Oligo-metastatic neoPlasms from the gastro-intestinal tract: iDentIfiCaTIon of cliNical and molecular drivers: the PREDICTION study.

BACKGROUND: Metastatic disease in tumors originating from the gastrointestinal tract can exhibit varying degrees of tumor burden at presentation. Some patients follow a less aggressive disease course, characterized by a limited number of metastatic sites, referred to as "oligo-metastatic disease" (OMD). The precise biological characteristics that define the oligometastatic behavior remain uncertain. In this study, we present a protocol designed to prospectively identify OMD, with the aim of proposing novel therapeutic approaches and monitoring strategies. METHODS: The PREDICTION study is a monocentric, prospective, observational investigation. Enrolled patients will receive standard treatment, while translational activities will involve analysis of the tumor microenvironment and genomic profiling using immunohistochemistry and next-generation sequencing, respectively. The first primary objective (descriptive) is to determine the prevalence of biological characteristics in OMD derived from gastrointestinal tract neoplasms, including high genetic concordance between primary tumors and metastases, a significant infiltration of T lymphocytes, and the absence of clonal evolution favoring specific driver genes (KRAS and PIK3CA). The second co-primary objective (analytic) is to identify a prognostic score for true OMD, with a primary focus on metastatic colorectal cancer. The score will comprise genetic concordance (> 80%), high T-lymphocyte infiltration, and the absence of clonal evolution favoring driver genes. It is hypothesized that patients with true OMD (score 3+) will have a lower rate of progression/recurrence within one year (20%) compared to those with false OMD (80%). The endpoint of the co-primary objective is the rate of recurrence/progression at one year. Considering a reasonable probability (60%) of the three factors occurring simultaneously in true OMD (score 3+), using a significance level of α = 0.05 and a test power of 90%, the study requires a minimum enrollment of 32 patients. DISCUSSION: Few studies have explored the precise genetic and biological features of OMD thus far. In clinical settings, the diagnosis of OMD is typically made retrospectively, as some patients who undergo intensive treatment for oligometastases develop polymetastatic diseases within a year, while others do not experience disease progression (true OMD). In the coming years, the identification of true OMD will allow us to employ more personalized and comprehensive strategies in cancer treatment. TRIAL REGISTRATION: ClinicalTrials.gov ID NCT05806151.

Rectal Sparing Approach After Neoadjuvant Therapy in Patients with Rectal Cancer: The Preliminary Results of the ReSARCh Trial.

BACKGROUND: Rectum-preservation for locally advanced rectal cancer has been proposed as an alternative to total mesorectal excision (TME) in patients with major (mCR) or complete clinical response (cCR) after neoadjuvant therapy. The purpose of this study was to report on the short-term outcomes of ReSARCh (Rectal Sparing Approach after preoperative Radio- and/or Chemotherapy) trial, which is a prospective, multicenter, observational trial that investigated the role of transanal local excision (LE) and watch-and-wait (WW) as integrated approaches after neoadjuvant therapy for rectal cancer. METHODS: Patients with mid-low rectal cancer who achieved mCR or cCR after neoadjuvant therapy and were fit for major surgery were enrolled. Clinical response was evaluated at 8 and 12 weeks after completion of chemoradiotherapy. Treatment approach, incidence, and reasons for subsequent TME were recorded. RESULTS: From 2016 to 2019, 160 patients were enrolled; mCR or cCR at 12 weeks was achieved in 64 and 96 of patients, respectively. Overall, 98 patients were managed with LE and 62 with WW. In the LE group, Clavien-Dindo 3+ complications occurred in three patients. The rate of cCR increased from 8- to 12-week restaging. Thirty-three (94.3%) of 35 patients with cCR had ypT0-1 tumor. At a median 24 months follow-up, a tumor regrowth was found in 15 (24.2%) patients undergoing WW. CONCLUSIONS: LE for patients achieving cCR or mCR is safe. A 12-week interval from chemoradiotherapy completion to LE is correlated with an increased cCR rate. The risk of ypT > is reduced when LE is performed after cCR.

Colonic J-Pouch or Straight Colorectal Reconstruction After Low Anterior Resection For Rectal Cancer: Impact on Quality of Life and Bowel Function: A Multicenter Prospective Randomized Study.

BACKGROUND: Patient-reported outcomes associated with different bowel reconstruction techniques following anterior resection for rectal cancer are still a matter of debate. OBJECTIVE: This study aimed to assess quality of life and bowel function in patients who underwent colonic J-pouch or straight colorectal anastomosis reconstruction after low anterior resection. DESIGN: Bowel function and quality of life were assessed within a multicenter randomized trial. Questionnaires were administered before the surgery (baseline) and at 6, 12, and 24 months after surgery. SETTINGS: Patients were enrolled by 19 centers. The enrollment started in October 2009 and was stopped in February 2016. The study was registered at www.clinicaltrials.gov (Identifier: NCT01110798). PATIENTS: Patients who underwent low anterior resection for primary mid-low rectal cancer and who were randomly assigned in a 1:1 ratio to receive either stapled colonic J-pouch or straight colorectal anastomosis were selected. MAIN OUTCOME MEASURES: The primary outcomes measured were quality of life and bowel function. RESULTS: Of the 379 patients who were evaluable, 312 (82.3%) completed the baseline, 259 (68.3%) the 6-month, 242 (63.9%) the 12-month, and 199 (52.5%) the 24-month assessment. Bowel functioning and quality of life did not significantly differ between arms for almost all domains. The total bowel function score, the urgency, and the stool fractionation scores significantly worsened after surgery and remained impaired over time in both arms (p < 0.0032), whereas constipation improved after surgery but recovered to baseline levels from 1 year onward (p < 0.0036). All patients showed a significant and continuous improvement in emotional functioning (p < 0.0013) and future perspective (p < 0.0001) from baseline to the end of the study. LIMITATIONS: Limitations of the study include missing data, which increased over time; the possibility that some treatments have slightly changed since the study was conducted; and investigators not blind to treatment allocation. CONCLUSION: The findings of this study do not support the routine use of colonic J-pouch reconstruction in patients with rectal cancer who undergo a low anterior resection. See Video Abstract at http://links.lww.com/DCR/B328. BOLSA J COLÓNICA O RECONSTRUCCIÓN COLORRECTAL RECTA DESPUÉS DE RESECCIÓN ANTERIOR BAJA PARA CÁNCER RECTAL: IMPACTO EN LA CALIDAD DE VIDA Y LA FUNCIÓN INTESTINAL: UN ESTUDIO ALEATORIZADO PROSPECTIVO MULTICÉNTRICO: Los resultados informados por el paciente asociados con diferentes técnicas de reconstrucción intestinal después de la resección anterior para el cáncer de recto aún son tema de debate.Evaluar la calidad de vida y la función intestinal en pacientes que se sometieron a una bolsa en J colónica o reconstrucción de anastomosis colorrectal recta después de una resección anterior baja.La función intestinal y la calidad de vida se evaluaron en un ensayo aleatorizado multicéntrico. Los cuestionarios se administraron antes de la cirugía (basal) y a los 6, 12 y 24 meses después de la cirugía.Los pacientes fueron incluidos en 19 centros. La inscripción comenzó en Octubre de 2009 y se detuvo en Febrero de 2016. El estudio se registró en www.clinicaltrials.gov (Identificador: NCT01110798).Pacientes que se sometieron a resección anterior baja por cáncer rectal primario medio-bajo y que fueron aleatorizados en una proporción de 1: 1 para recibir bolsa J colónica con grapas o anastomosis colorrectal recta.calidad de vida y función intestinal.De los 379 pacientes que fueron evaluables, 312 (82.3%) completaron la evaluación inicial, 259 (68.3%) a los 6 meses, 242 (63.9%) a los 12 meses y 199 (52.5%) a los 24 meses. . El funcionamiento intestinal y la calidad de vida no difirieron significativamente entre los dos grupos en casi todos los dominios. La puntuación total de la función intestinal, la urgencia y las puntuaciones de fraccionamiento de las heces empeoraron significativamente después de la cirugía y continuaron con el tiempo extra en ambos grupos (p <0.0032), mientras que el estreñimiento mejoró después de la cirugía pero se recuperó a los niveles basales a partir de 1 año en adelante (p <0.0036). Todos los pacientes mostraron una mejora significativa y continua en el funcionamiento emocional (p <0.0013) y la perspectiva futura (<0.0001) desde el inicio hasta el final del estudio.Datos faltantes, que aumentaron con el tiempo; la posibilidad de que algunos tratamientos hayan cambiado ligeramente desde que se realizó el estudio; investigadores no cegados a la asignación del tratamiento.Los hallazgos de este estudio no respaldan el uso rutinario de la reconstrucción de la bolsa J colónica en pacientes con cáncer rectal que se someten a una resección anterior baja. Consulte Video Resumen en http://links.lww.com/DCR/B328. (Traducción-Dr. Yesenia Rojas-Khalil).

Surgery has a key role for quality assurance of colorectal cancer screening programs: impact of the third level multidisciplinary team on lymph nodal staging.

PURPOSE: From 2011 to 2013 in the area of the Naples 3 public health district (ASL-NA3), a colorectal cancer screening program (CCSP) was developed. In order to stress the need of quality assurance procedures for surgery and pathology, a third level oncologic pathway was added and set up at a referral colorectal cancer center (RC). Lymph nodal (LN) harvesting, as a process indicator, and nodal positivity were adopted for an interim analysis. METHODS: The program was implemented by a series of audit meetings and a double type of multidisciplinary team (MDT): "horizontal" and "vertical." Three hundred and forty colorectal cancer (CRC) patients underwent surgery: 119 chose to be operated at the RC (Gr In), 65 were operated at 22 district hospitals (DH) (Gr Out), and 156 symptomatic not screened patients were operated at the RC (Gr Sym). RESULTS: Statistical analysis revealed differences between Gr In and Gr Out colon groups both for LN harvesting (median of 26 and 11, respectively, P = 0.0001), and for nodal positivity after the first screening round (34.78 and 19.45%, respectively, P = 0.0169). Results were all the more significant in a subset analysis on early T stage colon subgroups (In vs Out) both for LN harvesting (P < 0.0001) and nodal positivity (P < 0.0001). CONCLUSION: xSignificant differences between RC and DHs were found, particularly for early-stage CRC patients. LN harvesting should be considered as a surrogate marker of quality assurance for at least screening hospitals for "minimum best" standard of care. This should lead to set up a third level in any CCSP.

Short stump and high anastomosis pull-through (SHiP) procedure for delayed coloanal anastomosis with no protective stoma for low rectal cancer.

Despite advances in coloanal anastomosis techniques, satisfactory procedures completed without complications remain lacking. We investigated the effectiveness of our recently developed 'Short stump and High anastomosis Pull-through' (SHiP) procedure for delayed coloanal anastomosis without a stoma. In this retrospective study, we analysed functional outcomes, morbidity, and mortality rates and local recurrence of 37 patients treated using SHiP procedure, out of the 282 patients affected by rectal cancer treated in our institution between 2012 and 2020. The inclusion criterion was that the rectal cancer be located within 4 cm from the anal margin. One patient died of local and pulmonary recurrence after 6 years, one developed lung and liver metastases after 2 years, and one experienced local recurrence 2.5 years after surgery. No major leak, retraction, or ischaemia of the colonic stump occurred; the perioperative mortality rate was zero. Five patients (13.51%) had early complications. Stenosis of the anastomosis, which occurred in nine patients (24.3%), was the only long-term complication; only three (8.1%) were symptomatic and were treated with endoscopic dilation. The mean Wexner scores at 24 and 36 months were 8.3 and 8.1 points, respectively. At the 36-month check-up, six patients (24%) had major LARS, ten (40%) had minor LARS, and nine (36%) had no LARS. The functional results in terms of LARS were similar to those previously reported after immediate coloanal anastomosis with protective stoma. The SHiP procedure resulted in a drastic reduction in major complications, and none of the patients had a stoma.

Two-Stage Turnbull-Cutait Pull-Through Coloanal Anastomosis for Low Rectal Cancer: A Randomized Clinical Trial.

Importance: Two-stage Turnbull-Cutait pull-through hand-sewn coloanal anastomosis seems to provide benefits in terms of postoperative morbidity compared with standard hand-sewn coloanal anastomosis associated with diverting ileostomy and further ileostomy reversal in patients operated on for low rectal cancer. Objective: To compare 30-day postoperative and 1-year follow-up results of Turnbull-Cutait pull-through hand-sewn coloanal anastomosis and standard hand-sewn coloanal anastomosis after ultralow rectal resection for rectal cancer. Design, Setting, and Participants: Multicenter randomized clinical trial. Neither patients nor surgeons were blinded for technique. Patients were recruited in 3 centers, Bellvitge University Hospital and Valle d'Hebron University Hospital in Spain and Instituto Nazionale Tumori Fondazione G. Pascale-Istituto di Ricovero e Cura a Carattere Scientifico in Italy. Patients undergoing ultralow anterior rectal resection needing hand-sewn coloanal anastomosis were randomly assigned to 2-stage Turnbull-Cutait pull-through hand-sewn coloanal anastomosis or standard hand-sewn coloanal anastomosis associated with diverting ileostomy. Data were analyzed between June 2012 and October 2018. Interventions: All patients underwent ultralow anterior resection. Patients assigned to the 2-stage Turnbull-Cutait pull-through group underwent exteriorization of a segment of left colon through the anal canal and, after 6 to 10 days, the exteriorized colon was resected and a delayed hand-sewn coloanal anastomosis was performed. For patients assigned to standard coloanal anastomosis, the hand-sewn coloanal anastomosis was performed with diverting ileostomy at first operation. Closure of the ileostomy was planned after 6 to 8 months. Main Outcomes and Measures: Primary outcome was 30-day postoperative morbidity. For the standard hand-sewn coloanal anastomosis with diverting ileostomy group, overall postoperative morbidity includes 30-day postoperative complications of the ileostomy closure. Results: Ninety-two white patients, 72 men and 20 women, with a median age of 62 years, were randomized and included in the analysis. Forty-six patients received standard hand-sewn coloanal anastomosis with diverting ileostomy and 46 received the 2-stage pull-through hand-sewn coloanal anastomosis. Seven patients (15.2%) in the standard hand-sewn coloanal anastomosis group did not undergo reversal ileostomy, and 1 patient (2.2%) in the 2-stage pull-through hand-sewn coloanal anastomosis group did not undergo delayed coloanal anastomosis. The 30-day overall composite postoperative complications rate was similar between the 2 groups (34.8% in 2-stage pull-through hand-sewn coloanal anastomosis group vs 45.7% in standard hand-sewn coloanal anastomosis group; P = .40), with a difference of -10.9 (95% CI, -29.5 to 8.9). Conclusions and Relevance: The 2-stage pull-through hand-sewn coloanal anastomosis after ultralow anterior resection for low rectal cancer is safe and does not increase the postoperative morbidity rate compared with standard coloanal anastomosis with covering ileostomy followed by ileostomy closure. Trial Registration: ClinicalTrials.gov Identifier: NCT01766661.

"Scarless" and no-stoma surgery for low rectal cancer: the laparoscopic pull-through delayed "high" colo-anal anastomosis.

Despite recent improvements in surgical technique, low rectal anastomoses for rectal cancer still carry a not negligible incidence of anastomotic leakage and pelvic related morbidity. The Turnball-Cutait delayed colo-anal anastomosis, also referred as pull-through procedure was introduced with the aim to reduce the surgical anastomotic related complications and overcome the need of diverting ileostomy creation. Recently, this technique regained popularity as a viable option not only as salvage procedure after anastomotic failure or in case of hostile pelvis but also as first choice option in case of low rectal cancer. We report our experience with a personal technique for delayed "high" colo-anal anastomosis and its combination with a minimally invasive approach in order to reduce surgical morbidity, avoid the need for stoma creation and minimize the impact of surgery. Between 2011 and 2015, eight consecutive patients were operated for low rectal cancer by the described technique by a minimally invasive approach. The procedure was successfully completed in all cases. Post-operative major morbidity and 60 days mortality were nihil. There was no need for stoma creation or service laparotomy resulting in a virtually "scarless" surgery. Mean cumulative hospital stay (combining the two stages of the procedure) was 7, 6 days (range 7-9). The proposed technique by combining the advantage of a minimally invasive approach to those of a delayed "high" colo-anal anastomoses can be considered a viable option for the surgical treatment of low rectal cancer.

Gastric schwannoma misdiagnosed as GIST: A case report with immunohistochemical and molecular study.

Schwannomas are tumors derived from Schwann cells. Generally, they are benign and their typical site of origin is the subcutaneous tissue of the distal extremities or of the head and neck region. Gastrointestinal localization of schwannomas is extremely rare, and the stomach is the prevalent site. The present study describes the case of a gastric schwannoma in a 61-year-old male who underwent subtotal gastrectomy following a clinical diagnosis of a gastrointestinal stromal tumor (GIST). A histological, immunohistochemical and molecular study was performed to exclude the misdiagnosis of GIST. The histomorphological features of the lesion and absence of c-Kit and PDGFRA mutations indicated the diagnosis of gastric schwannoma.

Multidisciplinary approach and anesthetic management of a surgical cancer patient with methylene tetrahydrofolate reductase deficiency: a case report and review of the literature.

INTRODUCTION: Hyperhomocysteinemia is a known risk factor for myocardial infarction, stroke, peripheral vascular disease, and thrombosis. Elevated plasma homocysteine levels have been demonstrated in patients with recurrent episodes or a single episode of thrombosis. Here we describe the development of cardiovascular disease as a complication of a surgical intervention in a patient with colorectal cancer and hyperhomocysteinemia. CASE PRESENTATION: A 65-year-old Caucasian man complained of pain and constipation, attributed to previously diagnosed adenocarcinoma (stage IIB) of the hepatic flexure. An anamnestic investigation showed that he had undergone two surgical interventions. During both, he suffered thrombotic postoperative complications, a deep vein thrombosis of the upper extremity after the first operation and retinal vein occlusion after the second. He was diagnosed with hyperhomocysteinemia associated with a homozygous C677T mutation of the gene encoding the enzyme methylenetetrahydrofolate reductase. Our patient was initially treated with folic acid and high-dose B vitamins. On day 7 he underwent a right hemicolectomy. Anesthesia was performed with sevoflurane in 40% O2 and without the use of nitrous oxide. Postoperatively, our patient remained on folic acid and B vitamins and was without immediate or subsequent complications. CONCLUSIONS: Neoplastic disease and related surgery followed by the administration of chemotherapeutic drugs alter the hemostatic balance in cancer patients. Those suspected of also having a thrombophilic disease require a thorough laboratory diagnostic workup, including a molecular analysis aimed at identifying the genetic mutation responsible for the hyperhomocysteinemia, as indicated. The case described in this report highlights the importance of a multidisciplinary approach that includes expertise in peri-operative anesthesia, surgery, oncology, and hematology.

Vascular resection in pancreaticoduodenectomy: is it worthwhile?

Pancreaticoduodenectomy (PD) is the gold standard treatment for cancer of pancreatic head in all the cases that are supposed to be resectable. Although the overall survival depends on many heterogeneous factors, the main aim of the treatment must be to achieve a R0 resection with microscopically and macroscopically free margins. As in recent reports vascular involvement does not represent anymore a technical limit, it is mandatory pointing out whether or not vascular resection modifies overall survival and if that is the case vascular invasion should not be considered as an exclusion criterion but as part of a standard resection. The review analysis demonstrated a progressive trend of inversion in the treatment of head pancreatic cancer over the last years. Recently, provided that a R0 resection may be performed, a more aggressive surgical approach has led to consider the possibility of venous and arterial resections. The basis for this new approach has been that the superior mesenteric vein or spleno-portal mesenteric vein invasion is not a measure of the tumor malignancy but merely a consequence of the tumor location. On the contrary, the controversial results in terms of overall survival and local recurrences achieved with major arterial resections are more likely due to a biological aggressivity than to the tumor site. The "artery first" technique seems to be the most promising approach to the problem although it needs further trials to determine whether or not this approach may be beneficial for patients in terms of overall survival and local recurrences.