Gender Comparisons of Surgical Outcomes in Patients Undergoing One Anastomosis Gastric Bypass (OAGB): a Historical Cohort Study.

INTRODUCTION AND PURPOSE: Clinical trials in the field of bariatrics have frequently been gender imbalanced, with males representing only 20% of examinees. Long-term gender-oriented results in one anastomosis gastric bypass (OAGB), and specifically quality of life (QOL) parameters, have not been addressed sufficiently. A better understanding of gender's effect on OAGB outcomes can play an important role in selecting the appropriate bariatric surgery for patients. Our study was aimed at examining mid-term gender-associated outcome of OAGB, including the effect on QOL. MATERIALS AND METHODS: A retrospective cohort study of patients who underwent OAGB at surgical ward A, SUMC, Israel, between 2015 and 2020. Demographics, body mass index (BMI), and comorbidities were extracted from the national medical records system. Follow-up quality of life (QOL) and weight parameters were supplemented via telephone questionnaires, using the Bariatric Analysis and Reporting Outcome System (BAROS). RESULTS: A total of 152 patients were included; of these, 51 (33.6%) were males, with an average follow-up period of 4.1 (± 1.3) years post-surgery. Basic demographics showed no significant pre- or post-surgery differences between males and females, except for pre-op weight (which as expected was higher for males). Males had a higher overall BAROS score than females (3.8 ± 2.1 vs. 2.6 ± 2.1, p < 0.001). CONCLUSIONS: OAGB surgery results in better outcomes for male than for female patients as measured by the BAROS, despite a similar BMI reduction, and with no difference in complications. Gender-specific outcomes are one of the variables that one should be aware of in optimizing patient selection and pre-operative patient counseling.

Laser tissue soldering of the gastrointestinal tract: A systematic review LTS of the gastrointestinal tract.

Background: Laser Tissue Soldering (LTS) is a promising tissue bonding technique in which a solder is applied between the tissues and then irradiated by laser, causing it to solidify and form links with the tissue. Methods: A comprehensive systematic review summarizing the state of research of LTS in the gastrointestinal tract. Results: Most studies were conducted on large animal tissues, using liquid proteinaceous solder, and irradiated by a continuous wave laser at 808 nm. LTS can provide better sealing and burst pressure than conventional methods. The application of LTS on top of or in addition to sutures showed an impressive increase in burst pressures. LTS may decrease the inflammatory and foreign body reaction caused by sutures. Conclusions: LTS has strong potential to be applied in a clinical setting in leak prevention and in closure of gastrointestinal structures as an adjunct or additional anastomotic technology, decreasing leak rates, morbidity, and mortality.

[SURGICAL PALLIATION FOR PANCREATIC CANCER].

INTRODUCTION: Pancreatic cancer (PC) is the 11th most common malignancy worldwide, however, entailing a mortality in excess of 90% within 5 years from diagnosis, it is the 4th most fatal malignant disease. PC is commonly diagnosed at an advanced stage, in which curative resection is no longer possible. Even patients who present with potentially curable disease will have upward of 30% recurrence of their disease within the first year. Thus, palliative therapy has paramount importance in patient management. The purpose of palliative care in these patients is to relieve symptoms and improve quality of life. This article reviews the current state of invasive palliation techniques for advanced PC, which are commonly directed towards three main symptoms: gastric/duodenal obstruction, obstructive jaundice, and epigastric pain. We describe the pros and cons of the different techniques, along with current front-line technology advancements. Endoscopic stenting is highly efficient in patients with gastric/duodenal obstruction or obstructive jaundice, with a generally low complication rate, short hospitalization and sustained quality of life. Bypass surgery should be considered in patients with a long-anticipated life expectancy, following higher rates of long-term stent failure, or when endoscopic stent procedure is not possible or has failed. When treating abdominal pain, celiac plexus neurolysis is considered as the first-line treatment. Pancreatic cancer is a complex and commonly lethal disease strongly affecting patient quality of life. It is important to consider the specific patient's personal characteristics and disease status when planning their palliative care.

PO2 21% oxygenated hypothermic machine perfusion in kidney transplantation: Any clinical benefit?

BACKGROUND: In deceased donor kidney transplantation (KT), the use of hypothermic machine perfusion (HMP) has been acquiring the status of best practice in the pre-transplant management of kidney grafts. Two types of HMP are currently available, oxygenated HMP and non-oxygenated HMP. However, data on the real clinical impact of oxygenation on KT outcome are still heterogeneous. METHODS: Retrospective study on a cohort of 103 patients transplanted with a single kidney graft that was managed either with end-ischemic oxygenated (O2 group, Waves Machine, n = 51, 49.5%) or non-oxygenated HMP (no-O2 group, Life Port Kidney Transporter Machine, n = 52, 50.5%), during the period January 2016-December 2020. Oxygenation was performed at pO2 21%. RESULTS: The median cold ischemia time was 29 h:40 min [IQR 26 h:55 min-31 h:10 min] and the prevalence of grafts from extended criteria donors (ECD) was 46.7%, with a median kidney donor profile index (KDPI) of 72 [41-94]. The study groups were homogeneous in terms of recipient characteristics, ischemia times and donor characteristics. O2 and no-O2 groups showed comparable outcomes in terms of delayed graft function (O2 vs no-O2, 21.5% vs 25%, p = 0.58), vascular (0.2% vs 0.2%, p > 0.99) and urologic (13.7% vs 11.5%, p = 0.77) complications, and episodes of graft rejection (11.7% vs 7.7%, p = 0.52). At 1 year follow up, even creatinine serum levels were comparable between the groups (1.27 mg/dL [1.09 and 1.67] vs 1.4 mg/dL [1.9-1.78], p = 0.319), with similar post-transplant trend (p = 0.870). No significant benefit was either observed in ECD or KDPI > 60 subgroups, respectively. CONCLUSIONS: Oxygenation at pO2 21% during HMP seems not to significantly enhance the KT outcomes in terms of postoperative complications or graft function.

A Comparison of One- and Two-Stage Laparoscopic Sleeve Gastrectomy Following Failed Laparoscopic Adjustable Gastric Banding Using the BAROS Score.

INTRODUCTION: Revision of a failed band can be done by laparoscopic sleeve gastrectomy (LSG). It can be performed synchronously with band removal or during two separate procedures. AIM: Comparing single- and two-staged LSG following a failed LAGB in terms of short- and mid-term outcomes, with an emphasis on postoperative quality of life. METHODS: A retrospective cohort study comparing revisional LSG's safety and efficacy after failed LAGB removal. Data included patients' medical files, as telephone interviews. We compared demographics, weight loss, complications, long-term outcomes, and quality-of-life measures, including the Bariatric Analysis and Reporting Outcome System (BAROS). RESULTS: Ninety-three patients were enrolled, of which 68 (73.1%) underwent a single-stage revisional LSG. Of these, 40 were males (35.1%) with a mean age of 44.9 years (± 12.9). The two-staged group were older. The reasons for band removal differed between the groups: whereas in the two-stage surgery, the common causes were slippage (29.2%) or band intolerance (25%); in the single-stage group, it was weight gain (51%). There were no differences in short- and mid-term complications, weight loss, and quality of life. CONCLUSION: In selected cases, laparoscopic sleeve gastrectomy as a revision of failed gastric banding in one stage is as safe as a two-stage procedure in terms of short- and mid-term complications, weight loss, and quality of life. We believe that there is little benefit in performing elective surgery in two stages unless there are clinical indications. Exceptions for two-stage revision should include cases of band erosion and acute slippage with patient preference for band removal.

Laparoscopic Sleeve Gastrectomy Following Failed Laparoscopic Adjustable Gastric Banding-a Comparison Between One- and two-Stage Procedures, an Israeli National Database Study.

PURPOSE: The optimal revisional bariatric surgery procedure following a previous failed gastric band surgery is yet to be determined. The aim of our study was to compare single- and two-stage laparoscopic sleeve gastrectomy (LSG) following laparoscopic adjustable gastric banding (LAGB) in terms of short- and mid-term outcomes. MATERIALS AND METHODS: Patients who underwent LSG after a failed LAGB in Israel during 2014-2017 were included. Data were obtained from the Israeli National Bariatric Surgery Registry. Data analyzed included comorbidities, postoperative complications, and anthropometric outcomes. RESULTS: Of 595 patients included in the data analysis, 381 (64%) underwent one-stage and 214 (36%) had two-stage LSG. No differences were observed between the groups in complication rates (5.0 vs. 5.1%, p=0.93). Percent of total weight loss was lower following one-stage than two-stage procedure at both 6 months (19.3±9.3 vs. 21.5±8.1%; p=0.02) and 1 year postoperative (24.9±10.4 vs. 27.8±9.9%; p=0.02). No difference was observed in the percent excess weight loss (51 vs. 56%; p=0.34 and 66 vs. 72%; p=0.38, at 6 months and 12 months postoperative, respectively). In a regression analysis, percent excess weight loss was greater in the two-stage procedure (p=0.02), with no difference in the complication rates (p=0.98). CONCLUSION: Single-step LSG had a similar safety profile as two-stage LSG following a failed LAGB. Better weight loss was seen following two-stage LSG. Further prospective studies should investigate long-term follow-up after one- and two-stage procedure.

Hypothermic machine perfusion can safely prolong cold ischemia time in deceased donor kidney transplantation. A retrospective analysis on postoperative morbidity and graft function.

In deceased donor kidney transplantation (KT), a prolonged cold ischemia time (CIT) is a negative prognostic factor for KT outcome, and the efficacy of hypothermic machine perfusion (HMP) in prolonging CIT without any additional hazard is highly debated. We conducted a retrospective study on a cohort of 154 single graft deceased donor KTs, in which a delayed HMP, after a preliminary period of static cold storage (SCS), was used to prolong CIT for logistic reasons. Primary outcomes were postoperative complications as well as 1 year graft survival and function. 73 cases (47.4%) were managed with HMP and planned KT, while 81 (52.6%) with SCS and urgent KT. The median CIT in HMP group and SCS group was 29 hour:57 minutes [27-31 hour:45 minutes] and 11 hour:25 minutes [9-14 hour:30 minutes], respectively (P < .001). The period of SCS in the HMP group was significantly shorter than in the SCS group (10 vs. 11 hour:25 minutes, P = .02) as well as the prevalence of expanded criteria donors was significantly higher (43.8% vs. 18.5%, P < .01). After propensity score matching for these two baseline characteristics, the HMP and SCS groups showed comparable outcomes in terms of delayed graft function, vascular, and urologic complications, infections, and episodes of graft rejection. At 1 year follow-up, serum creatinine levels were comparable between the groups. Therefore, the use of HMP to prolong the CIT and convert KT into a planned procedure seemed to have an adequate safety profile, with outcomes comparable to KT managed as an urgent procedure and a CIT nearly three time shorter.

Predictive Value of Intraoperative Doppler Flowmetry for Delayed Graft Function in Kidney Transplantation: A Pilot Study.

BACKGROUND: The delayed graft function (DGF) in kidney transplantation (KT) is a risk factor for long-term poor graft survival. The pathogenesis is multifactorial but mainly related to an ischemia-reperfusion injury. However, the graft hemodynamics have been recently identified as a key aspect for early DGF risk assessment and potential therapeutic intervention. METHODS: A pilot study on 20 single kidney grafts from donor after brain death with intraoperative measurement of graft arterial flowmetry, 30 minutes after reperfusion. Exclusion criteria were grafts with multiple arteries or severe atherosclerosis of the recipient's external iliac artery. RESULTS: KT recipients with DGF (n = 4, 20%) were homogenous with controls (n = 16) in terms of cold ischemia time, donor age, recipients' hemodynamic parameters, renal artery, and recipients' external iliac artery diameters. Nonetheless, at transplant, the kidney grafts that developed DGF were characterized by a significantly higher renal artery resistive index (DGF vs no-DGF 0.96 ± 0.04 vs 0.77 ± 0.13, P = .02), as well as lower flow extraction rate (24.8% ± 11.8 vs 59.2% ± 21.1, P < .01). CONCLUSIONS: Intraoperative arterial graft flowmetry seems to be an effective tool to identify grafts at high risk of DGF.

Treatment of Peritoneal Surface Malignancies with Cytoreductive Surgery and Hyperthermic Intra-peritoneal Chemotherapy (HIPEC): Experience in Israel.

The treatment of peritoneal surface malignancies, either primary or secondary (peritoneal metastasis), has evolved over the past two decades. A nihilistic approach of incurable "carcinomatosis" is changing into treatment of peritoneal metastasis with curative intent. The aim of the present study is to review the current practice, past history, and future of peritoneal surface oncology in Israel. A systematic review of all patients treated in institutions performing cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies. Each center provided the following data: start year, number of total cases, number of cases performed in 2017, and the method used (open vs. closed technique). Between 1990 and 2018, there were 1462 patients treated by CRS/HIPEC in Israel by eight different surgical groups in six medical centers. Currently, there are seven surgical groups in six medical centers routinely performing CRS/HIPEC. The annual rate of CRS/HIPEC was 171 cases in 2017 with a range of (4-69 cases/center). This is the first step of establishing an Israeli Peritoneal Surface Oncology Group that will have joined database and perform clinical trials in this challenging field of surgical oncology.

Loss of PDPK1 abrogates resistance to gemcitabine in label-retaining pancreatic cancer cells.

BACKGROUND: Label-retaining cancer cells (LRCC) have been proposed as a model of slowly cycling cancer stem cells (CSC) which mediate resistance to chemotherapy, tumor recurrence, and metastasis. The molecular mechanisms of chemoresistance in LRCC remain to-date incompletely understood. This study aims to identify molecular targets in LRCC that can be exploited to overcome resistance to gemcitabine, a standard chemotherapy agent for the treatment of pancreas cancer. METHODS: LRCC were isolated following Cy5-dUTP staining by flow cytometry from pancreatic cancer cell lines. Gene expression profiles obtained from LRCC, non-LRCC (NLRCC), and bulk tumor cells were used to generate differentially regulated pathway networks. Loss of upregulated targets in LRCC on gemcitabine sensitivity was assessed via RNAi experiments and pharmacological inhibition. Expression patterns of PDPK1, one of the upregulated targets in LRCC, was studied in patients' tumor samples and correlated with pathological variables and clinical outcome. RESULTS: LRCC are significantly more resistant to gemcitabine than the bulk tumor cell population. Non-canonical EGF (epidermal growth factor)-mediated signal transduction emerged as the top upregulated network in LRCC compared to non-LRCC, and knock down of EGF signaling effectors PDPK1 (3-phosphoinositide dependent protein kinase-1), BMX (BMX non-receptor tyrosine kinase), and NTRK2 (neurotrophic receptor tyrosine kinase 2) or treatment with PDPK1 inhibitors increased growth inhibition and induction of apoptosis in response to gemcitabine. Knockdown of PDPK1 preferentially increased growth inhibition and reduced resistance to induction of apoptosis upon gemcitabine treatment in the LRCC vs non-LRCC population. These findings are accompanied by lower expression levels of PDPK1 in tumors compared to matched uninvolved pancreas in surgical resection specimens and a negative association of membranous localization on IHC with high nuclear grade (p < 0.01). CONCLUSION: Pancreatic cancer cell-derived LRCC are relatively resistant to gemcitabine and harbor a unique transcriptomic profile compared to bulk tumor cells. PDPK1, one of the members of an upregulated EGF-signaling network in LRCC, mediates resistance to gemcitabine, is found to be dysregulated in pancreas cancer specimens, and might be an attractive molecular target for combination therapy studies.

Technical Feasibility of Tissue Microarray (TMA) Analysis of Tumor-Associated Immune Response in Prostate Cancer.

Introduction: The androgen receptor (AR) regulates immune-related epithelial-to-mesenchymal transition (EMT), and prostate cancer (PCa) metastasis. Primary tumor-infiltrating lymphocytes (TILs) [CD3+, CD4+, and CD8+ TILs] are potential prognostic indicators in PCa, and variations may contribute to racial disparities in tumor biology and PCa outcomes. Aim: To assess the technical feasibility of tumor microarray (TMA)-based methods to perform multi-marker TIL profiling in primary resected PCa. Methods: Paraffin-embedded tissue cores of histopathologically-confirmed primary PCa (n = 40; 1 TMA tissue specimen loss) were arrayed in triplicate on TMAs. Expression profiles of AR, CD3+, CD4+, and CD8+ TILs in normal prostate, and the center and periphery of both the tumor-dominant nodule and highest Gleason grade were detected by IHC and associated with clinical and pathological data using standard statistical methodology. An independent pathologist, blinded to the clinical data, scored all samples (percent and intensity of positive cells). Results: TMAs were constructed from 21 (53.8%) Black and 18 (46.2%) White males with completely-resected, primarily pT2 stage PCa [pT2a (n = 3; 7.7%); pT2b (n = 2; 5.1%); pT2c (n = 27; 69.2%); pT3a (n = 5; 12.8%); mean pre-op PSA = 8.17 ng/ml]. The CD3, CD4, CD8, and CD8/CD3 cellular protein expression differed from normal in the periphery of the dominant nodule, the center of the highest Gleason grade, and the periphery of the highest Gleason grade (P < 0.05). Correlations between TIL expression in the center and periphery of the dominant nodule, with corresponding center and periphery of the highest Gleason grade, respectively, were robust, and the magnitude of these correlations differed markedly by race (P < 0.05). Conclusions: Multi-marker (AR, CD3, CD4, CD8) profiling with IHC analysis of TMAs consisting of primary, non-metastatic resected prostate cancer is technically feasible in this pilot study. Future studies will evaluate primary tumor immunoscore using semi-quantitative, IHC-based methodology to assess differences in the spectrum, quantity, and/or localization of TILs, and to gain insights into racial disparities in PCa tumor biology and clinical outcomes.

A novel serum based biomarker panel has complementary ability to preclude presence of early lung cancer for low dose CT (LDCT).

Low Dosage Computerized Tomography (LDCT) has been shown to improve early detection of lung cancer and mortality rates in high-risk individuals, which was, however, limited by specifically coverage for heavy smokers and high rates of false positivity. Here, we aim to investigate a novel biomarker for early detection of lung cancer, and further extend to concentrate high-risk subjects for increasing specificity and coverage of LDCT. We performed retrospective blinded evaluation of lung cancer and healthy controls in training and validation cohorts. Macrophage inhibitory cytokine 1 (MIC-1) alone and panel were assessed. Our data showed the sensitivity of MIC-1 was 72.2% and 67.1% for lung cancer diagnosis and early diagnosis respectively, at 96.6% specificity, which were significantly higher than Cyfra21-1, NSE CA125, CEA and SCC. At 90% specificity, the panel of MIC-1, Cyfra21-1, CA125 and CEA provided 89.5% sensitivity for early diagnosis of lung cancer, which could be used to concentrate the high-risk subjects for further LDCT screening. We conclude that MIC-1 have great capacity in early lung cancer diagnosis. The algorithmic panel of MIC-1, Cyfra21-1, CA125 and CEA could be used to refine the preselection criteria of high-risk subjects, and thus might facilitate the widespread implementation of LDCT screening.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in treatment of gastric cancer with peritoneal carcinomatosis.

Although gastric cancer with peritoneal carcinomatosis is associated with poor prognosis and is generally treated with palliative systemic therapy, recent studies have shown that cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) may prove to be an efficacious treatment option. In addition to reviewing the natural history of gastric cancer with peritoneal carcinomatosis, this mini-review examines literature on the efficacy of CRS and HIPEC as compared to chemotherapy and surgical options. Both randomized and non-randomized studies were summarized with the emphasis focused on overall survival. In summary, CRS and HIPEC are indeed a promising treatment option for gastric cancer with peritoneal carcinomatosis and large randomized clinical trials are warranted.

Prospective randomized controlled trial comparing standard analgesia with combined intra-operative cystic plate and port-site local anesthesia for post-operative pain management in elective laparoscopic cholecystectomy.

BACKGROUND: Various mechanisms, including somatic and visceral nociceptive stimulation, have been suggested as a cause for pain after laparoscopic cholecystectomy (LC). We therefore conducted a prospective randomized controlled trial (PRCT) to evaluate whether somatovisceral pain blockade reduces pain after LC. HYPOTHESIS: Analgesic efficacy of multimodal analgesia is superior to standard analgesia for patients undergoing elective LC for symptomatic cholelithiasis. Specifically, topical cystic plate and port-site injection with 0.25 % bupivacaine significantly reduces pain after LC. DESIGN: This study was designed as single-blinded PRCT. SETTING: This study was conducted in an academic medical center. PATIENTS AND METHODS: Between February and May 2010 we randomly assigned 63 patients with symptomatic cholelithiasis in a 1:1 ratio to non-opioid/opioid analgesic combinations (Control Group, n = 32) and non-opioid/opioid analgesic combinations plus topical 0.25 % bupivacaine onto the cystic plate and local 0.25 % bupivacaine port-site injection, post-LC (Study Group, n = 31). Primary endpoint was patient-reported pain 1, 4, 6, 12, 24 h and 1 week post-LC using the Visual Analog Scale (VAS 0-10). RESULTS: Study groups were comparable clinicopathologically. There were no adverse events. A statistically significant reduction in mean pain score was apparent in Study Group patients in comparison with Control Group (mean VAS 4.83 ± 2.33 vs. 6.80 ± 1.87; p < 0.001) at all early (1-6 h) post-operative time points following LC. CONCLUSION: This PRCT shows significantly improved pain control with somatovisceral pain blockade over non-opioid/opioid analgesic combinations following LC for symptomatic cholelithiasis. For centers not utilizing adjunctive local anesthetic for LC, this topical use of bupivacaine may improve patient comfort during recovery. This trial was registered on www.ClinicalTrials.gov NCT# 01972620.

Liver Label Retaining Cancer Cells Are Relatively Resistant to the Reported Anti-Cancer Stem Cell Drug Metformin.

BACKGROUND & AIMS: Recently, we reported that liver Label Retaining Cancer Cells (LRCC) can initiate tumors with only 10 cells and are relatively resistant to the targeted drug Sorafenib, a standard of practice in advanced hepatocellular carcinoma (HCC). LRCC are the only cancer stem cells (CSC) isolated alive according to a stem cell fundamental function, asymmetric cell division. Metformin has been reported to preferentially target many other types of CSC of different organs, including liver. It's important to know if LRCC, a novel class of CSC, are relatively resistant to metformin, unlike other types of CSC. As metformin inhibits the Sorafenib-Target-Protein (STP) PI3K, and LRCC are newly described CSC, we undertook this study to test the effects of Metformin on Sorafenib-treated HCC and HCC-derived-LRCC. METHODS: We tested various STP levels and phosphorylation status, associated genes' expression, proliferation, viability, toxicity, and apoptosis profiles, before and after treatment with Sorafenib with/without Metformin. RESULTS: Metformin enhances the effects of Sorafenib on HCC, and significantly decreased viability/proliferation of HCC cells. This insulin-independent effect was associated with inhibition of multiple STPs (PKC, ERK, JNK and AKT). However, Metformin increased the relative proportion of LRCCs. Comparing LRCC vs. non-LRCC, this effect was associated with improved toxicity and apoptosis profiles, down-regulation of cell death genes and up-regulation of cell proliferation and survival genes in LRCC. Concomitantly, Metformin up-regulated pluripotency, Wnt, Notch and SHH pathways genes in LRCC vs. non-LRCC. CONCLUSIONS: Metformin and Sorafenib have enhanced anti-cancer effects. However, in contradistinction to reports on other types of CSC, Metformin is less effective against HCC-derived-CSC LRCC. Our results suggest that combining Metformin with Sorafenib may be able to repress the bulk of tumor cells, but as with other anti-cancer drugs, may leave LRCC behind leading to cancer recurrence. Therefore, liver LRCC, unlike other types of CSC, are relatively resistant to the reported anti-cancer stem cell drug metformin. This is the first report that there is a type of CSC that is not relatively resistant to the CSC-targeting drug. Our findings suggest that a drug targeting LRCC may be critically needed to target CSC and prevent cancer recurrence. These may significantly contribute to the understanding of Metformin's anti-cancer effects and the development of novel drugs targeting the relatively resistant LRCC.

Point Mutations in Exon 1B of APC Reveal Gastric Adenocarcinoma and Proximal Polyposis of the Stomach as a Familial Adenomatous Polyposis Variant.

Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS) is an autosomal-dominant cancer-predisposition syndrome with a significant risk of gastric, but not colorectal, adenocarcinoma. We mapped the gene to 5q22 and found loss of the wild-type allele on 5q in fundic gland polyps from affected individuals. Whole-exome and -genome sequencing failed to find causal mutations but, through Sanger sequencing, we identified point mutations in APC promoter 1B that co-segregated with disease in all six families. The mutations reduced binding of the YY1 transcription factor and impaired activity of the APC promoter 1B in luciferase assays. Analysis of blood and saliva from carriers showed allelic imbalance of APC, suggesting that these mutations lead to decreased allele-specific expression in vivo. Similar mutations in APC promoter 1B occur in rare families with familial adenomatous polyposis (FAP). Promoter 1A is methylated in GAPPS and sporadic FGPs and in normal stomach, which suggests that 1B transcripts are more important than 1A in gastric mucosa. This might explain why all known GAPPS-affected families carry promoter 1B point mutations but only rare FAP-affected families carry similar mutations, the colonic cells usually being protected by the expression of the 1A isoform. Gastric polyposis and cancer have been previously described in some FAP-affected individuals with large deletions around promoter 1B. Our finding that GAPPS is caused by point mutations in the same promoter suggests that families with mutations affecting the promoter 1B are at risk of gastric adenocarcinoma, regardless of whether or not colorectal polyps are present.

Role of multi-modality therapy in peritoneal carcinomatosis and visceral metastasis: a case report and review of the literature.

INTRODUCTION: Treatment for advanced stage colorectal cancer with synchronous peritoneal carcinomatosis (PC) and hepatic metastasis (HM) has progressed significantly over the past 10 years. CASE REPORT: We present the case of a 39-year-old female patient with stage IV colorectal cancer with bilateral HM, pulmonary oligometastatic disease, and diffuse PC who underwent hyperthermic intraperitoneal chemotherapy (HIPEC) and complete cytoreductive surgery (CRS) for her intra-abdominal disease. The patient had an uneventful immediate post-operative recovery, and subsequently tolerated multiple cycles of adjuvant chemotherapy and percutaneous radiofrequency ablation of pulmonary lesions. At her 22-month follow-up assessment, the patient remains alive with disease. CONCLUSION: Current recommendations for surgical management of synchronous colorectal cancer PC and HM indicate that patients with less than three HMs, a low peritoneal cancer index (PCI), and good functional status will benefit most from CRS and HIPEC. Our patient had an elevated PCI of 12 as measured by computed tomography imaging, and five HMs (all less than 3 cm in size); however, given that her life expectancy on systemic chemotherapy was estimated to be approximately 12 months, we have observed carefully selected patients to benefit from an aggressive multi-modality approach. This case report demonstrates an all too common scenario for surgeons managing patients with advanced CRC, and highlights the importance of patient selection for surgical management as part of multidisciplinary cancer care in this patient population.