Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic: Chilean Air Force Experience in the Air Transport of Critically Ill Patients-The First 100 Cases.

OBJECTIVE: Critical care air transport has played an important role during the coronavirus disease 2019 (COVID-19) pandemic. The goal of this article is to analyze results and lessons learned from the evacuation of the first 100 COVID-19 patients transported between medical facilities in Chile. METHODS: We reviewed prospective data of patients who were referred for air transport between March 27, 2020, and July 9, 2020. RESULTS: Of 115 referred patients, 100 were transported by air. All patients were intubated and mechanically ventilated. Hypertension, diabetes, and obesity were the most commonly observed comorbidities. Our service did not experience any major problems in patient care en route or among the crewmembers. We did not observe any severe acute respiratory syndrome coronavirus 2 infections among our flight team members during the study period. Twelve (12%) patients died at their destination intensive care unit, whereas the remaining 88 patients (88%) returned to their primary hospitals after recovery. CONCLUSIONS: Air transport of mechanically ventilated patients with COVID-19 infection has been shown to be a safe way of transport, with no in-flight deaths and an in-hospital mortality of 12%, which compares favorably with the in-hospital mortality of similar patients who did not undergo air transport.

Incidental Gallbladder Cancer: How Residual Disease Affects Outcome in Two Referral HPB Centers from South America.

BACKGROUND: Residual disease (RD) has been described as one of the most relevant prognostic factors after radical surgical resection for incidental gallbladder cancer (IGC). The purpose of the present study was to analyze patterns of RD and determinant prognostic factors in patients undergoing re-resection for IGC. METHODS: Patients undergoing re-exploration due to IGC between 1990 and 2014 were identified in two referral centers from different South-American countries. Patients submitted to a radical definitive operation were included in the study. Demographics and tumor-treated related variables were analyzed in correlation with RD and survival. The site of RD, local (gallbladder bed) or regional (lymph nodes and bile duct) was correlated with disease-specific survival (DSS). RESULTS: Of 265 patients with IGC submitted to surgery, 168 underwent a radical re-resection and RD was found in 58 (34.5%). Demographic, clinical and surgical variables were compared between both centers showing differences in type of resection, laparoscopic approach, T stages and disease stage. Location of RD was regional in 34 (20.2%) and local in 24 (14.3%), and no residual disease was found in 110 (65.5%) patients. T stage (T1b = 20%, T2 = 23.8%, T3 = 71.7%, p < 0.001) and disease stage (p < 0.001) were independent predictors of RD. Finding RD at any location reduced the DSS in comparison with non-RD patients (19.6 months vs. 62.7 months p < 0.001). No differences in DSS according to the location of RD were found, and all anatomic sites were equally poor (p = 0.27). RD at any site predicted DSS (p < 0.001), independently of all other IGC variables. CONCLUSIONS: IGC presented similar clinical parameters in two different countries of South America. RD was demonstrated as the most critical prognostic variable in patients with IGC treated by a radical resection. The presence of RD was associated with poor outcome, independently of any anatomic location. Future studies incorporating neoadjuvant chemotherapy in the treatment of patients with prognostic factors for RD are required to improve survival in this entity.

Laparoscopic management of incidental gallbladder cancer.

BACKGROUND: The laparoscopic cholecystectomy has allowed the detection of an increasing number of incidental gallbladder cancers (IGBC). Although laparoscopy is employed in the management of a variety of abdominal tumors, its use in gallbladder cancer is reduced and controversial. This study analyzes the role of laparoscopy in gallbladder cancer with the focus in IGBC. METHOD: We evaluated our prospective series of 51 patients with an IGBC who were treated by laparoscopy between 2006 and 2016 at the Clinica Alemana in Santiago, Chile. RESULTS: The series comprised 7 men and 44 women. Age ranged from 43 to 76 years (mean age 60). Regarding wall involvement, 29 patients had a T2 tumor, which was the most common. 8 and 14 patients had T1b and T3 tumors, respectively. Of the patients, 17 underwent only laparoscopic exploration. This was due to the presence tumor dissemination not being observed in the preoperative staging. 10 patients had to be converted to complete the resection, whereas 24 patients were laparoscopically resected. The quality of the resected material was not different between those who were converted and those who were treated by laparoscopy. In the laparoscopic group, the average number of harvested lymph nodes was 7.9, not statistically different from the converted group. The mean of hospital stay in the laparoscopic group (4.3 days) was significantly lower than the converted group. CONCLUSIONS: Laparoscopy has been shown to be a safe and feasible method for the management of IGBC. This method not only allows for a complete exploration, identifying a previously unseen residual tumor, but also makes it possible to accomplish the same oncology objectives as the open procedure. Therefore, laparoscopy should be considered a valid alternative in the management of IGBC.

Inactivation of tumor suppressor gene pten in early and advanced gallbladder cancer.

BACKGROUND: PTEN is a tumor suppressor gene that regulates the PTEN/PI3k/AKT/mTOR pathway, which is frequently altered in human cancers including gallbladder cancer (GBC). To determine the frequency of PTEN expression in GBC and to establish its relation to clinical and morphological parameters and survival in GBC. METHODS: The immunohistochemical expression of PTEN was studied in 108 GBC. All the cases included areas of non-tumor mucosa adjacent to the tumor. RESULTS: The group was comprised of 108 patients, 91 women (84.3%) and 17 men (15.7%) with an average age of 65.2 years (SD ± 12.3 years). Thirty-five cases (33%) were early carcinomas (EC) and the remaining 73 (67%) were advanced cases (AC). All the internal controls were positive (moderate or intense in 96.3%). Only in three AC (4.1%) was there a complete absence of PTEN immunohistochemical expression. There were no significant differences in relation between PTEN expression and tumor infiltration or degree of differentiation. The three patients with PTEN inactivation died before 10 months; however, the other patients with AC had a survival of 53% at 10 months. DISCUSSION: Loss of PTEN expression was observed in 4.1% of the advanced GBC. All the patients with this alteration died before 10 months. PTEN inactivation could be a rare event, but with a poor prognosis in advanced GBC.

Gallbladder cancer in Chile: what have we learned?

PURPOSE OF REVIEW: Gallbladder cancer (GBC) should be considered an orphan disease in oncology and represent a unique carcinogenetic model. This review will analyse some of the current aspects of GBC. RECENT FINDINGS: Chile has the highest incidence and mortality of GBC in the world. Most patients are diagnosed in advanced stages with few treatment options. During the last two decades, little progress has been made in early diagnosis and treatment. At the molecular level, recent access to next-generation sequencing and other techniques for detecting the mutations of multiple genes have made advances in this area. SUMMARY: The use of therapies targeted according to the detection of specific molecular alterations is in the early stages of evaluation and could represent a significant advance in the treatment of a large number of patients from developing countries.

A review of recent data in the treatment of gallbladder cancer: what we know, what we do, and what should be done.

Gallbladder cancer is now considered a distinct clinical entity, allowing for a separate analysis from that of other malignancies of the biliary tree. Symptoms related to a malignant tumor of the gallbladder include jaundice and abdominal pain, or a palpable abdominal mass that occurs in a late stage of the disease. The majority of patients with operable gallbladder cancer are diagnosed by cholecystectomy performed for presumed benign disease, mostly cholelithiasis, a clinical entity known as incidental gallbladder cancer. Given the poor prognosis if tumor invasion beyond the muscular layer and/or nodal metastasis is found, adjuvant treatments have been implemented, but few data are available to guide treatment decisions in this setting. For advanced disease, a multidisciplinary treatment approach including biliary drainage procedures and palliative support is needed in the management of this aggressive disease. Palliative chemotherapy with a combination of gemcitabine and cisplatin or oxaliplatin is the standard treatment based on the findings of two phase III trials that showed improved overall survival compared to single-agent chemotherapy and best supportive care. Several phase II studies have been reported investigating the role of targeted agents against EGFR, VEGF, HER2, and MEK. International collaboration to enhance our knowledge of gallbladder cancer should be encouraged.

Overexpression of the HER2/neu Gene: A New Therapeutic Possibility for Patients With Advanced Gallbladder Cancer.

BACKGROUND: The HER2/neu gene is a proto-oncogene that can predict the response to treatment with trastuzumab, pertuzumab, and lapatinib. This study was conducted to determine the frequency of HER2/neu overexpression and to identify a subgroup of patients with gallbladder cancer who would benefit from targeted therapy. METHODS: Patients with gallbladder cancer (n = 187; 165 women and 22 men) with a recorded follow-up of at least 5 years were included, along with control subjects (n = 75). An automated immunohistochemical technique was used with an anti-ErbB2 antibody. Scoring was conducted according to the CAP/ASCO (College of American Pathologists/American Society of Clinical Oncology) criteria for breast cancer. RESULTS: Overexpression of HER2/neu was observed in 12.8% of the cases. Of those, 0% were mucosal, 14.3% muscular, 12.8% subserosal, and 10.6% serosal. In 20% of the cases, equivocal staining was observed. Overexpression was more frequent in the advanced cancers and in the better differentiated tumors (13.8% and 17.4%, respectively), but the difference was nonsignificant. The patients with overexpression of HER2/neu had a worse overall survival, when compared with those who had no expression at 5 years (34% vs. 41%). CONCLUSION: This is the single largest study of HER2/neu expression in gallbladder cancer to use commonly accepted scoring criteria. The results indicate that HER2/neu overexpression occurred in 14% of the advanced gallbladder cancer cases. This subgroup may benefit from inhibitors of the HER2/neu pathway.

Gallbladder cancer in Chile: Pathologic characteristics of survival and prognostic factors: analysis of 1,366 cases.

OBJECTIVES: To explore gallbladder cancer (GBC), the second leading cause of cancer-related death in women in Chile. METHODS: Analysis of macroscopic and microscopic variables, morphometry, and survival in 1,366 patients with GBC. RESULTS: Patients comprised 1,138 women and 228 men; diagnoses included 213 (15.6%) cases of mucosal carcinoma, 132 (9.7%) cases of muscular carcinoma, 316 (23.1%) cases of subserosal carcinoma, 382 (28.0%) cases of serosal carcinoma, and 323 (23.6%) cases beyond the serosa. Women older than 55 years with a gallbladder length greater than 9.5 cm had a five-times-greater relative risk of cancer. Those with a gallbladder wall thickness less than 7 mm had a better 5-year survival rate than those with a gallbladder wall thickness greater than 10 mm (P = .0001). Patients who had cholesterolosis of the gallbladder had 9.2 times less probability of having cancer. The infiltration level of the gallbladder wall was the most important independent prognostic factor (P < .001), followed by differentiation and lymphatic involvement (P < .001 and P = .05, respectively). Vascular infiltration had a mortality rate of 100%. CONCLUSIONS: Morphologic features are strongly associated with the prognosis of GBC and must be taken into consideration when supplementary treatment is recommended.

¿Es posible utilizar las muestras de colecistectomías con cáncer en investigación?: Calidad del ADN de muestras obtenidas del sistema público y privado de salud / Quality of DNA from archival pathological samples of gallbladder cancer

Background: The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. Aim: To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. Material and Methods: One hundred ninety four samples coming from fve medical centers in Chile, were analyzed. DNA extraction was quantifed determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (β-globin products of 110, 268 and 501 base pairs). Results: The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. Conclusions: Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

[HER2 gene amplification and overexpression in advanced gastric cancer]. / Expresión y amplificación del gen HER2 en el cáncer gástrico avanzado.

BACKGROUND: Overexpression/amplification of the HER2 gene in advanced gastric cancer is a predictor of response to adjuvant therapy with monoclonal antibodies. AIM: To determine the frequency of HER2 gene overexpression and amplification in advanced gastric cancer. MATERIAL AND METHODS: One hundred nine advanced gastric cancer biopsy specimens, from 76 men and 33 women aged 67 ± 14 and 62 ± 12 years respectively, were selected. Three histological patterns (diffuse, intestinal and mixed) were recognized. Automated immunohistochemistry was performed with monoclonal c-erbB-2 (NCL-356) Novocastra. Fluorescent in situ hybridization (FISH) for HER2 was performed in positive cases. RESULTS: In 39% of cases, immunohistochemical staining was negative. It was 1+, 2+ and 3+ positive in 15, 36 and 11% of cases, respectively. It was positive in 16% and 3% of intestinal type and mixed carcinomas, respectively. It was negative in all diffuse carcinomas. FISH was performed in 39 (2 +) cases and in 11 (3 +) cases. The gene amplification was positive in two (2 +) and 11 (3 +) cases (11.9%). The overall concordance between immunohistochemical staining and in situ hybridization was 85%. CONCLUSIONS: In advanced gastric cancer, HER2 gene overexpression or amplification was observed in 11% and 12% of cases, respectively.

[Quality of DNA from archival pathological samples of gallbladder cancer]. / ¿Es posible utilizar las muestras de colecistectomías con cáncer en investigación?: Calidad del ADN de muestras obtenidas del sistema público y privado de salud.

BACKGROUND: The quality of the archival samples stored at pathology services could be a limiting factor for molecular biology studies. AIM: To determine the quality of DNA extracted from gallbladder cancer samples at different institutions. MATERIAL AND METHODS: One hundred ninety four samples coming from five medical centers in Chile, were analyzed. DNA extraction was quantified determining genomic DNA concentration. The integrity of DNA was determined by polymerase chain reaction amplification of different length fragments of a constitutive gene (ß-globin products of 110, 268 and 501 base pairs). RESULTS: The mean DNA concentration obtained in 194 gallbladder cancer samples was 48 ± 43.1 ng/µl. In 22% of samples, no amplification was achieved despite obtaining a mean DNA concentration of 58.3 ng/ul. In 81, 67 and 22% of samples, a DNA amplification of at least 110, 268 or 501 base pairs was obtained, respectively. No differences in DNA concentration according to the source of the samples were demonstrated. However, there were marked differences in DNA integrity among participating centers. Samples from public hospitals were of lower quality than those from private clinics. CONCLUSIONS: Despite some limitations, in 80% of cases, the integrity of DNA in archival samples from pathology services in our country would allow the use of molecular biology techniques.

[Palliative treatment for locally advanced or metastatic gallbladder cancer: conclusions of the Latin American Consensus meeting for the management of gallbladder cancer]. / Manejo paliativo del cáncer de vesícula biliar irresecable o metastásico: conclusiones del Consenso Latinoamericano de Manejo del Cáncer de Vesícula Biliar.

Gallbladder cancer is a rare disease in Western developed countries, but it is a highly prevalent and lethal disease in Chile and other countries in Latin America. No randomized controlled trials have been performed in gallbladder cancer to establish standard treatments. We therefore performed the first Latin American consensus meeting for the management of gallbladder cancer. In this article we present the conclusions of the panel of experts for the palliative treatment of unresectable or metastatic gallbladder cancer based on a review of the literature, the discussion of the participating experts and the opinion of the assistants. The topics reviewed included: (1) Gallbladder cancer and cholangiocarcinoma--are they the same disease?; (2) Palliative chemotherapy: indications, drugs and schedules; (3) Palliative radiotherapy; (4) Palliative Surgery; (5) Management of malignant biliary obstruction.

Gastric leak after sleeve gastrectomy: analysis of its management.

BACKGROUND: Bariatric surgery is increasingly being performed and sleeve gastrectomy (SG) has proved to be effective and safe. Among its complications, leaks are the most serious and life threatening. METHODS: The focus of the study is nine patients who underwent a SG and developed a gastric leak after surgery. Our data were obtained from the clinical charts of the patients and through interviews with the surgeon who performed the index surgery. RESULTS: Eight patients underwent SG at outside institutions while one was operated at Clinica Alemana. Three patients developed symptoms within 5 days after surgery, while the rest were diagnosed after 10 days from the surgery. A CT scan was the method used to confirm the diagnosis in all patients. The three patients who had a leak detected during the immediate postoperative period underwent laparoscopic reoperation. Among the rest of the patients, percutaneous drainage was employed in one patient as the primary procedure while the other underwent surgical drainage. An esophageal endoluminal stent was employed in four patients. The leak closed in all patients with the healing time ranging from 21 to 240 days. CONCLUSIONS: Diagnosis of a leak after a SG required a greater index of suspicion in order to perform an early diagnosis. Sepsis control and nutritional support are the cornerstones of this treatment. Evolution is characterized by longer periods of time that are necessary in order to wait until the leak closes. Management must be tailored to each patient.

Manejo paliativo del cáncer de vesícula biliar irresecable o metastásico: Conclusiones del Consenso Latinoamericano de Manejo del Cáncer de Vesícula Biliar / Palliative treatment for locally advanced or metastatic gallbladder cancer: conclusions of the Latin American Consensus meeting for the management of gallbladder cancer

Gallbladder cancer is a rare disease in Western developed countries, but it is a highly prevalent and lethal disease in Chile and other countries in Latin America. No randomized controlled trials have been performed in gallbladder cancer to establish standard treatments. We therefore performed the first Latin American consensus meeting for the management of gallbladder cancer. In this article we present the conclusions of the panel of experts for the palliative treatment of unresectable or metastatic gallbladder cancer based on a review of the literature, the discussion of the participating experts and the opinion of the assistants. The topics reviewed included: 1.- Gallbladder Cancer and Cholangiocarcinoma -are they the same disease?; 2. - Palliative Chemotherapy: Indications, Drugs and Schedules; 3. - Palliative Radiotherapy; 4.- Palliative Surgery; 5.-Management of Malignant Biliary Obstruction.

ERCC1 (excision repair cross-complementing 1) expression in pT2 gallbladder cancer is a prognostic factor.

Gallbladder cancer (GBC) is the main cause of death by malignant tumour in women in Chile. There is no information regarding the role of excision repair cross-complementing group 1 (ERCC1) in GBC. Our aim is to determine the expression and significance of ERCC1 as a prognostic factor in GBC. Tissue microarrays were prepared using 200 surgically resected GBCs and 50 non-malignant gallbladders as controls. In 190 cases, ERCC1 was determined by immunohistochemistry. The correlation between ERCC1 expression and GBC pathological characteristics and patient survival were analysed. Ninety-five percent of the non-malignant gallbladder epithelia showed intense and diffuse ERCC1 expression. GBC cases showed ERCC1 expression in the tumour cells in 100/190 (53%) cases. The best differentiated tumours showed significantly greater expression than the less differentiated (p<0.05). Patients with ERCC1-positive status with subserosal carcinomas (pT2) had significantly better survival than ERCC1-negative patients at 20 and 60 months of follow-up (p=0.005), and the probability of dying was 6 times lower for ERCC1-positive than for ERCC1-negative patients. Our preliminary results show that chole-cystectomised patients with GBC in stage pT2 and with ERCC1 expression have significantly better survival than patients at the same stage that did not present ERCC1 expression.

[Association between cholesterolosis and gallbladder cancer]. / Colesterolosis y cáncer de la vesícula biliar.

BACKGROUND: Cholesterolosis is frequently observed in cholecystectomies performed for lithiasis or chronic cholecystitis. AIM: To determine the degree of association between cholesterolosis and gallbladder cancer. MATERIAL AND METHODS: In a prospective study of gallbladder cancer, all gallbladders obtained during cholecystectomies were processed for pathological study, following a special protocol. As part of this study, 23,304 surgical samples obtained between 1993 and 2002 were studied, looking for a relationship between cholesterolosis and chronic cholecystitis, adenomas, dysplasia and gallbladder cancer. RESULTS: Seventy nine percent of patients were women. Cholesterolosis was observed in 3123 cases (13.4%). Cholesterolosis was more common in women (14.2%) than in men (10.2%9) (p < 0.001). In the same period, 29 patients were diagnosed with adenomas (0.12%), 179 cases with dysplasia not associated with gallbladder cancer (0.8%) and 739 gallbladder cancer (3.2%). The frequency of cholesterolosis was 13.8% in chronic cholecystitis, 13.7% in adenomas, 12.1% in dysplasias and 1.35% in patients with gallbladder cancer (p < 0.01). Of the thirteen cases with gallbladder cancer and cholesterolosis, 10 were early gallbladder carcinomas. Patients with cholesterolosis were 9.2 times less likely td have cancer than those who did not have cholesterolosis. CONCLUSIONS: Cholesterolosis has a strong negative association with gallbladder cancer.

Alcohol absorption modification after a laparoscopic sleeve gastrectomy due to obesity.

BACKGROUND: The different bariatric surgery techniques that alter the digestive anatomy also modify the gastric absorption surface. Since alcohol is a substance that is mainly metabolized in the stomach, the goal of this study was to determine alcohol absorption before and after a laparoscopic sleeve gastrectomy (LSG) in the same patients. METHODS: Studies were carried out on 12 morbidly obese patients who underwent a LSG (eight men and four women). Each patient was given 3.6 ml of red wine to drink at 14% for each liter of body water mass. Alcotest values (Alcoscan Alcomate AL-6000) were measured 10 min after the wine dose had been consumed. Measurements were then repeated every 5 min until the alcohol had been completely eliminated from the bloodstream. During the postoperatory period (median of 2.3 months), the measurement was repeated with the total dose per kg adjusted to the new water body mass. The results were measured with a nonparametric analysis for repeated samples. RESULTS: The maximum average peak of the Alcotest was 2.02 g/l during the postoperative period compared to 0.87 g/l during the preoperative period (p = 0.001 Wilcoxon). At 175 min, the blood alcohol level value reaches zero (0) in all pre-operatory patients, while after surgery, an average value of 0.26 g/l was observed (p = 0.027 Wilcoxon). After 4 h, an Alcotest average of 0.20 g/l was observed in these patients. CONCLUSION: Alcohol absorption was considerably modified after LSG with higher and longer blood alcohol values for equivalent amounts of alcohol.

Gallbladder cancer: role of laparoscopy in the management of potentially resectable tumors.

BACKGROUND: The aim of this study was to evaluate the role that laparoscopy plays in the management of gallbladder cancer. METHOD: From August 2005 to March 2009, 23 patients affected by gallbladder cancer detected after the study of a cholecystectomy specimen underwent laparoscopy as part of their management. RESULTS: Among the patients, 5 underwent only an exploratory laparoscopy, while 11 were converted due to the existence of dense adhesions that precluded a complete exploration. Of the patients with adhesions who underwent conversion, three were unresectable. The remainder underwent a lymphadenectomy and liver resection after conversion. Of the seven who underwent a complete laparoscopic exploration, five had a lymphadenectomy and liver resection done completely by laparoscopy while conversion was needed for two. Conversion was required due to lymphatic metastasis at the hepatic pedicle and the presence of a bile leak. Postoperative time was uneventful, with patients discharged within 3 days of the operation. CONCLUSIONS: Laparoscopy may be employed in the management of patients with early forms of gallbladder cancer undergoing reoperation. Although the presence of adhesions may result in inadequate exploration, there is a subset of patients for whom it is possible to perform a complete exam. Furthermore, laparoscopic lymphadenectomy and gallbladder bed resection is a promising technique in well-selected patients.