Comparison of oncological outcomes after open and laparoscopic re-resection of incidental gallbladder cancer.

BACKGROUND: The safety and oncological efficacy of laparoscopic re-resection of incidental gallbladder cancer have not been studied. This study aimed to compare laparoscopic with open re-resection of incidentally discovered gallbladder cancer while minimizing selection bias. METHODS: This was a multicentre retrospective observational cohort study of patients with incidental gallbladder cancer who underwent re-resection with curative intent at four centres between 2000 and 2017. Overall survival (OS) and recurrence-free survival (RFS) were analysed by intention to treat. Inverse probability of surgery treatment weighting using propensity scoring was undertaken. RESULTS: A total of 255 patients underwent re-resection (190 open, 65 laparoscopic). Nineteen laparoscopic procedures were converted to open operation. Surgery before 2011 was the only factor associated with conversion. Duration of hospital stay was shorter after laparoscopic re-resection (median 4 versus 6 days; P < 0·001). Three-year OS rates for laparoscopic and open re-resection were 87 and 62 per cent respectively (P = 0·502). Independent predictors of worse OS were residual cancer found at re-resection (hazard ratio (HR) 1·91, 95 per cent c.i. 1·17 to 3·11), blood loss of at least 500 ml (HR 1·83, 1·23 to 2·74) and at least four positive nodes (HR 3·11, 1·46 to 6·65). In competing-risks analysis, the RFS incidence was higher for laparoscopic re-resection (P = 0·038), but OS did not differ between groups. Independent predictors of worse RFS were one to three positive nodes (HR 2·16, 1·29 to 3·60), at least four positive nodes (HR 4·39, 1·96 to 9·82) and residual cancer (HR 2·42, 1·46 to 4·00). CONCLUSION: Laparoscopic re-resection for selected patients with incidental gallbladder cancer is oncologically non-inferior to an open approach. Dissemination of advanced laparoscopic skills and timely referral of patients with incidental gallbladder cancer to specialized centres may allow more patients to benefit from this operation.

ANTECEDENTES: No se conoce la seguridad y la eficacia oncológica de la re-resección laparoscópica del cáncer incidental de vesícula biliar. Este estudio tiene como objetivo comparar las re-resecciones del cáncer incidental de vesícula biliar por vía laparoscópica y vía abierta, minimizando el sesgo de selección. MÉTODOS: Estudio de cohortes observacional, retrospectivo y multicéntrico de pacientes con cáncer incidental de vesícula biliar que se sometieron a una re-resección con intención curativa en 4 centros entre 2000 y 2017. Se analizó la supervivencia global (overall survival, OS) y la supervivencia libre de recidiva (recurrence free survival, RFS) según intención de tratamiento. Se calculó la probabilidad inversa de la ponderación del tratamiento quirúrgico utilizando puntuación de propensión. RESULTADOS: Se incluyeron 255 pacientes con re-resección (190 por vía abierta y 65 por vía laparoscópica). Se convirtieron 19 pacientes del grupo laparoscópico. El único factor relacionado con la conversión fue la realización de la cirugía antes de año 2011. La mediana de la estancia hospitalaria fue más corta tras la re-resección laparoscópica (4 versus 6 días; P < 0,001). La OS a tres años fue del 87% y del 62% (P = 0,502) para las re-resecciones laparoscópicas y abiertas, respectivamente). Los factores predictivos independientes relacionados con una peor OS fueron el hallazgo de cáncer residual en el momento de la re-resección (cociente de riesgos instantáneos, hazard ratio, HR 1,91; i.c. del 95% 1,17-3,11), una pérdida hemática > 500 ml (HR 1,83; i.c. del 95% 1,23-2,74) y la presencia de ≥ 4 ganglios positivos (HR 3,11; i.c. del 95% 1,46-6,65). En el análisis de riesgo competitivo, la RFS fue mayor para la resección laparoscópica (P = 0,038), pero no hubo diferencias en la OS entre ambos grupos. Los factores predictivos independientes de peor RFS fueron la detección de 1-3 ganglios positivos (HR 2,16; i.c. del 95% 1,29-3,60), ≥ 4 ganglio positivos (HR 4,39; i.c. del 95% 1,96-9,82) y el cáncer residual (HR 2,42; i.c. de 95% 1,46-4,0). CONCLUSIÓN: En pacientes seleccionados, los resultados oncológicos de la re-resección laparoscópica de un cáncer incidental de vesícula biliar no son inferiores a los que se obtienen por vía abierta. Una mayor difusión de las técnicas laparoscópicas avanzadas y una oportuna derivación de los pacientes con cáncer de vesícula biliar incidental a centros especializados podrían permitir que un mayor número de pacientes se beneficiaran de este abordaje.

Retrospective analysis of the prognostic significance of DNA ploidy patterns and S-phase fraction in gastric carcinoma.

Paraffin-embedded tumor samples from 493 gastric carcinoma patients were analyzed by DNA flow cytometry. The results were correlated with clinicopathological findings and S-phase fractions measured by in vivo bromodeoxyuridine (BrdUrd) labeling. Of the 493 patients, 183 (37%), 225 (46%), and 85 (17%) showed diploidy, single DNA-aneuploidy, and DNA-multiploidy patterns, respectively. When the DNA histogram and all the clinicopathological parameters were entered simultaneously into the Cox regression model, DNA ploidy, liver metastasis, peritoneal dissemination, and nodal status emerged as independent prognostic parameters. The relative risk of death was twofold higher in single DNA-aneuploid and threefold higher in DNA-multiploid tumors than in DNA-diploid tumors. BrdUrd labeling indices (LIs) also proved to be an independent prognostic factor. Multiploid tumors showed the highest median BrdUrd LI associated with the most frequent peritoneal dissemination and liver metastasis. The simultaneous evaluation of DNA ploidy patterns and BrdUrd LIs gave more prognostic information than the determination of tumor DNA ploidy only. Namely, DNA diploid, together with low BrdUrd LIs, was associated with favorable prognosis, whereas DNA aneuploid with high BrdUrd LIs was related to the poorest prognosis. These results indicate that DNA ploidy and BrdUrd labeling indices may be possibly useful prognostic factors for gastric carcinoma.

DNA ploidy pattern and tumor suppressor gene p53 expression in gallbladder carcinoma.

The relationship between p53 gene expression and DNA content in advanced gallbladder carcinoma was studied. Fifty-three cases of advanced gallbladder carcinoma (45 primary tumors and 8 metastases) were analyzed, p53 protein expression was determined by immunohistochemistry, DNA content was measured by cytophotometric techniques. Study subjects included 45 (85%) female and 8 male patients, with an overall mean age of 58.6 years. Positive staining for p53 protein was observed in 27 (51%) cases. In subserosal tumors, the expression was significantly less than that in tumors that reached the serosa (P = 0.01). Twenty-nine (55%) cases were diploid and 24 were aneuploid. Sixty-seven % of primary tumors were diploid, whereas 87% of metastases showed an aneuploid DNA content. Both diploid and aneuploid tumors were positive for the p53 protein in the same proportion, and p53 was also expressed equally in both primary and secondary tumors. In advanced gallbladder carcinoma, the expression of the p53 gene was earlier than the accumulation of abnormal quantities of chromosomal DNA in the tumor cells. The determination of these events as markers in preneoplastic lesions is warranted in gallbladder carcinogenesis.

Experience in the surgical treatment of 331 patients with pulmonary hydatidosis.

Echinococcus disease is prevalent in Chile, with a rate of occurrence of 8.2 per 100,000. During a 15-year-period (1970 to 1985) we operated on 331 patients for pulmonary hydatidosis. Chest roentgenography was the main method of diagnosis. Among the total of 508 surgical procedures performed, pulmonary cystectomy was the most common (61.4%), whereas pulmonary resection was used in 31.4% of patients. The arc 5 test was used to confirm the diagnosis. Results were positive in 85% of the patients in whom it was done. There were 12.9% immediate postoperative complications in 12.9%, with late complications occurring in 4.10% and an overall mortality rate of 4.21%. These data suggest that hydatid cyst is still a common disease in our country, causing an important number of hospital admissions and a high percentage of complications.

Pancreatojejunostomy.

Pancreatoduodenectomy is a complex procedure associated with considerable mortality and morbidity. Pancreatojejunostomy is probably the main cause of morbidity, and controversy concerning the best type of reconstruction still exists. In this report the technique of pancreatojejunostomy is demonstrated. An end-to-side pancreatojejunostomy is performed on all patients. For patients with a pancreatic duct of less than 4 mm in diameter, the top of the pancreatic duct is inserted into a stab-wound of jejunum. It is secured with a purse-string suture. Furthermore, two layers of reinforcement are done. By using this technique, an end-to-side anastomosis was done on patients with soft glands and small ducts. In patients with a pancreatic duct greater than 4 mm, a three-layer anastomosis is done between pancreas and jejunum. This is a technique that allows the performance of an end-to-side anastomosis regardless of the pancreas consistency or pancreatic duct diameter.

Preoperative chemoradiotherapy in the treatment of gallbladder cancer.

Gallbladder cancer is generally associated with a poor prognosis, with local recurrence being the main pattern of failure. In an attempt to improve on the present status of management, we evaluated a prospective Phase II study involving preoperative 5-fluorouracil and radiation. Among 27 eligible patients with a potentially resectable gallbladder cancer detected after cholecystectomy, 18 were treated with preoperative radiation (4500 cGy; 180 cGy/fraction, 5 days/week) concurrent with a continuous infusion of 5-fluorouracil (350 mg/m2/day, days 1-5 and 21-25). Toxicity included leukopenia (8 patients) and thrombocytopenia (7 patients). Delay in surgery due to hematological toxicity was seen in 6 patients. Of the 18 patients, 15 underwent a reoperation. Resection was performed in 13 (86%). Pathologic findings after reoperation revealed residual tumor in both liver and lymph nodes in 3 patients. At a median follow-up of 24 months, 7 patients are alive. Among the patients who died after curative resection, local recurrence was demonstrated in only 1. This is the first report concerning preoperative chemoradiation in gallbladder cancer. To assess its effect on survival, a prospective randomized trial will be necessary.

Gallbladder cancer, management of early tumors.

In spite of the fatal course associated with patients with gallbladder cancer, there is a subgroup of them in whom prognosis could be improved. Although early gallbladder cancer is considered a tumor with invasion of the mucosa or the muscular layer, in this manuscript we analyze those with invasion confined to the gallbladder. Pre-operative diagnosis of these patients is rare with cholecystectomy specimen histologic analysis being the most common way of detecting these tumors. The level of wall invasion represents a useful and practical way of dividing the patients according to their prognosis and treatment. Mucosal and muscular invasion tumors could be cured by simple cholecystectomy. Among patients with a tumor confined to the gallbladder, those with subserosal infiltration represent the largest group. Residual tumor after cholecystectomy is a common fact in these patients, thus a more aggressive procedure than simple cholecystectomy should be performed. Generally, extended cholecystectomy is the preferred approach for dealing with these patients. Unfortunately, in spite of the employment of extended and potentially curative surgery, prognosis is still poor and additional therapeutic procedures are needed. Finally, when tumors compromise the serosal layer, 5-year survival is poor irrespective of the type of therapy. However, well-selected cases deserve to undergo aggressive treatment.

Gallbladder cancer in a high risk area: morphological features and spread patterns.

BACKGROUND/AIMS: Gallbladder carcinoma is one of the most frequent malignant tumors in Chile. The aim of this paper is to show our experiences in gallbladder carcinoma. METHODOLOGY: Six-hundred-sixty-nine cases of gallbladder carcinoma were included in this prospective study; 557 females (83.5%) and 112 males (16.5%). In 466 cases (70%), diagnosis was carried out in the cholecystectomy sample, 45 cases were partial cholecystectomies and 158 cases were metastases of gallbladder carcinoma. RESULTS: Ninety-eight per cent of the cases were adenocarcinomas, and in 85% of the cases gallstones were observed. Thirty-seven per cent of the primary tumors were macroscopically inapparent. One-hundred-thirty-one cases (29%) were early carcinomas and 323 cases (71%) were advanced carcinomas. A relationship between differentiation grade and infiltration level (p=0.0001) was observed. Lymph-node metastasis was found in 18.5%, 4.5% and 3.3% in the first, second and third lymph-node barriers respectively. Muscular tumors presented no lymph-node metastasis, while in serosal tumors lymph node metastasis reached 62% (p=0.04). Hepatic tumor infiltration was observed in 11%, 19% and 38% of muscular, subserosal and serosal tumors. CONCLUSIONS: The high frequency of inapparent carcinomas, gallstones and inflammatory changes of the vesicular wall are elements that make the pre-operative diagnosis of gallbladder carcinoma difficult. Differentiation grade and infiltration level are the most reliable prognostic factors in gallbladder carcinoma. Lymph-node metastasis or liver tumor infiltration are infrequent in early gallbladder carcinoma.

Intraoperative chemohyperthermic peritoneal perfusion as an adjuvant to gastric cancer: final results of a randomized controlled study.

BACKGROUND/AIMS: Although the most frequent cause of death after curative resection of advanced gastric cancer is peritoneal recurrence, there was no effective therapy for the prevention of peritoneal recurrence. This randomized trial sought to determine whether intraoperative chemohyperthermic peritoneal perfusion could eliminate microscopic residual disease and thereby improve survival of patients with advanced gastric cancer. METHODOLOGY: One-hundred and thirty-nine patients with T2-4 gastric cancer underwent curative gastrectomy with extended lymphadenectomy. These patients were randomly allocated into the following three groups. Patients in the CHPP group received surgery + chemohyperthermic peritoneal perfusion, and those in the CNPP group underwent surgery + chemonormothermic peritoneal perfusion. The third group was surgery alone group. In the CHPP and CNPP groups, peritoneal cavity was perfused with 6-8 liters of heated saline at, respectively, 42-43 degrees C and 37 degrees C with 30 mg of mitomycin C and 300 mg of cisplatin by a extracorporeal circulation machine. RESULTS: Major operative complication occurred in 19% (9/48), 14% (6/44) and 19% (9/47) of the CHPP, CNPP and surgery alone group, respectively. Complication which uniquely developed after chemohyperthermic peritoneal perfusion was bowel perforation. Mortality rates of each group were 4% (2/48), 0% (0/44) and 4% (2/47) in the CHPP, CNPP and surgery alone group, respectively. Overall 5-year survival rates of CHPP, CNPP and surgery alone groups were 61%, 43% and 42%, respectively. In a subset analysis, patients with gastric cancer having serosal invasion or lymph node metastasis have shown a statistically significant improvement in survival when treated with chemohyperthermic peritoneal perfusion. However, chemonormothermic peritoneal perfusion had no survival benefit. By analyzing with Cox proportional hazard model, chemohyperthermic peritoneal perfusion emerged as an independent prognostic factor for good survival. Surgery alone had three-fold higher risk of death than chemohyperthermic peritoneal perfusion. CONCLUSIONS: Chemohyperthermic peritoneal perfusion had an efficiency for the prophylaxis of recurrence after curative resection of advanced gastric cancer, and is indicated for patients with tumor infiltrating beyond serosal layer and node positive tumor.

Choledochoduodenostomy for common bile duct stones.

Among the techniques for dealing with common bile stones, choledochoduodenostomy (CDS) represents a useful alternative. This operation is indicated mainly in patients with recurrent stones, giant stones, or concomitant common bile stricture and duct stones. At the present time most of the patients undergoing CDS have been already undergone endoscopic retrograde cholangiography or ultrasonography to study the common bile duct and the cause of symptoms. The common bile duct diameter is of paramount importance when determining the feasibility of performing a CDS, the critical size being 1.2 cm. The most common operation is a side-to-side anastomosis employing absorbable sutures. Stomal patency is the most important factor for preventing classic complications such as cholangitis and sump syndrome. These complications are rare, being observed in only 5% of the patients. Long-term results of the operation show that it is a safe procedure that should be considered a good option in selected patients with choledocholithiasis.

[Hereditary chronic pancreatitis. Report of a case]. / Pancreatitis crónica hereditaria. Comunicación de un caso.

Childhood hereditary pancreatitis is a rare entity of uncertain etiology, characterized by recurrent episodes of acute pancreatitis, abdominal pain and other unspecific symptoms. Among several therapeutic alternatives, pancreatojejunostomy is presently the treatment of choice. We report a 17 years old male with chronic hereditary pancreatitis that was treated with pancreatojejunostomy drainage.

[Gallbladder cancer: a review]. / Cáncer de la vesícula biliar. Algunas consideraciones.

In Chile, gallbladder cancer is the tumor with the highest mortality rates among women. Cholelithiasis is the most common associated factor and the reduction in cholecystectomy rates could be an important factor in the incidence of gallbladder cancer. Unfortunately, the disease is diagnosed late and the study of the surgical piece is the main form of early recognition. The degree of gallbladder wall infiltration by the tumor is the simplest and best staging method that has prognostic value. Gallbladder fat must be considered as a separate tissue, since its biological behavior differs from that of the subserous. The treatment of these tumors is based in their dissemination modality that is mainly local and regional. Surgical resection and radiotherapy are potentially effective. However the detection of high risk patients that should be subjected to cholecystectomy should be the better therapeutic alternative.

[Determination of DNA content by means of cytophotometry. Technical and methodological considerations and its application in tumor pathology]. / Determinación del contenido de ADN mediante citofotometría. Consideraciones técnicas, metodológicas y su aplicación en patología tumoral.

The cytofluorometric determination of ADN content in tumoral cells from 33 tumors is reported. Twenty five epithelial (2 benign and 23 malignant) and 8 non epithelial tumors (1 benign and 7 malignant) were studied. All the benign tumors had a normal ADN content (2c); on the other hand, 65% of malignant tumors had an abnormal ADN content. All non epithelial malignant tumors were aneuploid. Among aneuploid tissues, epithelial tumors were frequently tetraploid (4c) and non epithelial tumors were frequently polyploid 6c, 8c, 12c). It is concluded that this technique gives valuable information about the biological characteristics of tumoral cells and that its results could be incorporated to the routine anatomopathological study of tumoral lesions.

[Stomach neoplasms in the IX Region of Chile: comparison of the anatomo-pathological study of lymph node emptying in 2 periods]. / Cáncer gástrico en la IX Región de Chile. Comparación del estudio anatomopatológico de vaciamientos ganglionares linfáticos en dos periodos.

Complete resection of lymph nodes may help achieve a cure in patients with gastric cancer. In this paper we evaluate the yield of a careful search for lymph nodes in fresh tissue obtained immediately after resection. A mean of 42.5 nodes per gastric piece was obtained, which is significantly higher than that previously reported with examination of fixed tissue. The yield was higher for all node groups except the left para-cardial one.

[Nucleolus organizer regions and ploidy pattern of DNA in stomach neoplasms]. / Regiones del organizador nucleolar y patrón de ploidía del ADN en el cáncer gástrico.

We studied 20 gastric adenocarcinoma to determine DNA ploidy pattern by flow cytometry and nucleolar organizer regions by the colloidal silver method. There were 12 diffuse and 8 intestinal type lesions. 11 tumors were classified as diploid and 9 as aneuploid. No correlation was observed between DNA ploidy pattern and mean number of nucleolar organizer regions. The histologic type was significantly related to the number of nucleolar organizer regions (p < 0.01). Poorly differentiated lesions had significantly less nucleolar organizer regions than intestinal type lesions. Lesions with ring cells (n = 6) had similar number of nucleolar organizer regions than poorly differentiated lesions.

[Lithiasis of gallbladder in the IX region. Study of the autopsies in a zone with a high proportion of Mapuche population]. / Litiasis de la vesicula biliar en la IX region. Estudio de autopsias en una zona con alta proporcion de poblacion mapuche.

The frequency of gallbladder stones in he IXth Region of Chile with a large indigenous population, was studied in forensic necropsies from 1980 to 1989. Among 2,505 autopsies, 85% were males and 15% females. At least 1 "mapuche" surname occurred in 27% of cases. Stones were found in 34% of females and 12.7% of males. No differences were found between "mapuche" and non mapuche cases. Cholecystectomy had been performed in 2.3% of males and 9.1% of males. These results do not differ from those reported from other regions in Chile.

p53 detection as a prognostic factor in early gastric cancer.

Immunohistochemical detection of p53 was performed in archival material of 129 early gastric cancers. Positive staining was detected in 22.5% (29/129) of the cases. No significant association could be established with any clinicopathological criteria but a trend of a higher rate of p53 detection was observed among large tumors (> 6 cm) and in cases with lymph node involvement. Prognosis was significantly worse for patients with p53-positive staining tumors. The 5-year survival rate was 92.1% for patients with p53-negative tumors and 71.2% for those with positive malignancies (p = 0.001). p53 detection and lymph node involvement emerged as independent prognostic factors in a Cox model including other clinicopathological criteria. Immunochemical detection of p53 may become an important aid in the preoperative evaluation of patients with early gastric cancer.

[Advances in the diagnosis and treatment of pancreatic carcinoma]. / Avances en el diagnóstico y tratamiento del cáncer de páncreas.

Pancreatic carcinoma has a dismal prognosis. In the last years, great efforts have been made to improve diagnosis and preoperative staging of potentially curable carcinomas. Actually, the diagnosis of fairly small tumours is possible. Chemoradiation therapy protocols prior to pancreatectomy, aiming to improve survival, are currently being held. This therapy allows radiation to be distributed into well oxygenated cells before surgical devascularization. This procedure can be done with acceptable morbidity and mortality rates. In selected cases of irresectable carcinoma, surgical palliation allows a better quality of life. Pancreatoduodenal resection, along with other traditional oncological therapies, will continue to be the therapy of choice for patients with carcinoma of the head of the pancreas, without local or regional metastases. However, an intensive search for new therapeutic strategies, specially in the field of molecular biology, is being carried out.

[Gallbladder cancer in the IX Region of Chile. Impact of the anatomopathological study of 474 cases]. / Cáncer de vesícula biliar en la IX región de Chile. Impacto del estudio anatomopatológico en 474 casos.

We studied prospectively 474 cases (83% female with a female:male ratio of 5:1) of gallbladder carcinoma diagnosed in a period of 7 years. Twenty two percent of patients were younger than 50 years old. Ninety percent of tumors were adenocarcinomas. In 1987, 45% of cases were diagnosed in metastases compared to 1993, when only 10% of tumors were diagnosed in such histological material. Thirty four percent of tumors were not macroscopically identified; all these inapparent tumors were advanced in 1987, whereas 53% were incipient in 1993. Moreover, inapparent tumors had a significantly lower degree of gallbladder wall infiltration and higher degree of differentiation. Well differentiated tumors had a lesser degree of wall infiltration. It is concluded that the careful histopathological study of gallbladder cancer has allowed a thorough knowledge of the natural history and clinical presentation of gallbladder carcinoma.