Immunohistochemistry staining for DNA mismatch repair proteins in endoscopic biopsies and the corresponding surgical specimen in colorectal cancer.

Microsatellite instability is found in 15% of sporadic colorectal cancers (CRC) and 95% of hereditary CRC cases. Lynch syndrome (LS) diagnosis begins with the analysis of the surgical specimen using methods such as immunohistochemistry (IHC), which identifies changes in the nuclear expression of DNA mismatch repair (MMR) proteins. However, IHC analysis on endoscopic biopsies could provide substantial benefits. Our goal was to assess the accuracy of MMR IHC status on endoscopic biopsies in comparison to corresponding surgical specimen in a series of CRC. We retrospectively selected patients who had undergone CRC surgery between February 2011 and January 2020 and had IHC testing for MMR proteins on the surgical specimen. The study was then performed on the corresponding endoscopic biopsies and results were compared. MMR IHC staining on surgical specimens were available for 361 CRC patients and only in 154 cases for preoperative endoscopic biopsies. The concordance between MMR IHC status of the endoscopic biopsy and the surgical specimen analysis was 98.6% for the MLH1/PMS2 proteins and 100% for MSH2/MSH6. In conclusion, endoscopic biopsies of colorectal tumors serve as a suitable tissue source for the immunohistochemical analysis of DNA repair proteins. The correlation with results from the surgical specimen was notably high and discrepancies were primarily as a result of intratumoral heterogeneity within the same sample. The features of MMR protein loss in endoscopic biopsies can provide clinicians with valuable information for specific therapeutic approaches and genetic counseling.

Quality Standards for Surgery of Colorectal Peritoneal Metastasis After Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

BACKGROUND: The standardization of surgical outcomes throughout surgical procedures is mandatory. Cytoreductive surgery with hyperthermic intraperitoneal chemotherapy (CRS + HIPEC) should provide proficient oncological and surgical outcomes. STUDY DESIGN: The aim of this study was to identify clinically relevant quality indicators and their quality standard, and to determine their acceptable quality limit. A systematic review on cytoreductive results from 2000 to 2018 was performed focusing on clinical guidelines, consensus conferences, and publications. After the selection of quality indicators, a systematic review of indexed references was performed in order to calculate the quality standard for each indicator. STUDY SELECTION: Unicentric/multicentric series, comparative studies, and clinical trials. Studies were to include outcomes after cytoreduction of colorectal origin and series with more than 50 patients. Quality indicators with at least 10 series were mandatory and objective measurements were also mandatory for inclusion. MAIN OUTCOME MEASUREMENTS: Quality indicators selected were 1- to 5-year survival, overall disease-free survival, 1- to 5-year disease-free survival, complete surgical resection, duration of surgery, length of stay, overall morbimortality, major morbidity, re-intervention, postoperative hemorrhage, intestinal fistula, anastomotic leakage, wound infection, postoperative medical complications, overall recurrence, and failure to rescue. RESULTS: The most relevant quality indicators and critical quality limits were overall disease-free survival and 5-year overall disease-free survival (14 months and <10 months, and 14% and <4%, respectively), completeness of surgical resection (89% and <80%, respectively), overall mortality (3% and >8%, respectively), overall morbidity (47% and >63%, respectively), failure to rescue (12% and <30%, respectively), reintervention (13 and <22%, respectively), anastomotic leakage (6% and <13%, respectively), and overall recurrence (60% and <74%, respectively). CONCLUSION: This is the first study to assess quality standards in CRS + HIPEC for colorectal peritoneal metastases. The current data are of particular relevance for future studies to control the variability of this surgery.

GECOP-MMC: phase IV randomized clinical trial to evaluate the efficacy of hyperthermic intraperitoneal chemotherapy (HIPEC) with mytomicin-C after complete surgical cytoreduction in patients with colon cancer peritoneal metastases.

BACKGROUND: The French PRODIGE 7 trial, published on January 2021, has raised doubts about the specific survival benefit provided by HIPEC with oxaliplatin 460 mg/m2 (30 minutes) for the treatment of peritoneal metastases from colorectal cancer. However, several methodological flaws have been identified in PRODIGE 7, specially the HIPEC protocol or the choice of overall survival as the main endpoint, so its results have not been assumed as definitive, emphasizing the need for further research on HIPEC. It seems that the HIPEC protocol with high-dose mytomicin-C (35 mg/m2) is the preferred regime to evaluate in future clinical studies. METHODS: GECOP-MMC is a prospective, open-label, randomized, multicenter phase IV clinical trial that aims to evaluate the effectiveness of HIPEC with high-dose mytomicin-C in preventing the development of peritoneal recurrence in patients with limited peritoneal metastasis from colon cancer (not rectal), after complete surgical cytoreduction. This study will be performed in 31 Spanish HIPEC centres, starting in March 2022. Additional international recruiting centres are under consideration. Two hundred sixteen patients with PCI ≤ 20, in which complete cytoreduction (CCS 0) has been obtained, will be randomized intraoperatively to arm 1 (with HIPEC) or arm 2 (without HIPEC). We will stratified randomization by surgical PCI (1-10; 11-15; 16-20). Patients in both arms will be treated with personalized systemic chemotherapy. Primary endpoint is peritoneal recurrence-free survival at 3 years. An ancillary study will evaluate the correlation between surgical and pathological PCI, comparing their respective prognostic values. DISCUSSION: HIPEC with high-dose mytomicin-C, in patients with limited (PCI ≤ 20) and completely resected (CCS 0) peritoneal metastases, is assumed to reduce the expected risk of peritoneal recurrence from 50 to 30% at 3 years. TRIAL REGISTRATION: EudraCT number: 2019-004679-37; Clinicaltrials.gov: NCT05250648 (registration date 02/22/2022, ).

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer with Peritoneal Carcinomatosis: Multicenter Study of Spanish Group of Peritoneal Oncologic Surgery (GECOP).

BACKGROUND: Gastric cancer (GC) with peritoneal carcinomatosis (PC) is traditionally considered a terminal stage of the disease. The use of a multimodal treatment, including cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), can benefit these patients. Our goal was to evaluate the morbidity and survival outcomes of these patients. METHODS: This is a retrospective, multicenter study from a prospective national database of patients diagnosed with PC secondary to GC treated with CRS and HIPEC from June 2006 to October 2017. RESULTS: Eighty-eight patients from seven specialized Spanish institutions were treated with CRS and HIPEC, with median age of 53 years; 51% were women. Median Peritoneal Cancer Index (PCI) was 6, and complete cytoreduction was achieved in 80 patients (90.9%). HIPEC was administered in 85 cases with 4 different regimens (Cisplatin + Doxorubicin, Mitomycin-C + Cisplatin, Mitomycin-C and Oxaliplatin). Twenty-seven cases (31%) had severe morbidity (grade III-IV) and 3 patients died in the postoperative period (3.4%). Median follow-up was 32 months. Median overall survival (OS) was 21.2 months, with 1-year OS of 79.9% and 3-year OS of 30.9%. Median disease-free survival (DFS) was 11.6 months, with 1-year DFS of 46.1% and 3-year DFS of 21.7%. After multivariate analysis, the extent of peritoneal disease (PCI ≥ 7) was identified as the only independent factor that influenced OS (hazard ratio [HR] 2.37, 95% confidence interval [CI] 1.26-4.46, p = 0.007). CONCLUSIONS: The multimodal treatment, including CRS and HIPEC, for GC with PC can improve the survival results in selected patients (PCI < 7) and in referral centers.

Outcomes of cytoreductive surgery with hyperthermic intraperitoneal chemotherapy for peritoneal mesothelioma and predictors of survival.

BACKGROUND: Cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) benefits selected patients with peritoneal mesothelioma. We present the outcomes of this treatment strategy in a UK peritoneal malignancy national referral centre. METHODS: Observational retrospective analysis of data prospectively collected in a dedicated peritoneal malignancy database between March 1998 and January 2016. RESULTS: Of 1586 patients treated for peritoneal malignancy, 76 (4.8%) underwent surgery for peritoneal mesothelioma. Median age was 49 years (range 21-73 years). 34 patients (45%) were female. Of the 76 patients, 39 (51%) had low grade histological subtypes (mostly multicystic mesothelioma), and 37 (49%) had diffuse malignant peritoneal mesothelioma (DMPM; mostly epithelioid mesothelioma). Complete cytoreduction was achieved in 52 patients (68%) and maximal tumour debulking (MTD) was performed in 20 patients (26%); the remaining 4 patients (5%) underwent a laparotomy with biopsy only. HIPEC was administered in 67 patients (88%). Median overall (OS) and disease-free survival (DFS) after CRS was 97.8 (80.2-115.4) and 58.8 (47.4-70.3) months, respectively. After complete cytoreduction, 100% overall survival was observed amongst patients with low-grade disease. Ki-67 proliferation index was significantly associated with survival outcomes after complete cytoreduction for DMPM and was an independent predictor of decreased survival. CONCLUSION: With adequate patient selection (guided by histological classification and Ki-67 proliferation index) and complete cytoreduction with HIPEC, satisfactory outcomes can be achieved in selected patients with peritoneal mesothelioma.

[Histological factors predicting loco-regional lymph node metastasis in early invasive colorectal adenocarcinoma pT1]. / Estudio de factores histológicos predictivos de metástasis ganglionar locorregional en adenocarcinoma colorrectal mínimamente invasivo pT1.

INTRODUCTION: Endoscopic resection is the common treatment in pT1 colorectal adenocarcinoma whenever possible. The presence of adverse histological factors requires subsequent lymph node evaluation. MATERIALS AND METHODS: We selected 29 colorectal pT1 adenocarcinoma including endoscopic polypectomies and the corresponding surgical specimens. All histologic parameters associated with N+ were evaluated by 2 pathologists, including: tumor differentiation grade, depth of invasion in the submucosa, angiolymphatic invasion (ALI), perineural invasion, chronic inflammation, tumor budding, poorly differentiated cluster, pre-existing adenoma, tumor border, and endoscopic resection margin. Univariate and multivariate logistic regression analysis were performed to assess the individual capacity of each variable to predict N+. RESULTS: In the univariate analysis, rectal tumor localization, ALI and poorly differentiated cluster was significantly associated with N+. Among the significant parameters, ALI had the highest area under the ROC curve (0.875). Multivariate analysis showed no independent variables associated with N+. CONCLUSIONS: We confirm that ALI and the presence of poorly differentiated cluster are frequently associated with N+ in early colorectal cancer. Consequently, these parameters should be routinely evaluated by pathologists.

A prospective multicentre study evaluating the outcomes of the abdominal wall dehiscence repair using posterior component separation with transversus abdominis muscle release reinforced by a retro-muscular mesh: filling a step.

BACKGROUND: This study aimed to evaluate the results of posterior component separation (CS) and transversus abdominis muscle release (TAR) with retro-muscular mesh reinforcement in patients with primary abdominal wall dehiscence (AWD). The secondary aims were to detect the incidence of postoperative surgical site occurrence and risk factors of incisional hernia (IH) development following AWD repair with posterior CS with TAR reinforced by retromuscular mesh. METHODS: Between June 2014 and April 2018, 202 patients with grade IA primary AWD (Björck's first classification) following midline laparotomies were treated using posterior CS with TAR release reinforced by a retro-muscular mesh in a prospective multicenter cohort study. RESULTS: The mean age was 42 ± 10 years, with female predominance (59.9%). The mean time from index surgery (midline laparotomy) to primary AWD was 7 ± 3 days. The mean vertical length of primary AWD was 16 ± 2 cm. The median time from primary AWD occurrence to posterior CS + TAR surgery was 3 ± 1 days. The mean operative time of posterior CS + TAR was 95 ± 12 min. No recurrent AWD occurred. Surgical site infections (SSI), seroma, hematoma, IH, and infected mesh occurred in 7.9%, 12.4%, 2%, 8.9%, and 3%, respectively. Mortality was reported in 2.5%. Old age, male gender, smoking, albumin level < 3.5 gm%, time from AWD to posterior CS + TAR surgery, SSI, ileus, and infected mesh were significantly higher in IH. IH rate was 0.5% and 8.9% at two and three years, respectively. In multivariate logistic regression analyses, the predictors of IH were time from AWD till posterior CS + TAR surgical intervention, ileus, SSI, and infected mesh. CONCLUSION: Posterior CS with TAR reinforced by retro-muscular mesh insertion resulted in no AWD recurrence, low IH rates, and low mortality of 2.5%. Trial registration Clinical trial: NCT05278117.

Efficacy and Safety of Intraoperative Hyperthermic Intraperitoneal Chemotherapy for Locally Advanced Colon Cancer: A Phase 3 Randomized Clinical Trial.

Importance: Peritoneal metastasis in patients with locally advanced colon cancer (T4 stage) is estimated to recur at a rate of approximately 25% at 3 years from surgical resection and is associated with poor prognosis. There is controversy regarding the clinical benefit of prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) in these patients. Objective: To assess the efficacy and safety of intraoperative HIPEC in patients with locally advanced colon cancer. Design, Setting, and Participants: This open-label, phase 3 randomized clinical trial was conducted in 17 Spanish centers from November 15, 2015, to March 9, 2021. Enrolled patients were aged 18 to 75 years with locally advanced primary colon cancer diagnosed preoperatively (cT4N02M0). Interventions: Patients were randomly assigned 1:1 to receive cytoreduction plus HIPEC with mitomycin C (30 mg/m2 over 60 minutes; investigational group) or cytoreduction alone (comparator group), both followed by systemic adjuvant chemotherapy. Randomization of the intention-to-treat population was done via a web-based system, with stratification by treatment center and sex. Main Outcomes and Measures: The primary outcome was 3-year locoregional control (LC) rate, defined as the proportion of patients without peritoneal disease recurrence analyzed by intention to treat. Secondary end points were disease-free survival, overall survival, morbidity, and rate of toxic effects. Results: A total of 184 patients were recruited and randomized (investigational group, n = 89; comparator group, n = 95). The mean (SD) age was 61.5 (9.2) years, and 111 (60.3%) were male. Median duration of follow-up was 36 months (IQR, 27-36 months). Demographic and clinical characteristics were similar between groups. The 3-year LC rate was higher in the investigational group (97.6%) than in the comparator group (87.6%) (log-rank P = .03; hazard ratio [HR], 0.21; 95% CI, 0.05-0.95). No differences were observed in disease-free survival (investigational, 81.2%; comparator, 78.0%; log-rank P = .22; HR, 0.71; 95% CI, 0.41-1.22) or overall survival (investigational, 91.7%; comparator, 92.9%; log-rank P = .68; HR, 0.79; 95% CI, 0.26-2.37). The definitive subgroup with pT4 disease showed a pronounced benefit in 3-year LC rate after investigational treatment (investigational: 98.3%; comparator: 82.1%; log-rank P = .003; HR, 0.09; 95% CI, 0.01-0.70). No differences in morbidity or toxic effects between groups were observed. Conclusions and Relevance: In this randomized clinical trial, the addition of HIPEC to complete surgical resection for locally advanced colon cancer improved the 3-year LC rate compared with surgery alone. This approach should be considered for patients with locally advanced colorectal cancer. Trial Registration: ClinicalTrials.gov Identifier: NCT02614534.

[Accreditation and dedication in coloproctology is associated with good perioperative care]. / La acreditación y dedicación en coloproctología se asocian a buenos cuidados perioperatorios.

UNLABELLED: Complex data analysis methods require optimisation techniques such as evolutionary algorithms in order to generate reliable results. The objective of this study is to analyse the relationships of particular perioperative care in colorectal surgery (CRS) with surgeon epidemiological data, performing partition grouping to look for significant relationships. METHODS: Data were used from a survey of members of Spanish coloproctology associations on perioperative care in colorectal surgery, and analysing the responses associated with mechanical bowel preparation (MBP), nasogastric intubation (NGI), drainages (D), and early feeding (EF), over the existing scientific evidence (SE) which shows that the first ones are unnecessary and the importance of the last one. We applied a variant of particle swarm optimization (PSO), to group data conglomerates, optimising variables with statistical grouping criteria. RESULTS: A total of 130 surveys were analysed, finding 2 clear groups which included 21.5% and 78.5% of the sample, respectively. Sixty eight per cent of the surgeons in Group A belonged to the European Board in Coloproctology, compared to none in Group B, and the former performed 80% of the coloproctology activity, compared to 60% of the rest. A responded homogeneously to questions on MBP, NGI, D and EF, those of group A following the SE, while the others did it randomly and without following it. Age, work position or academic range were not significant in the grouping. CONCLUSIONS: The evolutionary algorithm was shown to be able to identify groups according to the use of perioperative care in CRS. Accreditation and dedication was associated with behaviour based on the SE.

[Selective intestinal preparation in a multimodal rehabilitation program. Influence on preoperative comfort and the results after colorectal surgery]. / Preparación intestinal selectiva en un programa de rehabilitación multimodal. Influencia en el confort preoperatorio y resultados tras cirugía colorrectal.

INTRODUCTION: Despite there being no evidence of the advantages of its use, mechanical bowel preparation (MBP) continues to be routine in colorectal surgery. Our objective is to analyse the impact of its selective use, as regards patient comfort and results, comparing a perioperative multimodal rehabilitation program (MMRH) with conventional care (CC). MATERIAL AND METHODS: A prospective study of 108 patients proposed for elective surgery, assigned consecutively 2:1 to an MMRH protocol which only included MBP in rectal surgery with low anastomosis, or to CC in whom MBP was used except in right colon surgery. We also studied two Groups (A and B) with and without the use of MBP. Their tolerance, results and postoperative recovery variables were analysed. RESULTS: Thirty-nine patients were included in Group A, and 69 in Group B. A MMRH protocol was used in another 69 patients. The Group A patients had more abdominal pain, anal discomfort, nausea and thirst, but there were no differences as regards, death, overall or local complications, whilst there was less complications, suture failures and death in the MMRH when compared with CC Group (P<.05). There were no advantages observed in the use of MBP as regards the start of bowel movements, tolerance to diet or hospital stay, but these parameters were favourable to the MMRH when compared with CC Group. CONCLUSIONS: The restriction of MBP is safe, and associated with an MMRH program, contributes to a faster and more comfortable recovery, without increasing complications.

Clinical presentation, diagnosis, classification and management of peritoneal mesothelioma: a review.

Peritoneal mesothelioma (PM) is an uncommon but a serious, and often, fatal primary peritoneal tumour, with increasing incidence worldwide. Conventional systemic chemotherapy, generally based on experience with pleural mesothelioma, usually has disappointing results considering PM as a terminal condition. Patients usually present with non-specific symptoms of abdominal distension and pain making the diagnosis challenging. As PM is confined to the abdomen for all, or much, of its clinical course, a multimodality treatment combining cytoreductive surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) has emerged as a new standard of care, and has been reported to achieve promising survival outcomes and local disease control in selected patients with PM. This review updates the presentation, diagnosis, classification and treatment strategies for PM.

[Use of nasogastric tubes and drains after colorectal surgery. Have attitudes changed in the last 10 years?]. / Utilización de sonda nasogástrica y drenajes tras cirugía colorrectal. Se ha modificado la actitud en los últimos 10 años?

OBJECTIVE: To evaluate attitudes and opinions of Spanish surgeons on the use of nasogastric tubes (NGT) and drainages after colorectal surgery. MATERIAL AND METHOD: E-mail survey to the members of the Spanish Association of Coloproctology, and Coloproctology Division of the Spanish Surgical Association comparing the results with a previous survey from 1996. RESULTS: Of the 413 surveys sent out, 131 (31.7%) were returned, this compared with 190 from 1996. NGT is routinely used by 22%, selectively by 35% and never by 43%, vs 62%, 31% and 7% in 1996 (p < 0.001). Experience and accreditation in colorectal surgery was associated with its lower use. NGT is removed by 16% 24 hours after surgery, 9% later and 51% when peristalsis begins vs. 6%, 21% and 66% in 1996 (p < 0.001). Of the total, 76% believe that the ileus is not reduced by NGT and 89% that it does not increase comfort vs 27% and 48% (p < 0.001). Drainages are routinely used by 38.5% and selectively by a 57.7%, more than in 1996 (25% and 63%) (p < 0.05). Board-Certification in colorectal surgery was associated with a lower use of drains (p < 0.0001). Drains are not used by 46% in right colon surgery; 22% in left colon and 3.1% in rectal surgery. A total of 66% believe that its used reduce fluid collections and 43% that they drain anastomosis leaks without any differences from previous survey. Drains are considered very useful by 16% in colon surgery and by 52% in rectal surgery. CONCLUSIONS: There is a tendency to decrease the use of NGT. However, drainages continue to be widely employed.

[Results of Longo's stapled hemorrhoidectomy in ambulatory surgery for grade III-IV hemorrhoids]. / Resultados de la anopexia grapada de Longo en el tratamiento quirúrgico ambulatorio de las hemorroides de grados III-IV.

INTRODUCTION: We prospectively evaluated the results of stapled hemorrhoidectomy for grade III-IV hemorrhoids in the ambulatory setting. METHOD: Eighty-five consecutive patients with grade III-IV hemorrhoids, treated with the stapled technique with PPH01 in the Ambulatory Surgery Service of the General Hospital of Valencia were studied. Symptomatic, ASA I-II patients who agreed to undergo ambulatory surgery (vehicle, an accompanying adult, address with telephone, elevator, and basic hygiene conditions) were included. RESULTS: Thirty-nine percent were women and 61% were men, with a mean age of 47.6 years. A total of 85.9% had grade IV hemorrhoids and 14.1% had grade III. The average surgical time was 29.81+/- 12 minutes with a mean length of hospital stay of 168.88 +/- 88 minutes. Surgical complications consisted of 16 hemorrhages of the staple line (18.8%) and five hemorrhages due to mucous tear (5.9%). During the first 8 days the most frequent complication was pain (45.9%); only 7.1% of the patients required analgesia with opiates, and one patient required admission for 24 hours for analgesic purposes. Bleeding occurred in 10 patients, five of whom reported slight bleeding on defecation that stopped spontaneously; the remaining five required admission for 24 hours after surgical revision. Nine patients (10.6%) were admitted to the hospital for 24 hours, three due to intraoperative hemorrhage, five due to postoperative hemorrhage and one due to pain. A second intervention was required in 8.2%. CONCLUSIONS: Stapled hemorrhoidectomy can be applied in an ambulatory regime. Although technically simple with a short learning curve, this technique is not free of complications. Suitable patient selection and adequate perioperative information are indispensable for the ambulatory management of this disorder.