Abstract
Many changes have occurred in the surgical treatment of the cancer patient. For many tumors, surgery has been modified or eliminated. These changes are due to the realization that, for some cancers, more extensive surgical procedures are not more beneficial, to improvements in radiation therapy and chemotherapy, to the availability of better noninvasive or less invasive diagnostic and therapeutic techniques, and to improved surgical equipment (such as videoscopic surgery).
Recent changes in surgical oncology may eliminate much of what was previously considered standard surgical therapy. There is a clearer understanding that, for some cancers, more extensive surgery may not increase the cure rate. Radiation therapy and chemotherapy have improved and often can substitute for, or limit the extent of, surgical resection. Combined chemoradiotherapy protocols take advantage of the ability of chemotherapy to enhance local radiotherapy effects and treat occult micrometastatic disease. In addition, surgery is less often needed for diagnosis given the availability of cross-sectional imaging techniques, fine needle aspiration and biopsy (
1
). Improved pathological techniques, including immunoperoxidase and flow cytometric techniques utilizing monoclonal antibody staining, and molecular genetic techniques allow tumor classification with even small samples. Improved imaging techniques have also decreased the need for surgical staging purposes. Tumors of the head and neck, gastrointestinal, pulmonary, and genitourinary systems can be seen and biopsied with fiberoptic endoscopy; some can even be treated. Finally, improved surgical techniques, such as videoscopic surgery, have allowed for less invasive surgical approaches in the thorax, abdomen, and pelvis.Breast cancer
Breast cancer can be considered the paradigm for the decreasing extent of surgery in cancer diagnosis and treatment, including limiting the extent of mastectomy, breast preservation techniques, conservative management of the axillary lymph nodes, the use of medical rather than surgical hormonal therapies, and the availability of stereotactic biopsy of mammographic abnormalities (Table 1).
Table 1Changing (Diminishing) Extent of Surgical Intervention in Breast Cancer
| Older | Newer |
|---|---|
| Radical mastectomy | Total mastectomy |
| Mastectomy | Lumpectomy and irradiation |
| Axillary lymph node dissection | Axillary lymph node sampling |
| Axillary lymph node sampling | Irradiation or observation without sampling or sentinel node biopsy |
| Surgical biopsy of mammographic abnormalities | Stereotactic or ultrasound guided biopsy |
| Oophorectomy | Tamoxifen; LH-RH agonists |
| Adrenalectomy | Aromatase inhibitors |
legend LH-RH = luteinizing hormone-releasing hormone.
It is now recognized that more extensive surgical procedures, including the radical or extended radical mastectomy, are not superior to simple mastectomy (
2
). Indeed, for most patients diagnosed with breast cancer, breast conservation with lumpectomy and radiation therapy may substitute safely for mastectomy. At least six randomized controlled trials have found that, for appropriately selected patients, survival is equivalent for lumpectomy and radiation therapy compared with mastectomy (3
, 4
, 5
). Radiation therapy following lumpectomy reduces the risk of recurrence in the breast, although its impact on overall survival is less clear (6
). Patients with tumors greater than 3 cm also appear to be eligible for breast preservation, provided an adequate margin of resection can be obtained with an acceptable cosmetic result. Even patients with very advanced tumors are being considered for breast preservation following the use of neoadjuvant chemotherapy. While extensive results from randomized trials are not available, most prospective studies support that about 85% of patients will have substantial shrinkage of their primary cancer enabling many to undergo lumpectomy with breast preservation. Preliminary reports on survival do not appear worse than expected for similarly staged patients undergoing mastectomy (7
).The extent of surgical treatment of the axilla in patients with breast cancer is also lessening. Previous surgical treatment included formal axillary dissection; it now seems clear that such extensive dissections are unnecessary. They do not increase the cure rate, and they do not generally provide further prognostic information compared to a more limited axillary sampling (
8
). Morbidity is therefore reduced, as fewer patients develop lymphedema with its associated complications. Although controversial, some surgeons no longer perform even axillary node sampling in selected patients, such as the elderly, with invasive breast cancer. This is partly due to the realization that, although axillary dissection reduces the risk of axillary recurrence, the procedure does not affect survival. In addition, the axilla may be treated by radiation if necessary. Finally, since chemotherapy or tamoxifen may be beneficial in many node-negative as well as node-positive patients, the presence of axillary lymph node metastases may not affect the decision to administer systemic adjuvant therapy. The technique of sentinel lymph node sampling is also being investigated in patients with breast cancer (9
); this technique is discussed in the section on melanoma.Screening mammography has increased the number of women diagnosed with noninvasive (intraductal) breast cancer. These patients were traditionally treated with mastectomy and axillary dissection. Provided the disease appears unifocal mammographically and pathologically and can be resected with an adequate margin, these women can be treated with lumpectomy (
10
). Whether all of these patients need radiotherapy following lumpectomy is debated (11
). Moreover, since the chance of positive lymph nodes in these patients is less than 5%, lymph node sampling is generally no longer recommended (8
, 10
).The overall approach has been to be less aggressive surgically in women with noninvasive lobular carcinoma (lobular carcinoma in situ) as well (
12
). Many are managed by observation alone, whereas in the past, unilateral, or sometimes bilateral, mastectomies were performed, or “mirror-image” biopsies were recommended because of the increased risk for malignancy in both breasts.The need for open surgical biopsy of nonpalpable, mammographically detected abnormalities is also changing. These women typically have had needle placement performed in the mammography suite and then have gone to the operating room for directed open biopsy. The availability of stereotactic breast biopsy systems, as well as ultrasound-guided biopsy units, eliminates the need for open surgical biopsy in some of the patients. Studies show good sensitivity and specificity in comparison to results of open biopsy (
13
, 14
, 15
, 16
, 17
, 18
, 19
). When cancer is diagnosed by stereotactic biopsy of nonpalpable lesions, definitive surgery can be planned and performed with only a single operating room visit.Finally, for patients with metastatic breast cancer who require hormonal therapy, ablative surgical procedures have largely been replaced by medication. In premenopausal patients, tamoxifen or luteinizing hormone-releasing hormone (LH-RH) agonists appear to be similar to oophorectomy in inducing responses (
20
, 21
, 22
). While (laparoscopic) oophorectomy is still an appropriate treatment, tamoxifen or LH-RH agonists are reasonable alternatives for premenopausal patients. Furthermore, adrenalectomy and hypophysectomy, once common in post-menopausal patients with advanced breast cancer, have been eliminated in favor of aromatase inhibitors such as aminoglutethimide or anastrazole as second-line hormonal therapy (23
).Lymphoma
For patients with non-Hodgkin’s lymphoma, open biopsy of a lymph node to provide information on cell type and architecture is preferable to the limited information available from a fine needle aspirate or biopsy. However, in selected patients who have intrathoracic or intra-abdominal nodes only, information obtained from needle aspirates and biopsies may be adequate (
24
, 25
). The use of flow cytometry can demonstrate monoclonality consistent with malignancy in a B-cell population, and studies for immunoglobulin or T-cell receptor gene rearrangements can also be done to distinguish monoclonal from polyclonal populations of B and T cells (26
).Staging laparotomy is generally no longer performed for non-Hodgkin’s lymphoma. Computerized tomographic (CT) scanning usually provides adequate staging information. In addition, whereas in the past some patients with stage I intermediate or high grade lymphomas might have been treated with radiation therapy alone, most stage I patients now receive chemotherapy, so that pathologic staging would have little effect on management (
27
, 28
).Though controversial, staging laparotomy is being less commonly performed for patients with Hodgkin’s disease (
29
). Despite clinical staging with CT scanning, bone marrow biopsy, and lymphangiography, laparotomy will still upstage some clinical stage I and IIA patients, and will also downstage some thought to have subdiaphragmatic disease. Although staging laparotomy has a very low mortality rate, it can be associated with both acute (infections, pulmonary embolism) and delayed (postsplenectomy sepsis) complications. To avoid this procedure, some centers treat “good risk” clinical stage I and IIA patients with radiation therapy alone or combined modality therapy, while those with “poor risk” stage I and II disease (bulky disease, multiple sites, B symptoms) are treated with chemotherapy or combined modality therapy. Another approach is to perform staging for Hodgkin’s disease with the laparoscope (30
, 31
), which allows splenectomy, liver biopsy, and nodal sampling.Head and neck cancers
Laryngectomy for advanced squamous cell carcinoma of the larynx may be performed less frequently in the future. Radiation therapy is generally preferable for early stage laryngeal carcinoma since it leads to better voice preservation than surgery. For patients with more advanced (T3 and T4) tumors, radiation therapy alone has a substantial failure rate, and total laryngectomy with postoperative radiation therapy has been standard treatment. However, several investigators have reported the use of neoadjuvant chemotherapy, followed by radiation therapy, for patients with laryngeal tumors (
32
, 33
). Approximately 85% of patients with squamous cell cancers of the head and neck will achieve a complete or partial response to neoadjuvant chemotherapy. Responders are then treated with radiation therapy. Laryngectomy is reserved for patients with residual or recurrent disease after combined chemoradiotherapy. This approach results in similar survival as with standard laryngectomy and postoperative radiation therapy. In the Veterans Administration study, about 60% of patients were able to avoid laryngectomy, although 40% of these eventually required salvage laryngectomy for residual or recurrent disease (32
). Similar results have been reported for head and neck cancers of other sites, such as the hypopharynx (34
). Ongoing trials are comparing alternate approaches, including concomitant chemoradiotherapy and hyperfractionated radiation schedules.Management of regional lymph nodes in patients with head and neck cancer may include surgery, radiation therapy, or both. Instead of radical neck dissection, a selective neck dissection technique may be used in certain patients. These modifications allow preservation of the sternocleidomastoid muscle, internal jugular vein and spinal accessory nerve, providing better cosmetic and functional results (
35
). In certain primary sites, such as the oropharynx and oral cavity, limited supraomohyoid dissection may be feasible (36
).Hairy cell leukemia
Until about 15 years ago, splenectomy was a standard approach to treat patients with hairy cell leukemia (
37
, 38
), and many patients would have subsequent improvement in their pancytopenia. However, with the advent of effective systemic therapy for this disease, initially with interferon (39
) and more recently with the purine nucleoside analogues pentostatin and 2-chlordeoxyadenosine (40
, 41
), splenectomy is rarely performed. After only a single course, 2-chlordeoxyadenosine is associated with durable and complete remissions in most patients.Anal carcinoma and rectal adenocarcinoma
Standard therapy before 1980 for anal canal carcinomas involved abdominoperineal resection with colostomy. After the discovery that the use of preoperative chemotherapy and radiation occasionally caused complete remission before surgery (
42
), prospective trials were conducted of chemotherapy and radiation alone, with surgery reserved for patients with residual or recurrent disease. Cure rates of about 70% have been observed (43
, 44
, 45
). Most regimens have included mitomycin with infusional 5-fluorouracil for two cycles during the course of radiotherapy.Adenocarcinomas, if located in the upper and mid-third of the rectum, can usually be treated with a low anterior resection, without the need for colostomy. However, lesions in the distal rectum have generally required abdominoperineal resection. While this step represents standard therapy, a number of centers have performed sphincter-preserving procedures in an attempt to avoid colostomy in selected patients (
46
, 47
). These surgical techniques are sometimes combined with radiation therapy or with chemotherapy and radiation therapy.Malignant melanoma
Surgical resection is the treatment for localized melanoma. One surgical controversy is the width of the excision margin. Although it was believed that very wide margins were necessary to ensure local control, randomized trials have found no advantage to wider margins, at least for patients with thin melanomas. One study of patients with thin melanoma (<2 mm of invasion) treated with either 1- or 3-cm resection margins showed no difference in local recurrence or survival (
48
). A second study that looked at patients with intermediate-thickness melanoma (2 to 4 mm of invasion) compared 2- and 4-cm margins and found no significant difference in outcome (49
). Narrower margins require less skin grafting, as primary closure is more readily achieved.A second controversy is the use of prophylactic lymphadenectomy. Metastases to regional lymph nodes occur in 5% to 70% of patients, depending on the depth of invasion and other characteristics of the primary lesion. Surgical resection of these nodes can cure some of these patients. The controversy is whether performing the lymph node dissection prophylactically (before the appearance of any clinically suspicious nodes) leads to a greater overall cure rate than performing delayed lymphadenectomy (waiting until patients have palpable nodes). Two randomized trials have failed to show an increase in survival for patients undergoing prophylactic as opposed to delayed lymphadenectomy (
50
, 51
). There is still controversy over the benefit of prophylactic nodal dissection in patients with intermediate-thickness lesions, as subset analysis of data from the randomized trials suggests that such surgery may reduce mortality in these patients (52
, 53
).Some centers sample the so-called sentinel lymph node (
54
, 55
), which represents the first site of drainage, as identified with lymphoscintigraphy. If the sampled sentinel lymph node is negative, no further surgery is performed as the probability that other nodes are involved is extremely low. If the sampled sentinel node is positive, nodal dissection is required.Recent data have shown a modest benefit for adjuvant alpha-interferon administration in patients with positive lymph nodes (
56
). This finding may increase the frequency with which lymph node sampling or dissection is performed in order to select patients who may benefit from interferon treatment.For many patients with ocular melanoma, radiation therapy has replaced enucleation (
56
). Radiation therapy may be delivered by episcleral application of a radioactive plaque.Prostate cancer
Several alternatives to standard radical prostatectomy are available, including nerve-sparing radical prostatectomy, which has a lower risk of impotence (
57
, 58
). Another modification is the use of laparoscopic pelvic lymph node sampling before resection. Patients with positive lymph nodes are spared open surgery (59
). Interest is also increasing for cryosurgical treatment of early prostate cancer; about 85% of patients have histologically negative biopsy results 3 months after the procedure (60
, 61
). In this procedure, cryoprobes are placed in the prostate under ultrasonic guidance, and prostatic tissue is destroyed by freezing. Hospitalization and recovery are considerably shorter than for open prostatectomy. However, long-term follow-up is needed to see if disease control is comparable to radical prostatectomy.Radiation therapy, either by external beam or brachytherapy, is also an alternative to surgery with survival rates comparable to radical prostatectomy, although this point is still debated (
57
). Renewed interest has also developed in brachytherapy treatment of prostate cancer, revitalized by the use of ultrasound or CT-guided transperineal radioactive seed placement (62
).For patients with metastatic prostate cancer, orchiectomy is now performed less frequently due to the availability of medical hormonal therapies (
63
). Depot forms of LH-RH agonists, with or without the use of androgen receptor antagonists such as flutamide, offer a nonsurgical alternative that many patients and physicians find more acceptable (64
). Randomized trials reveal no difference in survival between orchiectomy and LH-RH agonists (65
).Bladder cancer
Most patients with superficial bladder cancer undergo transurethral resection of the lesion with preservation of the bladder; sometimes surgery is combined with intravesical chemotherapy or immunotherapy. Traditional treatment for muscle-invasive bladder cancer, however, has been radical cystectomy. Radiation therapy can be an alternative to surgery in some of these patients with invasive bladder cancer, although it may be associated with local and distant recurrence. However, transitional cell carcinoma of the bladder is a chemotherapy-responsive tumor, and combined chemotherapy and irradiation, with or without induction chemotherapy, has shown high response rates (
66
, 67
, 68
). Transurethral resection has been incorporated into these protocols for both restaging and treatment of residual superficial disease. Randomized trials comparing surgery with combined chemotherapy-radiation protocols are not available, however. Still, there is now the potential for bladder preservation in a majority of patients, with others needing salvage cystectomy; overall survival rates are similar to those expected with standard radical cystectomy. In the future, newer techniques of bladder reconstruction may dampen enthusiasm for combined chemotherapy/radiation therapy (69
).Testicular cancer
For patients with stage I nonseminomatous testicular carcinoma, retroperitoneal lymph-node dissection had been considered standard therapy. However, this procedure benefits only a minority of patients: only 25% of patients with negative markers and CT scans have metastatic disease in the nodes, and about half of these patients would relapse despite attempted curative surgery. Thus, some centers avoid lymph-node dissection in selected patients with clinical stage I disease (
70
, 71
, 72
). This is a reasonable approach if the patient is in a favorable risk group (generally T1 tumors, no vascular invasion, absence of embryonal carcinoma elements) and will comply with frequent follow-up surveillance.For patients who do undergo lymph-node dissection, limiting the extent of the dissection in the absence of gross nodal involvement has been advocated (
73
). In these patients, nodal dissection is limited on the contralateral side, thereby reducing the risk of nerve damage and the complication of retrograde ejaculation.Other investigators have considered attempts to eliminate the need for lymph-node dissection in patients with clinical stage II disease (
74
, 75
). These patients are first treated with chemotherapy. Surgery is reserved for patients with residual disease. This approach is considered investigational, although overall survival rates are high. However, chemotherapy will not rid patients of metastatic teratomatous disease, which may still require surgery.Sarcomas
The treatment of sarcomas of soft tissue and bone several decades ago routinely included amputation. However, many series indicate excellent rates of local control with limb-sparing surgery, without evident changes in survival (
76
, 77
, 78
, 79
). The use of neoadjuvant and adjuvant chemotherapy for osteogenic sarcoma and adjuvant radiation therapy for soft tissue sarcomas has contributed to overall improved systemic and local control rates without the need for amputation.Videoscopic surgery
Videoscopic approaches in the chest, abdomen, and pelvis are used for diagnostic purposes, for staging, for palliative procedures, and in some cases for resection of cancers (
80
, 81
). Laparoscopic procedures may help in the evaluation of unexplained ascites by showing evidence of peritoneal studding that was not revealed by cytology samples obtained percutaneously. Laparoscopic lymph node biopsy can be performed in patients with non-Hodgkin’s lymphoma in only intra-abdominal sites. Before laparotomy for patients with hepatoma, esophageal, pancreatic, and gastric carcinoma, laparoscopic inspection may reveal findings that make tumors unresectable. The use of specialized ultrasound probes enhances the information obtained visually. This approach may avoid laparotomy in as many as a third of patients who would otherwise undergo exploration for intra-abdominal malignancies.The resection of colon cancers through the laparoscope is under investigation. Although there has been some concern that there may be an increased risk of abdominal wall implants at the site of trocar placement, several series suggest comparable results to open colectomy (
82
, 83
). A randomized trial is in progress to compare open and laparoscopic techniques.A variety of palliative procedures can be performed laparoscopically. Feeding gastrostomies (in those patients unable to undergo endoscopic placement), feeding jejunostomies, lysis of adhesions, and ileostomy and colostomy formation for patients with obstruction can often be performed laparoscopically.
Thoracoscopic procedures can assist in the diagnosis of unexplained pleural effusions, for example, when mesothelioma cannot be diagnosed by pleural fluid cytology or closed pleural biopsy (
84
). Thoracoscopy has been used for the resection of solitary pulmonary nodules, metastatic nodules, and peripheral lung cancers (particularly in patients in whose overall pulmonary status does not permit lobectomy), for the sampling of mediastinal adenopathy and tumors, for the diagnosis and treatment of pleural effusions and pericardial effusions, and for open lung biopsy in immunocompromised patients with pulmonary infiltrates.Sterotactic radiosurgery
Focused radiation therapy, delivered either via a cobalt source such as the gamma knife or from a linear accelerator as stereotactic radiosurgery, can be utilized to treat intracranial lesions (
85
, 86
). While standard external beam radiotherapy offers local control for many patients, radiosurgery can deliver higher doses of radiotherapy to a circumscribed area. Radiosurgery may be able to substitute for surgery for lesions in crucial areas of the brain where neurosurgical intervention is not feasible.For selected patients with a solitary brain metastasis, surgery with postoperative radiation therapy offers better palliation and perhaps improved survival compared to conventional radiotherapy alone (
87
). However, most of these patients will develop further systemic or intracranial disease, so that an invasive surgical approach probably benefits only a few. Radiosurgery could represent a noninvasive approach to the management of these patients. It can also be applied to patients who have more than one metastasis more readily than surgery.Palliative and supportive procedures
Many procedures that previously required the use of an operating room can now be done at the bedside or in the radiology suite. The placement of gastrostomy tubes is now routinely done endoscopically or percutaneously (
88
). Biliary decompression for patients with obstruction from malignancy can be performed either percutaneously or endoscopically (89
). Peripherally inserted central catheter (PICC) lines are often used instead of Hickman-type catheters (90
, 91
). Placement of inferior vena caval filters for patients with cancer complicated by lower extremity thrombosis is now commonly done percutaneously (92
). Invasive techniques for intractable pain that require cordotomy can be done percutaneously (93
). Chemoembolization of the liver for debulking of metastatic disease, as for example with neuroendocrine tumors, can substitute for surgical debulking (94
, 95
). Proton pump inhibitors may obviate the need for total gastrectomy in patients with gastrinoma (96
).Combined chemotherapy and radiation therapy protocols
Combined chemotherapy and radiation therapy has also been investigated for patients with esophageal cancer and non–small cell lung cancer. For both of these cancers, radiation therapy alone can cure a small percentage of patients, and randomized trials have shown that the combination of chemotherapy and radiation is superior to radiation therapy alone (
97
, 98
). Whether combined therapy can replace the need for surgery will be determined by the results of ongoing randomized trials.Discussion
While the extent of surgery is diminishing in many areas (Table 2), the role of the surgeon in the management of the cancer patient is not. Surgery remains the main and most effective way to treat most patients with solid tumors. Indeed, in many areas the extent of surgery is increasing, not decreasing. With improvements in surgical technique, anesthesia and medical support, many procedures considered too formidable in the past are now done routinely, such as resection of metastatic lesions in the brain, spine, and liver. Patients with lung cancer that was considered too advanced for surgery because of chest wall invasion or ipsilateral mediastinal nodal involvement are now considered candidates for resection. Aggressive debulking of advanced ovarian cancer is now routine.
Table 2Changes in the Extent of Surgery in Various Malignancies
| Malignancy | Older Technique | Newer Technique |
|---|---|---|
| Non-Hodgkin’s lymphoma | Staging laparotomy in stage I aggressive histology | Clinical staging and chemotherapy |
| Hodgkin’s | Staging laparotomy in clinical stage I or II | Staging laparoscopy or radiation therapy alone or radiation therapy/chemotherapy depending on clinical stage |
| Hairy cell leukemia | Splenectomy | Interferon, pentostatin, or 2-chlordeoxyadenosine |
| Head and neck cancers | Total laryngectomy for stages T3 and T4 | Larynx preservation with combined chemotherapy/radiation therapy |
| Radical neck dissection | Modified or selective node dissection | |
| Anal carcinoma | Abdominoperineal resection | Combined chemotherapy/radiation therapy |
| Melanoma | Wide margins | Narrower margins |
| Prophylactic lymphadenectomy | Observation | |
| “Sentinel” node sampling | ||
| Prostate cancer | Radical prostatectomy | Nerve-sparing prostatectomy |
| Cryosurgery | ||
| Radiation therapy | ||
| Radioactive seed implant | ||
| Orchiectomy | LH-RH agonists | |
| Testicular cancer (nonseminomatous) | Retroperitoneal lymph node dissection for stage I | Modified lymph node dissection |
| Observation/surveillance for selected stage I | ||
| Sarcomas | Amputation | Limb-sparing surgery |
| Gastrinoma (unresectable) | Total gastrectomy | Histamine (H2) blockers and proton pump inhibitors |
| Colon cancer | Open colectomy | Laparoscopic colectomy |
| Gastric and pancreatic cancer | Exploratory laparotomy | Laparoscopic evaluation before laparotomy |
legend LH-RH = luteinizing hormone-releasing hormone.
It is important to recognize that alternatives to surgery may not be less expensive. In the treatment of metastatic prostatic carcinoma, several years of therapy with LH-RH agonists may be more expensive than orchiectomy. Lumpectomy and radiation therapy for breast cancer are more expensive than total mastectomy. Savings made on shorter hospital stays for patients undergoing videoscopic surgery techniques may be partially offset by the expense of equipment and longer operating times.
Of course, these changes do benefit patients by easing postoperative recovery, producing better long-term cosmetic or functional results, or eliminating the need for an invasive procedure entirely. However, despite these improvements in care, there is no evidence of improvement in the overall survival or cure rate for most of these modifications. Although this does not nullify the importance of these advances, it does point out the need for continued investigation of better overall therapeutic approaches that not only minimize the frequency and extent of surgery, but, more importantly, improve patients’ chances for cure.
References
- Imaging-guided percutaneous abdominal biopsy.Oncology. 1991; 5: 27-38
- Ten year results of a randomized clinical trial comparing radical mastectomy and total mastectomy with or without radiation.NEJM. 1985; 312: 674-681
- Eight year results of a randomized clinical trial comparing total mastectomy and lumpectomy with or without irradiation in the treatment of breast cancer.NEJM. 1989; 320: 822-828
- Comparing radical mastectomy with quadrantectomy, axillary dissection and radiotherapy in patients with small cancers of the breast.NEJM. 1981; 305: 6-11
Harris JR, Lippman ME, Veronesi U, et al. Breast cancer. NEJM 1992:319–328,390–398,473–480.
- Effects of radiotherapy and surgery in early breast cancer—an overview of the randomized trials.NEJM. 1995; 333: 1444-1455
- Preoperative chemotherapy.J Clin Oncol. 1995; 13: 537-540
- Axillary lymph nodes and breast cancer.Cancer. 1995; 76: 1491-1512
- Surgical resection and radiolocalization of sentinel lymph node in breast cancer using a gamma probe.Surg Onc. 1993; 2: 335-340
- Ductal carcinoma in situ.in: Harris J.R Lippman M.E Morrow M Hellman S Diseases of the Breast. Lippincott-Raven, 1995: 353-373
- Lumpectomy compared with lumpectomy and radiation therapy for the treatment of intraductal breast cancer.NEJM. 1993; 328: 1581-1586
- Ductal carcinoma in situ.in: Harris J.R Lippman M.E Morrow M Hellman S Diseases of the Breast. Lippincott-Raven, 1995: 369-373
- Stereotactic breast biopsy is accurate, minimally invasive and cost effective.Am J Surg. 1996; 171: 474-476
- The role of stereotactic biopsy in assessment of nonpalpable breast lesions.Am J Surg. 1996; 171: 471-473
- Are sterotaxic breast biopsies adequate?.Surgery. 1994; 116: 610-614
- Stereotactic breast biopsy is accurate, minimally invasive and cost effective.Am J Surg. 1996; 171: 474-476
- The role of stereotactic biopsy in assessment of nonpalpable breast lesions.Am J Surg. 1996; 17: 471-473
- Are stereotaxic breast biopsies adequate?.Surgery. 1994; 116: 610-614
- Stereotactic fine-needle aspiration biopsy for the evaluation of nonpalpable breast lesions; report of an experience based on 2,988 cases.Ann Surg Oncol. 1996; 3: 185-191
- Randomized trial of bilateral oophorectomy versus tamoxifen in premenopausal women with metastatic breast cancer.J Clin Oncol. 1986; 4: 178-185
- A randomized comparison of tamoxifen with surgical oophorectomy in premenopausal patients with advanced breast cancer.J Clin Oncol. 1986; 4: 1326-1330
- Medical castration produced by the GnRH analogue leuprolide to treat metastatic breast cancer.J Clin Oncol. 1985; 3: 1068-1072
- A randomized trial comparing surgical adrenalectomy with aminoglutethimide plus hydrocortisone in women with advanced breast cancer.NEJM. 1981; 305: 545-551
- Role of image-guided core-needle biopsy in the management of patients with lymphoma.J Clin Oncol. 1996; 14: 2427-2430
- Image-guided core-needle biopsy in malignant lymphoma.J Clin Oncol. 1996; 14: 2431-2434
Sklar J, Longtine J. The clinical significance of antigen receptor gene rearrangements in lymphoid neoplasia. Cancer 1992;70(suppl):1710–1708.
- Initial chemotherapy for clinically localized lymphomas of unfavorable histology.Blood. 1983; 62: 413-418
- Brief chemotherapy and involved field radiation therapy for limited-stage, histologically aggressive lymphoma.Ann Intern Med. 1987; 107: 25-30
- Controversies in the management of early stage Hodgkin’s disease.Blood. 1994; 83: 318-329
- Laparoscopy and lapartomomy combined with bone marrow biopsy in staging Hodgkin’s disease.BMJ. 1975; 4: 554-556
- Laparscopic staging of Hodgkins disease.Surg Oncol. 1993; 2: 217-220
- Induction chemotherapy plus radiation compared with surgery plus radiation in patients with advanced laryngeal cancer.NEJM. 1991; 325: 1685-1690
- Larynx preservation with combined chemotherapy and radiation therapy in advanced but resectable head and neck cancer.J Clin Oncol. 1991; 9: 850-859
- Larynx preservation in pyriform sinus cancer.J Nat Can Inst. 1996; 88: 890-899
- Modified neck dissection.Am J Surg. 1980; 150: 414-421
- Supraomohyoid neck dissection.Head Neck. 1989; 11: 111-122
- Hairy cell leukemia.Ann Intern Med. 1978; 89: 677-683
- Response to splenectomy in 65 patients with hairy cell leukemia.Blood. 1983; 61: 349-352
- Treatment of hairy cell leukemia with recombinant alpha interferon.Blood. 1985; 68: 493-497
- Lasting remissions in hairy-cell leukemia induced by a single infusion of 2-chlorodeoxyadenosine.NEJM. 1990; 322: 1117-1121
- Treatment of hairy cell leukemia with 2-chlorodeoxyadenosine (2-CdA).Blood. 1992; 79: 882-887
- Combined therapy for cancer of the anal canal.Dis Colon Rectum. 1974; 17: 354-356
- Cancer of the anal canal.Am J Med. 1985; 78: 211-216
- Improved survival in epidermoid carcinoma of the anus in association with pre-operative multi-disciplinary therapy.Arch Surg. 1986; 121: 1386-1390
- Epidermoid anal cancer.Int J Radiat Oncol Biol Phys. 1991; 21: 1115-1125
- Local excision of rectal carcinoma.Am J Surg. 1990; 106: 306-312
- Conservative management of rectal carcinoma.Semin Surg Oncol. 1993; 9: 39-45
- Thin stage I primary cutaneous malignant melanoma. Comparison of excision with margins of 1 or 3 cm.NEJM. 1988; 318: 1159-1162
- Efficacy of 2-cm surgical margins for intermediate-thickness melanomas (1 to 4 mm): results of a multi-institutional randomized surgical trial.Ann Surg. 1993; 218: 262-267
- Delayed regional lymph node dissection in stage I melanoma of the skin of the lower extremities.Cancer. 1982; 49: 2420-2430
- Lymphadenectomy in the management of stage I malignant melanoma.Mayo Clinic Proc. 1986; 61: 697-705
- Elective node dissection: pros and cons.in: Balch C.M Houghton A.N Milton G.W Sober A Soong S-j Cutaneous Melanoma. 2nd ed. JF Lippincott, Philadelphia1992: 345
- Efficacy of an elective regional lymph node dissection of 1 to 4 mm. thick melanomas for patients 60 years of age and younger.Ann Surg. 1996; 224: 255-266
- Technical details of intraoperative lymphatic mapping for early stage melanoma.Arch Surg. 1992; 127: 392-399
- Selective lymphadenectomy.Semin Surg Oncol. 1993; 9: 219-223
- Interferon alfa-2b adjuvant therapy of high-risk resected cutaneous melanoma.J Clin Oncol. 1996; 14: 7-17
- Current management of posterior uveal melanoma.Mayo Clin Proc. 1993; 68: 1196-1200
- Cancer control following anatomical radical prostatectomy.J Urol. 1991; 145: 1197-1200
- Complications of laparoscopic pelvic lymph node dissection.J Urol. 1993; 149: 322-325
- Prostate cancer: ultrasound-guided percutaneous cryoablation. Work in progress.Radiology. 1995; 194: 551-556
- Transrectal ultrasound-guided percutaneous radical cryosurgical ablation of the prostate.Cancer. 1993; 72: 1291-1299
- Role of interstitial radiotherapy in the management of clinically organ-confined prostate cancer.J Clin Oncol. 1996; 14: 304-315
- Drug therapy.NEJM. 1994; 331: 996-1004
- Gonadotropin-releasing hormone and its analogues.NEJM. 1991; 324: 93-103
- Randomised controlled study of orchiedectomy vs. long-acting D-Trp-6-LHRH microcapsules in advanced prostatic carcinoma.Lancet. 1985; 2: 1201-1205
- Combined modality program with possible organ preservation for invasive bladder carcinoma.Int J Radiat Oncol Biol Phys. 1993; 25: 783-790
- Neoadjuvant combined modality program with selective organ preservation for invasive bladder cancer.J Clin Oncol. 1996; 14: 119-126
- Selective bladder preservation by combination treatment of invasive bladder cancer.NEJM. 1993; 329: 1377-1382
- Indiana continent urinary reservoir.J Urol. 1987; 137: 1136-1139
- Surveillance versus nerve-sparing retroperitoneal lymphadenectomy in stage I nonseminomatous germ-cell tumors.Urol Clin N Am. 1993; 20: 75-83
- Surveillance alone for patients with clinical stage I nonseminomatous germ cell tumors of the testis.J Urol. 1984; 131: 491-493
- Orchiectomy alone in clinical stage I nonseminomatous testis cancer; a critical appraisal.J Clin Oncol. 1986; 4: 35-40
- Clinical stage I testicular cancer.J Urol. 1990; 144: 1160-1163
- Primary chemotherapy for clinical stage II nonseminamatous germ cell tumors of the testis.J Clin Oncol. 1987; 5: 906-911
- Primary chemotherapy for clinical stage II nonseminomatous germ cell testicular tumors.Mayo Clin Proc. 1995; 70: 821-828
- The treatment of soft tissue sarcoma of the extremities.Ann Surg. 1982; 196: 305-314
- The role of multimodality therapy in soft-tissue sarcoma.Ann Surg. 1991; 214: 328-338
- Sarcomas of Bone.in: DeVita Jr, V.T Hellman S Rosenberg S.A Cancer Principles and Practice of Oncology. 4th ed. JB Lippincott, 1993: 1509-1566
- Adjuvant chemotherapy for osteosarcoma; a randomized prospective trial.J Clin Oncol. 1987; 5: 21-26
- Laparoscopic general surgery.NEJM. 1994; 330: 409-419
- Larparoscopy in malignant disease.Surg Clin North Am. 1992; 72: 1125-1137
- Controversies regarding laparoscopic colectomy for malignant diseases.Curr Opin Gen Surg. 1994; : 208-213
- Port site recurrences after laparoscopic and thoracoscopic procedures in malignancy.J Clin Oncol. 1996; 14: 1950-1956
- The role of video-assisted thoracic surgery in thoracic oncological practice.Canc Invest. 1995; 13: 526-539
- Stereotactic radiosurgery for the definitive, noninvasive treatment of brain metastases.J Nat Canc Inst. 1995; 87: 34-40
- Stereotactic radiosurgery.J Clin Oncol. 1994; 23: 1085-1099
- A randomized trial of surgery in the treatment of single metastases to the brain.NEJM. 1990; 322: 494-500
- Percutaneous endoscopic gastrostomy.Gastrointest Endosc. 1981; 27: 9-11
- Randomized trial of endoscopic vs. percutaneous stent insertion for malignant obstructive jaundice.Lancet. 1987; ii: 57-61
- The upper arm approach for placement of peripherally inserted central catheters for protracted venous access.Am J Roentgenol. 1992; 158: 427-429
- Peripherally inserted central catheters.J Intraven Nurs. 1989; 13: 287-290
- Percutaneous inferior vena cava filters.Radiology. 1990; 174: 987-992
- Safety of unilateral and bilateral percutaneous cervical cordotomy in 80 terminally ill cancer patients.J Clin Oncol. 1995; 13: 1509-1512
- Islet cell tumors metastatic to the liver.Ann Intern Med. 1988; 108: 340-344
- Chemoembolization of liver tumors.Semin Invest Radiol. 1993; 10: 150-160
- The use omeprazole in patients with Zollinger-Ellison syndrome.Dig Dis Sci. 1991; 36: 394-404
- Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus.NEJM. 1992; 326: 1593-1598
- A randomized trial of induction chemotherapy plus high-dose radiation versus radiation alone in stage III non-small cell lung cancer.NEJM. 1990; 323: 940-945
Article info
Publication history
Published online: August 16, 2004
Accepted:
August 7,
1998
Received:
February 17,
1998
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© 1999 Excerpta Medica Inc. Published by Elsevier Inc.
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