Intraoperative Staging Research Articles

Clinical and Surgical Staging of Non-Small Cell Lung Cancer

The necessity for a compulsive attitude toward preoperative assessment of lung cancer is to be emphasized, since rational treatment and prognosis depend largely on the stage of disease at the time of diagnosis. In the preoperative setting, the techniques used should be sequential, logical, and help to identify patients suitable for treatment with curative intent. With regard to the primary tumor (T status), the accuracy of CT or MRI to predict the need for extended resections is limited. Similarly, all noninvasive methods to determine the nodal status (N) are valuable, but mediastinoscopy has a greater sensitivity and specificity than either CT or MRI. The role of routine organ screening for the detection of distant occult metastasis in the asymptomatic patient is still controversial. Ultimately, the prognosis of the resected patient with lung cancer is based on complete intraoperative staging, which can be done by either systematic node sampling or complete lymphadenectomy. At present, neither of these techniques has been shown to improve the quality of staging or survival.

Pathologic Examination of Sentinel Lymph Nodes in Breast Cancer

Lymphatic mapping with selective sentinel lymphadenectomy allows accurate pathologic examination of the nodes most likely to contain macro- or micrometastastic disease for staging and proper adjuvant chemotherapy. The hypothesis of SLN biopsies was histopathologically validated by Turner et al that if the node is tumor free by H&E and immunohistochemistry, the probability of non-SLN involvement is less than 0.1%. Giuliano et al and Veronesi et al reported that detection of metastases in SLNs by frozen section technique is 89% and 64%, respectively. At MCC, frozen section evaluation of SLN is not performed because of its potential loss of micrometastasis in the cryostat, freezing artifacts, sampling error, and perhaps radioactive contamination. Intraoperative detection of macro- or micrometastasis is critical because it enables conversion of patients with positive SLN to CLND in one surgical setting more cost-effectively. IIC of the lymph nodes has been used routinely in the diagnosis of hematologic malignancies and also in breast cancer as a useful method in many series. In the author's experience, IIC by Diff-Quik stain converted 100% of grossly positive and suspicious SLNs and 22% of grossly negative SLNs. The significance of detecting micrometastases in axillary lymph nodes using immunohistochemical techniques has been reported in many series. At the MCC, routine use of CKI on paraffin sections of grossly negative SLNs enabled the upstaging of 10.6% of patients from N0 to N1. Recent addition of intraoperative rapid CKI as an adjunct to complement Diff-Quik stain has proven to be more sensitive in detecting micrometastases than using Diff-Quik stain alone. IIC technique using either Diff-Quik stain or CKI requires intensive training and experience to avoid potential pitfalls and errors in interpretation. Evaluation of SLN should use methods that enhance the ability to detect micrometastasis, however, in a cost-effective manner. The cost-effectiveness of IIC by Diff-Quik stain is incomparable with frozen section evaluation. The added cost of routine immunohistochemical stain and perhaps multiple levels of H&E stain should be offset by the decreased costs of IIC and clinically by treating most patients in the outpatient settings. In summary, IIC by Diff-Quik stain is simple, rapid, and has excellent diagnostic accuracy in grossly positive and suspicious SLNs allowing cost-effective, immediate CLND. IIC by CKI is an extremely useful ancillary technique that complements Diff-Quik stain in detecting micrometastases particularly in low grade ductal or lobular carcinoma and low tumor cell volume. Appropriate combined use of both stains may lead to intraoperative nodal staging and cost-effective CLND. SLN mapping technology at MCC using IIC in conjunction with serial sections, entire tissue submission, routine use of CKI, and multiple levels of the SLN have led us to uncover micrometastasis in high-risk, traditionally node-negative patients. These results have encouraged investigators to pursue even more sensitive techniques to detect micrometastases, including molecular biology techniques such as RT-PCR. Experienced cytopathologists and active cytopathology services are required to avoid potential pitfalls in performing and interpreting IIC. More long-term follow-up and prospective trials are needed to determine the prognostic significance of upstaging by ancillary techniques, which may lead to a revision of the current TNM staging system.

Antero-superior approaches in the practice of thoracic surgery.

To review our experience using antero-superior approaches for resection of a heterogeneous group of tumors, both benign and malignant, involving the thoracic inlet and adjacent structures. These included Pancoast type bronchial carcinomas, primary neurogenic tumors, soft-tissue neoplasms, and metastases from a variety of primary sites. Between October 1993 and January 1998 we undertook 22 operations on 21 patients using a variety of antero-superior approaches. The anterior cervical-transsternal approach was used in 11 operations, the Dartevelle technique was used in five cases, the modification described by Nazari in one patient and that described by Grunenwald in five cases. 21 of the 22 operations were considered to be complete resections with negative margins. There were no intraoperative or postoperative deaths. Major complications occurred in five patients; acute respiratory distress syndrome (n = 4), and thrombosis of the arterial graft and acute respiratory distress syndrome (n = 1). Chronic morbidity was observed in 12 patients; prolonged arm pain (n = 1), arm edema (n = 2), motor and sensory deficits (n = 2), phrenic nerve paresis (n = 1), disfigurement and instability of the pectoral girdle (n = 4), and disturbances in shoulder girdle function (n = 2). The anterior cervical-transsternal approach we previously described provides adequate exposure for the resection of neurogenic tumors originating in the brachial plexus and sympathetic chain, and for metastatic nodal disease at the base of the neck or in the superior mediastinum. We have found it to be associated with little morbidity, the postoperative stay has been short, and it has proven flexible enough to cope with the changed circumstances found at surgery. For Pancoast type bronchogenic carcinomas and other malignancies with extensive invasion of major structures at the thoracic inlet, we believe the best present option is the clavicle sparing antero-superior technique described by Grunenwald as a modification of the Dartevelle approach. When operating for lung cancer we presently feel that the antero-superior approach should be combined with a posterolateral thoracotomy, to accomplish complete intraoperative staging and undertake anatomical pulmonary resection under optimal conditions.

The Radioimmunoguided Surgery (rigs) System as a Diagnostic Tool

Radioimmunoguided surgery (RIGS) was developed to improve on the intraoperative detection of malignancy. The RIGS system uses a hand-held gamma radiation detection probe to identify radioactive tissues targeted by a preadministered tumor-associated radiolabeled targeting antibody or peptide. Clinical experience with RIGS in colorectal cancer has been favorable; better intraoperative staging has provided the surgeon more information regarding the pattern of disease and individual patients. Pancreatic, breast, ovarian, and prostate cancer have also been studied in clinical trials using RIGS and early results are encouraging. In the future, marked improvements with the RIGS system will be realized with the development of better targeting agents.

Role of laparoscopy in the lymph-node staging of urological malignancies

SummaryPreoperative or intraoperative staging is often necessary in malignancy in order to plan further treatment. Although various imaging techniques are already being used, new minimally-invasive approaches, such as laparoscopy, may change staging strategies. The role of laparoscopic lymphnode staging of urological malignancies is described. Most urologists agree that the use of laparoscopy for lymphnode staging of penile cancer or transitional-cell carcinoma (TCC) of the bladder or upper urinary tract, as well as for renal tumours, has no benefit in terms of changing treatment. In patients with testicular cancer, inguinal orchiectomy is almost always the first therapeutic step. In non-seminomatous tumours, inguinal orchiectomy is followed by either retroperitoneal lymphadenectomy (LAD), chemotherapy or surveillance. Recently, laparoscopic retroperitoneal LAD has been presented by a few centres with acceptable results. In patients with localised prostate cancer, pelvic LAD is the first operative step during radical prostatectomy, to exclude lymph-node metastasis. In the one-step retropubic prostatectomy, lymph nodes are ‘on the way’ to the prostate. A few European and many American urologists prefer the two-step perineal prostatectomy. In such cases a laparoscopic LAD is performed according to a relevant elevation of the prostate-specific antigen (PSA) and radical prostatectomy negated when lymph nodes are positive. Laparoscopic lymph-node staging in urological malignancies is limited to a group of patients with prostate cancer who are likely to have positive lymph nodes and to a few patients with testicular cancer.

Radioimmunoguided surgery and intraoperative lung cancer staging

Radioimmunoguided surgery (RIGS) has proven its worth, especially when used in primary, recurrent, and metastatic colon-rectum adenocarcinomas, and in liver metastases from other intestinal adenocarcinomas. Until now, RIGS has not been investigated for lung cancer surgery, chiefly because of problems related to the blood pool radioactivity background which is at its highest in the thoracic area. The positive RIGS experience with other tumors encouraged us to investigate its effectiveness in lung adenocarcinomas. In six cases, RIGS gave excellent results in the detection of primary pulmonary lesions; no false negatives or false positives were shown. Data on lymph nodes revealed one false negative. Immunohistochemical staining was always performed in association with traditional pathology of the resected specimens. In one case, a noncancerous lesion, as defined by traditional hematoxylin-eosin (H&E) staining, confirmed RIGS intraoperative finding of nonmalignant tissue. Semin. Surg. Oncol. 15:215–219, 1998. © 1998 Wiley-Liss, Inc.

Radioimmunoguided surgery for patients with liver metastases secondary to colorectal cancer.

Hepatic resection for metastatic colorectal cancer offers a 5-year survival rate of 30%. Selection of patients who are most likely to benefit from excision is challenging. The judgment is made by radiographic techniques preoperatively and by sight and touch and the instinct of the surgeon intraoperatively. Confirmation that all tumor tissue has been excised relies on the appearance and texture of the tissue and is verified by routine histology. The authors' objective was to evaluate (1) the ability of radioimmunoguided surgery (RIGS) to improve the intraoperative detection of metastatic disease, and (2) any change in the operative plan originating from the information gained in patients with colorectal liver metastases. Charts and tumor registry data for patients who underwent planned liver resection for colorectal cancer using the RIGS method from January 1985 to December 1993 were reviewed. This group of patients was compared to a similar group that underwent traditional liver resection for metastatic colorectal cancer during the same period. Patients who had the RIGS procedure during the earlier part of the period (1985-1990), were injected with tumor-associated glycoprotein (TAG) antibody B72.3; those in the later period (1990-1993) were injected with the second-generation anti-TAG monoclonal antibody CC49. Both monoclonal antibodies were labeled with sodium iodide I 125. Both traditional and RIGS exploration were used to determine the extent of the malignant process and any change in operative plan. Seventy-four cases of planned liver resection were performed with the RIGS method (group I), and 215 cases were performed with the traditional method (group II). Age and sex distribution were similar in both groups, as were morbidity and mortality, with an overall perioperative mortality of 1%. The distribution and number of metastatic lesions to the liver were the same, although group I included more cases with smaller metastatic lesions and more patients with anatomic resections. No extrahepatic tumor was found in 140 patients (65%) in group II, whereas there were only 21 patients (28%) in group I in whom no extrahepatic disease was detected (P < .001). RIGS exploration identified additional tumor in 12 (16%) of 74 cases: in the gastrohepatic ligament lymph nodes (LN) in five patients, in the celiac axis LN in one patient, and in the periaortic LN in six patients. These discoveries changed the operative plan for all of these patients, avoiding excision in the latter six patients and extending the resection in the other six. RIGS surgery provides an immediate and more accurate intraoperative staging system of patients with colorectal liver metastases than does traditional exploration by identifying additional metastatic disease, mainly to the lymph nodes, thus changing the plan of resection in a significant number of patients. More studies are needed to evaluate any significant survival advantage of patients who undergo removal of all RIGS-positive tissue.

Intraoperative determinants of unresectability for patients with colorectal hepatic metastases.

Intrahepatic and extrahepatic factors are utilized by the surgeon in the decision-making process for the performance of hepatic resection for patients with colorectal metastases. Accurate preoperative and intraoperative staging are mandatory to avoid unnecessary surgery. In this report the intraoperative determinants of hepatic unresectability were evaluated. This was a retrospective review of medical records from January 1985 to March 1996 of 62 patients with colorectal hepatic metastases who at the time of exploratory laparotomy were deemed to have unresectable disease based on intrahepatic or extrahepatic factors. The stage of the primary tumor, disease free interval, preoperative carcinoembryonic antigen, computed tomography portography, intraoperative ultrasound, and assessment of intrahepatic and extrahepatic tumor extension were evaluated. Intraoperative determination of the extent of required hepatic resection, including trisegmentectomy (9 patients; 15%) and total hepatectomy (10 patients; 16%), accounted for the majority of unresectable patients. Patients with > 4 metastases (8 patients; 13%) and satellitosis (6 patients; 10%) accounted for 23% of unresectable patients. Four patients had extensive nonmalignant hepatic parenchymal disease precluding resection. Thorough abdominal exploration revealed extrahepatic disease in 13 of 62 patients (21%). Routine periportal/celiac lymph node biopsies revealed metastases in an additional 12 patients (19%), 7 of whom (11%) had only periportal/celiac lymph node metastases. A meticulous abdominal exploration prior to hepatic resection for patients with colorectal metastases is essential to identify those patients with extrahepatic disease. Periportal and celiac lymph nodes commonly are involved by tumor. Therefore, routine periportal/celiac lymph node biopsies should be performed in the absence of other extrahepatic disease.

MR of malignant nasosinusal neoplasms frequently asked questions

This paper focuses on the role of MR imaging of malignant neoplasms through a particular layout that emphasizes: (a) the rationale for the application of imaging; (b) the factors influencing the selection of sequences, planes and their proper arrangement; (c) the correlation between MR findings, imaging staging and clinical decision making. Since in most cases surgery is the treatment of choice, the precise assessment of the local extent and spread of tumour plays a key role in planning the surgical approach and influences either the therapy and the prognosis. However, the degree of spatial/anatomical detail required in treatment planning significantly differs between surgery and radiotherapy. Planning of the examination technique focuses on: (a) assembling sequences and planes in the shortest time possible; (b) the solution of specific problems: distinction between neoplasm and retained secretions within nasosinusal cavities; staging of submucosal spread toward the anterior cranial fossa, the orbit, the pterygo-palatine and superior orbital fissures. Since the most effective barrier to spread of neoplasms beyond sinusal walls does not depend on the mineral content of bone, but on the periosteum, assessment of the integrity of periorbita or dura mater is an essential information. Although MR cannot detect focal erosions of the thin sinusal walls, it reliably demonstrates both residual barriers (periorbita and dura), even though the bone has been completely destroyed. However, the final decision concerning orbital exenteration is made according to intraoperative staging. MR imaging can accurately precise the degree of anterior cranial fossa involvement. Furthermore, since either MR and CT accurately indicate the need to perform an anterior craniofacial resection and adequately exclude neoplastic invasion requiring orbital exenteration, more comparative studies are required to demonstrate that MR preoperative staging of nasosinusal malignancies is cost-effective.

Recent advances in lung cancer surgery in Europe

Prof. Clifton F. Mountain’s proposal of the New International Staging System for Lung Cancer at the IV IASLC World Conference on Lung Cancer in 1985 began the present era of lung cancer research and treatment. Besides offering a common language for grouping patients in key stages of tumoral progression that was closely related to the end results of surgical treatment, the New System represents an obligation for the surgeon, who has the main responsible for staging the disease. Starting with the preoperative surgical mediastinal assessment which concludes clinical staging, throughout intraoperative staging, which is based on a visual evaluation of the extent of the tumour aided by frozen tissue sections, the surgeon is in a unique position of being able to examine the actual TNM descriptors as well as their prognostic significance. Histological findings of pathological staging should complete the surgical work-up. Thus, the constant effort to recognise and classify various clinical features can easily push the surgeon to develop either new rules for improving the clinical application of the Staging System or new predictors of prognosis to improve the System itself. This dynamic involvement reflects the

Pelvic autonomic nerve preservation for patients with rectal carcinoma: Oncologic and functional outcome

Serious problems in the surgical treatment of patients with rectal carcinoma are local failure and urinary and sexual dysfunction. To resolve these problems, pelvic autonomic nerve preservation (PANP) combined with lateral lymph note dissection has been introduced. Of 238 consecutive patients with middle or low rectal carcinoma who underwent potentially curative surgery between 1987 and 1992, 214 underwent PANP according to pre- and intraoperative staging. PANP was evaluated from the perspectives of oncologic outcome and urinary and male sexual function with a retrospective questionnaire in a group of patients followed prospectively. During the median follow-up of 53 months, local recurrence developed in 5.6% of patients; no local recurrence was observed in Dukes Stage A or Dukes Stage B patients. The 5-year survival rates of Dukes Stage A (n = 55), Dukes Stage B (n = 72), and Dukes Stage C (n = 87) patients were 96.4%, 84%, and 67.3%, respectively. Of patients undergoing preservation of the unilateral pelvic plexus alone, 93.5% maintained the ability to void spontaneously. Of patients who had complete preservation of the autonomic nerve system, 70.4% maintained male sexual function, and of patients who had removal of the hypogastric nerves and preservation of the pelvic nerve plexuses, 66.7%, were capable of erection and intercourse without normal ejaculation. Early stage rectal carcinoma should be treated both with local cure and complete preservation of urinary and sexual function. In high risk patients with suspected perirectal lymph node metastases and tumors invading the perirectal fat, the appropriate PANP should be applied with consideration of the balance between achieving a cure and preserving autonomic function.

Accuracy of intraoperative staging of the NO neck in squamous cell carcinoma.

Management of the neck in squamous cell carcinoma of the upper aerodigestive tract continues to be a topic of great debate. One major problem is that incorrect clinical staging is expected in approximately 20% of necks. This is true of both clinical stage NO and N+ necks, even when imaging studies are used. This prospective study of 108 necks in 79 patients examined the role of intraoperative palpation and inspection in improving the surgeon's ability to predict nodal stage. Of 62 patients with NO necks clinically on both sides, 26 were staged N+ by intraoperative node examination. Nineteen of the 26 were histologically negative (73% false-positive). Of the 36 patients staged intraoperatively as NO, 10 were histologically positive (28% false-negative). Of 108 necks judged clinically to be NO, 25 (23%) had occult metastases and 11 (10%) had extracapsular spread. Forty-one of 108 clinical NO necks were believed to have positive nodes at the time of neck dissection. Of these 41 necks, 30 (73%) were found to be histologically NO (false-positive). Of the 67 clinical NO necks that were also believed to be NO intraoperatively, occult metastases were found in 14 (21% false-negative). Therefore, intraoperative staging did not significantly improve the false-negative rate. Frozen-section biopsy obtained in the operating room was reliable in 24 (92.3%) of 26 patients. Although frozen-section biopsy was not performed in all patients, these data suggest that upstaging the neck without frozen-section biopsy is much less reliable. This study supports the use of frozen-section biopsy before converting the selective dissection to a radical or modified neck dissection in most instances.

Staging problems in the pre‐operative chemotherapy of Wilms' tumour

To determine the effect of the International Society of Paediatric Oncology (SIOP) Wilms' tumour protocols (pre-operative chemotherapy based on clinical and radiological findings, with no prior tumour verification by open or needle biopsy) on subsequent intra-operative tumour diagnosis and staging. The diagnosis and staging of possible Wilms' tumour by clinical, ultrasonographic and radiological assessment were compared with the intra-operative findings in 14 consecutive children (1-12 years of age) treated between 1989 and 1994. A diagnosis of Wilms' tumour was histologically verified in 11 of 14 children. In two children, verification was not possible due to complete necrosis of the tumour following pre-operative chemotherapy. In a 12-year-old boy with an estimated stage IV disease due to a solitary lung metastasis, a renal cell carcinoma was revealed in the nephrectomy specimen while subsequent thoracotomy revealed dysmorphic but not malignant tissue. The estimated tumour stage was correct with regard to localized or metastatic disease in nine of 11 children with histologically confirmed Wilms' tumour, while in two children with an estimated stage II tumour, liver metastases were found intra-operatively and the tumour was upstaged to IV. Exact tumour diagnosis and staging was difficult in these patients. Although the accuracy of tumour staging depends on the sensitivity of radiological and ultrasonographic examinations, difficulties in tumour diagnosis may be overcome by biopsies of the primary tumour. The justification of upstaging a low-stage I/II tumour to stage III, provoking a more intense post-operative treatment, should be proven by prospective randomized studies. The decision to perform a primary tumour biopsy would be facilitated if possible subsequent deterioration of outcome could be excluded.

Is total abdominal hysterectomy with bilateral salpingo-oophorectomy adequate for new FIGO stage I endometrial carcinoma?

The new FIGO staging for endometrial cancer cases complies with other forms of surgical staging and correlates better with clinical outcomes because it includes prognostic factors. This study was done to investigate whether total abdominal hysterectomy with bilateral salpingo-oophorectomy (TAH+BSO) is adequate for new FIGO Stage I endometrial carcinoma. Sixty-five cases of endometrial carcinoma defined according to the new FIGO Stage Ia (n = 26), Ib (n = 24) and Ic (n = 15) were analysed. They all received TAH+BSO only and were followed up for at least two years. The histologic type, grade, depth of myometrial invasion, lympho-vascular tumour emboli and tumour size were analysed by t-test to correlate the risk factors for treatment failure. There were no recurrences after TAH+BSO in Ia and Ib cases. However, recurrences occurred in five cases (33%) of Stage Ic with deep myometrial invasion, high histologic grade, large tumour size and tumour emboli. TAH+BSO is inadequate in some Ic cases with a high histologic grade, deep myometrial invasion and tumour emboli. Thus, thorough pre-operative and intra-operative staging, adequate operation method and prompt post-operative adjuvant therapy are indispensable for successful treatment.

Current Status of Surgical Resection for Lung Cancer

There have been no major breakthroughs in surgical management for primary lung cancer during the past 40 years. Improved 5-year survival relates primarily to improved preoperative staging and appropriate selection of patients for resection. Perioperative morbidity and mortality, however, has been significantly reduced. Certain principles pertain to current surgical management: resection remains the best treatment for patients with localized, non-small cell primary lung cancer. Accurate preoperative diagnosis and staging: whenever possible, it is desirable to establish the diagnosis and cell type before operation. Accurate evaluation of the N status warrants wide application of invasive staging with mediastinoscopy or a variant. Indications for resection: only patients in whom a complete resection is anticipated should be selected for surgery. Such cases included T1 to T4 stages, N0 and N1 tumors, and selected N2 cases. The indication for resection in patients with hematogenous metastases are anecdotal. Intraoperative staging: accurate and deliberate intraoperative staging with evaluation of nodes using the American Thoracic Society map is highly desirable. The nature of nodal metastases exerts a critical influence on prognosis and in the selection of patients for surgical resection. At present, there is no clear indication for adjuvant therapy in surgically resected cases other than for evaluation and clinical trials.

A Phase 3 Randomized Trial of Immediate Combination Chemotherapy vs Delayed Combination Chemotherapy in Patients With Completely Resected Stage II and III Non-small Cell Carcinoma of the Lung

The purpose of this trial (Lung Cancer Study Group [LCSG] 853) was to perform a comparative study of immediate combination chemotherapy (cyclophosphamide, doxorubicin, cisplatin [CAP]) vs delayed combination chemotherapy (CAP) administered at the time of first systemic relapse in patients with completely resected stage II and stage III non-small cell cancer of the lung. We randomly assigned 188 patients with resected stage II or stage III non-small cell lung cancer of the lung (squamous, 53%; nonsquamous, 47%) to receive either immediate or delayed combination chemotherapy. Careful intraoperative staging was performed in all patients. Before randomization, patients were stratified according to stage--II (hilar nodes positive) vs III (mediastinal nodes positive or T3)--and histologic features (squamous vs nonsquamous). Ninety-four patients were randomized to receive immediate CAP vs 94 patients randomized to receive delayed CAP. Prognostic variables such as extent of disease, histologic features, sex, race, TN status, and Karnofsky performance status were equally distributed between randomized groups. The treatment groups differed with respect to greater than 10% weight loss. Forty-one percent of patients had stage II disease and 59% of patients had stage III disease. Median time to recurrence (19.5 months) and survival (32.7 months) did not differ between treatment groups. Immediate combination chemotherapy was associated with a 12% reduction in risk of recurrence and an 18% reduction in risk of death, although these rates were not statistically significant. Histologic features, sex, race, Karnofsky performance status, nodal status, and weight change were associated with higher risks of recurrence.

General Principles of Surgery Quality Control

Randomized clinical trials are currently the most reliable research technique to generate reliable treatment data. Quality control and monitoring with statistical credibility are essential. This requires nurse data managers and coordinators and statisticians, as well as the surgeons and physicians. A well-structured operating infrastructure is key. From the surgical point of view, careful intraoperative staging and standardization of the surgical procedures are a must. Strict eligibility criteria must be documented and enforced. Finally, careful stratification for prognostic variables before randomization in phase 3 trials is essential.

Surgical Adjuvant Therapy for Stage II and Stage III Adenocarcinoma and Large Cell Undifferentiated Carcinoma

The Lung Cancer Study Group (LCSG) randomized 141 patients with resected stage II and III adenocarcinoma and large cell undifferentiated carcinoma to receive postoperative combined chemotherapy with cyclophosphamide, doxorubicin, and cisplatin (CAP) chemotherapy or bacillus Calmette-Guerin (BCG) and levamisole immunotherapy. Careful intraoperative staging was performed on all patients. Before randomization, patients were stratified by stage, weight loss, cardiac arrhythmia, and institution. Prognostic variables such as stage, age, weight loss, and nodal involvement were equally distributed between the two groups. Disease-free survival was significantly prolonged in the group receiving chemotherapy. There was no evidence of a deleterious effect of the immunotherapy. This study indicates that postoperative CAP chemotherapy is effective in prolonging disease-free survival in these patients.

Operation and intracavitary photodynamic therapy for malignant pleural mesothelioma: A phase II study

From April 1991 to May 1993,23 patients entered a phase II clinical study of surgical resection and adjuvant intracavitary photodynamic therapy for malignant pleural mesothelioma. Two days preoperatively, patients received an intravenous injection of 2 mg/kg of the photosensitizer Photofrin. Six patients underwent a pleuropneumonectomy, and 15 patients a pleurectomy, after which intracavitary photodynamic therapy was administered. A total light energy dose of 20 to 25 J/cm 2 was given. In 2 patients the tumor was unresectable due to intrapericardial invasion. Postoperative complications were noted in more than 50 percent of patients; 2 patients died of postoperative complications. Postoperative survival was analyzed according to intraoperative staging proposed by the American Joint Committee for Cancer Staging, published in 1992. The overall estimated median survival is 12 months; that of stage III and IV patients is 7 months. Five patients with stage I and II diseases (who had grossly complete resection by pleurectomy) are alive, disease-free, for 11, 17, 18, 21, and 33 postoperative months. Intraoperative staging is important in carrying out further clinical studies of malignant pleural mesothelioma.

The value of in vitro ultrasonography in the intraoperative staging of gastric cancer

The correct staging is of crucial importance in the choice of surgical treatment in patients affected by stomach carcinoma. In an attempt to achieve a greater accuracy in the diagnosis of depth of tumor invasion, we propose to perform ultrasonography of the gastric wall during surgery (in vitro ultrasonography). Immediately after removal by the surgeon, the portion of the stomach containing the tumor is submitted to ultrasonography with a linear 7.5-MHz probe. To obtain good ultrasonographic images it was necessary to interpose an echo-free standoff pad between the probe and the gastric wall and between the latter and support surface. On completion of ultrasonography, the surgical specimen was sent to the pathologist, who was unaware of the diagnosis formulated on the basis of in vitro ultrasonography (VUS). The VUS diagnosis of T corresponded to the pathological diagnosis in 87/93 cases (93.5% accuracy). In the early cancers the diagnosis was correct in 24/28 cases (85.7%); in the advanced cancers the diagnosis was correct in 63/65 cases (96.9%). In comparison with the results of the other preoperative and intraoperative techniques the accuracy of in vitro ultrasonography in diagnosing the depth of tumor invasion was clearly superior. We feel that VUS may become a basic instrument in T staging and an aid to the surgeon in deciding the extent of the resection and of lymphadenectomy in patients with gastric cancer.