairment of this pathway may underlie abnormal brain development and function associated with schizophrenia. Our data suggest that miR-382 elevation detected in patients' OE-derived samples might serve to strengthen current biomarker studies in schizophrenia. This study also illustrates the potential utility of OE-derived tissues and cells as surrogate samples for the brain.

Adenosine-to-inosine (A-to-I) editing modifies RNA transcripts from their genomic blueprint. A prerequisite for this process is a double-stranded RNA (dsRNA) structure. Such dsRNAs are formed as part of the microRNA (miRNA) maturation process, and it is therefore expected that miRNAs are affected by A-to-I editing. Editing of miRNAs has the potential to add another layer of complexity to gene regulation pathways, especially if editing occurs within the miRNA–mRNA recognition site. Thus, it is of interest to study the extent of this phenomenon. Current reports in the literature disagree on its extent; while some reports claim that it may be widespread, others deem the reported events as rare. Utilizing a next-generation sequencing (NGS) approach supplemented by an extensive bioinformatic analysis, we were able to systematically identify A-to-I editing events in mature miRNAs derived from human brain tissues. Our algorithm successfully identified many of the known editing sites in mature miRNAs and revealed 17 novel human sites, 12 of which are in the recognition sites of the miRNAs. We confirmed most of the editing events using in vitro ADAR overexpression assays. The editing efficiency of most sites identified is very low. Similar results are obtained for publicly available data sets of mouse brain-regions tissues. Thus, we find that A-to-I editing does alter several miRNAs, but it is not widespread.