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Keywords:

  • testicular carcinoma;
  • sentinel lymph node;
  • laparoscopy;
  • γ probe;
  • lymph node dissection

Abstract

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

BACKGROUND

The management of regional lymph nodes in patients with clinical Stage I testicular carcinoma is a controversial problem. The authors investigated the feasibility and accuracy of radio-guided mapping of sentinel lymph nodes (SLNs) for men with clinical Stage I testicular tumors.

METHODS

Twenty-two patients with clinical Stage I testicular carcinoma were enrolled in the study. One day before surgery, 99mTechnetium-labeled phytate was injected around the testicular tumor. After undergoing radical orchiectomy, patients underwent laparoscopic retroperitoneal lymph node dissection (L-RPLND). All radioactive lymph nodes were marked in the L-RPLND procedure, and three-dimensional SLN maps were made. All resected lymph nodes were evaluated by routine histopathologic examination, and the clinical significance of intraoperative SLN mapping was evaluated.

RESULTS

SLNs were detected in 21 of 22 patients (95%). Nearly all SLNs were detected at the ventral or lateral side of the vena cava or at the aorta between the levels of the aortic bifurcation. All SLNs were detected easily in a surgical procedure. Only 1 radio-positive area per patient was identified in 15 patients, and approximately 2–4 positive areas were detected in 6 patients. Two patients had micrometastasis only in SLNs. In 2 patients who had seminoma, lymph node recurrences (at the level of the renal vein and in the obturator lymph node area) occurred at 10 months and 20 months after surgery.

CONCLUSIONS

Radio-guided mapping of SLNs with laparoscopy was feasible, and nearly all SLNs were detected accurately by the procedure. In the near future, the standard retroperitoneal lymph node dissection may be avoided in most patients with clinical Stage I testicular carcinoma by utilizing focused examination of SLNs. Cancer 2005. © 2005 American Cancer Society.

The management of regional lymph nodes in patients with clinical Stage I testicular carcinoma is a controversial problem. Retroperitoneal micrometastases already may exist in approximately 30% of patients with nonseminomatous germ cell tumors.1 Among patients with Stage I seminoma, the recurrence rates are reported to range from 9% to 23%.2 Reports on standard adjuvant radiotherapy for patients with low-stage seminoma have indicated problems concerning impaired spermatogenesis, secondary malignancy, and an increased rate gastrointestinal disease on long-term follow-up.3–5 However, the morbidity of open retroperitoneal lymphadenectomy is too high for it to serve as a diagnostic procedure.6 Laparoscopic lymph node dissection (L-RPLND) is a minimally invasive method for precise pathologic lymph node staging of metastatic disease, but the technique is difficult to learn.7 There is a need for easy and safe surgical techniques for the accurate detection of occult retroperitoneal diseases.

Sentinel lymph node (SLN) dissection for small, early-stage breast carcinoma is well accepted. In patients with early-stage breast carcinoma, there is a lower likelihood of lymph node metastases, and lymphatic mapping and SLN biopsy are accurate predictors of axillary lymph node status.8

Recently, we reported that SLN in the patients with testicular carcinoma could be detected by lymphoscintigraphy and a hand-held γ probe.9 In the current study, we report our results from intraoperative, radioguided SLN mapping in patients with Stage I testicular carcinoma and its clinical significance in predicting the status of the entire lymph node basin.

MATERIALS AND METHODS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

Patient Characteristics

The Ethics Committee at Tohoku University approved this pilot study, and each patient provided written, informed consent. Before they underwent surgery, various therapeutic options were discussed with each patient. Staging was performed according to the 1997 AJCC TNMS system. All patients had no past history of surgery or injury related to the testis or testicular cord.

Between February 2002 and September 2004, 22 patients with a mean age of 34 years (range, 21–48 years) who had clinical Stage I testicular carcinoma underwent orchiectomy followed by L-RPLND under the guidance of an SLN navigation system. The primary tumor sites were on the right side in 11 patients and on the left side in 11 patients. We found seminoma in 16 patients and nonseminomatous carcinoma in 6 patients (Table 1).

Table 1. Patient Characteristics
PatientAge (yrs)SidePathologypT (TNM)No. of SLNsSLN metastasesLymph node recurrenceFollow-up (mos)
  1. pT (TNM): pathologic tumor classification according to the Tumor, Lymph Node, Metastasis classification system; SLNs: sentinel lymph nodes; +: positive; −: negative.

132LeftSeminomapT1131.0
221RightNonseminomapT11+31.0
337RightSeminomapT11+29.0
448RightSeminomapT2129.0
540RightSeminomapT11+26.0
639LeftSeminomapT1126.0
727LeftSeminomapT21+25.0
842LeftSeminomapT1125.0
927RightSeminomapT1121.0
1044LeftSeminomapT1121.0
1145LeftSeminomapT1121.0
1227RightNonseminomapT1121.0
1322LeftSeminomapT1118.0
1440LeftNonseminomapT1217.0
1537RightSeminomapT1116.0
1629RightNonseminomapT1215.0
1721RightNonseminomapT1214.0
1834LeftSeminomapT1311.0
1926RightNonseminomapT1011.0
2037LeftSeminomapT1310.0
2136RightSeminomapT147.0
2237LeftSeminomapT116.0
Average341.419.5

Lymphoscintigraphy

Twenty-four hours before surgery, 15 megabecquerels of technetium-99m-labelled phytate in 0.4 mL of saline were injected into the testicular tissue around the tumor inside the testicular tunica albuginea with a 29-gauge needle. A dynamic image was taken for the first 30 minutes followed by static imaging. Details of the lymph node mapping procedure by lymphoscintigraphy were reported previously.9

Intaoperative Detection of SLNs

After radical orchiectomy, patients underwent γ probe-guided, extraperitoneal L-RPLND. The surgical techniques consisted of an internal iliac extraperitoneal approach10 and a modified template L-RPLND.11 After establishing a pneumoretroperitoneum, the retroperitoneal space was extended greatly into a dome shape with a ceiling made up of the peritoneum, ureter, and testicular vein. At this point, the location of SLNs was confirmed by a hand-held γ probe (Navigator; Tyco Healthcare Japan, Tokyo, Japan) (Fig. 1). The lymph node dissection is started from the common iliac artery region toward the cephalad. We performed modified template dissection without dissection of the lymphatic tissue behind the lumbar vessels after it was confirmed that there were no radioactive lymph nodes located in this area.

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Figure 1. Sentinel lymph node detection by γ-probe guidance.

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After lymph node resection, the absence of residual radioactivity in the retroperitoneal cavity was confirmed intraoperatively using a hand-held γ probe. To confirm that the resected SLNs indeed were radiopositive lymph nodes, the radioactivity in the resected SLNs was measured with the γ probe by ex vivo measurement.

Pathologic Evaluation

All dissected lymph nodes were evaluated routinely for permanent sections with hematoxylin and eosin staining (H&E). Especially for SLNs, serial sections were processed at 50 μm per slice with H&E staining. If no tumor was identified, then immunohistochemical staining was performed with antihuman chorionic gonadotropin (HCG) (Immunotech Co., Marseilles, France), α-fetoprotein (AFP) (DakoCytomation; Copenhagen, Denmark), placental alkaline phosphatase (DakoCytomation), and cytokeratin AE1/AE3 (DakoCytomation).

Postoperative Follow-Up

Patients were scheduled to undergo computed tomography evaluations postoperatively every 3 months for the first 2 years 1–2 and every 6 months thereafter. Serum tumor markers (HCG, AFP, lactate dehydrogenase) also were examined every month postoperatively.

RESULTS

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

SLN Location

With the exception of one patient, all SLNs were detected easily by γ probe the day before lymphoscintigraphy. Only 1 SLN per patient was detected intraoperatively in 15 patients, and 2–4 SLNs were detected in 6 other patients. In 10 patients who had right-sided tumors, SLNs were detected at interaortocaval or preaortic locations. In 11 patients who had left-sided tumors, paraaortic lymph nodes near the inferior mesenteric artery were detected as SLNs (Figs. 2 and 3). In Patient 14, who had 2 SLNs, 1 SLN was detected at the right preexternal iliac artery. In Patient 21, who had 4 SLNs, 1 SLN was detected in the contralateral paraaortic area extratemplate dissection area (Fig. 3). All SLNs were detected at the ventral or lateral side of the great vessels, and no SLN was detected behind the vena cava or the aorta. All SLNs were detected under the levels of the gonadal artery.

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Figure 2. Sentinel lymph node mapping for patients who had only one sentinel lymph node. Open circles: sentinel lymph nodes; solid circles: sentinel lymph nodes with micrometastases; IMA: inferior mesenteric artery. The oblique area shown indicates the template lymph node dissection area.

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Figure 3. (A) Patient 14: Two hot spots are shown (white arrows) at the paraaortic and preexternal iliac artery regions on a static image. Navel: umbilicus marking. (B) Sentinel lymph node mapping for six patients who had two or more sentinel lymph nodes. IMA: inferior mesenteric artery.

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Pathologic Evaluation

Micrometastases were found only in the SLN in two patients, including one patient with seminoma and one patient with a nonseminoma. Adjuvant chemotherapy was given to these patients to reduce their risk of recurrence.12 No other SLNs showed metastases in H&E or immunohistochemical staining. None of our patients had tumor in nonsentinel retroperitoneal lymph nodes.

Follow-Up Data

Patient 7, who had seminoma, had a lymph node recurrence in the paraaortic lymph node at the level of left renal vein 10 months after undergoing L-RPLND. Patient 5, who also had seminoma, had a lymph node recurrence in the right obturator lymph node 20 months after undergoing L-RPLND (Fig. 4). Other patients were without evidence of disease at a mean follow-up of 19.5 months (range, 6–31 months).

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Figure 4. The position of recurrent lymph nodes. The oblique area shown indicates the template lymph node dissection area. IMA: inferior mesenteric artery.

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Patients who had histologically positive SLNs were treated with two cycles of bleomycin, etoposide, and cisplatinum adjuvant chemotherapy (BEP). These patients showed no recurrence at 15 months and at 6 months of follow-up. Patients who developed lymph node recurrences were treated with two or three courses of the BEP regimen.

Patient 7 achieved a complete remission, and Patient 5 underwent right obturatory lymph node dissection after receiving chemotherapy. This dissected obturatory lymph node tissue showed no pathologic malignant lesion.

DISCUSSION

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES

The accuracy of the modern imaging techniques used to identify lymph node metastases clearly has improved over the past few years, although the number of false-negative results remains unacceptably high. RPLND is the only method that permits reliable identification of micrometastases. Conversely, in this SLN era, most of the lymphatic region has been studied by lymphoscintigraphy using a variety of injection techniques and tracers. Lymphatic mapping and detection of SLNs in malignancies of the penis, bladder, and prostate have been demonstrated previously.13–15 In the current study, we used intraoperative, three-dimensional SLN mapping to identify SLNs during RPLND in patients with Stage I testicular carcinoma.

To detect micrometastases in all dissected lymph nodes, complete resection of all lymph nodes must be performed within the templates described by Weissbach and Boedefeld. In this procedure, whether the tissue behind the vena cava and aorta also must be removed is a controversial problem. Recently, Holtl et al. reported that they found no need to remove lymphatic tissue behind the lumbar vessels for a diagnostic procedure, because primary lymphatic metastatic spread in testicular carcinoma always occurs ventral to the lumbar vessels.16 Similarly, in our 21 patients, no SLNs were detected dorsal to the lumbar vessels by the γ probe. All SLNs were detected at the ventral and lateral side of the aorta or the vena cava. No patients demonstrated lymph node recurrence around these areas.

In our patients, 30 SLNs were detected between the levels of the aortic bifurcation and the gonadal artery within the standard template dissection area. However, in one patient, an SLN was detected in an extrastandard template dissection area. This SLN could not be dissected without the SLN navigation system.

In other patients, the radioactive lymph nodes sometimes shifted intraoperatively out from the conventional template dissection area by an extraperitoneal space-development maneuver. The SLNs that were shifted with this surgical maneuver and the SLNs that were located in an extrastandard template area could be detected easily by γ-probe guidance intraoperatively.

The accuracy of SLN status in breast carcinoma for predicting other lymph node involvement in recent studies exceeded 95%.17, 18 It is interesting to note that micrometastases were found only at the radiopositive lymph nodes in two patients in the current study. From our early experience, no conclusions can be drawn regarding the value of L-RPLND in patients with micrometastasis without adjuvant chemotherapy. Adjuvant chemotherapy for patients with low-volume, Stage II tumors reduces the risk of recurrence to 0–1%.12 For this reason, chemotherapy was given to these patients with micrometastases. The diagnostic and therapeutic accuracy of SLN status may be proven after more extensive experience and follow-up.

In the current study, 2 patients with seminoma showed lymph node recurrences after 10 months and 20 months of follow-up. In one of those patients, the lymph node recurrence was located in the renal vessel area. It was believed that this recurrence originated from an intraoperative SLN detection error and a dissection technique error that was due to an immature technique during early experience with the procedure. In another patient who had a lymph node recurrence, the recurrent lymph node was located in the right obturator nerve area. In this patient, the primary tumor (pT1) showed invasion to the tunica albuginea. Such tumors may have other routes of lymphatic drainage into the pelvic lymph nodes that could not be detected by intratunica albuginea injection of radioactive tracer. The problem with pelvic recurrences in patients with Stage I seminoma was reported previously in several publications.19 Further studies will be needed to evaluate the significance of this method for patients with Stage I seminoma.

Several issues, such as the sensitivity of intraoperative pathologic examination and the technique of laparoscopic SLN detection, remain to be resolved before the wide clinical application of this procedure. However, from this initial experience, it is reasonable to conclude that radioguided SLN detection has potential value in the staging and treatment of patients with early-stage testicular carcinoma. In the near future, SLN dissection alone may be a sufficient diagnostic procedure.

REFERENCES

  1. Top of page
  2. Abstract
  3. MATERIALS AND METHODS
  4. RESULTS
  5. DISCUSSION
  6. REFERENCES
  • 1
    Nicolai N, Pizzocaro G. A surveillance study of clinical Stage I nonseminomatous germ cell tumors of the testis: 10-year follow up. J Urol. 1995; 154: 10451049.
  • 2
    Suzuki K, Orikasa S, Hoshi S, et al. Surveillance study for clinical Stage I testicular seminomas and nonseminomatous germ cell tumors. Int J Urol. 1998; 5: 568574.
  • 3
    Hahn EW, Feingold SM, Simpson L, Batata M. Recovery from aspermia induced by low-dose radiation in seminoma patients. Cancer. 1982; 50: 337340.
  • 4
    Yeoh E, Horowitz M, Russo A, et al. The effects of abdominal irradiation for seminoma of the testis on gastrointestinal function. J Gastroenterol Hepatol. 1995; 10: 125130.
  • 5
    van Leeuwen FE, Stiggelbout AM, van den Belt-Dusebout AW,et al. Second cancer risk following testicular cancer: a follow-up study of 1,909 patients. J Clin Oncol. 1993; 11: 415424.
  • 6
    Spermon JR, Roeleveld TA, van der Poel HG, et al. Comparison of surveillance and retroperitoneal lymph node dissection in Stage I nonseminomatous germ cell tumors. Urology. 2002; 59: 923929.
  • 7
    Janetschek G, Hobisch A, Peschel R, Hittmair A, Bartsch G. Laparoscopic retroperitoneal lymph node dissection for clinical Stage I nonseminomatous testicular carcinoma: long-term outcome. J Urol. 2000; 163: 17931796.
  • 8
    Noguchi M. Sentinel lymph node biopsy and breast cancer. Br J Surg. 2002; 89: 2134.
  • 9
    Ohyama C, Chiba Y, Yamazaki T, et al. Lymphatic mapping and gamma probe guided laparoscopic biopsy of sentinel lymph node in patients with clinical Stage I testicular tumor. J Urol. 2002; 168: 13901395.
  • 10
    Ito A, Satoh M, Kaiho Y, et al. Extraperitoneal laparoscopic retroperitoneal lymph node dissection for early stage testis cancer [abstract]. J Endourol. 2003; 17: A309.
  • 11
    Weissbach L, Boedefeld EA. Localization of solitary and multiple metastases in Stage II nonseminomatous testis tumor as basis for a modified staging lymph node dissection in Stage I. J Urol. 1987; 138: 7782.
  • 12
    Steiner H, Peschel R, Janetschek G, et al. Long-term results of laparoscopic retroperitoneal lymph node dissection: a single-center 10-year experience. Urology. 2004; 63: 550555.
  • 13
    Horenblas S, Jansen L, Meinhardt W, et al. Detection of occult metastasis in squamous cell carcinoma of the penis using a dynamic sentinel node procedure. J Urol. 2000; 163: 100104.
  • 14
    Sherif A, De La Torre M, Malmstrom PU, Thorn M. Lymphatic mapping and detection of sentinel nodes in patients with bladder cancer. J Urol. 2001; 166: 812815.
  • 15
    Wawroschek F, Vogt H, Weckermann D, et al. Radioisotope guided pelvic lymph node dissection for prostate cancer. J Urol. 2001; 166: 17151719.
  • 16
    Holtl L, Peschel R, Knapp R, et al. Primary lymphatic metastatic spread in testicular cancer occurs ventral to the lumbar vessels. Urology. 2002; 59: 114118.
  • 17
    Veronesi U, Paganelli G, Galimberti V, et al. Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet. 1997; 349: 18641867.
  • 18
    Turner RR, Ollila DW, Krasne DL, Giuliano AE. Histopathologic validation of the sentinel lymph node hypothesis for breast carcinoma. Ann Surg. 1997; 226: 271276.
  • 19
    Fossa SD, Horwich A, Russell JM, et al. Optimal planning target volume for Stage I testicular seminoma: a Medical Research Council randomized trial. Medical Research Council Testicular Tumor Working Group. J Clin Oncol. 1999; 17: 11461154.