Antiperistaltic Transverse Coloplasty: A Salvage Procedure in Extensive Bowel and Colorectal Resections to Avoid Intestinal Failure.

INTRODUCTION: After extensive small and colon resections, quality of life can be affected. We propose the antiperistaltic transverse coloplasty as a solution that allows for preservation of the transverse colon after both right and left colectomies while achieving a tension-free colorectal anastomosis slowing the transit and increasing the absorption time, resulting in better stool consistency and quality of life compared with an ileorectal anastomosis. METHODS: This technique was performed in a 41-year-old woman with Goblet cell adenocarcinoma of the appendix with peritoneal metastasis. The transverse colon is rotated anticlockwise over the axis of the middle colic vessels toward the left parietocolic flank and relocated to the usual position of the descending colon. RESULTS: After 1 year of follow-up, the patient led a normal life without parenteral nutrition with five bowel movements per day and a weight gain of 15%. CONCLUSIONS: The use of an antiperistaltic transverse coloplasty may be worthwhile to perform in cases of extensive bowel resections during cytoreductive surgery leading to short-bowel syndrome to avoid a permanent stoma or intestinal failure and improve patient outcomes.

Simultaneous Surgical Approach with Hyperthermic Intraperitoneal Chemotherapy (HIPEC) in Patients with Concurrent Peritoneal and Liver Metastases of Colon Cancer Origin.

Background: Simultaneous liver resection and peritoneal cytoreduction with hyperthermic intraperitoneal chemotherapy (HIPEC) remains controversial today. The aim of the study was to analyze the postoperative outcomes and survival of patients with advanced metastatic colon cancer (peritoneal and/or liver metastases). Methods: Retrospective observational study from a prospective maintained data base. Patients who underwent a simultaneous peritoneal cytoreduction and liver resection plus HIPEC were studied. Postoperative outcomes and overall and disease free survival were analyzed. Univariate and multivariate analyses were performed. Results: From January 2010 to October 2022, 22 patients operated with peritoneal and liver metastasis (LR+) were compared with 87 patients operated with peritoneal metastasis alone (LR-). LR+ group presented higher serious morbidity (36.4 vs. 14.9%; p: 0.034). Postoperative mortality did not reach statistical difference. Median overall and disease free survival was similar. Peritoneal carcinomatosis index was the only predictive factor of survival. Conclusions: Simultaneous peritoneal and liver resection is associated with increased postoperative morbidity and hospital stay, but with similar postoperative mortality and OS and disease free survival. These results reflect the evolution of these patients, considered inoperable until recently, and justify the trend to incorporate this surgical strategy within a multimodal therapeutic plan in highly selected patients.

Challenges in precision medicine in pancreatic cancer: A focus in cancer stem cells and microbiota.

Pancreatic cancer adenocarcinoma (PDAC) is a lethal disease, with the lowest 5-years survival rate of all cancers due to late diagnosis. Despite the advance and success of precision oncology in gastrointestinal cancers, the frequency of molecular-informed therapy decisions in PDAC is currently neglectable. The reasons for this dismal situation are mainly the absence of effective early diagnostic biomarkers and therapy resistance. PDAC cancer stem cells (PDAC-SC), which are regarded as essential for tumor initiation, relapse and drug resistance, are highly dependent on their niche i.e. microanatomical structures of the tumor microenvironment. There is an altered microbiome in PDAC patients embedded within the highly desmoplastic tumor microenvironment, which is known to determine therapeutic responses and affecting survival in PDAC patients. We consider that understanding the communication network that exists between the microbiome and the PDAC-SC niche by co-culture of patient-derived organoids (PDOs) with TME microbiota would recapitulate the complexity of PDAC paving the way towards a precision oncology treatment-response prediction.

Cephalic pancreaticoduodenectomy for ductal adenocarcinoma in the elderly. Can we do it safely?

INTRODUCTION: Surgery and chemotherapy have increased the survival of pancreatic cancer. The decrease in postoperative morbidity and mortality and increase in life expectancy, has expanded the indications por cephalic pancreaticoduodenectomy (PDC), although it remains controversial in the geriatric population. METHODS: Retrospective study on a prospective database of patients with ductal adenocarcinoma of pancreas who underwent PDC between 2007-2018. The main objective was to analyse the morbidity-mortality and survival associated with PDC in patients ≥75 years (elderly). RESULTS: 79 patients were included, 21 of them older than 75 years (27%); within this group, 23'9% were over 80 years old. The ASA of both groups was similar. Patients ≥75 years required more transfusions. No differences in operating time were observed, although more vascular resection were performed in the elderly (26 vs. 8.7%; P = .037). Morbidity was higher in the elderly (61.9% vs. 46.6%), although without differences. Patients aged ≥75 years had more non-surgical complications (33.3%, P = .050), being pneumonia the most frequent. Postoperative mortality was higher in the ≥75 years (9 vs. 0%; P = .017). The overall survival and disease-free survival did not show significant differences in both groups. CONCLUSIONS: Elderly patients had higher postoperative mortality and more non-surgical complications. Survival did not show differences, so with an adequate selection of patients, age should not be considered itself as a contraindication for PDC.

Abdominal metastatic melanoma invading the transverse colon and stomach.

Gastrointestinal melanoma metastases are not uncommon, with the jejunum and ileum being the most common locations (58 %), followed by the stomach (26 %), colon (22 %), duodenum (12 %), and rectum (5 %).

Laparoscopy technique in the setting of peritoneal metastases to avoid port site relapse.

BACKGROUND: Laparoscopy is indicated in many patients with abdominal and pelvic malignancy. If cancer cells are present within the peritoneal space, there is a possibility for port site metastases to develop. METHODS: The pathophysiology for occurrence of port site metastases was reviewed. Technical modifications to reduce the incidence of these abdominal wall sites for disease progression were suggested. RESULTS: Evacuation of all gases and all fluid from the peritoneal space through the trocars prior to their removal will reduce the contamination of the tissue surrounding the port site by intraperitoneal cancer cells. If port sites are confined to the midline, they can be removed as part of a midline abdominal incision if metastases occur. If port site metastases occur through lateral port sites, the rectus abdominus muscle may need to be widely excised to achieve negative margins. CONCLUSION: Technical modifications of laparoscopy in patients with peritoneal metastases may reduce incidence of this iatrogenic dissemination of cancer.

Cephalic pancreaticoduodenectomy for ductal adenocarcinoma in the elderly. Can we do it safely? / Duodenopancreatectomía por adenocarcinoma ductal de páncreas en ancianos. ¿Podemos asumirla con seguridad?

INTRODUCTION: Surgery and chemotherapy have increased the survival of pancreatic cancer. The decrease in postoperative morbidity and mortality and increase in life expectancy, has expanded the indications por cephalic pancreaticoduodenectomy (PDC), although it remains controversial in the geriatric population. METHODS: Retrospective study on a prospective database of patients with ductal adenocarcinoma of pancreas who underwent PDC between 2007-2018.The main objective was to analyse the morbidity-mortality and survival associated with PDC in patients≥75 years (elderly). RESULTS: 79 patients were included, 21 of them older than 75 years (27%); within this group, 23.9% were over 80 years old. The ASA of both groups was similar. Patients≥75 years required more transfusions. No differences in operating time were observed, although more vascular resection were performed in the elderly (26 vs. 8.7%; P=.037). Morbidity was higher in the elderly (61.9 vs. 46.6%), although without differences. Patients aged≥75 years had more non-surgical complications (33.3%, P=.050), being pneumonia the most frequent. Postoperative mortality was higher in the≥75 years (9 vs. 0%; P=.017). The overall survival and disease-free survival did not show significant differences in both groups. CONCLUSIONS: Elderly patients had higher postoperative mortality and more non-surgical complications. Survival did not show differences, so with an adequate selection of patients, age should not be considered itself as a contraindication for PDC.

Diaphragmatic Peritonectomy and Full-Thickness Resection in CRS/HIPEC May Allow Higher Completeness of Cytoreduction Rates with a Low Rate of Respiratory Complications.

BACKGROUND: Cytoreductive surgery (CRS) provides a survival benefit when achieved without residual disease. As diaphragm is frequently affected in peritoneal malignancies, complete cytoreduction often requires surgical techniques over the diaphragm. The purpose of the study was to assess diaphragmatic resection impact on cytoreduction completeness, morbidity and mortality compared to less aggressive diaphragmatic peritonectomy in CRS and hyperthermic intraperitoneal chemotherapy (HIPEC) settings. MATERIALS AND METHODS: Patients with peritoneal carcinomatosis and supramesocolic disease undergoing CRS/HIPEC from 2011 to 2019 were included in a prospectively collected database. We compared patients who underwent full-thickness diaphragmatic resection (DR) and diaphragmatic peritonectomy (DP). Epidemiological and clinical data, morbidity, and mortality within 90 days of surgery were documented. RESULTS: 232 patients were initially selected. Inclusion criteria were met by 88 procedures. DR was performed on 32 patients and DP on 56. Number of resected organs was 5.21 in the DR cohort vs. 3.57 in the DP cohort (p<0.0001). Rate of Peritoneal Cancer Index (PCI) score >14 was higher in the DR group (75%) than in the DP group (50.9%) (p=0.027). Tumor invasion of diaphragmatic muscle after DR was confirmed in 89.3% patients. Postoperative pleural effusion was observed in 28 patients (50%) in the DP group and in 17 (53.1%) in the DR group. CONCLUSIONS: CRS/HIPEC requires specific surgical techniques over the diaphragm to achieve complete cytoreduction. As diaphragmatic muscle invasion is frequent, full-thickness resection may allow a cytoreduction completeness increase without an increased morbidity. Pleural drains are not systematically required as these procedures show low incidence of major respiratory complications.

Project IDentif.AI: Harnessing Artificial Intelligence to Rapidly Optimize Combination Therapy Development for Infectious Disease Intervention.

In 2019/2020, the emergence of coronavirus disease 2019 (COVID-19) resulted in rapid increases in infection rates as well as patient mortality. Treatment options addressing COVID-19 included drug repurposing, investigational therapies such as remdesivir, and vaccine development. Combination therapy based on drug repurposing is among the most widely pursued of these efforts. Multi-drug regimens are traditionally designed by selecting drugs based on their mechanism of action. This is followed by dose-finding to achieve drug synergy. This approach is widely-used for drug development and repurposing. Realizing synergistic combinations, however, is a substantially different outcome compared to globally optimizing combination therapy, which realizes the best possible treatment outcome by a set of candidate therapies and doses toward a disease indication. To address this challenge, the results of Project IDentif.AI (Identifying Infectious Disease Combination Therapy with Artificial Intelligence) are reported. An AI-based platform is used to interrogate a massive 12 drug/dose parameter space, rapidly identifying actionable combination therapies that optimally inhibit A549 lung cell infection by vesicular stomatitis virus within three days of project start. Importantly, a sevenfold difference in efficacy is observed between the top-ranked combination being optimally and sub-optimally dosed, demonstrating the critical importance of ideal drug and dose identification. This platform is disease indication and disease mechanism-agnostic, and potentially applicable to the systematic N-of-1 and population-wide design of highly efficacious and tolerable clinical regimens. This work also discusses key factors ranging from healthcare economics to global health policy that may serve to drive the broader deployment of this platform to address COVID-19 and future pandemics.

Prophylactic HIPEC with oxaliplatin might be of benefit in T4 and perforated colon cancer: another possible interpretation of the COLOPEC results.

The COLOPEC trial failed to show evidence for improved relapse-free survival (RFS) between the two study groups: 80,9% (95% CI 73.3-88.5) in the experimental group and 76.2 % (68.0-84.4) in the control group (one-sided log-rank p = 0.28). Nevertheless only 87 patients received the adjuvant HIPEC treatment in the experimental arm (n = 100). This group had a peritoneal relapse of 19 %, but only 10 % had a truly peritoneal relapse as 9 of them had stablished peritoneal carcinomatosis and 1 case was a peritoneal recurrence but did not receive adjuvant HIPEC. We conducted a per-protocol analysis comparing the 87 patients which truly received the adjuvant HIPEC to the 102 patients in the control arm and obtained an OR 0.396 (95 % CI 0.17-0.91) with a (Pearson Chi-Square p = 0.026, two-tailed Fisher exact test p = 0.032). This contradicts the COLOPEC reported conclusions and shows that adjuvant HIPEC could have an important protective role against peritoneal recurrence.

Secondary surgical cytoreduction needs to be assessed taking into account surgical technique, completeness of cytoreduction, and extent of disease.

Recent evidence suggested that secondary surgical cytoreduction followed by chemotherapy does not result in longer overall survival in patients with platinum-sensitive recurrent ovarian cancer.This statement is based on a phase III multicenter, randomized clinical trial that lacks a description of the surgical protocol, the surgical technique, and the surgical variables. In a study that evaluates surgical cytoreduction, it is mandatory to assess the grade of cytoreductive surgery achieved (Sugarbaker PH, Langenbeck's Arch Surg 384:576-87, 1999), the extent of disease using PCI (Peritoneal Cancer Index), the technique itself, and the existence of a multidisciplinary approach with extensive upper abdominal procedures in experienced centers (Ren et al, BMC Cancer 15:1-12, 2015). There is evidence proving that the quality of cytoreduction (Al Rawahi et al, Cochrane Database Syst Rev 2013, 2013), the measurement of the amount of disease by PCI (Elzarkaa et al, J Gynecol Oncol 29, 2018), and a multidisciplinary approach with supramesocolic procedures (Ren et al, BMC Cancer 15:1-12, 2015) impact overall survival.This study fails to compare chemotherapy with secondary cytoreductive surgery since, due to the lack of variables, we can assess neither the performed surgery nor its criteria. This study should not be taken into account to recommend chemotherapy alone over a surgical approach in this group of patients.

Results of a survey on peri-operative nutritional support in pancreatic and biliary surgery in Spain.

INTRODUCTION: Introduction: a survey on peri-operative nutritional support in pancreatic and biliary surgery among Spanish hospitals in 2007 showed that few surgical groups followed the 2006 ESPEN guidelines. Ten years later we sent a questionnaire to check the current situation. Methods: a questionnaire with 21 items sent to 38 centers, related to fasting time before and after surgery, nutritional screening use and type, time and type of peri-operative nutritional support, and number of procedures. Results: thirty-four institutions responded. The median number of pancreatic resections (head/total) was 29.5 (95% CI: 23.0-35; range, 5-68) (total, 1002); of surgeries for biliary malignancies (non-pancreatic), 9.8 (95% CI: 7.3-12.4; range, 2-30); and of main biliary resections for benign conditions, 10.4 (95% CI: 7.6-13.3; range, 2-33). Before surgery, only 41.2% of the sites used nutritional support (< 50% used any nutritional screening procedure). The mean duration of preoperative fasting for solid foods was 9.3 h (range, 6-24 h); it was 6.6 h for liquids (range, 2-12). Following pancreatic surgery, 29.4% tried to use early oral feeding, but 88.2% of the surveyed teams used some nutritional support; 26.5% of respondents used TPN in 100% of cases. Different percentages of TPN and EN were used in the other centers. In malignant biliary surgery, 22.6% used TPN always, and EN in 19.3% of cases. Conclusions: TPN is the commonest nutrition approach after pancreatic head surgery. Only 29.4% of the units used early oral feeding, and 32.3% used EN; 22.6% used TPN regularly after surgery for malignant biliary tumours. The 2006 ESPEN guideline recommendations are not regularly followed 12 years after their publication in our country.

INTRODUCCIÓN: Introducción: realizamos una encuesta sobre soporte nutricional perioperatorio en cirugía pancreática y biliar en hospitales españoles en 2007, que mostró que pocos grupos quirúrgicos seguían las guías de ESPEN 2006. Diez años después enviamos un cuestionario para comprobar la situación actual. Métodos: treinta y ocho centros recibieron un cuestionario con 21 preguntas sobre tiempo de ayunas antes y después de la cirugía, cribado nutricional, duración y tipo de soporte nutricional perioperatorio, y número de procedimientos. Resultados: respondieron 34 grupos. La mediana de pancreatectomías (cabeza/total) fue de 29,5 (IC 95%: 23,0-35; rango, 5-68) (total, 1002), la de cirugías biliares malignas de 9,8 (IC 95%: 7,3-12,4; rango, 2-30) y la de resecciones biliares por patología benigna de 10,4 (IC 95%: 7,6-13,3; rango, 2-33). Solo el 41,2% de los grupos utilizaban soporte nutricional antes de la cirugía (< 50% habian efectuado un cribado nutricional). El tiempo medio de ayuno preoperatorio para sólidos fue de 9,3 h (rango, 6-24 h), y de 6,6 h para líquidos (rango, 2-12). Tras la pancreatectomía, el 29,4% habían intentado administrar una dieta oral precoz, pero el 88,2% de los grupos usaron algún tipo de soporte nutricional y el 26,5% usaron NP en el 100% de los casos. Los demás grupos usaron diferentes porcentajes de NP y NE en sus casos. En la cirugía biliar maligna, el 22,6% utilizaron NP siempre y NE en el 19,3% de los casos. Conclusiones: la NP es el soporte nutricional más utilizado tras la cirugía de cabeza pancreática. Solo el 29,4% de las unidades usan nutrición oral precoz y el 32,3% emplean la NE tras este tipo de cirugía. El 22,6% de las instituciones usan NP habitualmente tras la cirugía de tumores biliares malignos. Las guías ESPEN 2006 no se siguen de forma habitual en nuestro país tras más de 10 años desde su publicación.

Comparison of anatomical resection and non-anatomical resection in patients with hepatocellular carcinoma: propensity score matching method.

OBJECTIVE: To evaluate the prognosis of anatomical resection (AR) and non-anatomical resection (NAR) of hepatocellular carcinoma. METHOD: We carried-out a retrospective study on a prospective database between May 2002 and December 2016. A propensity score matching (PSM) was performed to compare the outcomes between the groups to avoid possible confusion biases, because of non-random assignment. RESULTS: We included 86 patients, divided into two groups: 39 in the AR group and 47 in the NAR group. After PSM, 17 were selected into each group. There were no differences in any of the demographic and tumor variables. Overall survival (OS) after PSM was 93.9 and 55.9% at 1 and 5 years, and overall disease-free survival (DFS) was 91 and 45.7%, respectively. There were no differences in OS and DFS between groups (p = 0.47 and p = 0.31). The regression analysis did not observe differences between the groups in OS (p = 0.47), nor in DFS (p = 0.31). No differences were observed between the groups in recurrences. NAR was tended to recurrence before and after PSM. The time of recurrence was similar between the groups. CONCLUSIONS: The resection method does not influence in the long-term outcomes nor the recurrence.

OBJETIVO: Evaluar el pronóstico de la resección anatómica (RA) y la resección no anatómica (RNA) de los pacientes sometidos a cirugía de carcinoma hepatocelular. MÉTODO: Estudio retrospectivo sobre una base de datos prospectiva entre mayo de 2002 y diciembre de 2016. Para evitar posibles sesgos de confusión, se realizó un estudio de emparejamiento por análisis de propensión (EAP). RESULTADOS: Se incluyeron 86 pacientes, divididos en dos grupos: 39 RA y 47 RNA. Tras el EAP, quedaron 17 en cada grupo. No hubo diferencias en las variables demográficas ni del tumor. La supervivencia global (SG) tras el EAP fue del 93.9 y el 55.9% al año y los 5 años, y la supervivencia libre de enfermedad (SLE) global fue del 91 y el 45.7%, respectivamente. No se observaron diferencias entre los grupos (p = 0.47 y p = 0.31). El análisis de regresión no halló relación de los grupos con la SG (p = 0.47) ni con la SLE (p = 0.31). Respecto a la recidiva, no hubo diferencias. La RNA presenta mayor tendencia a la recidiva. Tampoco se encontraron diferencias en cuanto al tiempo de aparición de la recidiva. CONCLUSIONES: El tipo de resección hepática en el tratamiento del hepatocarcinoma no influye en los resultados a largo plazo ni en la aparición de recidiva.

Sir2 suppresses transcription-mediated displacement of Mcm2-7 replicative helicases at the ribosomal DNA repeats.

Repetitive DNA sequences within eukaryotic heterochromatin are poorly transcribed and replicate late in S-phase. In Saccharomyces cerevisiae, the histone deacetylase Sir2 is required for both transcriptional silencing and late replication at the repetitive ribosomal DNA arrays (rDNA). Despite the widespread association between transcription and replication timing, it remains unclear how transcription might impinge on replication, or vice versa. Here we show that, when silencing of an RNA polymerase II (RNA Pol II)-transcribed non-coding RNA at the rDNA is disrupted by SIR2 deletion, RNA polymerase pushes and thereby relocalizes replicative Mcm2-7 helicases away from their loading sites to an adjacent region with low nucleosome occupancy, and this relocalization is associated with increased rDNA origin efficiency. Our results suggest a model in which two of the major defining features of heterochromatin, transcriptional silencing and late replication, are mechanistically linked through suppression of polymerase-mediated displacement of replication initiation complexes.