Impact of a Multicomponent Exercise Training Program on Muscle Strength After Bariatric Surgery: A Randomized Controlled Trial.

PURPOSE: This study examined the benefits of an 11-months multicomponent exercise program (MEP) on muscular strength (MS) after bariatric surgery. METHODS: Of the 84 randomized patients, 41 participants from the exercise group (EG) and 20 participants from the control group (CG) were included in the analysis. The EG received supervised MEP for 11 months, starting 1-month post-bariatric surgery (BS) in addition to standard medical care, while the CG received medical care recommendations only. Knee and trunk MS was assessed by isokinetic dynamometry pre-surgery, 1-, 6-, and 12-month post-surgery, while body composition was assessed by dual-energy X-ray absorptiometry. RESULTS: The MEP did not significantly impact absolute MS in the dominant knee and trunk regions at 6- and 12-month post-BS. However, relative MS showed significant improvements. At 6-month post-BS, knee flexion at 60°/s relative to body weight (BW) increased significantly (p = 0.047), as did knee extension at 180°/s relative to BW (p = 0.009), and knee extension at 60°/s relative to total lean mass (p=0.040). At 12-month post-BS, knee flexion at 60°/s relative to BW also significantly improved (p=0.038). CONCLUSION: While absolute MS was not significantly improved with MEP, this study found significant enhancements in relative MS, particularly in dominant knee flexion post-MEP participation. Further research should explore different exercise intensities and frequencies to optimize postoperative MS recovery post-BS. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov (NCT02843048).

Effects of a supervised exercise training on body composition after bariatric surgery: a randomized controlled trial.

OBJECTIVE: This study aimed to determine the effects of a multicomponent exercise intervention during the first year post-bariatric surgery (BS) on body composition, weight loss (WL), energy expenditure, and nutrient intake. METHODS: A total of 84 patients were included in this study and were randomly assigned to either an exercise group (n = 41) or a control group (n = 20). The exercise group participated in a multicomponent exercise program that began 1-month post-BS, whereas the control group received only standard medical care post-BS. Body composition was assessed by dual-energy x-ray absorptiometry, and physical activity energy expenditure was assessed by accelerometers. Nutritional intake was assessed through a 4-day food diary. RESULTS: A total of 6-months post-BS, exercise was found to be effective in mitigating the loss of lower-limb and appendicular lean mass (LM), as well as favoring trunk fat mass (FM) loss. Moreover, it further decreased percent FM and promoted additional excess WL. After 12 months, exercise not only reduced waist circumference but also helped to lessen the loss of total, trunk, and appendicular LM. CONCLUSIONS: Exercise further induced trunk fat mass, percent FM, excess WL, and waist circumference reductions. Moreover, exercise attenuated the loss of total and regional LM.

Using Raw Accelerometer Data to Predict High-Impact Mechanical Loading.

The purpose of this study was to develop peak ground reaction force (pGRF) and peak loading rate (pLR) prediction equations for high-impact activities in adult subjects with a broad range of body masses, from normal weight to severe obesity. A total of 78 participants (27 males; 82.4 ± 20.6 kg) completed a series of trials involving jumps of different types and heights on force plates while wearing accelerometers at the ankle, lower back, and hip. Regression equations were developed to predict pGRF and pLR from accelerometry data. Leave-one-out cross-validation was used to calculate prediction accuracy and Bland-Altman plots. Body mass was a predictor in all models, along with peak acceleration in the pGRF models and peak acceleration rate in the pLR models. The equations to predict pGRF had a coefficient of determination (R2) of at least 0.83, and a mean absolute percentage error (MAPE) below 14.5%, while the R2 for the pLR prediction equations was at least 0.87 and the highest MAPE was 24.7%. Jumping pGRF can be accurately predicted through accelerometry data, enabling the continuous assessment of mechanical loading in clinical settings. The pLR prediction equations yielded a lower accuracy when compared to the pGRF equations.

Mechanical loading prediction through accelerometry data during walking and running.

Currently, there is no way to assess mechanical loading variables such as peak ground reaction forces (pGRF) and peak loading rate (pLR) in clinical settings. The purpose of this study was to develop accelerometry-based equations to predict both pGRF and pLR during walking and running. One hundred and thirty one subjects (79 females; 76.9 ± 19.6 kg) walked and ran at different speeds (2-14 km·h-1) on a force plate-instrumented treadmill while wearing accelerometers at their ankle, lower back and hip. Regression equations were developed to predict pGRF and pLR from accelerometry data. Leave-one-out cross-validation was used to calculate prediction accuracy and Bland-Altman plots. Our pGRF prediction equation was compared with a reference equation previously published. Body mass and peak acceleration were included for pGRF prediction and body mass and peak acceleration rate for pLR prediction. All pGRF equation coefficients of determination were above 0.96, and a good agreement between actual and predicted pGRF was observed, with a mean absolute percent error (MAPE) below 7.3%. Accuracy indices from our equations were better than previously developed equations. All pLR prediction equations presented a lower accuracy compared to those developed to predict pGRF. Walking and running pGRF can be predicted with high accuracy by accelerometry-based equations, representing an easy way to determine mechanical loading in free-living conditions. The pLR prediction equations yielded a somewhat lower prediction accuracy compared with the pGRF equations.

Peak ground reaction forces can be accurately predicted through raw accelerometry data.These predictions are valid for a broad range of body masses and for ankle, lower back and hip accelerometer placements.Peak loading rate prediction presented lower accuracy compared with peak ground reaction force prediction.These findings result in a simple method to predict mechanical loading in clinical practice, which is relevant in some areas of sports medicine such as bone health and injury prevention.

The impact of the prognostic nutritional index (PNI) in gastric cancer.

BACKGROUND: Regarding the assessment of patients' immune and nutritional status, prognostic nutritional index (PNI) has been reported as a predictive marker for surgical outcomes in various types of cancer. The aim of our study was to evaluate the effect of PNI in prognosis of gastric cancer patients submitted to curative-intent resectional surgery. MATERIAL AND METHODS: A retrospective analysis with 637 gastric cancer cases submitted to curative-intent surgery, between 2010 and 2017, in an upper GI surgery unit. We analyzed 396 patients that met the inclusion criteria for this study. The median follow-up was 37 (0-113) months. RESULTS: According to Youden's method, the optimal PNI cutoff for OS was 41.625 (sensitivity 89.3% and specificity 41.3%). OS was significantly shorter in the lower-PNI group of patients when compared to the higher-PNI group (40.26 vs 77.49 months; p < 0.001). Higher PNI had a positive impact on OS in univariable analysis. When adjusted to pStage, higher PNI was still significantly associated with better OS (HR 0.405; CI 95% 0.253-0.649; p < 0.001). Regarding DFS, higher PNI was associated with better DFS (HR 0.421; CI 95% 0.218-0.815; p = 0.010). Higher-PNI group had a protective effect regarding postoperative morbidity and mortality. CONCLUSIONS: In this cohort, PNI was disclosed to significantly impact GC patients' OS and DFS, including in multivariable analysis when adjusting for classical prognostic features. PNI can be used to predict patients at increased risk of postoperative morbidity and mortality. This index may be of use in identifying candidate patients who would benefit from perioperative nutritional support to improve surgical outcomes.

Effects of a Multicomponent Exercise Training Program on Balance Following Bariatric Surgery.

Patients who undergo bariatric surgery (BS) have an increased risk of falls. Our aim was to determine if a multicomponent exercise intervention after BS improves balance. Eighty-four patients with obesity enrolled for BS were recruited and 1 month after BS randomly allocated to a control (CG; standard medical care) or exercise group (EG; exercise plus standard medical care) consisting of a supervised multicomponent training program (3d/week; 75 min/session; 5 months). Anthropometry, lower limb muscle strength (isokinetic dynamometer), vitamin D (ELISA) and balance in bipedal stance (force platform) were assessed pre-BS, 1 month and 6 months post-BS. One month post-BS, significant balance improvements were observed, namely in antero-posterior center of gravity (CoG) displacement and velocity, and medio-lateral and total CoG velocity. Between 1- and 6-months post-BS, improvements in balance were observed only in the EG, with a significant treatment effect on CoG displacement area and antero-posterior CoG displacement. No significant differences were observed between EG and CG over time in any of the anthropometric, muscle strength, and vitamin D variables assayed. In conclusion, a multicomponent exercise intervention program improves some balance parameters in patients with severe obesity following BS and therefore should be part of post-BS follow-up care as a potential strategy to reduce falls and associated injuries.

Clinical Outcome of Patients Submitted to Liver Resection in the Context of Metastatic Breast Cancer: A Study of a Tertiary Hospital Center.

INTRODUCTION: Breast cancer is the most incident cancer in the world, accounting for 25% of new cancers per year in females. It is the most frequent malignancy in women, being the fifth cause of death from cancer worldwide. Approximately 5 to 10% of patients already present with metastases at diagnosis, and the liver is the site of metastases in half of these cases. Liver metastasis (LM) resection, performed after neoadjuvant systemic treatment, has been reported to increase median overall survival in this population. AIM: The aim of this analysis is to assess the outcomes of patients undergoing breast cancer liver metastasis surgical resection, including impact on survival, compared to patients where metastasectomy was not performed. METHODS: retrospective review of 55 female patients with breast cancer liver metastases, diagnosed and treated in a single tertiary university hospital from January 2011 to December 2016 was performed. RESULTS: In 32/55 patients (58.2%), multi-organ metastases were identified (the most common sites being bone, lungs, and lymph nodes). Of the remaining 23 patients, the liver was the unique metastatic site; thirteen patients had diffuse bilobar hepatic metastases. The remaining ten patients were proposed for surgical treatment; three of them had peritoneal carcinomatosis identified during surgery, and no hepatic metastasectomy was performed. As a result, only seven (12.7%) patients underwent liver metastasectomy. Overall survival was higher in patients who had LM surgery (65 months [Interquartile Range (IQR) 54-120]), in comparison to those diagnosed with diffuse bilobar hepatic metastases (17.5 months [IQR 11-41]), and with those showing concurrent liver and bone metastases (16.5 months [IQR 6-36]) (p = 0.012). In univariable analysis, the latter two groups showed worse overall survival outcomes (Hazard Ratio (HR) = 3.447, 95%CI: 1.218-9.756, p = 0.02 and HR = 3.855, 95% Confidence Interval (CI): 1.475-10.077, p = 0.006, respectively) when compared to patients with LM. CONCLUSION: In our series, patients submitted to metastasectomy had a median overall survival after diagnosis of LM three times greater than the non-operated patients with isolated LM, or concurrent LM and bone metastases (65 vs. 17.5 and 16.5 months, respectively). As is vastly known for colorectal cancer liver metastasis, resection of breast cancer liver metastasis may reduce tumor burden, and therefore may improve patient outcome.

The CDH1 c.1901C>T Variant: A Founder Variant in the Portuguese Population with Severe Impact in mRNA Splicing.

Hereditary diffuse gastric cancer (HDGC) caused by CDH1 variants predisposes to early-onset diffuse gastric (DGC) and lobular breast cancer (LBC). In Northern Portugal, the unusually high number of HDGC cases in unrelated families carrying the c.1901C>T variant (formerly known as p.A634V) suggested this as a CDH1-founder variant. We aimed to demonstrate that c.1901C>T is a bona fide truncating variant inducing cryptic splicing, to calculate the timing of a potential founder effect, and to characterize tumour spectrum and age of onset in carrying families. The impact in splicing was proven by using carriers' RNA for PCR-cloning sequencing and allelic expression imbalance analysis with SNaPshot. Carriers and noncarriers were haplotyped for 12 polymorphic markers, and the decay of haplotype sharing (DHS) method was used to estimate the time to the most common ancestor of c.1901C>T. Clinical information from 58 carriers was collected and analysed. We validated the cryptic splice site within CDH1-exon 12, which was preferred over the canonical one in 100% of sequenced clones. Cryptic splicing induced an out-of-frame 37bp deletion in exon 12, premature truncation (p.Ala634ProfsTer7), and consequently RNA mediated decay. The haplotypes carrying the c.1901C>T variant were found to share a common ancestral estimated at 490 years (95% Confidence Interval 445-10,900). Among 58 carriers (27 males (M)-31 females (F); 13-83 years), DGC occurred in 11 (18.9%; 4M-7F; average age 33 ± 12) and LBC in 6 females (19.4%; average age 50 ± 8). Herein, we demonstrated that the c.1901C>T variant is a loss-of-function splice-site variant that underlies the first CDH1-founder effect in Portugal. Knowledge on this founder effect will drive genetic testing of this specific variant in HDGC families in this geographical region and allow intrafamilial penetrance analysis and better estimation of variant-associated tumour risks, disease age of onset, and spectrum.

The effect of bariatric surgery on gravitational loading and its impact on bone mass.

INTRODUCTION: Mechanical unloading associated with weight loss might be one of the main causes for bariatric surgery (BS) induced bone loss. However, no study has tested this hypothesis through objectively measured accelerometry-derived gravitational loading. We aimed to assess how gravitational loading changes following BS and how this correlates with bone mass losses. METHODS: Twenty-one patients submitted to gastric bypass were assessed before, 1, 6 and 12 months after BS for areal bone mineral density (BMD), calciotropic hormones, sclerostin, body composition and daily physical activity. Gravitational loading was determined as the sum of ground reaction forces assessed by accelerometer which considered the interaction between weight and daily ambulation. RESULTS: Mechanical stimuli promoted through the significant increase in steps number counterbalanced the gravitational loading decreases derived from the significant weight loss after BS. Gravitational loading volume decreased between pre-BS and 1 month post-BS (-2215 kN·d-1; p = .023), but remained stable between 6 and 12 months post-BS, despite decreases on hip (-7.0%; p < .001), femoral neck (-8.8%; p < .001) and lumbar spine (-5.2%; p < .001) BMD. Serum sclerostin increased from pre-BS to 1 month post-BS (+0.118 ng·mL-1; p = .021), returning to pre-BS levels 6 months after surgery. Neither vitamin D nor parathyroid hormone were affected by BS. Weight variation was a predictor of BMD decreases at total hip (R2 = 0.06; p = .026) and femoral neck (R2 = 0.12; p = .022), whereas daily gravitational loading volume was not. Fat and lean mass changes were also predictors of BMD decrease at total hip (R2 = 0.05; p = .031) and femoral neck (R2 = 0.14; p = .010), respectively. CONCLUSION: Our findings suggest that gravitational loading only decreased during the first month after surgery remaining stable thereafter, and these changes do not seem to explain BS-induced bone loss. The association between weight and bone loss seems to result from other physiological aspects, fat and lean mass loss, rather than from gravitational loading decrease.

Appendiceal Neuroendocrine Tumours - Experience of One Service / Tumores neuroendócrinos do apêndice - Experiência de um serviço

Abstract Tumours of the appendix are rare and tend to be diagnosed incidentally, in cases of acute appendicitis. For some authors, appendiceal neuroendocrine tumours (ANETs) are the most frequent neoplasm of the appendix, observed in 0.3% to 0.9% of cases acute appendicitis. The present is a unicentric retrospective study conducted between January 2005 and March 2017. Out of a total of 3,007 surgeries for appendiceal pathologies performed in the adult population at the hospital where the present study was conducted, there were 70 (2.33%) malignant cases, 20 (28.6%) of which were ANETs. The patients had a median age of 44 years (range: 18 to 85 years), and were predominantly women (there were 1.9 times more women than men). In 16 cases (80%), a simple appendicectomy was performed (1 patient was submitted to a right hemicolectomy later). The cases of ANETs had a good prognosis in our series: 85% of the patients are either alive today or were alive after 5 years of follow-up. Despite the fact that ANETs are described as the most frequent tumor of the appendix, this was not confirmed in our series, in which they only represented 28.6% of the cases; adenocarcinoma was the most frequent tumor (65.7%) among our sample.

Resumo Tumores do apêndice são raros, e tendem a ser diagnosticados de forma incidental, em casos de apendicite aguda. Para alguns autores, tumores neuroendócrinos do apêndice (TNEAs) são as neoplasias mais frequentes do apêndice, e são observados em 0,3 a 0,9% de todos os casos agudos de apendicite. Este é um estudo monocêntrico e retrospectivo realizado entre janeiro de 2005 e março de 2017. Entre umtotal de 3.007 cirurgias para patologias do apêndice realizadas na população adulta no hospital em que o estudo foi conduzido, houve 70 (2,33%) casos de malignidade, 20 (28,6%) dos quais eram TNEAs. Os pacientes tinham uma idade média de 44 anos (gama: 18-85 anos), e eram predominantemente mulheres (havia 1,9 vezes mais mulheres do que homens). Em 16 casos (80%), realizou-se uma simples apendicectomia (1 paciente foi submetido a uma hemicolectomia direita mais tarde). Os casos de TNEAs tiveram um bom prognóstico em nossa série: 85% dos pacientes estão vivos hoje, ou estavam após um seguimento de 5 anos. Apesar de os TNEAs serem descritos como os tumores mais frequentes do apêndice, isso não foi confirmado nesta série, na qual eles representaram apenas 28,6% dos casos; adenocarcinoma foi o tumor mais frequente (65,7%) emnossa amostra.

How Does Bariatric Surgery Affect Fall Risk Factors?

PURPOSE: This study aimed to assess bariatric surgery (BS) effect on fall risk factors. MATERIALS AND METHODS: Fifteen patients undergoing BS (intervention group, IG) and 10 non-surgical obese patients (control group, CG) were recruited. IG was assessed at pre-surgery and 6 months after BS, while CG was assessed at baseline and reassessed after 6 months. At both time-points, anthropometry, lower limbs muscle strength (isokinetic dynamometer), balance in bipedal stance (force platform), daily physical activity (accelerometry), and health-related quality of life (SF-36 questionnaire) were assessed. RESULTS: At baseline, there were no differences between CG and IG for all parameters analyzed. Compared to CG, 6 months post-BS, the IG decreased weight, body mass index, waist and hip circumference. Balance showed limited improvements, with gains observed only on antero-posterior and total center of pressure velocity. Muscle strength displayed a divergent evolution 6 months after BS, with a decrease in absolute strength but an increase in relative strength. Although BS did not induce significant changes in time spent in different physical activity intensities, it decreased time in sedentary behavior and increased number of daily steps. Post-BS patients reported substantial improvements in quality-of-life, especially in physical function. CONCLUSION: Patients seem to overestimate their actual physical fitness improvements attained after BS, which combined with increases in physical activity, might increase the likelihood of engaging in risky daily tasks to what they are physically not prepared to, consequently increasing fall risk.

The Effect of an Exercise Intervention Program on Bone Health After Bariatric Surgery: A Randomized Controlled Trial.

Exercise has been suggested as a therapeutic approach to attenuate bone loss induced by bariatric surgery (BS), but its effectiveness remains unclear. Our aim was to determine if an exercise-training program could induce benefits on bone mass after BS. Eighty-four patients, submitted to gastric bypass or sleeve gastrectomy, were randomized to either exercise (EG) or control group (CG). One month post-BS, EG underwent a 11-month supervised multicomponent exercise program, while CG received only standard medical care. Patients were assessed before BS and at 1, 6, and 12 months post-BS for body composition, areal bone mineral density (BMD), bone turnover markers, calciotropic hormones, sclerostin, bone material strength index, muscle strength, and daily physical activity. A primary analysis was conducted according to intention-to-treat principles and the primary outcome was the between-group difference on lumbar spine BMD at 12 months post-BS. A secondary analysis was also performed to analyze if the exercise effect depended on training attendance. Twelve months post-BS, primary analysis results revealed that EG had a higher BMD at lumbar spine (+0.024 g∙cm-2 [95% confidence interval (CI) 0.004, 0.044]; p = .015) compared with CG. Among total hip, femoral neck, and 1/3 radius secondary outcomes, only 1/3 radius BMD improved in EG compared with CG (+0.013 g∙cm-2 [95% CI 0.003, 0.023]; p = .020). No significant exercise effects were observed on bone biochemical markers or bone material strength index. EG also had a higher lean mass (+1.5 kg [95% CI 0.1, 2.9]; p = .037) and higher number of high impacts (+51.4 [95% CI 6.6, 96.1]; p = .026) compared with CG. In addition, secondary analysis results suggest that exercise-induced benefits may be obtained on femoral neck BMD but only on those participants with ≥50% exercise attendance compared with CG (+5.3% [95% CI 2.0, 8.6]; p = .006). Our findings suggest that an exercise program is an effective strategy to ameliorate bone health in post-BS patients. © 2020 American Society for Bone and Mineral Research (ASBMR).

Accelerometry calibration in people with class II-III obesity: Energy expenditure prediction and physical activity intensity identification.

BACKGROUND: Almost all accelerometer calibration studies were developed for non-obese people, which hampers an accurate prediction of energy expenditure (EE) and induces a misclassification of sedentary activity (SA) and physical activity intensities (PAI) in class II-III obese people. RESEARCH QUESTION: The purpose of this study was to develop regression equations to predict EE and cut-points to classify SA and PAI in severe obese people based on several metrics obtained from hip and back accelerometer placement data. METHODS: 43 class II-III obese participants performed a protocol that included sitting and standing positions and walking at several speeds. During the protocol participants wore an accelerometer at hip and back, and respiratory gas exchange was measured by indirect calorimetry. Accelerometer metrics analyzed were: activity counts, mean amplitude deviation and euclidean norm minus one. EE was predicted through linear mixed models while cut-points to classify SA and PAI were obtained applying receiver operating characteristic curves. Leave-one-out cross-validation data was used to calculate Bland-Altman plots, prediction accuracy, Kappa statistic and percent agreement. RESULTS: All prediction models presented a quadratic equation that had as predictors body mass and one of the accelerometer metrics. Predicted EE indicated a good agreement and a root mean square error below 1.02 kcal min-1. Global classification agreement from developed cut-points was categorized as almost perfect with a percent agreement above 84 %. Prediction accuracy and classification agreement were similar among accelerometer metrics in each position and between them in hip and back placement. SIGNIFICANCE: Hip and back accelerometer data collected in severe obese people allow to accurately estimate EE and to correctly classify SA and PAI. These results enable future studies to adopt appropriate regression equations and cut-points developed for class II-III obese people rather than those established for non-obese people.

Large desmoid tumors in familial adenomatous polyposis: a successful outcome

Desmoid tumors develop from connective tissue, fasciae, and aponeuroses, and may occur in the context of familial adenomatous polyposis or may arise sporadically; also, they may be extra-abdominal, intra-abdominal, or located in the abdominal wall. These benign tumors have a great aggressiveness with a high rate of local recurrence. Familial adenomatous polyposis is an inherited condition with autosomal dominant transmission, and is characterized by the development of multiple colonic and rectal adenomatous polyps, as well as desmoid tumors. We present the case of a 54-year-old woman with germline APC gene mutation, who underwent a total colectomy, subsequently developing two large infiltrative solid intra-abdominal lesions consistent with desmoid tumors. Medical treatment with Cox-2 inhibitors was initiated without result. She was submitted to resection for intestinal obstruction, but developed local recurrence. The lesions were also unresponsive to tamoxifen, and chemotherapy was initiated with dacarbazine plus doxorubicin, switching to vinorelbine plus methotrexate, achieving a good response in all lesions after 12 months. The approach to these intra-abdominal lesions should be progressive, beginning with observation, then a medical approach with non-steroidal anti-inflammatory drugs or with an anti-hormonal agent. Afterwards, if progression is still evident, chemotherapy should be started. Surgery should be reserved for resistance to medical treatment, in palliative situations, or for extra-abdominal or abdominal wall desmoids tumors.

Pathological features of total gastrectomy specimens from asymptomatic hereditary diffuse gastric cancer patients and implications for clinical management.

Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant syndrome characterised by multigenerational diffuse gastric cancer, and is mainly caused by germline alterations in the CDH1 gene. Currently, endoscopy has limited diagnostic accuracy, and total gastrectomy (TG) is the treatment of choice for asymptomatic CDH1 carriers. In this study, we aimed to obtain a better understanding of HDGC syndrome by exploring the histopathological findings of TG specimens from asymptomatic HDGC patients. A comprehensive literature review was carried out, searching for TGs performed in asymptomatic HDGC patients. Fourteen unpublished cases, analysed in our institution, were also included. The series encompassed 174 CDH1 carriers. Preoperative endoscopic biopsies were positive in 28.3%. A macroscopic lesion was apparent in 11.7% of TGs. Histopathological analysis revealed intraepithelial lesions and/or intramucosal signet ring cell carcinoma in 87.9% of TGs. When we explored the type of protocol used for handling the specimens, we found that microscopic cancer foci were detected in 95.3% of TGs when a total-embedding protocol (assessment of the totality of gastric mucosa) was applied, and only in 62.5% when no specific protocol was used (P < 0.001). Helicobacter pylori infection was found in 23.4% cases. In conclusion, a thorough histopathological examination of gastric mucosa remains the gold standard for detection of cancer foci in HDGC gastrectomy specimens, requiring experienced pathologists for an accurate diagnosis. A better understanding of the natural history of HDGC will enable better clinical management of HDGC patients, particularly regarding the optimal timing for the performance of TG.

Phenotypic heterogeneity of hereditary diffuse gastric cancer: report of a family with early-onset disease.

BACKGROUND AND AIMS: The time course for the development of clinically significant hereditary diffuse gastric cancer (HDGC) is unpredictable. Little is known about the progression from preclinical, indolent lesions to widely invasive, aggressive phenotypes. Gastroendoscopy often fails to detect early lesions, and risk-reducing/prophylactic total gastrectomy (PTG) is the only curative approach. We present an HDGC family with early-onset disease in which clinical and histologic findings provided insight into the understanding of different HDGC phenotypes. METHODS: The proband was diagnosed at age 18 years with widely invasive, metastatic DGC. CDH1 genetic testing identified a pathogenic, germline CDH1 variant (c.1901C>T, p.Ala634Val). Thirty family members were tested, and 15 CDH1 carriers were identified. RESULTS: Six family members had PTG, with negative preoperative workup. The proband's 14-year-old sister is the youngest patient, reported to date, to have PTG after negative preoperative biopsy sampling. Intramucosal HDGC foci were detected in all PTG specimens (1-33). In contrast to the "indolent" phenotype of these foci, the aggressive DGC from the proband showed pleomorphic cells, absent E-cadherin expression, increased proliferation (Ki-67 index), and activation of oncogenic events (p53, pSrc and pStat3 overexpression). All family members had Helicobacter pylori gastritis. Cag-A-positive strains were detected in all specimens, except in the proband's sister. CONCLUSIONS: HDGC is a heterogeneous disease regarding clinical behavior, endoscopic findings, histopathologic features, and immunophenotypic/molecular profile. The presence of bizarre, pleomorphic cells in endoscopic biopsy specimens is suggestive of advanced disease and should prompt clinical intervention. The involvement of a full multidisciplinary team is essential for the management of these patients.

Large desmoid tumors in familial adenomatous polyposis: a successful outcome.

Desmoid tumors develop from connective tissue, fasciae, and aponeuroses, and may occur in the context of familial adenomatous polyposis or may arise sporadically; also, they may be extra-abdominal, intra-abdominal, or located in the abdominal wall. These benign tumors have a great aggressiveness with a high rate of local recurrence. Familial adenomatous polyposis is an inherited condition with autosomal dominant transmission, and is characterized by the development of multiple colonic and rectal adenomatous polyps, as well as desmoid tumors. We present the case of a 54-year-old woman with germline APC gene mutation, who underwent a total colectomy, subsequently developing two large infiltrative solid intra-abdominal lesions consistent with desmoid tumors. Medical treatment with Cox-2 inhibitors was initiated without result. She was submitted to resection for intestinal obstruction, but developed local recurrence. The lesions were also unresponsive to tamoxifen, and chemotherapy was initiated with dacarbazine plus doxorubicin, switching to vinorelbine plus methotrexate, achieving a good response in all lesions after 12 months. The approach to these intra-abdominal lesions should be progressive, beginning with observation, then a medical approach with non-steroidal anti-inflammatory drugs or with an anti-hormonal agent. Afterwards, if progression is still evident, chemotherapy should be started. Surgery should be reserved for resistance to medical treatment, in palliative situations, or for extra-abdominal or abdominal wall desmoids tumors.