Tumor lysate-based vaccines: on the road to immunotherapy for gallbladder cancer.

Immunotherapy based on checkpoint blockers has proven survival benefits in patients with melanoma and other malignancies. Nevertheless, a significant proportion of treated patients remains refractory, suggesting that in combination with active immunizations, such as cancer vaccines, they could be helpful to improve response rates. During the last decade, we have used dendritic cell (DC) based vaccines where DCs loaded with an allogeneic heat-conditioned melanoma cell lysate were tested in a series of clinical trials. In these studies, 60% of stage IV melanoma DC-treated patients showed immunological responses correlating with improved survival. Further studies showed that an essential part of the clinical efficacy was associated with the use of conditioned lysates. Gallbladder cancer (GBC) is a high-incidence malignancy in South America. Here, we evaluated the feasibility of producing effective DCs using heat-conditioned cell lysates derived from gallbladder cancer cell lines (GBCCL). By characterizing nine different GBCCLs and several fresh tumor tissues, we found that they expressed some tumor-associated antigens such as CEA, MUC-1, CA19-9, Erb2, Survivin, and several carcinoembryonic antigens. Moreover, heat-shock treatment of GBCCLs induced calreticulin translocation and release of HMGB1 and ATP, both known to act as danger signals. Monocytes stimulated with combinations of conditioned lysates exhibited a potent increase of DC-maturation markers. Furthermore, conditioned lysate-matured DCs were capable of strongly inducing CD4+ and CD8+ T cell activation, in both allogeneic and autologous cell co-cultures. Finally, in vitro stimulated CD8+ T cells recognize HLA-matched GBCCLs. In summary, GBC cell lysate-loaded DCs may be considered for future immunotherapy approaches.

Evaluación de la sobrevida a largo plazo del carcinoide del apéndice cecal. Un análisis a partir de 8.903 apendicectomías / Long-term survival in carcionoid tumour of the appendix. An analysis of 8903 appendectomies

IntroducciónEl tumor del apéndice cecal más frecuente es el carcinoide y en la mayoría de los enfermos es un hallazgo del estudio anatomopatológico. Los objetivos de este trabajo son analizar las características clínicas y anatomopatológicas, el tratamiento quirúrgico y la sobrevida a largo plazo de una serie de pacientes con un tumor carcinoide apendicular.Material y métodosEstudio retrospectivo de pacientes con diagnóstico anatomopatológico de carcinoide apendicular tratados entre 1980 y 2007. Se analizaron las características clínicas, el estudio anatomopatológico, el tratamiento quirúrgico y la sobrevida alejada.ResultadosDurante este período se realizaron 8.903 apendicectomías y a 40 pacientes (0,44%) se les diagnosticó un carcinoide apendicular: 25 mujeres y 15 varones con una edad de 37±18 años. En 33 enfermos la cirugía se realizó por sospecha de apendicitis aguda, la que se confirmó en 24 de ellos. El tumor se ubicó en el tercio distal del apéndice en 24 pacientes (60%) y en 28 enfermos (70%), y midió 1cm o menos. Veintinueve (72,5%) de estos tumores infiltraron la subserosa o la serosa. A 3 enfermos se les realizó una hemicolectomía derecha complementaria y en ninguno de ellos se observó afectación ganglionar. El tiempo de seguimiento promedio fue 81,2 meses. La sobrevida a 5 años de la serie fue del 97,5%.ConclusionesEl diagnóstico de un carcinoide apendicular en la mayoría de los enfermos es un hallazgo en pacientes operados por sospecha de apendicitis aguda. La mayoría de los enfermos logra una sobrevida prolongada sólo con la apendicectomía(AU)

IntroductionAppendiceal carcinoids are the most frequent tumors of the appendix and are usually detected as an incidental finding in the final pathology report. The aim of this study was to evaluate the clinical and pathological characteristics, surgical treatment and long-term survival in patients with an appendiceal carcinoid tumor.Material and methodsWe performed a retrospective study of patients treated from 1980 to 2007 with a pathological diagnosis of appendiceal carcinoid tumor. In all patients, clinical and pathological characteristics, surgical treatment and long-term survival were evaluated.ResultsIn this period, 8903 appendectomies were performed. Carcinoid tumor was diagnosed in 40 patients (25 women and 15 men), aged 37±18 years old. The appendectomy was performed for appendicitis in 33 of these patients, and the final pathology report confirmed the diagnosis in 24. The tumor was localized in the distal third of the appendix in 24 patients (60%), and the size of the tumor was less than 1cm in 28 (70%). Twenty-nine (72.5%) of these tumors infiltrated the subserosal and/or the serosal layer. Three patients were treated with a complementary right colectomy and none had lymph node compromise. The mean follow-up was 81.2 months. The overall 5- year survival was 97.5%.ConclusionsAppendiceal carcinoid tumor is usually detected incidentally in the pathological analysis in patients undergoing surgery for suspected appendicitis. Long-term survival is high with appendectomy alone(AU)

[Long-term survival in carcinoid tumour of the appendix. An analysis of 8903 appendectomies]. / Evaluación de la sobrevida a largo plazo del carcinoide del apéndice cecal. Un análisis a partir de 8.903 apendicectomías.

INTRODUCTION: Appendiceal carcinoids are the most frequent tumors of the appendix and are usually detected as an incidental finding in the final pathology report. The aim of this study was to evaluate the clinical and pathological characteristics, surgical treatment and long-term survival in patients with an appendiceal carcinoid tumor. MATERIAL AND METHODS: We performed a retrospective study of patients treated from 1980 to 2007 with a pathological diagnosis of appendiceal carcinoid tumor. In all patients, clinical and pathological characteristics, surgical treatment and long-term survival were evaluated. RESULTS: In this period, 8903 appendectomies were performed. Carcinoid tumor was diagnosed in 40 patients (25 women and 15 men), aged 37+/-18 years old. The appendectomy was performed for appendicitis in 33 of these patients, and the final pathology report confirmed the diagnosis in 24. The tumor was localized in the distal third of the appendix in 24 patients (60%), and the size of the tumor was less than 1cm in 28 (70%). Twenty-nine (72.5%) of these tumors infiltrated the subserosal and/or the serosal layer. Three patients were treated with a complementary right colectomy and none had lymph node compromise. The mean follow-up was 81.2 months. The overall 5- year survival was 97.5%. CONCLUSIONS: Appendiceal carcinoid tumor is usually detected incidentally in the pathological analysis in patients undergoing surgery for suspected appendicitis. Long-term survival is high with appendectomy alone.

[Postoperative radio-chemotherapy in locally advanced gastric cancer]. / Radio-quimioterapia postoperatoria en cáncer gástrico localmente avanzado.

BACKGROUND: Overall 5 years survival for surgically excised gastric cancer is 30%. Adjuvant treatment may improve the surgical results. AIM: To assess treatment results and toxicity in patients with surgically excised gastric cancer, treated with adjuvant radiotherapy and concomitant continuous 5-Fluorouracil (5-FU). MATERIAL AND METHODS: Forty one patients aged 32 to 73 years (29 males) with stage II-IVA gastric cancer, subjected to a total or subtotal gastrectomy and D2 nodal dissection between 1997 to 2006, were studied. They received adjuvant radiotherapy to the gastric bed and draining nodes in a total dose of 50.4 Gy in 28 fractions and chemotherapy with continuous infusion 5-FU, 200 mg/m(2)/day. Results were compared to historical controls matched according to demographic parameters and tumor characteristics. RESULTS: Eighteen patients were in stage II, 10 in stage IIIA, nine in stage IIIB and four in stage IVA. Twelve patients had an NO nodal status, 15 were NI, nine were N2 and five were N3. After a mean follow up of 32 months, 26 patients (63%) were alive. Five year overall survival was 49.6% for surgery plus radiochemotherapy compared to 30.7% for the historical group subjected only to surgery (p =0.002). Radiotherapy was associated with grade 1-2 toxicity and treatment was completed without interruptions in all patients. Chemotherapy was delayed temporarily in 3 patients. CONCLUSIONS: Adjuvant radio-chemotherapy improved overall survival in gastric cancer, compared to historical controls subjected only to surgical treatment.

Radio-quimioterapia postoperatoria en cáncer gástrico localmente avanzado / Postoperative radio-chemotherapy in locally advanced gastric cancer

Background: Overall 5 years survival for surgically excised gastric cancer is 30 percent. Adjuvant treatment may improve the surgical results. Aim: To assess treatment results and toxicity in patients with surgically excised gastric cancer, treated with adjuvant radiotherapy and concomitant continuous 5-Fluorouracil (5-FU). Material and Methods: Forty one patients aged 32 to 73 years (29 males) with stage II-IVA gastric cancer, subjected to a total or subtotal gastrectomy and D2 nodal dissection between 1997 to 2006, were studied. They received adjuvant radiotherapy to the gastric bed and draining lymphatic nodes in a total dose of 50.4 Gy in 28 fractions and chemotherapy with continuous infusión 5-FU, 200 mg/m²/day. Results were compared to historical controls matched according to demographic parameters and tumor characteristics. Results: Eighteen patients were in stage II, 10 in stage IIIA, nine in stage IIIB and four in stage IVA. Twelve patients had an NO nodal status, 15 were NI, nine were N2 and five were N3. After a mean follow up of 32 months, 26 patients (63 percent) were alive. Five year overall survival was 49.6 percent for surgery plus radiochemotherapy compared to 30.7 percent for the historical group subjected only to surgery (p =0.002). Radiotherapy was associated with grade 1-2 toxicity and treatment was completed without interruptions in all patients. Chemotherapy was delayed temporarily in 3 patients. Conclusions: Adjuvant radio-chemotherapy improved overall survival in gastric cancer, compared to historical controls subjected only to surgical treatment.

[Splenic abscesses. Report of seven cases]. / Abscesos esplénicos: Comunicación de siete casos y revisión de la literatura.

BACKGROUND: Splenic abscesses are uncommon, appear in subjects with predisposing factors such as systemic infections and have high mortality rates. AIM: To report seven patients with splenic abscesses. MATERIAL AND METHODS: Retrospective review of medical records of patients with a splenic abscess treated between 1987 and 2005. RESULTS: The records of four women and three males aged 20 to 74 years, were reviewed. The most common presenting symptoms were fever and abdominal pain and all had predisposing factors. Six patients had a leukocyte count of 19,500 x mm(3). Mean erythrocyte sedimentation rate and C reactive protein values were 75 mm/h and 13.5 mg/dl. Diagnosis was made with ultrasound in two patients and CT scan in five. Six patients had an unique abscess and one patient had multiple lesions. A splenectomy was done in three patients as the first choice treatment and in one, due to medical treatment failure. In two patients, a CT guided percutaneous drainage was performed and one patient was subjected to medical treatment only. Abscess cultures were positive in 50% of patients subjected to percutaneous drainage and in 50% of splenectomized patients. No patient died and no complications were observed in the early or late postoperative period. CONCLUSION: Splenic abscesses are associated to predisposing conditions. The first choice is surgical treatment, but percutaneous drainage is also a therapeutic option.

[Bouveret syndrome: report of four cases]. / Síndrome de Bouveret: Resolución endóscopica y quirúrgica de cuatro casos clínicos.

UNLABELLED: Bouveret syndrome is a duodenal obstruction caused by a biliary stone. AIM: To report patients with Bouveret syndrome. MATERIAL AND METHODS: Retrospective review of medical records of patients with Bouveret syndrome treated between 1976 and 2006. RESULTS: We report three women and one man with a mean age of 62.5 years. None had a previous diagnosis of cholelithiasis. AH presented with colicky pain in the right upper quadrant and vomiting, suggesting gastric retention. The diagnosis was suspected after a barium meal in two patients and with a CT scan on the other two. The endoscopical extraction or fragmentation of stones was attempted in three patients but was successful only in one. Three patients were operated and a stone impacted in the first portion of the duodenum was identified, along with a cholecystoduodenal fistula. A duodenostomy and stone extraction was performed. One patient was subjected to a cholecystectomy fistula repair and gastrojejunoanastomosis. No patient died and all were discharged within 8 to 12 days after surgery. CONCLUSIONS: Bouveret syndrome is an uncommon complication of cholelithiasis. Endoscopy can be diagnostic and therapeutic. Surgery is the other therapeutic option.

Síndrome de Bouveret: Resolución endóscopica y quirúrgica de cuatro casos clínicos / Bouveret syndrome: Report of four cases

Bouveret syndrome is a duodenal obstruction caused by a biliary stone. Aim: To report patients with Bouveret syndrome. Material and Methods: Retrospective review of medical records of patients with Bouveret syndrome treated between 1976 and 2006. Results: We report three women and one man with a mean age of 62.5 years. None had a previous diagnosis of cholelithiasis. AH presented with colicky pain in the right upper quadrant and vomiting, suggesting gastric retention. The diagnosis was suspected after a barium meal in two patients and with a CT scan on the other two. The endoscopical extraction or fragmentation of stones was attempted in three patients but was successful only in one. Three patients were operated and a stone impacted in the first portion of the duodenum was identified, along with a cholecystoduodenal fistula. A duodenostomy and stone extraction was performed. One patient was subjected to a cholecystectomy fistula repair and gastrojejunoanastomosis. No patient died and all were discharged within 8 to 12 days after surgery. Conclusions: Bouveret syndrome is an uncommon complication of cholelithiasis. Endoscopy can be diagnostic and therapeutic. Surgery is the other therapeutic option.

[Laparoscopic Heller myotomy for esophageal achalasia]. / Resultados inmediatos y tardíos de la miotomía de Heller laparoscópica en pacientes con acalasia esofágica.

BACKGROUND: Achalasia is characterized by an incomplete relaxation of the lower esophageal sphincter. The best treatment is surgical and the laparoscopic approach may have good results. AIM: To assess the results of laparoscopic Heller myotomy among patients with achalasia. MATERIAL AND METHODS: Prospective study of patients subjected to a laparoscopic Heller myotomy between 1995 and 2004. Clinical features, early and late operative results were assessed. RESULTS: Twenty seven patients aged 12 to 74 years (12 females) were operated. All had disphagia lasting for a mean of 32 months. Mean lower esophageal sphincter pressure ranged from 18 to 85 mmHg. Eight patients received other treatments prior to surgery but symptoms persisted or reappeared. The preoperative clinical score was 7. No patient died and no procedure had to be converted to open surgery. In a follow up of 21 to 131 months, all patients are satisfied with the surgical results and the postoperative clinical score is 1. Only one patient with a mega esophagus maintained a clinical score of six. CONCLUSIONS: In this series of patients, laparoscopic Heller myotomy was an effective and safe treatment for esophageal achalasia.

Resultados inmediatos y tardíos de la miotomía de Heller laparoscópica en pacientes con acalasia esofágica / Laparoscopic Heller myotomy for esophageal achalasia

Background: Achalasia is characterized by an incomplete relaxation of the lower esophageal sphincter. The best treatment is surgical and the laparoscopic approach may have good results. Aim: To assess the results of laparoscopic Heller myotomy among patients with achalasia. Material and methods: Prospective study of patients subjected to a laparoscopic Heller myotomy between 1995 and 2004. Clinical features, early and late operative results were assessed. Results: Twenty seven patients aged 12 to 74 years (12 females) were operated. All had disphagia lasting for a mean of 32 months. Mean lower esophageal sphincter pressure ranged from 18 to 85 mmHg. Eight patients received other treatments prior to surgery but symptoms persisted or reappeared. The preoperative clinical score was 7. No patient died and no procedure had to be converted to open surgery. In a follow up of 21 to 131 months, all patients are satisfied with the surgical results and the postoperative clinical score is 1. Only one patient with a mega esophagus maintained a clinical score of six. Conclusions: In this series of patients, laparoscopic Heller myotomy was an effective and safe treatment for esophageal achalasia.

[Multiple carcinoid tumors of the small bowel. Report of one case]. / Carcinoide intestina múltiple. Análisis de un caso y revisión de la literatura.

Small bowel carcinoid tumors are more common in the distal ileum and they are multiple in 30% of cases. The most common clinical manifestation is abdominal pain and the treatment of choice is surgical excision. We report a 63 years old female consulting for abdominal pain. An intestinal transit by computed axial tomography revealed multiple images compatible with small bowel carcinoid tumors. She had a surgical excision of the involved intestinal segment and the pathological study confirmed the imaging diagnosis. In the follow up, this patients has been asymptomatic.

[Advances in radiography of the small intestine: computed tomography enteroclysis]. / Avances en radiología del intestino delgado: enteroclisis por tomografía computarizada.

Computed tomography (CT) enteroclysis is a new technique consisting of helical CT of the abdomen and pelvis after administration of water through a nasojejunal tube and intravenous contrast, resulting in adequate distension and visualization of the small bowel wall. The use of this technique is especially recommended in patients with gastrointestinal bleeding of unknown etiology, possible neoplastic processes of the small bowel, partial small bowel obstruction, and inflammatory bowel disease. One-hundred consecutive patients underwent CT enteroclysis (multiple detectors; 8, 16, or 64) over a 1-year period for suspected lesions of the small bowel. Of these, 31 were positive: Crohn's disease (17), tumors (8), partial obstruction (2), radiation enteritis (1), sprue (1), pneumatosis cystoids (1), and dilatation of bowel loops (1). In 28 of the 31 patients, the findings were confirmed by pathology, endoscopy or clinical follow-up.

Avances en radiología del intestino delgado: enteroclisis por tomografía computarizada / Advances in intestinal radiology: computed tomography enteroclysis

La enteroclisis por tomografía computarizada (TC) es una nueva técnica que consiste en una TC helicoidal con múltiples detectores realizada tras la administración de agua a través de una sonda nasoyeyunal y medio de contraste intravenoso, lo que permite una adecuada distensión y visualización del intestino delgado. El uso de esta técnica está especialmente indicado en pacientes con enfermedad inflamatoria intestinal, hemorragia digestiva de causa no precisada, obstrucción parcial de intestino delgado y sospecha de neoplasia intestinal. Un total de 100 pacientes consecutivos se sometieron a una enteroclisis por TC (multiples detectores: 8, 16 o 64) debido a la sospecha de lesión en el intestino delgado. De ellos, 31 presentaron lesiones en esa localización: enfermedad de Crohn (n = 17), tumores (n = 8), obstrucción intestinal (n = 2), enteritis actínica (n = 1), enfermedad celíaca (n = 1), neumatosis cistoide (n = 1) y dilatación de asas (n = 1); 28 de los 31 casos fueron confirmados por anatomía patológica, hallazgos endoscópicos o seguimiento clínico

Computed tomography (CT) enteroclysis is a new technique consisting of helical CT of the abdomen and pelvis after administration of water through a nasojejunal tube and intravenous contrast, resulting in adequate distension and visualization of the small bowel wall. The use of this technique is especially recommended in patients with gastrointestinal bleeding of unknown etiology, possible neoplastic processes of the small bowel, partial small bowel obstruction, and inflammatory bowel disease. One-hundred consecutive patients underwent CT enteroclysis (multiple detectors; 8, 16, or 64) over a 1-year period for suspected lesions of the small bowel. Of these, 31 were positive: Crohn's disease (17), tumors (8), partial obstruction (2), radiation enteritis (1), sprue (1), pneumatosis cystoids (1), and dilatation of bowel loops (1). In 28 of the 31 patients, the findings were confirmed by pathology, endoscopy or clinical follow-up

[Appendectomies for suspected acute appendicitis during pregnancy: experience at a Chilean public hospital]. / Apendicectomía en la embarazada: experiencia en un hospital público chileno.

BACKGROUND: Acute appendicitis is the most common non obstetric surgical emergency during pregnancy. AIM: To asses our experience in the diagnosis and management of acute appendicitis occurring during pregnancy. PATIENTS AND METHODS: Data from all pregnant patients who were subjected to an appendectomy for a suspected acute appendicitis from January 1998 to December 2002, were retrospectively analyzed. All pathological, surgical, clinical records and the delivery outcome registry of each patient were reviewed. RESULTS: Among 47,322 deliveries, 46 pregnant women aged 29+/-9 years and with a gestational age of 21+/-7 weeks, were operated because of a presumptive acute appendicitis. Forty (87%) had a histopathologically proven appendicitis; ten (25%) cases had a perforated appendix and 30 (75%) had a non-perforated appendicitis. Five (10.9%) patients had a negative laparotomy and one had a necrotic ovarian tumor. Patients with perforated and non perforated appendices had a similar lapse from the onset of symptoms to operation (69+/-45 and 50+/-34 hours respectively, NS) and a similar white cell count (15,667+/-3,707 and 13,006+/-5,206 cells/mm(3), respectively, NS). Wound infection was the most common surgical complication in 15%. Seven (15%) patients had a premature delivery and there was one fetal death (2.2%). There were no pregnancy complications on negative appendectomy cases. CONCLUSIONS: Acute appendicitis continues to be a challenge in diagnosis and treatment during pregnancy. Maternal and fetal outcome was better than previously reported.

Survival of young patients after gastrectomy for gastric cancer.

It has been suggested that gastric cancer has a worse prognosis in young patients, but the data are controversial. The aim of this study was to compare the 5-year survivals after gastrectomy for gastric cancer in two groups of patients (those < or = 45 years of age and those (> 45 years) and to determine some of the prognostic factors. The 5-year survival was significantly better for patients < or = 45 years of age. Survival was also better for young patients with a curative resection and also for those with lymph node metastases. However, survival was not significantly different for the two groups when the resection was not curative and when the lymph nodes were not involved. Survival was no different for the two groups when compared at each stage, although a multivariate analysis showed that age > 45 years, moderate or poor degree of differentiation of the tumor, advanced tumors, the presence of lymph node involvement, and a noncurative resection were independent negative prognostic factors. Long-term survival after gastrectomy for gastric cancer depends on the stage of the disease; the age of the patient is not a decisive factor.