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Accidental iatrogenic intoxications by cytotoxic drugs: error analysis and practical preventive strategies.

OBJECTIVES: Drug errors are quite common. Many of them become harmful only if they remain undetected, ultimately resulting in injury to the patient. Errors with cytotoxic drugs are especially dangerous because of the highly toxic potential of the drugs involved. For medico-legal reasons, only 1 case of accidental iatrogenic intoxication by cytotoxic drugs tends to be investigated at a time, because the focus is placed on individual responsibility rather than on system errors. The aim of our study was to investigate whether accidental iatrogenic intoxications by cytotoxic drugs are faults of either the individual or the system. The statistical analysis of distribution and quality of such errors, and the in-depth analysis of contributing factors delivered a rational basis for the development of practical preventive strategies. METHODS: A total of 134 cases of accidental iatrogenic intoxication by a cytotoxic drug (from literature reports since 1966 identified by an electronic literature survey, as well as our own unpublished cases) underwent a systematic error analysis based on a 2-dimensional model of error generation. Incidents were classified by error characteristics and point in time of occurrence, and their distribution was statistically evaluated. The theories of error research, informatics, sensory physiology, cognitive psychology, occupational medicine and management have helped to classify and depict potential sources of error as well as reveal clues for error prevention. RESULTS: Monocausal errors were the exception. In the majority of cases, a confluence of unfavourable circumstances either brought about the error, or prevented its timely interception. Most cases with a fatal outcome involved erroneous drug administration. Object-inherent factors were the predominant causes. A lack of expert as well as general knowledge was a contributing element. In error detection and prevention of error sequelae, supervision and back-checking are essential. Improvement of both the individual training and work environment, enhanced object identification by manufacturers and hospitals, increased redundancy, proper usage of technical aids, and restructuring of systems are the hallmarks for error prevention. CONCLUSIONS: Errors follow general patterns even in oncology. Complex interdependencies of contributing factors are the rule. Thus, system changes of the working environment are most promising with regard to error prevention. Effective error control involves adapting a set of basic principles to the specific work environment. The work environment should allow for rectification of errors without penalty. Regular and ongoing intra-organisational error analysis needs to be an integral part of any error prevention strategy. However, it seems impossible to totally eliminate errors. Instead, if the environment guarantees timely error interception, most sequelae are avoided, and errors transform into a system-wide learning tool.

Antineoplastic Agents↗

Endodermal cyst ventral to the lower brain stem.

A 28-year-old woman presented with a rare case of endodermal cyst located ventral to the lower brain stem manifesting as recurrent aseptic meningitis. Computed tomography and magnetic resonance imaging demonstrated a cystic mass located ventral to the lower brain stem and extending from the prepontine to the upper cervical (C-2) cistern. The lesion was totally removed through a retrosigmoid craniotomy and C1-2 hemilaminectomy. Histological and immunohistochemical examination showed the cyst was derived from the endoderm. The histological diagnosis was endodermal cyst. Early diagnosis and surgical removal are important for patients with these cysts.

Adult↗

Endodermal sinus tumour of the ovary in pregnancy.

We present a case of a 30-year-old pregnant woman in whom an ovarian mass was identified by ultrasonography at 15 weeks' gestation. A markedly elevated maternal serum alphafetoprotein (MSAFP) suggested a diagnosis of endodermal sinus tumour of the ovary. A right salpingo-oophorectomy at 19 weeks' gestation enabled histological confirmation of the diagnosis and suggested a stage 1 tumour. Unfortunately tumour recurrence necessitated further laparotomy and delivery by caesarean section at 32 weeks' gestation. A total abdominal hysterectomy and left salpingo-oophorectomy was undertaken with resection of the splenic flexure and formation of a double-barrelled colostomy after which no gross intraperitoneal tumour remained. Three weeks later a new suprahepatic tumour mass was excised and the colostomy was closed. The patient then received four cycles of combination chemotherapy with cisplatin, etoposide, and bleomycin. Unfortunately she developed a faecal fistula at the site of the colostomy. Germ cell tumours are highly responsive to chemotherapy. Over-zealous surgery particularly involving bowel resection may cause unnecessary morbidity and compromise the outcome.

Adult↗

Mediastinal endodermal sinus tumour: surgical role in chemotherapy resistant cases.

We report two cases of aggressive mediastinal endodermal sinus tumours (EST) detected incidentally on a chest radiograph. The patients were being investigated for minor chest complaints. After three courses of cisplatin-based chemotherapy the tumour marker levels declined. However, the tumour size continued to increase. Complete surgical removal was possible in one case and significant reduction in tumour mass was achieved in the other. Reduction in the viable, tumour tissue load made the residual tumour sensitive to postoperative chemotherapy. It is important to be aware of endodermal sinus tumours refractory to chemotherapy which may require early surgical intervention.

Adult↗

An unusual presentation of an intra-parenchymatous frontal yolk sac tumour : case report.

Yolk sac tumours are rare conditions among the germ cell tumours. Intracerebral germ cell tumours are exceedingly rare. A 15 year old girl presenting with a one week history of raised intracranial pressure is described. She had bilateral papilloedema and a right 6th nerve palsy. CT scan showed an intra-parenchymatous right frontal ring enhancing lesion of 2 cms diameter. The patient underwent microsurgical total excision of the tumour, followed by chemotherapy. She was asymptomatic at three years following surgery.

Adolescent↗

[Mutation and expression of p16 in human ovarian neoplasms].

OBJECTIVES: To detect mutation and expression of p16 in human ovarian neoplasms and to understand the relations between p16 and development of ovarian neoplasms. METHODS: Polymerase chain reaction-single strand polymorphism analysis and immunohistochemistry were respectively used to detect mutations in exon 1 and 2 and protein expression in 14 patients with ovarian neoplasms. Metastasis tissue of 5 mentioned patients were screened at the same time. RESULTS: No expression of p16 was found in 7 ovarian neoplasm tissues. No mutation in exon 1 of p16 was found in any patient tissues, but mutations in exon 2 were found in 4 patients tissues and expression of p16 was not found in 2 of them. There was correspondence between primary focus and metastasis in either gene mutation or protein expression. CONCLUSIONS: Inactivation of p16 may be involved in the development of ovarian neoplasms. Gene mutation is a kind of inactivation. Alterations of p16 probably occur before metastasis.

Cyclin-Dependent Kinase Inhibitor p16↗

Primary pleuro-pulmonary malignant germ cell tumours.

Lungs and pleura are rare sites for malignant germ-cell tumours. Two cases, pure yolk-sac tumour and yolk sac-sac tumour/embryonal carcinoma are described in young males who presented with rapid progression of respiratory symptoms. The malignant mixed germ cell tumour occurred in the right lung, while the yolk-sac tumour had a pseudomesotheliomatous growth pattern suggesting a pleural origin. Alpha-foetoprotein was immunohistochemically demonstrated in both.

Adolescent↗

Primary mixed germ cell tumour of the liver--a case report.

Germ cell tumours in liver are uncommon. Fewer than 20 cases have been reported in the literature. Primary mixed malignant germ cell tumours of liver are even rare. Here we describe a case of primary mixed malignant germ cell tumour of left lobe of liver in a two and half year old male boy. This is the first reported case of primary mixed malignant germ cell tumour with components of yolk sac tumour and mature teratoma in an infant. The patient complained of gradual increase in abdominal distension, upper abdominal pain and loss of weight. Ultrasonography and computed tomography of the abdomen revealed a large hepatic mass. Serum alpha-feto protein levels were raised. Left lobectomy of liver was done and chemotherapy was initiated. Histopathology of specimen disclosed yolk sac tumour and mature teratoma. Levels of serum alpha-feto protein declined rapidly. Widespread intrahepatic metastasis developed and patient died due to liver dysfunction after six months of left lobectomy.

Child, Preschool↗

Prepubertal testicular tumours in Kashmir--a histopathological report of 15 cases.

A total of 15 cases of prepubertal testicular tumours were reported by the department of pathology, Government Medical College, Srinagar, Kashmir over a period of 15 years, from January 1984 to December 1998. The cases included yolk sac tumour (10 cases; 67%), teratoma [(mature) 2 cases (13%)], rhabdomyosarcoma [(paratesticular) 2 cases (13%)] and NHL-Burkitt's lymphoma [one case (7%)]. The youngest patient was 10 months old and the oldest was of 14 years age. Ten cases (67%) occurred at or below the age of 4 years. The youngest patient had yolk sac tumour and oldest had rhabdomyosarcoma. In 2 cases both the testes were involved with one of these two cases having bilateral undescended testes.

Adolescent↗

[Pancreas pseudocyst or metastasis?].

The authors review a case of a 24-year-old male patient hospitalised for repeated acute abdominal symptoms. His medical history included no diseases worth of mentioning. By imaging techniques (abdominal US and CT scan) a cystic lesion, measuring 40 x 35 x 30 mm in diameter was found, and was diagnosed as pseudocyst in the region of the tail of the pancreas. Jejunal feeding was introduced. The lesion did not improve and the second CT scan suggested a suspicion of pancreatic cystadenoma. Three months after first presentation the surgical resection was performed. The tumour, however, was found independent of the pancreas (90 x 80 x 50 mm). Both histologically and immunohistochemically the lesion proved to be the metastasis of a germ cell (yolk-sac) tumour. Following the morphological diagnosis, detailed urological and medical check up was performed. A previously nonpalpable small tumour was found in the left testis which was radically resected. The testicular tumour measuring 9 x 9 x 5 mm in diameter was diagnosed as embryonal carcinoma. Later on the patient underwent chemotherapy. He has been undergoing close oncological followup. Clinically, he is disease free. Authors emphasize the importance of imaging techniques and fine needle aspiration cytology in the case of retroperitoneal masses in young males. The possibility of a metastasis, especially of germ cell origin, should be excluded (not only by physical examination, but by ultrasound of testis also) in case of retroperitoneal cystic tumours even with unusual morphology.

Adult↗

Primary germ cell tumours of the mediastinum.

Twenty nine cases of primary mediastinal germ cell tumours (MGCT) were seen at the Tata Memorial Hospital over a 16--year period (1974-1989). There were 5 benign MGCT occurring predominantly in females (80%), with these patients having an excellent result after surgery with all patients disease free at an median follow-up of 27 months. Malignant MGCT occurred only in males and demonstrated wide variation in response to treatment depending upon whether the tumour was seminomatous or non-seminomatous. There were 11 Seminomas, 5 Embryonal carcinomas, 5 Endodermal sinus tumours and 3 Teratocarcinomas. The diagnosis was established by surgical exploration or by biopsy of a lymph node or chest wall nodule in 20 patients. Four patients had needle biopsy. Seminomatous MGCT received radiotherapy as their main treatment modality and did well with 75% of the patients alive without disease at an average follow up of 33 months. The non-seminomatous MGCT could be divided into two groups. The mean survival for patients receiving cisplatinum based chemotherapy was 14 months as compared to the group not receiving such therapy where the survival was only 5.3 months. However, because of the advanced disease at presentation even in the group receiving cisplatinum chemotherapy, a long term complete response rate of only 20% could be achieved.

Adolescent↗