Case Report. TRACO November 20, 2012 Oluwadamilola Olaku MD, MPH. NCI/DCTD/OCCAM. Objectives ● Describe the history of cancer case reports. ● Recognize potential roles of case reports. ● Describe case reports. ● Outline pertinent information for a good case report.
November 20, 2012
Oluwadamilola Olaku MD, MPH.
Objectives ●Describe the history of cancer case reports.●Recognize potential roles of case reports.●Describe case reports.●Outline pertinent information for a good case report.
Definition Case reports are brief reports describing an isolated clinical case or a small number of cases. They may describe new or uncommon diagnoses, unusual outcomes or prognosis, new or infrequently used therapies and side effects of therapy not usually discovered in clinical trials. (Khalid Khan, PeterThompson)
‘…Any patient that goes through the door of this hospital is a potential case report…’ Anonymous (The Montreal General Hospital)
History There has been a long descriptive history of case reporting in cancer patients.In the book titled Clinical Case Reporting in Evidence-Based Medicine, Milos Jenicek eloquently describes case reports as the first line of evidence, where everything begins.
CASE REPORTSSome of the earliest case reports describing individual patients afflicted with cancer can be traced back to the papyrus records of Ancient Egyptian medicine of approximately 1600 B.C.. These reports were the first recorded incurable tumors of the breast. Farrow JH
Case reports- New diagnosis ●Historically case reports were the subject of letters between colleagues that ultimately became the origin of journals.●Case reports of melanoma were described by Hippocrates in the fifth century B.C. and also by Rufus of Ephesus, a Greek physician, in the first century A.C. (Urteaga et al)●In January 1832, Thomas Hodgkin reported six cases to the Medical-Chirurgical Society of London, two of which were what we know today as Hodgkin’s lymphoma. (Altschuler EL)
Case report-New Diagnosis ● In1957, Dennis P. Burkitt described a tumor that presented as a growth in the angle of the jaw of African children. ●In 1990, Farcet et al. described two patients with a new type of lymphoma, called Hepatosplenic T-Cell lymphoma leading to more focused research of this new entity.
Case report-unusual response to treatment. More recently researchers have used the case report format to share unusual treatment combinations or responses. For example, Treon et al reported in 2004 about an interesting clinical response to sildenafil in Waldenstrom’smacroglobulinemia.
Case Report of Gastric Cancer 82 year old female patient diagnosed with gastric cancer via an abdominal computed tomography (CT) scan in September 2006. The CT detected a gastric mass in the gastric antrum and the small gastrohepatic lymph nodes without metastasis to any other organ. Her past medical history included hypertension, osteoarthritis and allergic rhinitis. She had a family history of gastric cancer.
Case report 1 She had a gastroscopy in October 2006 which revealed a polypoid gastric mass approximately 25mm in diameter at the middle body portion of the lesser curvature and a flat elevated lesion 50mm in diameter at the prepyloricantrum. Endoscopic biopsy confirmed well differentiated adenocarcinoma with a mutation in p53 that showed a high nuclear activity of more than 80%.
Case report 1 Surgery was recommended but not performed because of her age and concerns about quality of life after gastrectomy. She had daily therapy with 900mg of orally administered Rhusverniciflua Stokes (RVS) extract from September 2006. Five months later the gastroscopy and abdominal CT scans demonstrated that the polypoid mass in the mid body had markedly decreased
Case report 1 and the flat elevated lesion in the prepyloricantrum had shrunk slightly, although the gastrohepatic lymph nodes were not changed. The biochemical parameters associated with liver and renal function were within the normal range and no significant side effects from her RVS treatment were observed. Lee et al
Sustained Partial Remission of Metastatic Pancreatic Cancer following Systemic Chemothearpy with Gemcitabine and Oxaliplatin plus adjunctive treatment with Mistletoe extract ●A 43-year old woman was admitted to hospital following several weeks of abdominal pain and progressive weight loss (5kg in 3months). Initial computed tomography (CT) scan examination revealed a mass of 2x2cm in the pancreatic head infiltrating the surrounding connective tissue.
Case report 2. ● Furthermore, diffuse hepatic lesions of up to 3.5cm in diameter were detected in both hepatic lobes, and serum CA 19-9 levels were as high as 1136 U/l (normal range:<37U/l). Explorative surgery was performed for suspected metastatic pancreatic cancer.● Intraoperative histological evaluation of the pancreatic mass confirmed the presence of pancreatic adenocarcinoma.
Case report 2. The patient underwent a pylorus-preserving pancreatic head resection, including dissection of regional lymph nodes and atypical resection of a single liver segment. Based on the final histological evaluation, the tumor was classified as pT3, pN1(8/24), pM1hep, L1, V1, G2, corresponding to an International Union against Cancer (UICC) stage IV.
Case report 2 3 weeks post op, palliative chemotherapy with a combination of gemcitabine (cumulative dose 1600mg/week over 2 weeks) and oxaliplatin (cumulative dose 160mg every 3 weeks) was initiated over 9 cycles ( administered over a total period of 37 weeks due to treatment-associated side effects)
Case report 2. Restaging examination 9 weeks after initiation of chemotherapy showed a partial remission of hepatic metastases. At the same time the serum levels of CA19-9 decreased to 34U/ml. 10 months after finishing systemic chemotherapy, the patient still showed no evidence of tumor progression and CA 19-9 levels continued to be completely normalized.
Case report 2. Upon recommendation of her homeopathist , the patient had undergone adjunctive therapy with mistletoe extracts (Iscador 5mg thrice weekly) which was initiated concurrently with the systemic chemotherapy 3 weeks after pancreatic surgery.Ritter et al.
Case report 2. Fig. 1. Histological sections through the pancreas (a) and the liver (b) of the patient, showing diffuse pancreatic infiltration by the carcinoma and hepatic metastatic spreading.
Case report 2. (a) Abdominal CT scans of the patient prior to surgery, showing multiple liver metastases of up to 3.5 cm in diameter. (b) Abdominal CT scan of the same patient following resection of liver segment IV and 37 weeks of systemic chemotherapy with gemcitabine and oxaliplatin, showing sustained partial remission.
Rare cases In rare cases, a series or more definitive study may be impossible.The reporting of similar rare cases, affords the clinician an opportunity to read this discontinuous “case series” and inform a rational approach to disease.
Rare cases ● A well-written case report or small uncontrolled series of cases is often the first step in the discovery of new diseases and treatments.(Albrecht et al, Ruben RJ)● A good case report has the element of surprise
Case Report 3. A ● 54-year old man presented with a palpable mass in the right breast. No history of familial breast cancer, gynecomastia, solid organ tumors or hormonal medication.● He was not a heavy drinker and had a smoking history of 20 pack years.Body mass index (BMI) was 24.5.
Case report 3. Figure 1. A mass (arrowheads) with nipple retraction was detected in the right breast. Bilateral accessory breasts in the axilla with nipples (arrows)were also present. (A) Right. (B) Left.
Case report 3. ● On physical examination, a 2cm-sized mass was palpated just under the right nipple.● Bloody discharge developed with squeezing from a single duct of the left nipple.● There was no palpable mass in the left breast and axillary nodes were not palpable.
Case report 3. Physical examination of the external genitalia revealed unilateral undescended testis which was small (7-8ml) and located in the left inguinal canal. The size of the right testis was normal (15ml).
Case report 3. ● Patient’s hormonal profiles, including testosterone, prolactin and thyroid function tests were normal.● Estradiol 58.9pg/ml (NR 15-47), luteinizing hormone (LH) 6.3 m/U/ml (NR 1.0-5.3), and follicular stimulating hormone (FSH) 10.9m/U/ml (NR 1.0-5.3) were slightly increased.
Case report 3. ● Chromosomal studies revealed a normal male karyotype of 46XY, and genetic analyses for BRCA1/2 genes were normal.● CXR, Liver US, PET/CT showed no evidence of metastatic disease.● Mammography and ultrasonography showed a mass (BIRADS 5) in the subareolar area of both breasts.
Case report 3. Ultrasonography showed a hypoechoic breast mass (BIRADS Category 5) in the subareolar area of both breasts. (A) Right. (B) Left.
Case report 3. ●In preoperative PET/CT, bilateral uptake in the subareolar area of SUVmax 6.8 in the right breast and 5.2 in the left breast, and mild uptake in both axillaes.●Core needle biopsy revealed invasive ductal carcinoma in the right breast and ductal carcinoma insitu in the left breast.
Case report 3 ●Fine needle aspiration of the right axillary lymph node was negative.●Bilateral total mastectomy, sentinel lymph node biopsy and excision of the accessory breasts in the axilla were performed.●Histopathological examination revealed invasive ductal carcinoma of the right breast and solid papillary carcinoma in situ in the left breast.
Case report 3. (A) The invasive ductal carcinoma in the right breast was mainly composed of micropapillary components (H&E stain, ×200). The tumor cells were suspended in a clear space. (B) The solid papillary carcinoma in the left breast showed solid tumor cell nests with focal necrosis (H&E stain, ×100). Woo-Young et al.
Case Report 4. ●A 65 year old woman underwent surgery for papillary serous ovarian adenocarcinoma involving both ovaries and with extensive metastases (stage IIIC).●Exploratory laparotomy with total abdominal hysterectomy, bilateral salpingo-oophorectomy, and omentectomy with cancer staging was performed.
Case report 4 ●Chemotherapy- carboplatin, paclitaxel, and cisplatin.●CA-125 level was normal and no evidence of disease progression.●Presented with progressive neurological symptoms two years later starting with dysesthesias and numbness and progressing to quadriparesis with urinary retention.
Case report 4. ●Imaging studies of her spine revealed an enhancing heterogeneous C2-C5 intramedullary lesion with cord expansion and edema extending into the medulla and to the thoracic spinal cord.●CA-125 was normal, CT scan of chest, abdomen, and pelvis were negative for other lesions. Infection screen was negative.
Case report 4. ●C2-C5 laminectomies were performed for planned ultrasound guided dorsal midline biopsy and debulking of the intramedullary mass.●Post-operative MRI scan showed the expected post-laminectomy changes without any associated hematoma.●Pathologic analysis revealed histological and cytological features consistent with papillary serous ovarian adenocarcinoma.
Case report 4. ●Fractionated radiotherapy was initiated immediately in the post-operative period during her rehabilitation.●Patient required emergency re-operation three weeks later due to sudden paraplegia secondary to spinal epidural hematoma.●Patient died five months after discovery of spinal metastasis, presumably from pulmonary embolism.Miranpuri et al
Case Report 5. ●A 25-year old lady presented with a 12hr history of severe lower quadrant pain. She was 6 weeks pregnant and US scan confirmed the presence of a 9x6cm cytic solid mass in the left adnexa.●No ascites●Laparotomy was performed for torsion of the mass.
Case report 5. ●Tumor markers were measured preoperatively and CA 125 was elevated (121U/ml).●Laparotomy confirmed the presence of torsion of left ovarian cyst and a complex right ovarian mass (3x2cm).●She had a left salpingo-oophorectomy and a right cystectomy.●Omentum, liver and spleen were normal.
Case report 5. ●Histology of left mass confirmed a diagnosis of mucinous cyst-adenocarcinoma grade 1 with intact membrane.●Right mass was diagnosed as a mature teratoma.●CA 125 levels decreased from 121 to 93U/ml post surgery.
Case report 5. ●Patient expressed a strong desire to continue pregnancy after counseling by oncologists and pediatricians.●She was diagnosed as at least a Stage 1a ovarian carcinoma.●Patient presented again at 39 weeks gestation with abdominal bloating and dyspepsia for 7 days.
Case report 5. US scan identified a normal fetus and a complex mass measuring 12x11cm between the bladder and the CA 125 and AFP levels were 381U/ml and 3,810ng/ml respectively.Patient had a C-section and total abdominal hysterectomy, right salpingo-oophorectomy, complete omentectomy and pelvic and para-aortic lymph node resection.
Case report 5. ●Baby weighed 3,000g.●Histopathological diagnosis confirmed isolated metastatic ovarian cystadenocarcinoma.●The lymph nodes, uterus, right adnexa, omentum and placenta were negative for metastasis.●She was treated with cisplatinum and docetaxel.
Case report 5. ●CA 125 and AFP levels were normal 4 weeks after surgery and 3 cycles of chemotherapy.●The patient and her baby were followed up for 5 years.●There was no evidence of recurrence and the baby had normal physical and neurological development.
●Published case reports are a wonderful way to experience the clinical activity of distant practices and should lead to local discussions, further reading, and thinking with colleagues. (Bignall J)●Case reports offer an opportunity for young authors to participate in the preparation of the manuscript.
●In 1941, a Johns Hopkins University scholar, Stacy Guild, PhD, wrote a 231 word histological observation describing glomus bodies in the human temporal bone.●In the same year, a clinical practitioner in New York, Harry Rosenwasser MD, operated on a patient with what appeared to be a carotid body tumor in his ear. (Ruben RJ)
Dr. Rosenwasser communicated with Dr. Guild and the two gave substance to the final case report that established the clinical entity we know today as glomus tumors.
Are case reports necessary in an era of evidence based medicine? ●It has been said that “more often than not,” new ideas from case reports contain “misleading elements” in clinical presentation, and that they do “more harm than good” by emphasizing the bizarre (Hoffman JR).●Clinicians will protest that relegating case reports and case series to second-class status in the medical literature means that the babies are being thrown away with the bathwater. (Vandenbroucke JP)
Are case reports necessary in the era of evidence based medicine? ●Evidence-based medicine is exclusively concerned with finding the best evidence for clinical decisions; for example, should we apply a particular therapy or a diagnostic test to a particular patient?●A hierarchy of evidence with the randomized trial “on top” serves one purpose admirably: the final evaluation of therapies or tests especially when their clinical value is not immediately clear cut. (Vandenbroucke JP)
Are case reports necessary in the era of evidence based medicine? ●Case reports and case series, however, have other aims that are equally important in the progress of medical science and education.
Potential roles of case reports and case series. ●Recognition and description of new diseases.●Detection of drug side effects (adverse and beneficial).●Study of mechanisms of disease.Medical education and audit.●Recognition of rare manifestations of disease. (Vandenbroucke J)
Use of case reports and case series. ●In the summer of 1999, the use of a case series in the recognition of a new disease was exemplified by the epidemic of West Nile encephalitis in New York City.●Case reporting remains important for detection of side effects of drugs, whether adverse or beneficial, even in our modern age of “designer drugs” and “pharmacogenomics.” (Vandenbroucke J)
Use of case reports and case series. ●Case reporting prompts most if not all of a series of retractions of drugs from the market.●Conversely, a pharmaceutical success story grew from the detection of unanticipated effects: Sildenafil was developed from observation of a side effect of an antihypertensive agent. (Jenicek M)
Use of case reports and case series ●The observation that the nicotine withdrawal syndrome was linked to depression paved the way to the use of antidepressant drugs as smoking cessation agents. (Covey et al)
Use of case reports and case series ●New molecular disease mechanisms continue to be discovered, thanks to the age-old clinical observations on disease transmission in families.●A renewed look at a family tree led to the discovery of maternally inherited diabetes associated with deafness; this in turn led to further clues to the understanding of mitochondrial diseases. (Ballinger et al, Van den Ouweland et al)
Use of case reports and case series ●Case reports can serve as a substrate to further research many years after an original publication.●For example, in 1886, Felix Frankel described the first case report of pheochromocytoma in an 18 year old woman with bilateral adrenal tumor.●In 2007, almost 121 years later, Neumann et al studied four living relatives of the same patient reported by Frankel in 1886 and found that the patient had RET mutation and that her family had multiple endocrine neoplasia (MEN 2).
Meta-analysis or Systemic Reviews of cases and case series ●Nayfield and Gorin retrieved from the literature twenty-one cases of tamoxifen-related ocular toxicity in breast cancer patients.●This review produced a clearer picture of the nature and distribution of the toxicity, as well as the severity of the ocular findings.●They recognized the difficulty of attributing ocular findings to tamoxifen and other competing causes of retinal, macular and corneal abnormalities.
Meta-analysis or Systemic Reviews of cases and case series ●Nordin conducted a 20-year literature review of both case reports and case series reports of primary carcinoma of the fallopian tube.●This author was able to outline more appropriate patient characteristics.●Hypothesize on the underdiagnosing of cases●Causes of treatment failure●Lack of controlled trials and usefulness of a second look laparotomy for monitoring disease response to the treatment given.
Meta-analysis or Systemic Reviews of cases and case series . ●Olaku and White reviewed case reports of herbal therapy use by cancer patients.18 case reports with apparent anti-tumor effect and 21 case reports of toxic effect were identified.●Clinical trials in cancer populations were identified for green tea extracts or compounds (n=34), phytoestrogens (n=27), mistletoe (n=8), ●Ganodermalucidum, noni, and silymarin all had 1 trial each.
Case Report ●Daikenchuto, PC-SPES, Nyoshinsan/TJ and Saw Palmetto have also been studied prospectively.●Many of the herbs with promising case report findings have either not yet been explored or the results have not been reported in English.
Meta-analysis or Systematic Reviews of cases or case series ●It is obvious that none of these meta-analyses of cases is explanatory. Only case characteristics and case outcomes can be better assessed at this level of clinical research.● Anyone who searches for evidence of what is helpful or harmful to patients is not satisfied with conclusions drawn from case reports.● In situations where there is no other adequate evidence, the best of the first line of evidence must be taken into account. (Jenicek M)
Case reports and the Law
Case reports and the Law ●Federal regulations (45CFR46.102(d) and 45CFR164.501) define research as a systematic investigation, including research development, testing and evaluation, designed to develop or contribute to generalizable knowledge.●A case report is a medical/educational activity that does not meet DHHS definition of research.Medical education/consultation, such as occurs when a colleague presents a difficult case or case series at a teaching conference does not require ●IRB review●HIPAA●Office of Human Subjects Research (OHSR)
Ramulu et al
How to write a good case report ●The single message must be clear● Why is observation important?● What does it teach us?● Does it run counter to some cherished truth?● Is it an unexpected association?● Is it a rarity that would otherwise be missed?
Conclusion ●Case reports should be written in an organized and structured manner.●Case reports are still relevant in present day medicine.●In rare instances where clinical trials are not possible for ethical reasons, case reports/series may be the only evidence available to recommend treatment.