Stacey B Leibowitz Md Ramesh A Shivdasani Md PhD Philip W Kantoff Md

Although more than 90 of germ cell tumors in males arise in the testis, a distinct group of such tumors originates outside of the testes these tumors are known as primary extragonadal germ cell tumors (EGGCTs). EGGCTs account for approximately 1 to 5 of germ cell neoplasms and are histologically identical to primary gonadal germ cell tumors (GCTs). They are typically found in the retroperitoneum, the mediastinum, and the central nervous system, with no associated clinical abnormality of the...

Optimal Endoflife Care

Optimal end-of-life care for patients with germ cell tumors cannot be differentiated from optimal care throughout the course of life-threatening illness. The care of these patients and their families during the patients' last phase of life requires commitments from the individual oncologists to assisting patients and families through this difficult time and a broader commitment to fostering optimal care on the part of institutions involved in care delivery and on the part of those responsible...

Secondary Malignancies

Several international studies have used information from tumor registries in an attempt to determine whether there is an increased incidence of secondary malignancies in patients with testicular cancer and, Figure 28-5. Audiometry assessment of a patient after cisplatin-based chemotherapy, demonstrating bilateral hearing impairment, most notably at higher frequencies. O right ear X left ear. Figure 28-5. Audiometry assessment of a patient after cisplatin-based chemotherapy, demonstrating...

Presentation Of Testicular Cancer

The clinical presentation of testicular cancer is usually quite obvious. The typical patient is a man aged 17 to 45 years who notices a growing and relatively painless mass in the scrotum and seeks medical attention. However, as many as 10 of patients present with atypical complaints, such as sudden pain in the scrotum, a new-onset hydrocele, or recent trauma. Some patients are misdiagnosed as having epididymitis, causing an unnecessary delay in diagnosis. A high index of suspicion is required...

Etiology and Pathogenesis

Historically, cases of EGGCTs have been described in the literature at least since the 1930s.1 Through the years, there has been a debate as to whether these EGGCTs represent true primary lesions originating outside the gonads or are secondary metastases from occult testicular lesions. In 1961, Azzopardi and Hoffbrand published histologic evidence of testicular scars in 17 patients with presumed EGGCTs and hypothesized that these scars represented regression of primary testicular neoplasms.2...

Highdose Chemotherapy At First Relapse

High-dose chemotherapy as the first salvage treatment of relapsed germ cell tumors has been less extensively investigated.115 Unlike patients with multiply recurrent germ cell cancer, patients in first relapse can expect a 50 likelihood of complete remission and a 25 chance of long-term freedom from disease with conventional-dose salvage chemotherapy. The goal, therefore, is not the salvage of otherwise doomed patients but improvement in the efficacy of salvage therapy. Demonstrating efficacy...

Info

Bid twice daily GI gastrointestinal max maximum N V *Less of these effects occur with nortriptyline and desipramine, nausea vomiting qhs every night at bedtime tid three times daily. which are more suitable for elderly patients. bid twice daily GI gastrointestinal max maximum N V *Less of these effects occur with nortriptyline and desipramine, nausea vomiting qhs every night at bedtime tid three times daily. which are more suitable for elderly patients. A specific type of neuropathic pain...

Learning About Testicular Cancer

The Testicular Cancer Resource Center (TCRC) is a very comprehensive source of information oriented to patients and their families. This comprehensive database discusses all issues of testicular cancer and could be the first resource that patients and their families consult. It also includes links to many other sources of information. The TCRC began when one patient, diagnosed with testicular cancer, was unable to obtain comprehensive patient-oriented information. What information was...

Tumors of the Viscera and Other Sites

Endodermal Sinus Tumor

Teratomatous neoplasms have been reported in virtually every anatomic region and organ. Visceral ter-atomas vary, from incipient small lesions to massive disfiguring tumors.55 Most visceral mature ter- atomas of childhood behave in a benign fashion and prognosis is linked to resectability.31 One distinctive condition that frequently becomes manifest in the liver or lungs but that may affect other organs (including the brain) is infantile choriocarcinoma syndrome.56 Originally described by...

Jane M Ingham Mb Bs Fracp

Although germ cell cancer is often considered as the paradigm for curable malignancy, it remains a disease associated with a significant loss of life-years because of the youthful age group affected. While the incidence of germ cell tumors has continued to rise, ongoing research has provided patients with more effective medical and surgical treatments, resulting in a cure rate in excess of 90 . This combination of increasing incidence and survivability is producing a unique subset of cancer...

Treatment Planning

Supraclavicular Treatment Field

The hila of the left and right kidneys are 5 cm from the midline, the left at the L1-to-L2 interspace and the right opposite L2 (see also Chapter 3). The kidneys usually lie at an angle so that the superior pole is 1 cm closer and the inferior pole is 1 cm further away, relative to each hilum. This can be easily confirmed by CT. The left renal vein is longer than the right as it has to cross the aorta to reach the inferior vena cava. The lymphatics follow the gonadal venous system the left...

Incidence

Germ cell tumors are uncommon in children and are presumed to originate from primordial germ cells. These tumors occur at varied primary sites, both gonadal and extragonadal, and manifest in a variety of different histologies. Germ cell tumors represent approximately 7 of all cases of cancer in children and in adolescents less than 20 years of age. They account for 2 to 4 of all cancers in children younger than 15 years of age and approximately 14 for those between 15 and 19 years of age.1,2...

Postchemotherapy Histology

The histology of a residual mass after initial chemotherapy varies substantially in different series. Steyerberg and colleagues5 reviewed 996 postchemo-therapy resections from 19 studies published between 1983 and 1990. Residual cancer was present in an average of 16 of cases, mature teratoma was in 36 of cases, and fibrotic and or necrotic tissue was in 48 . In resected lung lesions, necrosis was found more often (57 of cases) and teratoma was found less frequently (27 of cases). The same...

Presentation

Precocious Puberty Boys

Ninety-five percent of intracranial germ cell tumors (ICGCTs) arise in the region of the third ventricle, along an axis from the suprasellar cistern to the pineal gland. The most common site involved is the pineal gland, followed closely by the suprasellar region. Rarely, these tumors present within the third ventricle, basal ganglia, thalamus, or other ventricular sites.27 Germinomas (a term used for intracranial seminoma) preferentially involve the suprasellar region whereas nonseminomatous...

Germ Cell Tumors with Embryonal Neoplasia or Somatic Differentiated Malignancy

Occasional development of somatic malignancy in the form of embryonic tumors or adult-type sarcoma has been found in gonadal and extragonadal sites (Figure 22-16).44-46 The recognition and confirmation of such malignancy may require immunohisto-chemistry and other ancillary techniques. Modification of treatment modalities is warranted, depending on the type of tumor.48 are increasingly recognized.38 They may be bilateral39 and may be associated with androgen secretion and ataxia-telangiectasia....

Gonadal Toxicity

In addition to impairment of spermatogenesis, injury to Leydig's cell function is a potential toxic effect of chemotherapy. Elevations of FSH levels were observed in 24 of a cohort of 32 patients who received platinum-based chemotherapy.54 Of these 24 patients, 15 had elevated LH levels. Two patients, each with a remaining testicle, had low testosterone levels. This underscores the problem of compensated (and sometimes uncompensated) Leydig's cell function. Testosterone replacement can be...

Results Of Waitandsee Policy

The results of 29 studies of wait-and-see policy, (including unpublished Daugaard results)2'3'7-916-18' 2633-51 which included 3,008 patients, have been noted. In some of the studies, high-risk patients have been excluded. The total number of relapses seen in these studies is 841 (28.1 ), and the overall survival Table 12-2. RISK FACTORS FOR RELAPSE OF PATIENTS WITH CLINICAL STAGE I NONSEMINOMATOUS GERM CELL TUMOR Presence of embryonal carcinoma +++ VEGF vascular endothelial growth factor. +++...

Human Chorionic Gonadotropin

Germs Cells The Gonad

Human chorionic gonadotropin is a 38 kD hormone secreted by placental syncytiotrophoblasts, whose function is to maintain the corpus luteum. It consists of two subunits, an a subunit and a P subunit. The a subunit is closely related to the a subunit of anterior pituitary hormones such as luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid-stimulating hormone (TSH). The P subunit is biologically active and structurally and antigenically distinct, allowing for the production...

Epidemiology

Sacrococcygeal Teratoma Adults

The proportion of EGGCTs is estimated at 1 to 5 of all GCTs.8 The American Cancer Society estimated that 7,500 new cases of testicular cancer would be diagnosed in the United States in 2002. Accordingly, it could be estimated that 75 to 375 new cases of EGGCT would be diagnosed in the United States in 2002, illustrating the rarity of these tumors. Rare cases of EGGCTs have been reported in a variety of locations, including the prostate,21 the seminal vesicle,22 the iliac fossa,23 and the...

Extragonadal Germ Cell Tumors

Extragonadal Germ Cell Tumors

After the testis, the next most common site for primary GCTs in males is the retroperitoneum, the anterior mediastinum, the pineal gland region, and the pre-sacrococcygeal area. There are several theories to explain the derivation of these tumors (see also Chapter 1). Some have proposed that these tumors develop within cell rests that have failed to orientate themselves properly towards the genital ridge in the embryo. In males, retroperitoneal GCTs may actually represent metastases from a...

Associations with Other Diseases

Gynecomastia Pain Relief

Klinefelter's syndrome (KS) is a genetic disorder of men that is characterized clinically by gynecomastia, testicular atrophy, and increased levels of follicle-stimulating hormone40 and is characterized genetically by the 47,XXY karyotype. An association between MNSGCT and KS exists. At Indiana University, 22 consecutive MNSGCT patients had chromosome studies performed on blood or a bone mar row aspirate 18 (4 of 22) of the patients were diagnosed with KS by karyotype, and a fifth patient...

Cancer Clinical Trials

Medical research as performed in a clinical trial is one of the most poorly understood practices of med-icine.3 A clinical trial is simply a regimented method of determining the better course of treatment. Clinical trials are required because not every treatment or state of illness has a rigidly defined treatment or because newly developed therapy needs formal evaluation. This is especially so in the case of cancer since current treatment is always being refined and new therapeutic entities are...

Standard Dose Salvage Chemotherapy Summary

Approximately 50 of recurrent testicular cancer patients will achieve a disease-free status when VeIP is administered as second-line therapy.72,73 Half of the patients who achieve complete remission on VeIP eventually relapse therefore, approximately 25 of patients with recurrent germ cell tumors can have the expectation of long-term disease-free survival with standard salvage chemotherapy. The substitution of paclitaxel for vinblastine has yielded impressive results in a patient population...

Psychological Functioning

Understandably, it is common for testicular cancer patients to exhibit symptoms of psychological distress at the time of diagnosis and during treatment. However, the evidence concerning the duration of this distress is inconsistent across studies. Rieker and colleagues19 were among the first to thoroughly assess the impact of testicular cancer treatment on the psychosocial functioning of survivors. Seventy-four men treated for either seminomatous or non-seminomatous germ cell tumors were...

Clinical Presentation And Diagnostic Evaluation

Patients may present with a variety of manifestations of their CNS metastases, including headache, focal neurologic deficit, focal or nonspecific visual changes, confusion, vomiting, and or seizures. Alternatively, they may be asymptomatic and may be diagnosed only when CNS imaging is undertaken.9 The intensity of diagnostic evaluation of the CNS in patients with testicular germ cell cancer is based on individual risk stratification. Patients with higher-risk Table 17-3. CORRELATION BETWEEN...

Commonly Used Chemotherapy Regimens For Metastatic Germ Cell Tumor

Previously treated (first-line salvage therapy) Etoposide, 100mg m2 IV daily x 5 days Cisplatin, 20 mg m2 IV daily x 5 days Bleomycin, 30 U IV weekly on days 2, 9, and 16 Ifosfamide, 1.2 mg m2 IV daily x 5 days Mesna, 400 mg m2 IV every 8 hours x 5 days Cisplatin, 20 mg m2 IV daily x 5 days plus either Vinblastine, 0.11 mg kg IV on days 1 and 2, or etoposide, 75 mg m2 IV daily x 5 days 4 cycles administered at 21-day intervals 9 Indiana U. PEB 77 73 61 10 NCI PVB 18 67 50 11 Indiana U. PEB 141...

Management of Nonseminomatous Testicular Cancer Chemotherapy for Poor Risk Patients Standard Dose Therapy

The survival of patients with metastatic nonsemino-matous germ cell tumors (NSGCTs) was poor prior to the introduction of cisplatin and etoposide in the mid-1970s. Only about 10 of these patients achieved durable remission with drugs such as the vinca alkaloids, methotrexate, actinomycin D, cyclophosphamide, doxorubicin, and bleomycin. In a phase I trial of cisplatin, Higby and colleagues1 noted the initial responses in patients with NSGCTs, as well as the nephrotoxicity of the drug if the...

Surgery for Testicular Cancer Radical Orchiectomy

SKINNER, MD Testicular cancer remains the most curable solid tumor in men. Careful histologic diagnosis and prompt evaluation for metastatic disease are essential for the selection of appropriate treatment. The first surgical step in the management of testicular cancer is inguinal orchiectomy. In the past, before the advent of good techniques for testicular imaging, inguinal exploration with open biopsy of the testis was the primary method of making a definitive...

Further Chemotherapy For Radically Resected Residual Cancer

The presence of viable cancer cells in completely resected residual masses carries the worst prognosis when compared with the presence of mature teratoma or necrosis alone (see also Chapter 16).26,33 Since the study by Einhorn and colleagues,37 which reported a dismal outcome for all 18 patients with residual cancer at postchemotherapy surgery who received no further therapy, many investigators have opted for the routine use of postoperative adjuvant chemotherapy.2,5,9,11,12,24,26,33 No...

Assistance For Cancerrelated Problems

Cancer Care is a national nonprofit organization whose mission is to provide free professional help to people with all cancers through counseling, education, information and referral, and direct financial assistance. Cancer Care's Web site (< http www. cancercare.org> ) offers practical assistance to all patients and not specifically to patients with testicu-lar cancer. Since 1944, Cancer Care has been dedicated to providing emotional support, information, and practical help to people with...

Pursuing A Good Death

Over the past several decades, Western medicine's concept of death has evolved from one viewing death as a failure of science and technology to one properly recognizing death as an experience every person must face. With this paradigm shift, educational and research projects in the United States, such as the American Medical Association's Education for Physicians on End-of-Life Care and the Robert Wood Johnson Foundation's Last Acts Campaign, have worked to focus the attention of clinicians on...

Family Members and Friends

Although most caregivers (primarily family members) are highly motivated and are committed to providing care, caregivers involved with patients who have cancer experience substantial burdens.67-76 Not only are caregivers called upon to provide emotional support for the patients through periods of stress, they are also increasingly being required to provide medical and nursing care in the home as a result of the shifts in care from inpatient to outpatient settings. Moreover, particularly in...

Placental Alkaline Phosphatase

Placental alkaline phosphatase (PLAP) is the fetal isoenzyme of the ubiquitous adult alkaline phosphatase. It is normally expressed in utero and in children less than 1 year of age and functions as a protein phosphotyrosine phosphatase, catalyzing the abstraction of inorganic phosphate from phosphate esters. Although widely accepted as a reliable histo-logic marker for seminoma, its merit as a serum tumor marker is uncertain (Figure 7-5). In seminoma, serum PLAP levels are elevated in 50 to 72...

Neurotoxicity

Cisplatin has been well documented to cause neuro-toxicity and ototoxicity. The peripheral neuropathy is predominantly sensory, manifested mostly by paresthesia and dysesthesia. These symptoms have been reported to persist beyond 6 years in about 30 to 40 of patients.1419 The long-term toxicity has been confirmed by other investigators.11 Nerve conduction studies have shown that the changes in conduction along peripheral and central pathways after tibial nerve stimulation are compatible with a...

Etiology

The dramatically increased occurrence of testicular cancer in this century suggests that environmental causes have become more prevalent, and observed cohort effects suggest that some factors act early in life. Patterns of familial occurrence suggest that inherited genetic factors also predispose to testicular cancer. Accordingly, etiologic studies have addressed environmental, perinatal, and genetic factors. A series of epidemiologic studies found the risk of testicular cancer to be associated...

Imaging Treated Disease

Blood Pressure Microbiota

Even in patients with advanced disease at diagnosis, excellent response to treatment can be achieved today. As a result, imaging is now frequently performed in patients who have undergone multiple courses of chemotherapy and multiple relapses. In such patients, the imaging findings are more complex and difficult to interpret than at the time of staging. For example, such patients also frequently have undergone previous surgery scarring in the lungs or in other tissues adds to the difficulties...

Social Functioning

Overall, findings suggest that survivors of testicular cancer have good social functioning. While it is difficult to reach definitive conclusions (for the reasons previously discussed), when assessed, survivors generally report equal or more satisfaction with relationships after cancer treatment, compared to before treatment. For example, early efforts to describe marital satisfaction among survivors indicate that men are more likely to report improvement as opposed to deterioration in their...

Nephrotoxicity

Nephrotoxicity was noted initially in early-phase studies of cisplatin-based chemotherapy a decreased glomerular filtration rate and elevated serum creatinine occurred in up to 36 of patients.16 Modern cisplatin administration schedules incorporating forced saline diuresis1317 have decreased the rate of significant renal impairment to fewer than 5 of patients.141718 Less commonly, damage to the proximal convoluted tubules can result in a magnesium-wasting nephropathy, which can cause...

Residual Masses And Postchemotherapy Radiation

Especially with cases of large-volume seminoma, it is common to find a residual mass on scanning the patient after a course of chemotherapy. However, approximately 90 of these masses do not contain residual malignancies and appear to be fibrotic remnants (Figure 20-3).30,31 Attempted resection can be hazardous because of extensive dense scar tissue involving the great vessels and retroperitoneal tissues. The analysis from the Memorial Sloan-Ketter-ing Cancer Center suggested that there was a...

Mortality

The initial spread of most germ cell tumors occurs to the lumbar para-aortic lymph nodes via the testic-ular lymphatics. Less frequently, direct lymphatic communication or hematogenous spread can occur, resulting in metastases to diverse areas. Two postmortem studies, one of 78 and the other of 154 patients with histologically confirmed germ cell tumors, found that metastatic disease often followed predictable patterns. In order of decreasing frequency, sites of metastases commonly reported...

Allergic Reactions And Other Toxicities

Acute allergic reactions to a number of cytotoxic agents used in the treatment of germ cell tumors have been documented these agents include bleomycin,60 paclitaxel,72-74 and (rarely) carboplatin or cisplatin.57,76 These can manifest as minor reactions such as flushing and rashes or as more severe symptoms such as urticaria, periorbital edema, bronchospasm, and hypotension. In the majority of cases, the hypersensi-tivity syndromes can be treated with corticosteroids and antihistamines, and the...

Assessment Of Patients

Seminoma is usually found in patients aged 25 to 40 years. In general, younger patients (less than 30 years of age) presenting with a testicular mass will have testicular nonseminomatous germ cell tumors Figure 19-3. A, Seminoma. Computed tomography shows a large abdominal mass. B, Total abdominal radiation to 15 Gy. 15Gy is delivered to the entire abdomen. Kidney blocks are placed in the path of radiation for an addition 10 Gy. The para-aortic region (and the right iliac region) is given an...

C

Testicular Cancer Metastasis Sites

Typical site of first metastases. A and B, Right testicular primary. Fluorodeoxyglucose positron emission tomography (FDG-PET) scan (A) of a patient with nonseminomatous germ cell tumor of the right testis demonstrates increased metabolic activity (arrow) at the typical location of first lymphatic spread of a right testis tumor, namely, the interaortocaval nodes just below the renal hila. This scan identified early metastatic spread in a patient with elevated tumor markers and a...

Recurrent Disease

Recurrent disease in seminoma cases is still a highly curable situation.47 Therefore, aggressive investigation of disease extent and treatment is warranted. Recurrence in the para-aortic lymph nodes after orchiectomy and surveillance may be treated with retroperitoneal RT or with chemotherapy. Local tumor control approximates 100 , and second relapse is uncommon but has been documented, especially in patients with large tumors at relapse. For patients with recurrence following RT and for...

New Directions

In addition to testing new drugs for their potential efficacy and possible dose escalation for germ cell cancers, it is essential to continue to study tumor-related prognostic factors that aid in the understanding of cancer biology and in the identification of new therapeutic targets. One such example was the recent report, by Bokemeyer and colleagues, of the clinical impact of circulating cancer cells from germ cell cancer patients undergoing stem cell collections for aPSCT. Among 57 patients...

Gedske Daugaard Md Mikael R0rth Md

The stage distribution of nonseminomatous germ cell tumor (NSGCT) has changed over the last two decades, apparently as the result of a shift of patients with low-volume disseminated disease to patients with stage I disease.1 About one-half of patients with NSGCT have clinical stage I disease at first presentation. The management of such patients has generated considerable interest and some controversy over the last 20 years. Adjuvant abdominal irradiation and retroperitoneal lymph node...

Overview

Testicular Tumor Staging

Oncologic imaging is a rapidly evolving subspecialty of general diagnostic radiology, its birth and continued growth being a much needed response to the importance of imaging in the management of patients with cancer. The radiologist undertaking examinations in patients with testicular tumors should have a special interest in oncology, should have a detailed knowledge of the patterns of spread of testicular tumors and the characteristic appearances of metastatic disease at different sites, and...

Combination Chemotherapy

There are relatively few prospective randomized trials of different chemotherapy regimens for advanced seminoma. When interpreting reports of uncontrolled trials, it should be remembered that over the last two decades there have been considerable changes in staging classifications, in the use of radiotherapy for metastatic seminoma, and in the definition of response. The modern era of successful chemotherapy for seminoma was heralded by the introduction of cisplatin. As early as 1974, there was...

Presentation with Systemic Symptoms

Testicular Atrophy Cirrhosis

In a few cases, GCT of the testis can present with systemic symptoms secondary to endocrine effects of the primary tumor itself. Gynecomastia (Figure 5-9) is a presenting feature in up to 5 of men with testicular tumors, due to an imbalance resulting from a relative deficiency of androgenic suppression and the predominance of estrogenic stimulation of the growth of breast tissue. This can be mediated by an increase in gonadotropin level, particularly that of human chorionic gonadotropin (hCG),...

Syndromes That Mimic Recurrence

Bleomycin Patients

Recognition of syndromes that can mimic tumor recurrence or progression is the first critical step in the evaluation of a patient suspected of having recurrent, persistent, or progressive germ cell tumor. Recognition of several special situations is also essential for the proper management of recurrent germ cell neoplasms. Figure 16-1 illustrates an unusual case of pseudorecurrence of germ cell cancer. One clinical situation frequently mistaken for progressive disease is the syndrome of growing...

Bone Marrow Suppression

Acute tri-lineage bone marrow suppression occurs after chemotherapy for germ cell tumors the predominant pattern reflects the selection and doses of agents. Although cisplatin causes a mild progressive anemia with only modest neutropenia and thrombocytopenia, carboplatin, etoposide, vinblastine, and paclitaxel all cause more significant neutropenia and thrombocytopenia. Cisplatin-induced hemolysis has also been described.48 The most commonly used first-line regimens that incorporate cisplatin...

Adjuvant Chemotherapy

The use of one or two courses of adjuvant carbo-platin for patients with stage I seminoma has been reported by a number of investigators over the past decade (see Chapter 19).61243-45 Oliver and colleagues, who treated stage I seminoma with one to two courses of adjuvant carboplatin chemotherapy, pioneered this approach. Dieckmann and colleagues, with a median follow-up of 48 months, reported no relapses among 32 patients treated with two courses of carboplatin and reported 8 relapses in 93...

Cryptorchidism

Superficial Inguinal Pouch

The incidence of cryptorchidism is 3.4 in neonates weighing > 2.5 kg and is 0.8 in the adult population.3 A history of testicular maldescent increases the risk approximately fivefold, and abdominal testes are 35 to 48 times more likely to undergo malignant change than a normal testis approximately 10 of testicular tumors develop within testes with a history of cryptorchidism.4,5 Delayed recognition of a cryptorchid testis can increase the risk of malignancy. In the developed world, the great...

Staging Investigations And Prognostic Factors

At Charing Cross Hospital, the routine staging investigation performed on these patients after their initial orchiectomy is computed tomography (CT) of the thorax and abdomen (usually omitting the pelvis, except in patients who have had a previous orchiopexy), to minimize the radiation to these patients. Patients are all routinely monitored with the three serum tumor markers hCG, AFP, and lactate dehydrogenase (LDH). Patients with pulmonary metastases routinely have a magnetic resonance imaging...

Treatment Recommendations

The approach to a patient with a suspected recurrence of germ cell cancer is complex and nuanced. Initial evaluation should focus on ensuring that the Table 16-3. ACTIVE MULTI-INSTITUTIONAL CLINICAL TRIALS OF SALVAGE CHEMOTHERAPY FOR GERM CELL NEOPLASMS Cisplatin etoposide ifosfamide or Relapse after complete remission or for 4 cycles vs same regimen for 3 cycles phase Ill progression after partial remission followed by high-dose chemotherapy with with cisplatin-based first-line therapy Arsenic...

Management of Stage I Seminoma Patients with Horseshoe Kidney

Horseshoe kidney occurs in approximately 1 of 400 persons in the general population. Patients with horseshoe kidneys are at an increased risk of testicu-lar tumors as there is an association between renal fusion abnormalities and cryptorchidism, a major risk factor for testicular germ cell tumors. There are two main problems in the management of patients with stage I seminoma and horseshoe kidney.46 The first is the difficulty in delivering RT to the retroperi-teonal nodes, as a large part of...

AFetoprotein

Structure Afp

The biochemistry and biology of AFP has been well described. AFP is a 70 kD single-chained glycoprotein that was first found in normal human fetal serum in 1954.2 It is a dominant serum protein of the early embryo, accounting for almost one-third of total serum protein. Concentrations peak at 12 to 14 weeks of gestation and decline after week 16. Although detectable at birth, serum levels fall by 1 year of age to the minimal level (< 10 ng dL) usually seen in adults. AFP belongs to a...

Assessment Of Prognosis

Pure seminoma is exquisitely sensitive to radiation therapy and chemotherapy.3 Therefore, there is no need for prognostic factors in stage I seminoma cases to predict survival. However, depending on the management approach, prognostic factors can be used to identify the risk of disease recurrence.4-15 In other testicular germ cell tumors, serum markers are of great prognostic significance. In seminoma, markers may help to identify nonseminomatous tumor elements by an elevated a-fetoprotein...

Inguinal Canal

Veins Human Skin Enlarged View

The nerves of the abdominal wall muscles are the seventh through eleventh intercostal nerves and the sub costal, iliohypogastric, and ilioinguinal nerves.3 The iliohypogastric nerve penetrates the internal abdominal oblique muscle several centimeters medial to the anterior superior iliac spine and continues medially below the external abdominal oblique muscle. After giving off a lateral cutaneous branch, the iliohypogas-tric nerve terminates with an anterior cutaneous branch, which penetrates...

Cytogenetics And Molecular Biology

Lymph Nodes Mediastinum Middle Anatomy

Recent investigations into the cytogenetics and molecular genetics of pediatric germ cell neoplasia have disclosed interesting and challenging findings as the foundation for future research endeavors.65-67 Two broad groups of germ cell tumors must be recognized in the pediatric population (1) those that present perinatally and in early childhood and (2) those that form a group analogous to adult germ cell tumors and that present in the postpubertal period. Cytogenetic studies of EST in infancy...

Radiation Therapy

For the past half-century, the traditional management of stage I seminoma patients after an orchiectomy has consisted of radiation therapy (RT) to the para-aortic and pelvic lymph nodes.2,3,14 Such management resulted in an overall survival rate in excess of 95 and a very low relapse rate (see Table 18-1). In the absence of reliable retroperitoneal imaging, adjuvant RT resulted in unprecedented success. Recent surveillance studies have shown that occult para-aortic lymph node metastasis is...

Richard S Foster Md Richard Bihrle Md John P Donohue Md

Rplnd Anatomy

With the introduction of cisplatin-based chemotherapy in the 1970s, testicular cancer became one of the most chemosensitive tumors. Over the years, medical oncologists have refined chemotherapeutic regimens in order to optimize efficacy and minimize toxicity. Currently, metastatic testicular cancer can be treated with chemotherapy in an outpatient setting, and the previously severe toxici-ties of nausea and vomiting are minimized with the use of modern antiemetics. Hence, over the last two...

Diagnosis

Abdominal Testis

In some men, the testicular swelling develops slowly while the rate of growth may be very rapid in others. Figure 5-2. Computed tomography scan showing a teratoma that has developed within a cryptorchid testis on the right side of the pelvis. Figure 5-2. Computed tomography scan showing a teratoma that has developed within a cryptorchid testis on the right side of the pelvis. Figure 5-3. A large undifferentiated malignant teratoma that developed within an abdominal testis in a 19-year-old man....

Mediastinal Germ Cell Tumor

Tomography Scan Pancreas Pictures

A, Axial computed tomography scan of chest shows a large multicystic anterior and middle mediastinum mass. There is also a right-sided pleural effusion. B, Cut surface of the mediastinal tumor shows fibrosis, cystic degeneration, hemorrhage, and necrosis despite its worrisome appearance, this was a mature teratoma in a 13-year-old male. The pathogenesis of degenerative changes are ischemia and the presence of pancreatic tissue. Figure 22-20. Chest radiograph left) and computed...

Sacrococcygeal Teratoma And Oxcarbamazepine

For nonseminomatous germ cell tumors, 254 Health care facilities, 290 Health care providers, 314-315 High-dose carboplatin, etoposide for nonseminomatous germ cell tumors, 254 High-dose chemotherapy (HDCT) for nonseminomatous germ cell tumors, 254 High-dose chemotherapy with autologous bone marrow support (HD ABMT), 160 Hockey stick, 219, 219f, 234 Horseshoe kidney stage I seminoma Human chorionic gonadotropin (hCG), 2, 41, 74, 75-76, 266 cerebrospinal fluid, 207t immunohistochemistry, 76f...

B

Of the epididymis make contact with the rete testis. These tubules do not fuse with the rete testis until the third month, after which they are called the efferent ductules. At the same time, the mesonephric tubules at the lower pole of the testis degenerate while a small remnant persists as the paradidymis (see Figure 3-2, B).1 The testis is initially located at the tenth thoracic level, and it descends into the scrotum between birth and the second week of life. The descent of the testis...

Histogenesis

Even though it is almost intuitively self-evident that GCTs originate from germ cells, this point of view was ardently disputed for many years. In this respect, it is quite instructive to read the 1911 paper of James Ewing, the leading American pathologist of the day. He reviewed the theories of germ cell neoplasia of the testis that were considered at that time and noted that essentially all cells of the testis had been deemed by some authorities as potential progenitors of testicular GCTs.1...

Invasive Therapy

Celiac Ganglion Level

Invasive therapies should be considered when pain continues despite adequate doses of appropriate analgesics or when side effects become intolerable. Nerve blocking techniques, neurolytic techniques, parenteral infusions, and implantation technologies improve overall quality of life and become cost-effective when less-invasive therapies fail to produce adequate analgesia.45 Regional and Peripheral Nerve Blocks Nerve blocks may provide diagnostic information about the causes of the pain or may...

Classification Of Pain

Classifications of pain are frequently based on the temporal nature of the pain acute or chronic or on the underlying mechanisms somatic, visceral, or neuropathic . Somatic and visceral pain are also known as nociceptive pain. By using the etiologic classification, the clinician can select an analgesic therapy that is more likely to have efficacy with that specific type of pain. Somatic pain arises from the activation of the pain receptors, or nociceptors, in the peripheral or deep tissues....

Basic Surgical Approach

Inguinal Orchiectomy

The rationale for an inguinal orchiectomy in a patient with scrotal cancer is well established. This approach allows for high ligation of the spermatic cord, without any significant risk of scrotal contamination. A transscrotal approach would potentially place the inguinal lymph nodes at risk for metastases, which could have a significant impact on treatment. The surgery is well tolerated and is easily adjusted to deal with very large masses or scrotal skin involvement. The surgery can be...

Surgical Anatomy

Testicles Dissection Human

The lymphatic drainage of the testis is to the retroperitoneum. The region of lymphatics draining the testicles includes that area bordered by the crus of the diaphragm superiorly, the bifurcation of the iliac arteries inferiorly, and the ureters laterally. The lymphatic drainage of the testicles is usually very predictable, and metastatic disease reliably involves the area described above. However, exceptions do occur when metastatic disease is found in the retroperitoneum of patients with...

Other Therapies

Epidural Catheter Placed

The management of the pain of bone metastasis is usually effective with an NSAID and an opioid. The bisphosphonates, such as pamidronate, inhibit osteoclast activity and were originally used for the management of hypercalcemia. They will reduce pain and the analgesic requirements by 20 to 50 in patients with bone metastasis pain,56 especially if the pain is predominantly movement related. Radiation therapy provides effective treatment for bone pain by shrinking an existing tumor and inhibiting...

Sacrococcygeal Teratomas

Types Intra Abdominal Tumors

Sacrococcygeal teratomas see also Chapter 22 by Malogolowkin and colleagues are the most common congenital tumors, occurring in 1 of 40,000 neonates.49 These tumors occur four times more often in females than in males. The tumors show an age-dependent malignancy that increases with the age of the patients. Thus, 7 of tumors diagnosed at birth, 37 of tumors diagnosed by the age of 1 year, and 50 of tumors diagnosed at the age of 2 years are malignant.50 Congenital tumors present as masses...

Paclitaxel

Paclitaxel is another agent with demonstrable activity against relapsed or resistant germ cell tumors. Its mechanisms of activity and resistance patterns differ from those of deoxyribonucleic acid DNA -damaging agents such as cisplatin and ifosfamide.39,40 In one study, no cross-resistance in cis-platin-resistant cell lines was demonstrated.39 Furthermore, in preclinical studies, paclitaxel showed significant cytotoxicity against teratocarcinoma cell lines, particularly those that were...

References

Union Internationale Contre le Cancer. TNM Classification of malignant tumours. 6th ed. New York Wiley-Liss, 2002. 2. Steele GS, Richie JP, Stewart AK, et al. The National Cancer Data Base report on patterns of care for testicular carcinoma, 1985-1996. Cancer 1999 86 2171-83. 3. Milosevic MF, Gospodarowicz M, Warde P. Management of testicular seminoma. Semin Surg Oncol 1999 17 240-9. 4. Bayley A, Warde P, Milosevic M, et al. Surveillance for stage I testicular seminoma. A review. Urol Oncol...

Hematologic Toxicity

Ovarian Cancer Karyotype

Leukemia and myelodysplasia are the other major long-term toxicities associated with the BEP regi men. These phenomena usually occur within 5 years of chemotherapy, were not reported with the PVB regimen, and also appear to be dose related. Nichols and colleagues reported that 2 0.37 of 538 patients receiving a cumulative etoposide dose lt 2,000 mg m2 developed an acute leukemia.38 Pedersen-Bjergaard and colleagues reported no incidence of leukemia in 130 patients with a cumulative etoposide...

Primary Extragonadal Germ Cell Tumors

Primary extragonadal germ cell tumors make up only 1 to 5 of all germ cell malignancies176 see Chapter 21 . They usually arise from the mediastinum or the retroperitoneum and have a histology similar to that of gonadal primaries seminoma and nonseminoma .176 Nonseminomatous extragonadal germ cell tumors have an inferior outcome with initial therapy and an exceedingly poor prognosis if they recur, and therefore represent a distinct clinical and biologic entity.177 Neither conventional salvage...

Spf

Mixed Gonadal Dysgenesis

Microscopic appearance and variation of endodermal sinus tumor. A, Conventional polyvesicular areas with a-fetoprotein globules. B, Solid and pseudoglandular morphology. C, Myxoid vesicular and enteric differentiation. Original magnification x200. Figure 22-12. A, Dysgerminoma of the ovary, a large lobulated firm tumor with a homogeneous appearance note the absence of teratoid elements, necrosis, or hemorrhage. B, Photomicrograph showing the typical appearance of dysgerminoma or...

Testicular Tumors

Tumor Testicle Sack

In infants and prepubertal children, the vast majority of testicular germ cell tumors consist of pure endodermal sinus tumor and, less frequently, teratoma.14 Testicular germ cell tumors in adolescent patients represent a rare but broader spectrum similar to that seen in adults. It behooves the pediatric surgical pathologist to maintain a broad differential diagnosis either in primary or in metastatic sites for these neoplasms. The gross appearance of mature testicular teratomas in infancy and...

Gonadoblastoma and Germ Cell Tumors in Intersex Syndromes

Skin Atrophy Reversible

The term gonadoblastoma refers to a tumorlike lesion that recapitulates the development of gonads by incorporating germ cell clusters or cords and sex cord-stromal components surrounding these elements. It usually originates in dysgenetic gonads in genotypes in which a Y chromosome exists. Most gonadoblastomas arise in streak gonads, a testis, or an indeterminate gonad. Rare instances in which they arise in the ovaries of normal genotypic females

Presentation with Symptoms from Metastases

Aortocaval Compression Image

In 10 or more of cases, the presentation of testicular GCT is a result of symptoms derived from metastatic disease. In some cases, this is due to the presence of a small primary tumor but massive fast-growing metastases. The most common first site for the development of metastatic disease is within retroperitoneal lymph nodes. The sentinel nodes from right-sided tumors are in the aortocaval area those from left-sided tumors are in the para- and preaortic areas, most frequently on the...

Mediastinal Tumors

Germ cell tumors always figure in the differential diagnosis of mediastinal neoplasms at any age. From the larger series, we can conclude that the whole spectrum of teratoma and germ cell malignancy occurs in the mediastinum of children and adoles-cents.50-53 Approximately half of mediastinal germ cell tumors are represented by pure teratomatous tumors, and the other half is represented by malignant mixed germ cell tumors that may include ter-atomatous tumors. Mature teratomas usually behave in...

Ns

BEP bleomycin etopside cisplatin carbo carboplatin chemo chemotherapy CISCA cyclophosphamide cisplatin doxorubicin CR complete response CTX Cis cyclophosphamide cisplatin EP etoposide cisplatin NED no evidence of disease NS not stated OS overall survival rate P prospective Pts patients PVB cisplatin vinblastine bleomycin R retrospective VAB vinblastine actinomycin bleomycin VelP vinblastine ifosfamide cisplatin VIP etoposide ifosfamide cisplatin. 'Includes only patients who were treated with...

Prognosis And Staging

For many years, it has been recognized that tumor markers correlate with underlying biologic aggressiveness, and indeed, all markers have been shown to be more commonly elevated in higher-stage disease. LDH, in particular, has been shown to be not only a reflection of tumor burden59 but also an independent significant prognostic factor for growth rate and disease-specific survival.60,61 Predicting how individual patients will respond to therapy is key, and as cure rates improve, the issue of...

Surgery

Craniotomy With Stealth

The decision to perform surgery for intracranial metastasis of a germ cell tumor needs to be based on the patient's overall medical condition, the number and size of intracranial metastases, and the feasibility of gamma knife radiosurgical treatment. Given the chemosensitivity of GCTs, chemotherapy should be used in the perioperative setting and can be commenced either just prior to or immediately after surgery, without compromising the safety of the patient. Indeed, delay in the commencement...

Teratoma Lung Mediastinum

Recovery After Fibroid Tumor Surgery

Surgery of metastatic disease after chemotherapy is indicated for the majority of patients with a residual mass normal STMs are mandatory only following first-line chemotherapy whereas every mass should be resected in the salvage setting every time it is technically feasible. Only patients with no evidence of a residual postchemotherapy mass and with normal or normalized markers do not need postchemo- Figure 11-19. A, Computed tomography scan showing a right para-tracheal residual tumor...

Symptom Distress in Patients with Advanced Cancer

Unfortunately, no studies that specifically examine the symptoms experienced by patients with germ cell tumors at the end of life have been conducted. The numerous projects that have been completed examined patient populations with a variety of advanced malignancies, requiring readers to extrapolate a generalized advanced-cancer experience to the subset of patients in which they are interested. The common symptoms reported in the advanced-cancer population include fatigue, pain, anxiety, and...

Histopathology Of Testicular Germ Cell Tumors

Mitotic Seminoma

Testicular GCTs account for less than 1 of all internal organ malignancies in adult males.25 Nevertheless, these tumors are important because they typically affect young adult males and men in their most productive years. Furthermore, testicular GCTs are readily curable if diagnosed on time and treated appropriately. GCTs account for more than 90 of all testicu-lar tumors. These tumors have many features in common. Thus, they have a peak incidence in the 25- to 40-year age group. All GCTs of...

Magea4

MAGE-A4 is a member of the MAGE-A gene family, which consists of at least 12 genes that are activated in various tumors, including melanoma and GCTs.6,76-79 These genes encode for tumor antigens that can be recognized by tumor-specific cytolytic T lymphocytes, and they appear to have a role in clinical immunity in some tumors. Takahashi and colleagues demonstrated the expression of MAGE proteins in human spermatogonia and to a lesser extent in human primary spermatocytes.80 Aubry and...

Damon J Vidrine DrPh Ellen R Gritz PhD

Although testicular cancer is relatively uncommon, representing only about 1 of all cancer incidence in males, it is the most common neoplasm in men between the ages of 15 and 35 years.1 According to estimates from the American Cancer Society, approximately 7,500 men are diagnosed with testicular cancer each year in the United States.2 For unknown reasons, the incidence of testicular cancer has been increasing in recent decades. Estimates suggest that the risk of testicular cancer has increased...

1

Adapted from von der Maase et al.23 'Modified to fit table. tjncludes 5 patients with relapse pelvic lymph nodes. showed nonseminomatous metastases in 44 of patients.1617 More recently, with the use of tumor markers for routine diagnosis, the few seminoma-tous patients who die from cancer do so most often from seminoma but exceptions do occur. Retroperitoneal masses are expected to shrink over time. It may take months for this shrinkage to occur. In the past, some investigators viewed patients...

Mediastinal Germ Cell Tumors

Mediastinal GCTs see also Chapter 21 typically occur in the anterior part of the mediastinum and account for appoximately 15 of all tumors and cysts at this site.53-57 The tumors are typically connected to the thymus, and it is assumed that they originate from displaced germ cells retained in that location. In the neonatal period, mediastinal ter-atomas are often intrapericardial or intracardiac.51 Mediastinal GCTs predominantly affect young males, and the mean age at diagnosis is about 28...

Ovarian Tumors

Characteristics Ovarian Tumor

Teratoma with Malignant Germ Cell Neoplasm Overall, the ovary is the second most common site after the sacrococcygeal region for teratomas with malignant germ cell neoplasm in children.31 These tumors are also frequent in the first and second decades of life. They are classified as mature, immature as graded on the amount of immature tissue present , and malignant. Mature teratoma of the ovary tends to be cystic and is readily recognizable by imaging studies Figure 22-9, A grossly, they are...

Risk Factors

In 1987, the UK Medical Research Group reported on a retrospective study of risk factors for predicting relapse in patients with clinical stage I nonsemino-matous tumors. The group found that invasion of testicular blood vessels, invasion of testicular lymphatics, the presence of embryonal carcinoma cells, and the absence of yolk sac elements were significantly important in this respect.16 Freedman and colleagues16 reported the following incidences of these poor-risk factors lymphatic invasion,...

Index

Page numbers followed by f indicate figure. Pages numbers followed by t indicate table. embryologic development of, 35 Abdominal wall muscles nerves of, 33 ACE. See Actinomycin D cyclophosphamide Web site, 291, 292 Actinomycin D, 142 Actinomycin D cyclophosphamide etoposide ACE , 159 central nervous system metastases, 210-211 schedule for, 161t standard-dose therapy, 163 toxicity of, 341 tumor markers in, 164f Acute monocytic leukemia etoposide-induced, 357f Adjuvant medications, 332-333...

Tumor Marker Decline As A Prognostic Factor

Tumor Marker

Investigators at Memorial Sloan-Kettering Cancer Center MSKCC have emphasized the prognostic role of tumor marker decline following the first cycle of chemotherapy.5 A prognostic model was performed at MSKCC. The half-life of the tumor marker was calculated between the first two values measured after day 7 from the start of chemotherapy. The cutoff values for the half-lives of hCG and AFP were 3 and 7 days, respectively. This study included 189 patients with good- , intermediate- , and...

Orchiectomy Scar

Clamp Sperm Cord

The spermatic cord C can be seen exiting from the superficial inguinal ring, formed by the edges of the external oblique aponeurosis EO . Figure 9-3. The spermatic cord C can be seen exiting from the superficial inguinal ring, formed by the edges of the external oblique aponeurosis EO . Figure 9-4. The ilioinguinal nerve can be seen in the inguinal canal straight arrow after the external oblique aponeurosis has been incised and reflected curved arrows . Figure 9-4. The ilioinguinal...

Desperation Surgery

The role of salvage surgery in the treatment of germ cell tumors is discussed in greater detail elsewhere in this textbook. It is important to note that there is substantial literature support for attempts at complete resection of residual tumor, even after the most extensive efforts at chemotherapy and in patients with persistently elevated tumor markers.166-173 Long-term disease-free survival is reported for such patients who have a solitary resectable recurrent or persistant mass.

Itt

Gynecomastia Exercise

Typical site of first metastases. A and B, Right testicular primary. Fluorodeoxyglucose positron emission tomography FDG-PET scan A of a patient with nonseminomatous germ cell tumor of the right testis demonstrates increased metabolic activity arrow at the typical location of first lymphatic spread of a right testis tumor, namely, the interaortocaval nodes just below the renal hila. This scan identified early metastatic spread in a patient with elevated tumor markers and a computed...

Primary Chemotherapy For Patients With Poorrisk Nsgct

The two schedules most commonly used in treating patients with poor-risk NSGCT are shown in Table 14-2. Einhorn and colleagues confirmed that BEP was superior to PVB8 in a randomized trial in 1987. Since then, BEP has been the most widely used schedule in the initial therapy for this disease. The results of the major randomized trials in patients with poor-risk disease that have reported the proportion of durable remissions are shown in Table 14-3.9-12 While the rate of complete response in...