Long-term outcomes and risk factors for diverticulitis recurrence after a successful laparoscopic peritoneal lavage in Hinchey III peritonitis.

PURPOSE: Recently, treatment of Hinchey III diverticulitis by laparoscopic peritoneal lavage has been questioned. Moreover, long-term outcomes have been scarcely reported. Primary outcome was to determine the recurrence rate of diverticulitis after a successful laparoscopic peritoneal lavage in Hinchey III diverticulitis. Secondary outcomes were identification of associated risk factors for recurrence and elective sigmoidectomy rate. METHODS: A retrospective cohort study in a tertiary referral center was performed. Patients with Hinchey III diverticulitis who underwent a successful laparoscopic peritoneal lavage between June 2006 and December 2019 were eligible. Diverticulitis recurrence was analyzed according to the Kaplan-Meier and log-rank test, censoring for death, loss of follow-up, or elective sigmoid resection in the absence of recurrence. Risk factors for recurrence were identified using Cox regression analysis. RESULTS: Sixty-nine patients had a successful laparoscopic peritoneal lavage (mean age: 63 years; 53.6% women). Four patients had an elective sigmoid resection without recurrences. Recurrence rate was 42% (n = 29) after a median follow-up of 63 months. The cumulative global recurrence at 1, 3, and 5 years was 30% (95% CI, 20-43%), 37.5% (95% CI, 27-51%), and 48.9% (95% CI, 36-64%), respectively. Smoking (HR, 2.87; 95% CI, 1.22-6.5; p = 0.016) and episodes of diverticulitis prior to laparoscopic peritoneal lavage (HR, 5.2; 95% CI, 2.11-12.81; p < 0.001) were independently associated with an increased risk of recurrence. CONCLUSIONS: Diverticulitis recurrence after a successful laparoscopic peritoneal lavage is high, decreasing after the first year of follow-up. Smoking and previous episodes of acute diverticulitis independently increase the risk of new episodes of diverticulitis.

Dominantly inherited micro-satellite instable cancer - the four Lynch syndromes - an EHTG, PLSD position statement.

The recognition of dominantly inherited micro-satellite instable (MSI) cancers caused by pathogenic variants in one of the four mismatch repair (MMR) genes MSH2, MLH1, MSH6 and PMS2 has modified our understanding of carcinogenesis. Inherited loss of function variants in each of these MMR genes cause four dominantly inherited cancer syndromes with different penetrance and expressivities: the four Lynch syndromes. No person has an "average sex "or a pathogenic variant in an "average Lynch syndrome gene" and results that are not stratified by gene and sex will be valid for no one. Carcinogenesis may be a linear process from increased cellular division to localized cancer to metastasis. In addition, in the Lynch syndromes (LS) we now recognize a dynamic balance between two stochastic processes: MSI producing abnormal cells, and the host's adaptive immune system's ability to remove them. The latter may explain why colonoscopy surveillance does not reduce the incidence of colorectal cancer in LS, while it may improve the prognosis. Most early onset colon, endometrial and ovarian cancers in LS are now cured and most cancer related deaths are after subsequent cancers in other organs. Aspirin reduces the incidence of colorectal and other cancers in LS. Immunotherapy increases the host immune system's capability to destroy MSI cancers. Colonoscopy surveillance, aspirin prevention and immunotherapy represent major steps forward in personalized precision medicine to prevent and cure inherited MSI cancer.

Benchmarks in colorectal surgery: multinational study to define quality thresholds in high and low anterior resection.

BACKGROUND: Benchmark comparisons in surgery allow identification of gaps in the quality of care provided. The aim of this study was to determine quality thresholds for high (HAR) and low (LAR) anterior resections in colorectal cancer surgery by applying the concept of benchmarking. METHODS: This 5-year multinational retrospective study included patients who underwent anterior resection for cancer in 19 high-volume centres on five continents. Benchmarks were defined for 11 relevant postoperative variables at discharge, 3 months, and 6 months (for LAR). Benchmarks were calculated for two separate cohorts: patients without (ideal) and those with (non-ideal) outcome-relevant co-morbidities. Benchmark cut-offs were defined as the 75th percentile of each centre's median value. RESULTS: A total of 3903 patients who underwent HAR and 3726 who had LAR for cancer were analysed. After 3 months' follow-up, the mortality benchmark in HAR for ideal and non-ideal patients was 0.0 versus 3.0 per cent, and in LAR it was 0.0 versus 2.2 per cent. Benchmark results for anastomotic leakage were 5.0 versus 6.9 per cent for HAR, and 13.6 versus 11.8 per cent for LAR. The overall morbidity benchmark in HAR was a Comprehensive Complication Index (CCI®) score of 8.6 versus 14.7, and that for LAR was CCI® score 11.9 versus 18.3. CONCLUSION: Regular comparison of individual-surgeon or -unit outcome data against benchmark thresholds may identify gaps in care quality that can improve patient outcome.

Colorectal cancer incidences in Lynch syndrome: a comparison of results from the prospective lynch syndrome database and the international mismatch repair consortium.

OBJECTIVE: To compare colorectal cancer (CRC) incidences in carriers of pathogenic variants of the MMR genes in the PLSD and IMRC cohorts, of which only the former included mandatory colonoscopy surveillance for all participants. METHODS: CRC incidences were calculated in an intervention group comprising a cohort of confirmed carriers of pathogenic or likely pathogenic variants in mismatch repair genes (path_MMR) followed prospectively by the Prospective Lynch Syndrome Database (PLSD). All had colonoscopy surveillance, with polypectomy when polyps were identified. Comparison was made with a retrospective cohort reported by the International Mismatch Repair Consortium (IMRC). This comprised confirmed and inferred path_MMR carriers who were first- or second-degree relatives of Lynch syndrome probands. RESULTS: In the PLSD, 8,153 subjects had follow-up colonoscopy surveillance for a total of 67,604 years and 578 carriers had CRC diagnosed. Average cumulative incidences of CRC in path_MLH1 carriers at 70 years of age were 52% in males and 41% in females; for path_MSH2 50% and 39%; for path_MSH6 13% and 17% and for path_PMS2 11% and 8%. In contrast, in the IMRC cohort, corresponding cumulative incidences were 40% and 27%; 34% and 23%; 16% and 8% and 7% and 6%. Comparing just the European carriers in the two series gave similar findings. Numbers in the PLSD series did not allow comparisons of carriers from other continents separately. Cumulative incidences at 25 years were < 1% in all retrospective groups. CONCLUSIONS: Prospectively observed CRC incidences (PLSD) in path_MLH1 and path_MSH2 carriers undergoing colonoscopy surveillance and polypectomy were higher than in the retrospective (IMRC) series, and were not reduced in path_MSH6 carriers. These findings were the opposite to those expected. CRC point incidence before 50 years of age was reduced in path_PMS2 carriers subjected to colonoscopy, but not significantly so.

Risk-reducing hysterectomy and bilateral salpingo-oophorectomy in female heterozygotes of pathogenic mismatch repair variants: a Prospective Lynch Syndrome Database report.

PURPOSE: To determine impact of risk-reducing hysterectomy and bilateral salpingo-oophorectomy (BSO) on gynecological cancer incidence and death in heterozygotes of pathogenic MMR (path_MMR) variants. METHODS: The Prospective Lynch Syndrome Database was used to investigate the effects of gynecological risk-reducing surgery (RRS) at different ages. RESULTS: Risk-reducing hysterectomy at 25 years of age prevents endometrial cancer before 50 years in 15%, 18%, 13%, and 0% of path_MLH1, path_MSH2, path_MSH6, and path_PMS2 heterozygotes and death in 2%, 2%, 1%, and 0%, respectively. Risk-reducing BSO at 25 years of age prevents ovarian cancer before 50 years in 6%, 11%, 2%, and 0% and death in 1%, 2%, 0%, and 0%, respectively. Risk-reducing hysterectomy at 40 years prevents endometrial cancer by 50 years in 13%, 16%, 11%, and 0% and death in 1%, 2%, 1%, and 0%, respectively. BSO at 40 years prevents ovarian cancer before 50 years in 4%, 8%, 0%, and 0%, and death in 1%, 1%, 0%, and 0%, respectively. CONCLUSION: Little benefit is gained by performing RRS before 40 years of age and premenopausal BSO in path_MSH6 and path_PMS2 heterozygotes has no measurable benefit for mortality. These findings may aid decision making for women with LS who are considering RRS.

Fluoroscopy and endoscopy-guided transanastomotic rendezvous: a novel technique for recanalization of a completely obstructed colorectal anastomosis.

BACKGROUND: Colorectal anastomotic stricture is a frequent complication that may affect up to 30% of patients. However, a complete obstruction is rare. Endoscopic balloon dilation is the first-line therapy, but it invariably requires being able to cross the stricture with the dilation device. When this is not possible, surgical revision is the alternative, but it is associated with higher morbidity. CASE PRESENTATION: A 76-year-old male patient underwent an urgent high anterior resection with transverse loop colostomy for an occlusive high rectal tumor. On postoperative day 8, he presented with anastomotic leakage and abscess formation, requiring percutaneous drainage. Ten months after surgery, a colonoscopy revealed a complete stricture of the anastomosis, refractory to negotiation of a guide wire, thus precluding balloon dilation. Hence, a modified rendezvous technique was planned. Simultaneously, a flexible endoscope and a rigid rectoscope were progressed through the distal loop colostomy, and the anus, respectively. A needle device was introduced through the rectoscope and used to pierce the colonic stump. A guide wire was progressed, and the stricture was dilated with a controlled radial expansion balloon catheter. Finally, a 12-Fr Foley catheter was left through the anastomosis. A total of three endoscopic balloon dilation sessions were completed, and successful colostomy reversal was carried out 10 days after the last session. CONCLUSION: Fluoroscopy-endoscopy-guided recanalization is an effective and safe treatment option for complete colorectal anastomotic stricture.

Correction: Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Cancer risks by gene, age, and gender in 6350 carriers of pathogenic mismatch repair variants: findings from the Prospective Lynch Syndrome Database.

PURPOSE: Pathogenic variants affecting MLH1, MSH2, MSH6, and PMS2 cause Lynch syndrome and result in different but imprecisely known cancer risks. This study aimed to provide age and organ-specific cancer risks according to gene and gender and to determine survival after cancer. METHODS: We conducted an international, multicenter prospective observational study using independent test and validation cohorts of carriers of class 4 or class 5 variants. After validation the cohorts were merged providing 6350 participants and 51,646 follow-up years. RESULTS: There were 1808 prospectively observed cancers. Pathogenic MLH1 and MSH2 variants caused high penetrance dominant cancer syndromes sharing similar colorectal, endometrial, and ovarian cancer risks, but older MSH2 carriers had higher risk of cancers of the upper urinary tract, upper gastrointestinal tract, brain, and particularly prostate. Pathogenic MSH6 variants caused a sex-limited trait with high endometrial cancer risk but only modestly increased colorectal cancer risk in both genders. We did not demonstrate a significantly increased cancer risk in carriers of pathogenic PMS2 variants. Ten-year crude survival was over 80% following colon, endometrial, or ovarian cancer. CONCLUSION: Management guidelines for Lynch syndrome may require revision in light of these different gene and gender-specific risks and the good prognosis for the most commonly associated cancers.

From colorectal cancer pattern to the characterization of individuals at risk: Picture for genetic research in Latin America.

Colorectal cancer (CRC) is one of the most common cancers in Latin America and the Caribbean, with the highest rates reported for Uruguay, Brazil and Argentina. We provide a global snapshot of the CRC patterns, how screening is performed, and compared/contrasted to the genetic profile of Lynch syndrome (LS) in the region. From the literature, we find that only nine (20%) of the Latin America and the Caribbean countries have developed guidelines for early detection of CRC, and also with a low adherence. We describe a genetic profile of LS, including a total of 2,685 suspected families, where confirmed LS ranged from 8% in Uruguay and Argentina to 60% in Peru. Among confirmed LS, path_MLH1 variants were most commonly identified in Peru (82%), Mexico (80%), Chile (60%), and path_MSH2/EPCAM variants were most frequently identified in Colombia (80%) and Argentina (47%). Path_MSH6 and path_PMS2 variants were less common, but they showed important presence in Brazil (15%) and Chile (10%), respectively. Important differences exist at identifying LS families in Latin American countries, where the spectrum of path_MLH1 and path_MSH2 variants are those most frequently identified. Our findings have an impact on the evaluation of the patients and their relatives at risk for LS, derived from the gene affected. Although the awareness of hereditary cancer and genetic testing has improved in the last decade, it is remains deficient, with 39%-80% of the families not being identified for LS among those who actually met both the clinical criteria for LS and showed MMR deficiency.

Evaluation of MLH1 variants of unclear significance.

Inactivating mutations in the MLH1 gene cause the cancer predisposition Lynch syndrome, but for small coding genetic variants it is mostly unclear if they are inactivating or not. Nine such MLH1 variants have been identified in South American colorectal cancer (CRC) patients (p.Tyr97Asp, p.His112Gln, p.Pro141Ala, p.Arg265Pro, p.Asn338Ser, p.Ile501del, p.Arg575Lys, p.Lys618del, p.Leu676Pro), and evidence of pathogenicity or neutrality was not available for the majority of these variants. We therefore performed biochemical laboratory testing of the variant proteins and compared the results to protein in silico predictions on structure and conservation. Additionally, we collected all available clinical information of the families to come to a conclusion concerning their pathogenic potential and facilitate clinical diagnosis in the affected families. We provide evidence that four of the alterations are causative for Lynch syndrome, four are likely neutral and one shows compromised activity which can currently not be classified with respect to its pathogenic potential. The work demonstrates that biochemical testing, corroborated by congruent evolutionary and structural information, can serve to reliably classify uncertain variants when other data are insufficient.

A survey of the clinicopathological and molecular characteristics of patients with suspected Lynch syndrome in Latin America.

BACKGROUND: Genetic counselling and testing for Lynch syndrome (LS) have recently been introduced in several Latin America countries. We aimed to characterize the clinical, molecular and mismatch repair (MMR) variants spectrum of patients with suspected LS in Latin America. METHODS: Eleven LS hereditary cancer registries and 34 published LS databases were used to identify unrelated families that fulfilled the Amsterdam II (AMSII) criteria and/or the Bethesda guidelines or suggestive of a dominant colorectal (CRC) inheritance syndrome. RESULTS: We performed a thorough investigation of 15 countries and identified 6 countries where germline genetic testing for LS is available and 3 countries where tumor testing is used in the LS diagnosis. The spectrum of pathogenic MMR variants included MLH1 up to 54%, MSH2 up to 43%, MSH6 up to 10%, PMS2 up to 3% and EPCAM up to 0.8%. The Latin America MMR spectrum is broad with a total of 220 different variants which 80% were private and 20% were recurrent. Frequent regions included exons 11 of MLH1 (15%), exon 3 and 7 of MSH2 (17 and 15%, respectively), exon 4 of MSH6 (65%), exons 11 and 13 of PMS2 (31% and 23%, respectively). Sixteen international founder variants in MLH1, MSH2 and MSH6 were identified and 41 (19%) variants have not previously been reported, thus representing novel genetic variants in the MMR genes. The AMSII criteria was the most used clinical criteria to identify pathogenic MMR carriers although microsatellite instability, immunohistochemistry and family history are still the primary methods in several countries where no genetic testing for LS is available yet. CONCLUSION: The Latin America LS pathogenic MMR variants spectrum included new variants, frequently altered genetic regions and potential founder effects, emphasizing the relevance implementing Lynch syndrome genetic testing and counseling in all of Latin America countries.

Right versus left laparoscopic colectomy for colon cancer: does side make any difference?

PURPOSE: To compare the intraoperative and postoperative outcomes between right laparoscopic colectomy (RLC) and left laparoscopic colectomy (LLC) for colon cancer. METHOD: Patients who underwent elective RLC or LLC for colon cancer between January 2004 and December 2014 were identified and elected for a retrospective analysis. Primary outcomes were technical difficulty (including operative time, intraoperative complications, and conversion rate) and postoperative outcome (including postoperative complications, length of hospital stay, reinterventions, readmissions, and mortality). RESULTS: A total of 547 patients (mean age: 68.5 years old; 48.4% males) were analyzed. The RLC group had a higher mean age (71 vs 65; p < 0.001), ASA 3/4 grade (36 vs 26%; p = 0.02), and comorbidity rate (61 vs 48%, p = 0.003). Regarding technical difficulty, no difference was found between the groups in intraoperative complications (4.1 vs 5.9%; p = 0.34) or conversion rate (6.2 vs 3.9%, p = 0.24). Mean operative time was significantly shorter for RLC (162 vs 185 min, p < 0.001). Regarding postoperative outcome, the RLC group had a higher overall morbidity (20.5 vs 13.3%, p = 0.03), ileus (10.6 vs 2.4%, p < 0.001), and a longer hospital stay (4.7 vs 3.9 days, p = 0.003), with no differences regarding reoperations, readmissions, or mortality. The multivariate analysis showed that RLC were independently associated with a longer operative time and postoperative ileus. CONCLUSIONS: RLC for colon cancer was independently associated with a shorter operative time, an increased risk of ileus, and a longer hospital stay than left laparoscopic colectomy in high-volume centers.

[Founder mutation in Lynch syndrome]. / Mutación fundadora en síndrome de Lynch tipo II.

Lynch syndrome is the most frequent syndrome in hereditary colorectal cancer, a family-specific deleterious mutations in genes encoding DNA reparation proteins: MLH1 (mutL homolog 1), MSH2, MSH6 (mutS homolog 2 y 6, respectively), PMS2 (PMS1 homolog 2, mismatch repair system component) y MUTYH (mutY DNA glycosylase). The c.2252_2253delAA, p.Lys751Serfs*3 mutation in MLH1 gene segregates with a haplotype reported in the northern region of Italy and whose origin was attributed to a founder effect. This mutation co-segregates with typical characteristics of Lynch syndrome, including early age at onset and multiple primary tumors in the same individual, a high frequency of pancreatic cancer, high microsatellite instability and lack of PMS2 expression. This report describes a mutation in an Argentinian patient with endometrioid adenocarcinoma of uterus. Her first-degree relatives had a history of colon cancer diagnosed before 50 years, fulfilling the Amsterdam Criteria I and Lynch syndrome II. The high pathogenicity associated to this mutation makes necessary the study of all members from families with hereditary cancer, allowing pre-symptomatic genetic diagnosis, early assessment and the instauration of preventive treatments.

Locally advanced rectal cancer: Preliminary results of rectal preservation after neoadjuvant chemoradiotherapy. / Cáncer de recto localmente avanzado: resultados preliminares de la preservación del recto después de quimiorradioterapia neoadyuvante.

INTRODUCTION: The standard treatment for locally advanced rectal cancer is total mesorectal excision. However, organ preservation has been proposed for tumors with good response to neoadjuvant treatment. The aim of this study was to evaluate the oncologic results of this strategy. METHODS: This is a retrospective cohort study (2005-2014) including a consecutive series of patients with rectal adenocarcinoma with complete or almost complete clinical response after preoperative chemo-radiotherapy, that were treated according to a strategy of preservation of the rectum. RESULTS: A total of 204 patients with rectal cancer received neoadjuvant therapy. Thirty (14.7%) had a good response and were treated with rectal preservation (23 «Watch and Wait¼ and 7 local resections). Median follow-up was 46 months (interquartile range: 30-68). In the group of «Watch & Wait¼, 4 patients had local recurrence before 12 months (actuarial local recurrence rate=18.5%). All of them underwent salvage surgery (2 with radical surgery and 2 local resections) without any further recurrence. Disease-free survival actuarial rate at 3 years follow-up was 94.1% (95% CI 82.9-100). None of the 7 patients that were treated by local excision had local recurrence. The organ preservation rate for the whole group was 93%. CONCLUSION: The strategy of organ preservation in locally advanced rectal cancer is feasible in cases with good response to neoadjuvant therapy. When implemented in a highly selected group of patients this strategy is associated with satisfactory oncologic results.

Postoperative complications at a university hospital: is there a difference between patients operated by supervised residents vs. trained surgeons?

BACKGROUND: The surgical residency system ensures supervised practices to progressively move from simple to complex surgical procedures. However, ethical dilemmas could arise if patient outcome is negatively affected by this learning methodology. The objective of this study was to evaluate whether the supervised participation of residents acting as operating surgeons influences the postoperative complication rate. METHODS: Surgeries performed between June 2010 and May 2011 were analyzed. The Dindo-Clavien classification was used to stratify the severity of complications. The complication rates of patients operated by supervised residents (SR) and trained surgeons (TS) were compared considering potential confounders related to the patient and surgical procedure. RESULTS: A total of 3697 consecutive surgical procedures were included. Age, gender, and American Society of Anesthesiologists (ASA) risk were not different between patients of both groups. The overall complication rate was 10.8 %, without significant differences between the SR and TS groups (9.8 vs. 11.4 %; P = 0.14). The severity of complications was similar in both groups. Multivariate analysis adjusted for confounders confirmed that resident participation was not an independent risk factor for complications (odds ratio 1.52; 95 % CI 0.79-2.92; P = 0.20). CONCLUSIONS: Supervised resident participation, as operating surgeon, does not negatively impact postoperative patient outcome. Residency training may therefore be considered as an ethical and safe learning methodology whenever implemented in the framework of an academic teaching hospital.

[Magnetic resonance and extramural vascular invasion in patients with rectal cancer and liver metastases]. / Resonancia magnética e invasión vascular extramural en pacientes con cáncer rectal y metástasis hepaticas.

BACKGROUND: Extramural vascular invasion (EMVI) in patients with rectal cancer (RC) is associated with more locally advanced tumors, and independently predicts local and distant recurrence and poor overall survival. OBJETIVE: To determine the association between EMVI and synchronous liver metastases in patients with RC. METHODS: We performed a retrospective cohort study including patients with cancer of middle and lower rectum, which were evaluated with magnetic resonance (MRI) for initial staging in the period from January 2011 to January 2012 inclusive. All patients were evaluated with MRI for EMVI and were followed for a year to detect synchronous liver metastases by imaging methods (January 2012 to January 2013 inclusive). Multivariate analysis was performed by logistic regression. RESULTS: We included 68 patients. Twenty had liver metastases during the observation period (29.41%), of whom 15 had signs of MRI EMVI (75%). The incidence of synchronous liver metastases had a marginally significant association with the presence of EMVI (RR 3.35, 95% CI: 1.0001-11.2187, P = 0.050). CONCLUSION: The presence of MRI EVMI is a poor prognostic predictor factor of development of synchronous liver metastases in patients with RC.

Laparoscopic colorectal resections: a simple predictor model and a stratification risk for conversion to open surgery.

BACKGROUND: The advantages associated with the laparoscopic approach are lost when conversion is required. Available predictive models have failed to show external validation. Body surface area is a recently described risk factor not included in these models. OBJECTIVE: The aim of this study was to develop a clinical rule including body surface area for predicting conversion in patients undergoing elective laparoscopic colorectal surgery. DESIGN: This was a prospective cohort study. SETTING: This study was conducted at a single large tertiary care institution. PATIENTS: Nine hundred sixteen patients (mean age, 63.9; range, 14-91 years; 53.2% female) who underwent surgery between January 2004 and August 2011 were identified from a prospective database. MAIN OUTCOME MEASURES: Conversion rate was analyzed related to age, sex, obesity, disease location (colon vs rectum), type of disease (neoplastic vs nonneoplastic), history of previous surgery, and body surface area. A predictive model for conversion was developed with the use of logistic regression to identify independently associated variables, and a simple clinical prediction rule was derived. Internal validation of the model was performed by using bootstrapping. RESULTS: The conversion rate was 9.9% (91/916). Rectal disease, large patient size, and male sex were independently associated with higher odds of conversion (OR, 2.28 95%CI, 1.47-3.46]), 1.88 [1.1-3.44], and 1.87 [1.04-3.24]). The prediction rule identified 3 risk groups: low risk (women and nonlarge males), average risk (large males with colon disease), and high risk (large males with rectal disease). Conversion rates among these groups were 5.7%, 11.3%, and 27.8% (p < 0.001). Compared with the low-risk group, ORs for average- and high-risk groups were 2.17 (1.30-3.62, p = 0.004) and 6.38 (3.57-11.4, p < 0.0001). LIMITATIONS: The study was limited by the lack of external validation. CONCLUSION: This predictive model, including body surface area, stratifies patients with different conversion risks and may help to inform patients, to select cases in the early learning curve, and to evaluate the standard of care. However, this prediction rule needs to be externally validated in other samples (see Video, Supplemental Digital Content 1, http://links.lww.com/DCR/A137).

Laparoscopic peritoneal lavage for Hinchey III diverticulitis: is it as effective as it is applicable?

BACKGROUND: Over the past few years, the laparoscopic peritoneal lavage has emerged as a therapeutic alternative to standard resection procedures. However, its effectiveness and applicability remain debatable. OBJECTIVE: The aim of this study was to assess laparoscopic lavage in controlling abdominal sepsis secondary to purulent peritonitis. DESIGN: This study was conducted as a retrospective analysis of prospectively collected data. SETTING: This study was conducted at a single tertiary care institution. PATIENTS: Patients requiring emergency surgery for perforated diverticulitis and generalized peritonitis between June 2006 and June 2013 were identified from a prospective database. Laparoscopic assessment was considered in all of the hemodynamically stable patients, and laparoscopic lavage was performed according to intraoperative strict criteria. MAIN OUTCOME MEASURES: Primary outcomes were the effectiveness and applicability of laparoscopic lavage. Secondarily, feasibility, morbidity, and mortality were also assessed. RESULTS: Seventy-five patients required emergency surgery for generalized peritonitis secondary to perforated diverticulitis. Forty-six patients who underwent laparoscopy presented a purulent generalized (Hinchey III) peritonitis and were examined under the intention-to-treat basis to perform a laparoscopic lavage. Thirty-two patients (70.0%; 95% CI 56.2-82.7) had no previous episodes of diverticulitis. Thirty-six patients (78.0%; 95% CI 66.3-90.1) had free air on a CT scan. The conversion rate was 4% (95% CI 0-10). The feasibility of the method was 96.0% (95% CI 90.4-100), and its applicability was 59.0% (95% CI 44.8-73.2). Median operative time was 89 minutes (range, 40-200 minutes). Postoperative morbidity was 24.0% (95% CI 11.7-36.3), and the mortality rate was 0%. We registered 5 failures, and all of them underwent reoperation. The effectiveness of the procedure was 85% (95% CI 76-93). LIMITATIONS: This was a single-institution retrospective study. CONCLUSIONS: The effectiveness of laparoscopic lavage seems to be high. Although its applicability is lower, it could be applied in more than half of patients requiring emergency surgery. This alternative strategy should be considered when laparoscopic assessment reveals Hinchey III diverticulitis.

A comprehensive characterization of the spectrum of MUTYH germline pathogenic variants in Latin America.

MUTYH-Associated Polyposis (MAP) is caused by biallelic pathogenic germline variants in the MUTYH gene. However, individuals harboring monoallelic MUTYH pathogenic variants in the presence of a positive family history have been reported to have a twofold increased risk of colorectal cancer (CRC) and extra colonic cancers. Our aim was to characterize the spectrum of monoallelic and biallelic germline MUTYH pathogenic variants in Latin American patients and to describe their clinical and genetic characteristics. Patients were identified from eight high-risk genetic cancer centers of five Latin American countries. Statistical analysis was performed using the two-sided P test using the Vassarstats statistical tools. Statistical significance was set at a p value ≤ 0.05. Of the 105 unrelated patients with cancer or colorectal polyposis, 84.8% and 15.2% carried pathogenic monoallelic and biallelic MUTYH variants, respectively. The most common pathogenic variants were p.Gly396Asp and p.Tyr179Cys (55% and 23%, respectively). The mean age at first diagnosis was 48.29 years (range 31-71) and 49.90 years (range 27-87) in biallelic and monoallelic MUTYH patients, respectively. CRC was the only cancer diagnosed in patients with biallelic MUTYH pathogenic variants (75%), while breast cancer (46.1%) was more common than CRC (24.7%) in individuals with monoallelic MUTYH pathogenic variants. We reported a high frequency of European founder variants in our diverse population. Some phenotypic differences from current studies were identified, such as a higher breast cancer burden in monoallelic carriers and a complete absence of extra-colon tumors in biallelic patients.

International Validation of the Immunoscore Biopsy in Patients With Rectal Cancer Managed by a Watch-and-Wait Strategy.

PURPOSE: No biomarker capable of improving selection and monitoring of patients with rectal cancer managed by watch-and-wait (W&W) strategy is currently available. Prognostic performance of the Immunoscore biopsy (ISB) was recently suggested in a preliminary study. METHODS: This international validation study included 249 patients with clinical complete response (cCR) managed by W&W strategy. Intratumoral CD3+ and CD8+ T cells were quantified on pretreatment rectal biopsies by digital pathology and converted to ISB. The primary end point was time to recurrence (TTR; the time from the end of neoadjuvant treatment to the date of local regrowth or distant metastasis). Associations between ISB and outcomes were analyzed by stratified Cox regression adjusted for confounders. Immune status of tumor-draining lymph nodes (n = 161) of 17 additional patients treated by neoadjuvant chemoradiotherapy and surgery was investigated by 3'RNA-Seq and immunofluorescence. RESULTS: Recurrence-free rates at 5 years were 91.3% (82.4%-100.0%), 62.5% (53.2%-73.3%), and 53.1% (42.4%-66.5%) with ISB High, ISB Intermediate, and ISB Low, respectively (hazard ratio [HR; Low v High], 6.51; 95% CI, 1.99 to 21.28; log-rank P = .0004). ISB was also significantly associated with disease-free survival (log-rank P = .0002), and predicted both local regrowth and distant metastasis. In multivariate analysis, ISB was independent of patient age, sex, tumor location, cT stage (T, primary tumor; c, clinical), cN stage (N, regional lymph node; c, clinical), and was the strongest predictor for TTR (HR [ISB High v Low], 6.93; 95% CI, 2.08 to 23.15; P = .0017). The addition of ISB to a clinical-based model significantly improved the prediction of recurrence. Finally, B-cell proliferation and memory in draining lymph nodes was evidenced in the draining lymph nodes of patients with cCR. CONCLUSION: The ISB is validated as a biomarker to predict both local regrowth and distant metastasis, with a gradual scaling of the risk of pejorative outcome.