Aryl hydrocarbon receptor interacting protein (AIP) significantly influences prognosis of pancreatic carcinoma.

INTRODUCTION: Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor. Aryl hydrocarbon receptor interacting protein (AIP) in one of AHR ligands. The aim of this study is to analyze the prognostic influence of AIP in pancreatic carcinoma. MATERIAL AND METHODS: Retrospective case series with immunohistochemical analysis of AIP. We have estimated a multivariate Cox's model for the outcome (progression free and overall survival). RESULTS: 204 patients were included in the study. As expected prognosis was poor and 67.8% died of disease. As for AIP 9.8% of the cases showed nuclear staining of the epithelial tumor cells and 59.4% a cytoplasmic one. Stroma was stained in 53.1% of the cases. Univariate survival analysis revealed a significantly worse prognosis of patients with cytoplasmic AIP expression (stroma and epithelium), but nuclear expression was associated to a better prognosis. In the multivariate analysis stromal AIP expression was an independent prognosticator of progression free survival, together with pT stage, histological grade and history of diabetes. DISCUSSION: AIP Is a conserved cochaperone protein binding to many proteins. AIP has been proposed as a potential tumor suppressor gene. To date, no study has analyzed the immunohistochemical expression of AIP in pancreatic carcinoma. Our results indicate that both epithelial and stromal cytoplasmic expression of AIP is associated to bad prognosis, while nuclear translocation seems to improve prognosis. CONCLUSION: Although we must deepen into the complex signaling pathways underlying this potential association, our results open a way to inhibiting AHR as a potential target against pancreatic carcinoma.

Spanish multicenter study of surgical resection of pancreatic tumors infiltrating the celiac axis: does the type of pancreatectomy affect results?

BACKGROUND: Pancreatectomy plus celiac axis resection (CAR) is performed in patients with locally advanced pancreatic cancer. The morbidity rates are high, and no survival benefit has been confirmed. It is not known at present whether it is the type of pancreatectomy, or CAR itself, that is the reason for the high complication rates. METHODS: Observational retrospective multicenter study. INCLUSION CRITERIA: patient undergoing TP, PD or DP plus CAR for a pancreatic cancer. RESULTS: Sixty-two patients who had undergone pancreatic cancer surgery (PD,TP or DP) plus CAR were studied. Group 1: 17 patients who underwent PD/TP-CAR (13TP/4PD); group 2: 45 patients who underwent DP-CAR. Groups were mostly homogeneous. Operating time was longer in the PD/TP group, while operative complications did not differ statistically in the two groups. The number of lymph nodes removed was higher in the PD/TP group (26.5 vs 17.3), and this group also had a higher positive node ratio (17.9% vs 7.6%). There were no statistical differences in total or disease-free survival between the two groups. CONCLUSION: It seems that CAR, and not the type of pancreatectomy, influences morbidity and mortality in this type of surgery. International multicenter studies with larger numbers of patients are now needed to validate the data presented here.

CD133 + cell infusion in patients with colorectal liver metastases going to be submitted to a major liver resection (CELLCOL): A randomized open label clinical trial.

BACKGROUND: Treatment of liver metastases of colorectal carcinoma is surgical resection. However, only 10-15% of the patients in this context will be candidate for curative resection arising other 10-13% after response to neoadyuvant chemotherapy. In order to perform the liver metastases surgery, it is necessary to have a sufficient remnant liver volume (RLV) which allows maintaining an optimal liver function after resection. Studies on liver regeneration have determined that CD133 + stem cells are involved in liver hypertrophy developed after an hepatectomy with encouraging results. As presented in previous studies, CD133 + stem cells can be selected from peripheral blood after stimulation with G-CSF, being able to obtain a large number of them. We propose to treat patients who do not meet criteria for liver metastases surgery because of insufficient RLV (<40%) with CD133 + cells together with portal embolization, in order to achieve enough liver volume which avoids liver failure. METHODS: /Design: The aim of this study is to evaluate the effectiveness of preoperative PVE plus the administration of CD133 + mobilized from peripheral blood with G-CSF compared to PVE only. SECONDARY AIMS ARE: to compare the grade of hypertrophy, speed and changes in liver function, anatomopathological study of hypertrophied liver, to determine the safety of the treatment and analysis of postoperative morbidity and surveillance. STUDY DESIGN: Prospective randomized longitudinal phase IIb clinical trial, open, to evaluate the efficacy of portal embolization (PVE) together with the administration of CD133 + cells obtained from peripheral blood versus PVE alone, in patients with hepatic metastasis of colorectal carcinoma (CCRHM). DISCUSSION: The number of CD133 + obtained from peripheral blood after G -CSF stimulation will be far greater than the number obtained with direct puncture of bone marrow. This will allow a greater intrahepatic infusion, which could have a direct impact on achieving a larger and quicker hypertrophy. Consequently, it will permit the treatment of a larger number of patients with an increase on their survival. TRIAL REGISTRATION: ClinicalTrials.gov, ID NCT03803241.

Splenic volume as a biomarker of hepatic damage after chemotherapy in patients with resected colorectal liver metastases (CRLM).

BACKGROUND: Chemotherapy-associated liver injury (CALI) is a matter of concern for hepatobiliary surgeons as it can entail postoperative liver failure after an extensive hepatectomy. Recent studies have taken special interest in liver function parameters which can correlate with CALI to decrease this adverse event. Therefore, the current study investigates the usefulness of splenic volume as a biomarker of CALI through a portal hypertension mechanism, in patients with colorectal liver metastases (CRLM). STUDY DESIGN: We carried out a study in patients with CRLM operated on between 2009 and 2014 in our center. All samples of healthy liver were graded for non-alcoholic fatty liver disease (NAFLD) and sinusoidal obstructive syndrome. Computarized tomography scans for spleen volumetry were analyzed for each patient at CRLM diagnosis, after neoadjuvant chemotherapy, 1 and 6 months after resection. RESULTS: A group of 65 consecutive patients with CRLM of large bowel adenocarcinoma submitted to liver resection were included. Patients receiving neoadjuvant chemotherapy had a greater spleen volume increase than those who did not receive treatment (p = 0.053), finding a statistically significant spleen growth in patients with NAFLD (p = 0.036). There was no correlation between spleen enlargement and postoperative complications or average stay. However, survival was decreased in patients with spleen growth and CALI. CONCLUSIONS: Patients who receive neoadjuvant chemotherapy for liver metastasis surgery have a greater splenic volume increase, which correlates with NAFLD and a lower survival.

Still a place for conventional histopathological analysis in the era of molecular medicine: predicting prognosis of resectable ductal pancreatic adenocarcinoma.

INTRODUCTION: Our aim is to find features that define prognosis in surgically resected ductal pancreatic adenocarcinoma readily accessible in everyday practice. MATERIALS AND METHODS: Longitudinal retrospective case series of pancreatic adenocarcinoma operated with a curative intent in a large tertiary hospital in Madrid between 2009 and 2015. RESULTS: 162 were enrolled. 40.8% survived less than 1 year. Multivariate Cox's regression model revealed that gender, presence of symptoms, T and N stage independently influenced progression-free survival, while overall survival was determined by gender, smoking, presence of symptoms and N stage. Logistic regression analysis revealed that only symptoms at diagnosis could predict death, while gender, symptoms, histopathological type, vessel invasion, T stage and necrosis could independently predict recurrence. DISCUSSION: Our series show that patients with symptomatic disease at the time of diagnosis and females showed a shorter progression-free and overall survival. We herein propose a regression model to predict outcome.

Dissemination of hepatocellular carcinoma in subcutaeous tissue after fine needle aspiration cytology (FNAC).

The hepatocellular carcinoma (HCC) is the fifth most frequent tumor in the world, and the third cause of death related to cancer. Histological samples obtained from diseased liver likely to have HCC are currently prescribed in selected patients in whose imaging studies and tumor markers are not sufficient for the diagnosis. In recent years, a risk of tumoral seeding along needle tract of FNAC to obtain histological samples has been reported. We present a case of tumor implantation of HCC cells in the needle tract, a year and four months after a percutaneous fine needle aspiration cytology (FNAC).

Injury patterns from major urban terrorist bombings in trains: the Madrid experience.

BACKGROUND: Terrorist urban mass casualty incidents (MCI) in the last 3 years have targeted commuter trains at rush hour, producing large numbers of casualties. Civilian care providers are usually not familiar with the types of blast injuries sustained by victims of these MCI. METHODS: We focus on the injury patterns sustained by casualties of the Madrid, 11 March 2004, terrorist bombings, at the seven hospitals that received most victims. Data were gathered of casualties who had injuries other than superficial bruises, transient hearing loss from barotrauma without eardrum perforation, and/or emotional shock. The degree of severity in critical patients was assessed with the ISS. RESULTS: The bombings resulted in 177 immediate fatalities, 9 early deaths, and 5 late deaths. Most survivors had noncritical injuries, but 72 (14%) of 512 casualties assessed had an Injury Severity Score (ISS) >15. The critical mortality rate was of 19.5%. The most frequently injured body regions were the head-neck and face. Almost 50% of casualties had ear-drum perforation, and 60% of them were bilateral. There were 43 documented cases of blast lung injury, with a survival rate of 88.3%. Maxillofacial and open long-bone fractures were most prevalent. Gustillo's grade III of severity predominated in tibia-fibular and humeral fractures. Upper thoracic fractures (D1-6 segment) represented 65% of all vertebral fractures and were associated with severe blast to the torso. Severe burns were uncommon. Eye injuries were frequent, although most were of a mild-to-moderate severity. Abdominal visceral lesions were present in 25 (5%) patients. A multidisciplinary approach was necessary in most operated patients, and orthopedic trauma procedures accounted for 50% of the caseload in the first 24 h. CONCLUSIONS: Ninety-three percent of the fatalities of the Madrid trains terrorist bombings were immediate, and most survivors had noncritical injuries. Closed doors increased the immediate fatality rate in the trains. Severely wounded casualties presented specific patterns of injuries, some of them life-threatening and unusual in other types of trauma mechanisms. Ear-lobe amputations and upper thoracic spine fractures were markers of critical injuries.

Overexpression of c-myc and loss of heterozygosity on 2p, 3p, 5q, 17p and 18q in sporadic colorectal carcinoma.

AIM: The aim of the present study is to evaluate the prognostic influence of loss of heterozygosity on 2p, 3p, 5q, 17p and 18q, and c-myc overexpression on surgically treated sporadic colorectal carcinoma. METHODS: Tumor and non-tumor tissue samples from 153 patients were analyzed. Fifty-one percent of patients were male, and mean age in the series was 67 years. Tumors were located in the proximal colon in 37 cases, in the distal bowel in 37, and in the rectum in 79 patients. c-myc overexpression was studied by means of Northern blot analysis, and loss of heterozygosity through microsatellite analysis. RESULTS: c-myc overexpression was detected in 25% of cases, and loss of heterozygosity in at least one of the studied regions in 48%. There was no association between clinical and pathologic features, and genetic alterations. The disease-free interval was significantly shorter for patients with both genetic alterations; the presence of both events was an independent prognostic factor for poor outcome in the multivariate analysis (RR: 4.34, p < 0.0001). CONCLUSIONS: The presence of both loss of heterozygosity and overexpression of the c-myc oncogene separates a subset of colorectal carcinoma patients who have a shorter disease-free interval after curative-intent surgery.

Recurrence pattern of esophageal cancer after esophagectomy with two-field lymphadenectomy.

AIM: To analyze the pattern of recurrence of esophageal carcinoma after a curative-intention surgical resection. PATIENTS: Ninety-two patients with non-metastatic esophageal carcinoma were included. Ninety percent of patients were male, and the mean age of this series was 61 years. The most frequent histologic subtype was squamous cell carcinoma. Fifty percent of tumors were at or above the tracheal bifurcation. All patients were submitted for transthoracic subtotal esophagectomy plus two-field radical lymphadenectomy, leaving no apparent residual disease. No adjuvant therapy was applied to any patient. RESULTS: Follow-up was complete for 76 out of 80 patients surviving the operation. Thirty-four tumoral recurrences were detected for a disease-free survival af 39% at 9 years after surgery. All recurrences were detected during the first two years after treatment. Tumoral relapse was related to the presence of T3 or T4 tumors, with positive lymph nodes, squamous cell carcinoma subtype and supracarinal location. Nine percent of patients had a distant relapse, 15% had a locorregional relapse and 12% a combination of both. Distant relapse presented significantly earlier. There was no statistical association between type of recurrence and clinico-pathological or surgical features. CONCLUSIONS: After radical surgery for carcinoma of the esophagus, half of the patients relapse in the following two years. Distant metastases happen to appear earlier in the follow-up, but the most frequent recurrence is the locorregional one.

Heterotopic gastric mucosa in the upper esophagus ("inlet patch"): a rare cause of esophageal perforation.

We report the case of a 21-yr-old woman who presented with a perforation of an upper esophageal ulcer on a patch of gastric-type mucosa. Despite surgical closure of the perforation and reinforcement with a pleuro-muscular flap the patient developed an esophageal leakage and died in the postoperative period. Heterotopic gastric mucosa in the upper esophagus is usually an asymptomatic abnormality, discovered incidentally during endoscopic studies carried out for some other reason; however, complications secondary to the inlet patch acid secreting capacity can arise, and this has to be kept in mind to elude life-threatening conditions.

Two-field radical lymphadenectomy in the treatment of esophageal carcinoma.

This paper retrospectively compares post-operative complications, mortality and long-term survival of patients with esophageal carcinoma who were treated with standard esophagectomy or with extended two-field lymph node clearance. Fifty-seven patients with resectable esophageal carcinoma were included in the study. Twenty-eight patients were submitted to a radical two-field esophagectomy and lymphadenectomy, while the remaining 29 were submitted to a standard, more conservative, esophagectomy performed mostly through a transhiatal route. The two groups of patients were similar in all clinical, laboratory and pathologic features. There was a significant lower anastomotic leakage rate in the group of patients submitted to a radical lymph node resection; post-operative respiratory complication rate and mortality were similar in both groups. The overall 5-year survival was 20%. When lymph node resection was performed, the 5-year survival rate rose to 36%; it was 44% when nodal involvement was negative and 19% for N1 patients; when standard esophagectomy was the procedure, these figures were 9% (p < 0.05), and 6% respectively.

Multiple solitary leiomyomata of the esophagus.

The present report communicates a case of multiple solitary leiomyomata of the esophagus. This is an uncommon condition in which multiple, non-confluent, benign esophageal tumors arise in the same patient. The ideal treatment is enucleation of the lesions, but when these are--as in the case reported--huge and annular, or affect the gastroesophageal junction, resection of the gullet must be performed.

Hydatid liver cyst perforation into the digestive tract.

Complications of liver hydatid disease include those related to the compression of adjacent viscus, to the infection of the cyst's contents or to the perforation of the cyst. Perforations into hollow abdominal organs are rare, and can occur secondary to the infection of the cyst or to a primary pathology of the perforated organ. We report on 2 cases of perforation of a liver cyst into the duodenum, 1 due to the presence of a duodenal ulcer, and 1 secondary to a hydatid abscess. The surgical treatment of the lesions and their complications was, in both cases, successful.

[Bochdalek hernia in adults. Apropos of a case in the right side]. / Hernia de Bochdalek en el adulto. A propósito de un caso en el lado derecho.

Posterolateral diaphragmatic hernia (Bochdalek's hernia) is an infrequent finding in adult patients. Most of them are asymptomatic. Symptomatic cases present with digestive symptoms. Sometimes the clinical picture is related to the associated congenital malformations and not to the hernia itself. It is more common on the left side and in most of the cases it lacks of hernia sac. Simple radiologic study is the clue for the diagnosis. A case of Bochdalek's hernia in a 85 year-old patient is presented.