Histopathologic patterns as markers of prognosis in patients undergoing hepatectomy for colorectal cancer liver metastases - Pushing growth as an independent risk factor for decreased survival.

INTRODUCTION: Liver resection combined with neoadjuvant chemotherapy (NAC) has reported notable results in patients with colorectal liver metastases (CRLM). Tumoral response to NAC is associated with specific histopathologic patterns with prognostic implications. The main objective of this study was to evaluate the influence of pathological findings on overall survival (OS), disease-free survival (DFS) and liver recurrence-free survival (LRFS). PATIENTS AND METHODS: Analysis of clinical and outcome data from 110 patients who underwent first CRLM resection between January 2010 and July 2013. Blinded pathological review of histological material of several parameters: resection margin, tumor regression grade (TRG), tumor thickness at the tumor-normal interface (TTNI) and the growth pattern (GP). RESULTS: The median survival following hepatic resection was 52 months and 3- and 5- year Kaplan-Meier estimates were 69 and 48%, respectively. Seventy-four patients developed recurrent disease. Oxaliplatin-based chemotherapy was significantly associated with a pushing GP. A positive resection margin was an independent predictor of decreased DFS (p = 0.018) but not of decreased OS. LRFS was strongly reduced by the absence of histologic tumor response (p = 0.018). The pushing pattern had an adverse impact on both OS (p = 0.007) and DFS (p = 0.004) on multivariate analysis. CONCLUSION: The prognostic value of histopathological features in patients who underwent CRLM's resection is undeniable. The pushing GP was related with worse prognosis. Further studies are required to clarify the biological mechanisms underlying these findings in order to enhance a more personalized and efficient treatment of these patients.

Hepatic Angiosarcoma Masquerading as Hemangioma: A Challenging Differential Diagnosis.

Hemangiomas are usually diagnosed based on ultrasound findings. The presence of symptoms, rapid growth or atipical imagiological findings should make us consider other diagnoses, including malignant tumors such as angiosarcomas. We describe the case of a previously healthy 46-year-old female without a history of exposure to carcinogens who presented with abdominal pain for two months. Diagnostic work-up revealed elevated gamma-glutamyl transferase and lactate dehydrogenase levels. Abdominal ultrasound described a large nodular lesion in the right lobe of the liver described as a hemangioma. One month later, a computed tomography-scan was made and revealed the same lesion, which had grown from 13.5 to 20 cm, maintaining typical imaging characteristics of a hemangioma. A right hepatectomy was performed and pathology revealed an angiosarcoma. After surgery, a positron emission tomography-computed tomography scan showed hepatic and bone metastasis. The patient started taxane-based chemotherapy and lumbar palliative radiotherapy, but died 10 months after surgery. This case shows how difficult it is to diagnose hepatic angiosarcoma relying only on imaging findings. Two abdominal computed tomography -scans were performed and none suggested this diagnosis. Angiosarcoma is a very aggressive tumour with an adverse prognosis. Surgery is the only curative treatment available. However, it is rarely feasible due to unresectable disease or distant metastasis.

Apesar do diagnóstico de hemangioma ser habitualmente simples e baseado na ecografia, a presença de sintomas, o crescimento rápido ou a presença de atipias imagiológicas devem-nos fazer considerar a hipótese de outras entidades, algumas delas malignas como o angiossarcoma. É descrito o caso de doente do sexo feminino de 46 anos, previamente saudável sem exposição a carcinogéneos, refere queixas de dor abdominal durante dois meses. O estudo analítico revelou elevação da gama glutamil transferase e lactato desidrogenase e a ecografia abdominal evidenciou uma lesão nodular de grandes dimensões no lobo direito do fígado, descrita como hemangioma. Um mês mais tarde, realizou uma tomografia computadorizada abdominal que revelou aumento das dimensões da lesão (13,5 para 20 cm), mantendo características imagiológicas de hemangioma. A doente foi submetida a hepatectomia direita e a histologia revelou a presença de angiossarcoma. Após cirurgia, uma tomografia por emissão de positrões-tomografia computadorizada evidenciou metastização hepática e óssea. A doente foi submetida a radioterapia e quimioterapia paliativa com paclitaxel, tendo falecido 10 meses após a cirurgia. Este caso exemplifica a dificuldade do diagnóstico do angiosarcoma baseado apenas nos exames de imagem. Foram realizadas duas tomografias computadorizadas abdominais e nenhuma sugeriu o diagnóstico. Os angiossarcomas são tumores muito agressivos com prognóstico reservado, sendo a cirurgia o único tratamento curativo. No entanto, raramente é realizada devido a doença irressecável ou disseminação à distância.

Bioenergetic adaptations of the human liver in the ALPPS procedure - how liver regeneration correlates with mitochondrial energy status.

BACKGROUND: The Associating Liver Partition and Portal Ligation for Staged Hepatectomy (ALPPS) depends on a significant inter-stages kinetic growth rate (KGR). Liver regeneration is highly energy-dependent. The metabolic adaptations in ALPPS are unknown. AIMS: i) Assess bioenergetics in both stages of ALPPS (T1 and T2) and compare them with control patients undergoing minor (miHp) and major hepatectomy (MaHp), respectively; ii) Correlate findings in ALPPS with volumetric data; iii) Investigate expression of genes involved in liver regeneration and energy metabolism. METHODS: Five patients undergoing ALPPS, five controls undergoing miHp and five undergoing MaHp. Assessment of remnant liver bioenergetics in T1, T2 and controls. Analysis of gene expression and protein content in ALPPS. RESULTS: Mitochondrial function was worsened in T1 versus miHp; and in T2 versus MaHp (p < 0.05); but improved from T1 to T2 (p < 0.05). Liver bioenergetics in T1 strongly correlated with KGR (p < 0.01). An increased expression of genes associated with liver regeneration (STAT3, ALR) and energy metabolism (PGC-1α, COX, Nampt) was found in T2 (p < 0.05). CONCLUSION: Metabolic capacity in ALPPS is worse than in controls, improves between stages and correlates with volumetric growth. Bioenergetic adaptations in ALPPS could serve as surrogate markers of liver reserve and as target for energetic conditioning.

Validity and Reliability of the Hearing Handicap Inventory for Elderly: Version Adapted for Use on the Portuguese Population.

BACKGROUND: The use of the Hearing Handicap Inventory for the Elderly (HHIE) questionnaire enables us to measure self-perceived psychosocial handicaps of hearing impairment in the elderly as a supplement to pure-tone audiometry. This screening instrument is widely used and it has been going through adaptations and validations for many languages; all of these versions have kept the validity and reliability of the original version. PURPOSE: To validate the HHIE questionnaire, translated into Portuguese of Portugal, on the Portuguese population. RESEARCH DESIGN: This study is a descriptive correlational qualitative study. The authors performed the translation from English into Portuguese, the linguistic adaptation, and the counter translation. STUDY SAMPLE: Two hundred and sixty patients from the Ear, Nose, and Throat (ENT) Department of Coimbra University Hospitals were divided into a case group (83 individuals) and a control group (177 individuals). INTERVENTION: All of the 260 patients completed the 25 items in the questionnaire and the answers were reviewed for completeness. DATA COLLECTION AND ANALYSIS: The patients volunteered to answer the 25-item HHIE during an ENT appointment. Correlations between each individual item and the total score of the HHIE were tested, and demographic and clinical variables were correlated with the total score, as well. The instrument's reproducibility was assessed using the internal consistency model (Cronbach's alpha). RESULTS: The questions were successfully understood by the participants. There was a significant difference in the HHIE-10 and HHIE-25 total scores between the two groups (p < 0.001). Positive correlations can be seen between the global question and HHIE-10 and HHIE-25. In the regression study, a relationship was observed between the pure-tone average and the HHIE-10 (p < 0.001). Reliability of the instrument was proven by a Cronbach alpha index of 0,79. CONCLUSIONS: The HHIE translation into Portuguese of Portugal maintained the validity of the original version and it is useful to assess the psychosocial handicap of hearing impairment in the elderly.

Mitochondrial bioenergetics and posthepatectomy liver dysfunction.

BACKGROUND: Liver regeneration requires an enormous energy supply. Experimental evidence suggests that mitochondrial function is of paramount importance for liver regeneration. However, this has not been investigated in the clinical setting. We aimed to: (i) evaluate changes in mitochondrial function during hepatectomy, especially after hepatic pedicle clamping; and (ii) correlate these changes with postoperative hepatocellular function and clinical outcome. MATERIALS AND METHODS: Prospective study of thirty patients undergoing hepatectomy. Measurement of mitochondrial membrane potential, respiration and adenosine triphosphate content in intra-operative liver biopsies performed in nonresected parenchyma. Correlation of findings with duration of hepatic pedicle clamping, postoperative markers of hepatocellular necrosis and function (aminotransferases, arterial lactate, international normalized ratio, bilirubin), and morbidity. RESULTS: Longer hepatic pedicle clamping was associated with worse mitochondrial depolarization (r = -0·519; P = 0·011) and longer lag phase (r = 0·568; P = 0·006). Higher postoperative peak aminotransferases, international normalized ratio and bilirubin correlated with worse mitochondrial function (P < 0·05). After major hepatectomy, mitochondrial respiration correlated with postoperative arterial lactate clearance (r = 0·756; P = 0·049). Mitochondrial bioenergetic parameters were significantly decreased in patients with liver-specific morbidity and postoperative liver failure (P < 0·05). On multivariate analysis, decrease in mitochondrial potential was an independent risk factor for liver-specific morbidity (OR = 13·7; P = 0·043). Worse lag phase was highly predictive of posthepatectomy liver failure (area under the curve: 0·933; P = 0·008). CONCLUSIONS: There is a relationship between mitochondrial function, duration of hepatic pedicle clamping and clinical outcome after hepatectomy. Mitochondrial bioenergetics can potentially translate into clinical practice, assisting in earlier diagnosis of postoperative liver dysfunction, and as a target for future pharmacological therapies.

Oxaliplatin toxicity presenting as a liver nodule - case report.

BACKGROUND: Oxaliplatin based chemotherapy is often used as adjuvant therapy in colon and rectal cancer. A reported side effect is Sinusoidal Obstruction Syndrome which is characterized by a spectrum of pathologic changes, from sinusoidal dilation, peri-sinusoidal haemorrhage, peliosis and nodular regenerative hyperplasia. Very rarely it can cause the development of liver nodules mimicking liver metastases. Herein, we report a case of Sinusoidal Obstruction Syndrome causing a liver nodule suspicious of liver metastasis on imaging. This is the third reported case of this complication of oxaliplatin toxicity, in which resection was performed and pathological diagnosis confirmed. CASE PRESENTATION: We report the case of a 59 year old man with stage III colon cancer who underwent sigmoidectomy followed by adjuvant chemotherapy with oxaliplatin. One year after surgery a liver nodule was detected and the patient underwent right hepatectomy. Pathology showed no liver nodule and diagnosed sinusoidal obstruction syndrome. CONCLUSION: We describe the third reported case of a liver lesion mimicking a liver metastasis after oxaliplatin-based chemotherapy for colon cancer. We suggest that in patients heavily treated with oxaliplatin with de novo liver nodules, this differential diagnosis should be considered. In particular, in this population of patients an intense imagiologic evaluation and even a preoperative biopsy should be pursued to confirm the diagnosis of malignancy and avoid overtreatment.

Amelioration of glycemic control by sleeve gastrectomy and gastric bypass in a lean animal model of type 2 diabetes: restoration of gut hormone profile.

BACKGROUND: In obese diabetic patients, bariatric surgery has been shown to induce remission of type 2 diabetes. Along with weight loss itself, changes in gut hormone profiles after surgery play an important role in the amelioration of glycemic control. However, the potential of gastrointestinal surgery regarding diabetes remission in non-severely obese diabetic patients has yet to be defined. In the present experimental study, we explored the effect of established bariatric procedures with and without duodenal exclusion on glycemic control and gut hormone profile in a lean animal model of type 2 diabetes. METHODS: Forty 12- to 14-week-old non-obese diabetic Goto-Kakizaki (GK) rats were randomly assigned to four groups: control group (GKC), sham surgery (GKSS), sleeve gastrectomy (GKSG), and gastric bypass (GKGB). Age-matched Wistar rats served as a non-diabetic control group (WIC). Glycemic control and plasma lipids were assessed at the beginning of the observation period and 4 weeks after surgery. Fasting and mixed meal-induced plasma levels of ghrelin, glucagon-like peptide-17-36 (GLP-1), and peptide tyrosine-tyrosine (PYY) were measured. RESULTS: In GK rats, glycemic control improved after sleeve gastrectomy (SG) and gastric bypass (GB). Mixed meal-induced gut hormone profiles in Wistar rats (WIC) were significantly different from those of sham-operated or control group GK rats. After SG and GB, GK rats showed a similar postprandial decrease in ghrelin as observed in non-diabetic WIC. Following both surgical procedures, a significant meal-induced increase in PYY and GLP-1 could be demonstrated. CONCLUSIONS: SG and GB induce a similar improvement in overall glycemic control in lean diabetic rodents. Meal-induced profiles of ghrelin, GLP-1, and PYY in GK rats are significantly modified by SG and GB and become similar to those of non-diabetic Wistar rats. Our data do not support the hypothesis that duodenal exclusion and early contact of food with the ileal mucosa alone explain changes in gut hormone profile in GK rats after gastrointestinal surgery.

Insulin resistance and beta cell function before and after sleeve gastrectomy in obese patients with impaired fasting glucose or type 2 diabetes.

BACKGROUND: Pathophysiology of type 2 diabetes (T2D) includes insulin resistance (IR) and insufficient insulin secretion. Remission in obese patients can be achieved through surgically induced weight loss. Sleeve gastrectomy is a novel technique for the treatment of morbid obesity, and its effects on the metabolic syndrome and T2D have not yet been fully understood. METHODS: From February 2008 to July 2010, sleeve gastrectomy as stand-alone treatment for severe or morbid obesity was performed in 23 patients with T2D or impaired fasting glucose (IFG). No postoperative complications occurred and patients were dismissed from hospital on day 2 after surgery. Body mass index (BMI), fasting blood glucose (FBG) and fasting insulin were determined before and up to 24 months after surgery. IR and beta cell function were calculated using the modified homeostasis model assessment (HOMA2). RESULTS: BMI, FBG and fasting insulin improved significantly as early as 3 months after surgery. Threefold increased preoperative insulin resistance (3.05) decreased to near-normal values (1.14) during the same period. Interestingly, overall beta cell function diminished at 12 months of follow-up (79.6 %), in comparison with preoperative values (117.8 %). Patients with a markedly reduced preoperative beta cell function (<40 %) did not achieve a complete remission after surgery. CONCLUSIONS: In obese patients with T2D and IFG, commonly characterized by an augmented beta cell function and an increased insulin resistance, sleeve gastrectomy induces remission through reduction of insulin resistance. Preoperative IR and beta cell function calculated by HOMA2 deserve further studies in patients undergoing metabolic surgery.

Glucagon secretion after metabolic surgery in diabetic rodents.

Excessive or inadequate glucagon secretion promoting hepatic gluconeogenesis and glycogenolysis is believed to contribute to hyperglycemia in patients with type 2 diabetes. Currently, metabolic surgery is an accepted treatment for obese patients with type 2 diabetes and has been shown to improve glycemic control in Goto-Kakizaki (GK) rats, a lean animal model for type 2 diabetes. However, the effects of surgery on glucagon secretion are not yet well established. In this study, we randomly assigned forty 12- to 14-week-old GK rats to four groups: control group (GKC), sham surgery (GKSS), sleeve gastrectomy (GKSG), and gastric bypass (GKGB). Ten age-matched Wistar rats served as a non-diabetic control group (WIC). Glycemic control was assessed before and 4 weeks after surgery. Fasting- and mixed-meal-induced plasma levels of insulin and glucagon were measured. Overall glycemic control improved in GKSG and GKGB rats. Fasting insulin levels in WIC rats were similar to those for GKC or GKSS rats. Fasting glucagon levels were highest in GKGB rats. Whereas WIC, GKC, and GKSS rats showed similar glucagon levels, without any significant meal-induced variation, a significant rise occurred in GKSG and GKGB rats, 30 min after a mixed meal, which was maintained at 60 min. Both GKSG and GKGB rats showed an elevated glucagon:insulin ratio at 60 min in comparison with all other groups. Surprisingly, the augmented post-procedural glucagon secretion was accompanied by an improved overall glucose metabolism in GKSG and GKGB rats. Understanding the role of glucagon in the pathophysiology of type 2 diabetes requires further research.

[Denture impaction in the thoracic esophagus: surgical treatment - a case report]. / Impactação de prótese dentária no esófago torácico: tratamento cirúrgico. A propósito de um caso clínico.

Esophageal foreign body impaction is mostly managed with endoscopic retrieval. However, in cases of large or irregularly shaped foreign bodies, or in cases of long standing impaction, this technique carries a high risk of perforation and a surgical approach is often mandatory.The authors report the case of a 55 year old woman, with a past history of mental retardation, presenting with dysphagia for solid food and regurgitation beginning one month earlier. After failed extraction by flexible esophagoscopy,the denture was removed by esophagotomy through a postero-lateral thoracotomy. In the postoperative period the patient developed a leakage of the suture line with resultant esophago-pleural fistula which was managed with double esophageal exclusion. She was discharged on the 40th postoperative day on semi-solid diet and is presently (eight months after the first surgery) symptom free.