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...

Info

No difference at preliminary analysis E500P x 4 Total Published only in abstract form B bleomycin C carboplatin E etoposide P cisplatin MSKCC Memorial Sloan-Kettering Cancer Center MRC Medical Research Council Indiana Indiana University IGCCC International Germ Cell Cancer Consensus Classification EORTC European Organization for Research and Treatment of Cancer IGV Institut Gustave Roussy. *Subscript numerals refer to dose and schedule (eg, E100X5 etoposide 100 mg m2 days 1 to 5 B90 bleomycin...

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...

C

Microscopic Anatomy Muscle Cells

This 37-year-old man had a history of nonseminomatous germ cell tumor and nodal relapse in the retroperitoneum, treated with chemoradiotherapy and surgical dissection. A rising level of serum beta-human chorionic gonadotropin was detected during follow-up. A, Computed tomography CT showed some residual soft tissue in the aortocaval space arrow , just above the aortic bifurcation. B, The residual tissue was better visualized by T2-weighted magnetic resonance...

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

Ovarian Tumor With Teeth

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...

Pns

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...

Patterns Of Presentation Of Advanced Seminoma

As described elsewhere in this volume, there is considerable overlap in the biology and natural history of testicular seminoma and nonseminomatous germ cell tumors NSGCTs . This is hardly surprising in view of the common germ cell origin of both histologic types, the shared expression of the i 12p chromosome, and their shared responsiveness to chemotherapy. Notable differences between semi-noma and NSGCT cases include an older age of presentation, a more dramatic sensitivity to radiation, and a...

Presentation of Germ Cell Tumors

CHRISTMAS, MD, FRCS ALAN HORWICH, PhD, FRCR, FRCP In the male, the classic presenting symptom of a germ cell tumor GCT is a painless hard swelling within the body of the testis in a young man. In the United States, the lifetime risk for developing a testicular tumor is about 1 in 300, and the incidence has been increasing.1 The swelling within the testis may be noticed by the patient or his sexual partner. The presence of tes-ticular atrophy, which is a predisposing factor for GCT,...

Intracranial Germinoma

Given the exquisite sensitivity of intracranial germinomas ICGs to both radiation and chemotherapy, the role for radical surgery is questionable. Sawa-mura and colleagues retrospectively reviewed the experience of 29 patients who underwent surgery for germinoma and found that radical resection offered no benefit in either response rate or overall survival when compared to biopsy alone.93 Because of the potential risks of radical surgery including seeding of the cerebrospinal fluid , once a...

Oxaliplatin

In vitro studies of oxaliplatin trans-1-diaminocy-clohexane oxaliplatin, a platinum analogue have demonstrated incomplete cross-resistance with cisplatin in nonseminomatous germ cell tumor cell lines.161 The German Testicular Cancer Study Group recently reported the initial results in 32 patients whose disease progressed after at least two cisplatin-containing regimens, after high-dose therapy, or during initial induction or salvage treatment.162 Treatment included oxaliplatin at 60 mg m2 on...

Interdisciplinary Management

Images Germ Cell Brain Tumors

The outcomes for patients with CNS metastases from GCTs have improved significantly since the 1970s, when the average survival from time of diagnosis was less than 6 months.6 This improvement has occurred in the context of better efficacy of systemic chemotherapy for GCT and improved local management of CNS metastases7,31 Recent reports of results from multimodal therapy demonstrate disease-free survival greater than 2 years from diagnosis in up to 80 of patients presenting with cerebral...

Ovarian Germ Cell Tumors

Cystic Teratoma

Ovarian GCTs account for approximately 25 to 30 of all ovarian tumors. The classification of the World Health Organization recognizes several entities that roughly correspond to testicular GCTs Table 4-2 . Most ovarian GCTs are classified as benign ter-atomas dermoid cysts , which account for 95 of all ovarian GCTs.21 Most patients are younger than 30 years of age. In the first two decades, ovarian GCTs account for 60 of all ovarian tumors, one-third of which are malignant.40,41 Dysgerminoma is...

Robert Kagan Md

Drainage Aortic Lymph Nodes

Patients with early and advanced seminoma have at least a 95 and an 80 chance of cure, respectively. Since the mid-1970s, radiation therapy for early seminoma and chemotherapy for advanced seminoma have usually achieved cure. The confidence engendered by this success has led to the exploration of less intensive strategies of treatment for stage I seminoma see Chapter 18 . However, the relatively standard treatment approaches mentioned above remain the most widely used strategies for the...

Retroperitoneal Tumors

Teratoma Infant

The retroperitoneum is an unusual site for germ cell tumors. Germ cell tumors in the retroperitoneum represent 4 of all gonadal and extragonadal germ cell tumors in this pediatric age group. In respect to age, they occur in a wide range of individuals, from new-borns to persons in the sixth decade of life. Approximately 7 of these tumors are malignant.54,55 The spectrum of gross and microscopic morphology is very similar to that seen in all other sites. Most arise in Figure 22-16. A,...

Carbo Vp Oncology Chemo

Abs absolute carbo carboplatin CDDP cisplatin CR complete response ECOG Eastern Cooperative Oncology Group IFX ifosfamide IGCCCG International Germ Cell Consensus Collaborative Group int intermediate MSKCC Memorial Sloan-Kettering Cancer Center retro retrospective Rx therapy UBC University of British Columbia VP-16 etoposide. 'Refractory responsive or stable disease with tumor progression within 4 weeks of exposure to cisplatin-containing chemotherapy. tAbsolute refractory disease progression...

Gastrointestinal Toxicity

The major acute gastrointestinal side effects of chemotherapy for germ cell tumors are nausea and vomiting diarrhea, paralytic ileus or constipation, and mucositis occur less commonly. Cisplatin and vinblastine as used in the cisplatin vinblastine bleomycin PVB regimen are responsible for the majority of this toxicity,10,11 with a lesser contribution from ifosfamide, methotrexate, and actinomycin D in men receiving salvage therapy or treatment for poor-prognosis disease.12 The vinca alkaloids...

Management of Primary Mediastinal Seminoma

Prior to the advent of cisplatin-based chemotherapy, the traditional treatment of primary mediastinal seminoma was surgery and or radiation therapy. Although surgical resection was curative in some patients in the past, the tumor is not amenable to complete resection in the majority of cases as a result of extramediastinal or extensive local disease. Given the potential morbidity of extensive debulking surgery and the sensitivity of seminoma to other modalities such as radiation or...

Body Image

Another disease-specific outcome sometimes considered is body image. Gritz and colleagues36 reported that 24 of survivors perceived themselves to be less attractive as a result of testicular cancer treatment. The perception of decreased attractiveness was significantly associated with treatment modality, with survivors who had received RPLND and or chemotherapy being the most likely survivors to report perceived decreases in attractiveness. Patients who underwent only orchiectomy were the least...

Management Of Scrotal Contamination

The possibility of testicular cancer must be entertained before performing any scrotal surgery on a man between 17 and 45 years of age. However, diagnostic errors do occur. It was previously thought that scrotal surgery markedly increased the risk of local recurrence and inguinal node metastasis.9 However, more recent evidence suggests that the local recurrence rate ranges from 0 to 6.4 .10,11 A meta-analy-sis of 1,182 total cases, 206 with scrotal violation, showed that the risk of local...

Prognostication After Chemotherapy

Much experience has been gained in predicting outcomes of patients who complete chemotherapy and in regard to adjunctive therapies following chemotherapy. In particular, post-chemotherapy surgical findings have been analyzed in efforts to identify those who are at high risk for additional events. Foster and colleagues recently reported the role of retroperitoneal lymph node dissection RPLND in patients with persistently elevated markers after the completion of standard chemotherapy for...

Current Issues In The Treatment Of Highrisk Germ Cell Cancer With aPSCT

The choice of a regimen remains one of the major unresolved issues in the treatment of poor-risk germ cell cancer with high-dose chemotherapy and stem cell support. Elements of regimen design include 1 the safety of each agent at the dose and schedule and in the combination selected for study, 2 the timing of this modality and the use of alternative regimens such as multicycle highdose therapy, 3 tandem cycles using different agents in each cycle, and 4 the incorporation of new pharmacologic...

Alan Horwich PhD Frcr Frcp

Seminomatous germ cell tumors represent a relatively infrequent indication for chemotherapy. The majority of presentations are at an early stage and are managed currently by adjuvant radiotherapy or by surveillance. Since relapse from these stages is uncommon and the presentation of seminoma with disseminated metastases is also uncommon, the chemotherapy for semi-noma has developed mainly in parallel with chemotherapy for nonseminomatous germ cell tumors. However, there are important...

Epidemiologic Insights into the Occurrence and Causes of Testicular Cancer

Epidemiologic research has described the population distribution of testicular cancer and has suggested pathophysiologic mechanisms that are being investigated. Descriptive studies show that testicular cancer is becoming more common and that it occurs primarily in young men. This unusual age distribution accounts for much of the impact of disease and suggests some etiologic hypotheses. Analytic research has provided etiologic insights suggesting that testicular germ cell carcinoma has both...

Histopathology

Calcifying Placenta

All histologic subtypes seen with GCTs are reported in EGGCTs as well. Most investigators believe that both groups of tumors arise from primordial germ cells. The histologic patterns reflect the normal stages of embryonic and fetal development that these totipotential cells undergo. When primordial germ cells undergo malignant transformation, they can differentiate along a gamete lineage or anywhere along the spectrum of embryonic and extraembryonic differentiation. Tumor histologic type is...

Monitoring Tumor Response

Seminoma Stage

While surgery and platinum-based chemotherapy remain the mainstay of treatment, efforts are now focused on refining chemotherapy regimens in order to limit unnecessary treatment and reduce toxicity without compromising the chance of cure. CT remains the workhorse for monitoring chemothera-peutic response and for follow-up of all patients with testicular tumors. Radiotherapy still has a role in the management of testicular tumors particularly seminomas , and CT provides not only a method of...

Mary K Gospodarowicz Md Frcpc Frcr Hon Padraig Rwarde Mb Mrcpi Frcpc

The majority more than 75 of patients with seminoma present with clinical stage I disease that is, no apparent involvement is found outside the testis.1,2 The classic presentation of stage I disease is painless testicular enlargement although up to 30 of patients can have some pain at presentation. The traditional management of patients with stage I semi-noma involves inguinal orchiectomy, which provides detailed information on tumor pathology, information on the extent of primary disease, and...

Lung Metastases

Para Aortic Mass Germ Cell

Chest CT is generally regarded as an essential staging investigation for all germ cell tumors. It is the most sensitive imaging technique for detecting pulmonary nodules, and metastases down to the size of 3 to 4 mm can be diagnosed. However, the appearance of benign nodules is identical to that of small metastases, and in countries where there is a high incidence of granulomatous disease such as the United States , false-positive results may be a problem.28 If one or more suspicious lesions...

Other Sites of Metastasis

Seminoma Metastasis Brain

The liver is an unusual site of metastasis but is a more common site in NSGCT cases than in seminoma cases. In patients with NSGCTs, metastases can be mistaken for simple cysts because these metastases may be low-density cystic lesions see Figure 6-13 . If doubt exists regarding the presence or character of a lesion, then ultrasonography or MRI may provide useful additional information. Ultrasonography is also useful for guiding biopsies of focal lesions in the liver that are suspected of...

Extent Of Postchemotherapy Surgery

Rplnd Template Left Testis Tumor

The most frequent site of a postchemotherapy residual mass is the retroperitoneum.5-7 Other sites are lungs, mediastinal and supraclavicular nodes, liver, brain, and bone, in decreasing order.16 Furthermore, extra-retroperitoneal metastases are more frequent in the salvage setting than after primary chemother-apy.9,10 The treatment of brain metastases and extragonadal tumors is not considered here. They are covered in detail in Chapters 17 and 21, respectively. Two important questions must be...

CNS Imaging

Brain Mets From Teratoma

In an acute setting in which the patient has a rapidly progressive neurologic deficit or a fluctuating level of consciousness, initial computerized tomography Figure 17-1. Metastatic choriocarcinoma. The patient was a 38-year-old man who had been treated at other institutions over a 4-year period for metastatic germ cell tumor with multiple recurrences despite retroperitoneal lymph node dissection, standard cisplatin-based chemotherapy bleomycin etoposide cisplatin BEP , ifosfamide-based...

Patterns Of Occurrence

Testicular Cancer Rate Statistics

The lifetime risk of testicular cancer is less than 1 . Unlike the more common cancers, testicular cancer primarily affects young men Figures 2-1 and 2-2 . Among men between the ages of 20 and 35 years, testicular cancer was the most common cancer until it was surpassed by Kaposi's sarcoma, a cancer related to acquired immunodeficiency syndrome AIDS . The occurrence of testicular cancer has been increasing for decades,1-14 and where accurate incidence data have been collected, the rates have...

Strategic Planning

Aortocaval Lymph Node

Postchemotherapy surgery should be planned strategically in the case of multiple-site residual masses. At the very beginning of the cisplatin era, Merrin31 proposed a heroic operation contemporary median laparotomy and sternal split to remove, in a single operation, the abdominal, thoracic, and eventually supraclavicular metastases. This very heavy surgery had too many complications and has been practically abandoned. Usually, RPLND is performed first, with the contemporaneous removal of the...

Patterns Of Tumor Spread

Diagram Retrocrural Lymph Node

The presence of lymphatic or vascular invasion documented on histologic examination is an important prognostic indicator of primary testicular tumors because these are the pathways of metastatic spread. Lymphatic invasion leads to tumor spread along four to eight efferent lymphatic channels that accompany the spermatic cord. These channels pass through the internal inguinal ring, where they join together to form major lymphatic channels accompanying the tes-ticular vessels. These major vessels...

Cerebrospinal Fluid Marker Concentrations

Endodermal Sinus Tumor Cns

The evaluation of cerebrospinal fluid CSF for P-hCG can be a valuable tool in the diagnosis of CNS metastases from GCTs. In patients in whom P-hCG is the predominant marker, measurement of CSF P-hCG may detect patients with CNS involvement with metastatic disease that is below the limits of detection by CT.6 The original work undertaken by Bagshawe and colleagues29,30 in the era prior to CT and MRI suggested that a high CSF P-hCG level was predictive of CNS disease. The cutoff for prediction of...

Urogenital Conditions Associated With Testicular Cancer

Cryptorchidism is a common congenital disorder in which one or both testicles fail to descend into the scrotum before birth. Over half of the boys who are born with cryptorchidism experience spontaneous testicular descent during the first year of life. A history of persistent cryptorchidism, in which spontaneous descent does not occur, is the major established risk factor for testicular cancer. Epidemiologic studies consistently find associations between a personal history of cryptorchidism and...

Retroperitoneal Lymph Node Dissection

Ivc Retroperitoneal

A, Template for bilateral retroperitoneal lymph node dissection for retroperitoneal metastases from the left testis. B, The operative field at the end of dissection no nerves are spared. The inferior mesenteric artery was not divided. Figure 11-3. A, Modified bilateral template for retroperitoneal lymph node dissection for tumors of the right testis the contralateral dissection below the level of the inferior mesenteric artery was avoided. IVC inferior vena cava. B, The operative...

Lymph Node Metastases

Lymph Node Character

Lymph node metastases in patients with testicular tumors vary in size, from nodal masses that are lt 2 cm in diameter to huge retroperitoneal masses. The character of nodal masses is related to histology on CT, seminoma nodal deposits are usually of soft-tissue density whereas NSGCTs are often heterogeneous since they contain areas of necrosis and cystic degeneration see Figures 6-1, C, and 6-6 . Homogeneous low-density cystic lesions may be a feature of NSGCTs. Nodal masses associated with...

The Retroperitoneum

Celiac Trunk Divides Into

The distribution of metastases from each testis to the retroperitoneal lymph nodes has been described defin-itively.7 The technique of retroperitoneal lymph node dissection is the topic of a subsequent chapter see Chapter 10 and will not be addressed here. Rather, the major blood vessels and the autonomic nerve supply of the retroperitoneum will be discussed. The abdominal aorta passes through the diaphragm at the level of the twelfth thoracic vertebra and lies in front of the anterior...

Contributors

Beer, MD Department of Medicine Oregon Health and Science University Portland, Oregon Richard Bihrle, MD Department of Urology Indiana University Indianapolis, Indiana Thomas C. Chen, MD Department of Neurosurgery University of Southern California Timothy J. Christmas, MD, FRCS Academic Urology Unit The Royal Marsden Hospital London, United Kingdom Gary J. R. Cook, MSc, MD, FRCP, FRCR Department of Radioisotope Physics University of London London, United Kingdom Victoria Cortessis,...

Contents

1 Biology of Germ Cell Derek Raghavan, MD, PhD, A. Munro Neville, MD, PhD, FRCPath 2 Epidemiologic Insights into the Occurrence and Causes of Testicular Cancer 16 3 Surgical 5 Presentation of Germ Cell Timothy J. Christmas, MD, FRCS, Alan Horwich, PhD, FRCR, FRCP 6 Radiologic Janet E. S. Husband, OBE, FMedSci, FRCP, FRCR, Dow-Mu Koh, MRCP, FRCR, Gary J. R. Cook, MSc, MD, FRCP, FRCR 7 Tumor Markers in Germ Cell Tumors of the Avrum I. Jacobson, MD, Paul H. Lange, MD, FACS 8 Prognostic Factors in...