Radioimmunoguided surgery after primary treatment of locally advanced breast cancer.

PURPOSE: To assess the role of radioimmunoguided surgery (RIGS) using a handheld intraoperative gamma-detecting probe (GDP) to identify neoplastic disease after primary chemotherapy in locally advanced breast cancer (LABC) patients injected with iodine 125-labeled monoclonal antibodies (MAbs). PATIENTS AND METHODS: Twenty-one patients with histologically documented LABC were treated with a combined modality approach. After three courses of primary chemotherapy and before modified radical mastectomy, the 125I-radiolabeled MAbs B72.3 (anti-TAG72) and FO23C5 (anti-carcinoembryonic antigen [CEA]) were administered to 11 patients (group A) and 10 patients (group B), respectively. At surgery, a GDP was used to locate the primary tumor and to assess possible tumor multicentricity and the presence of ipsilateral axillary metastases. Routine pathologic examination was performed in neoplastic and normal tissue specimens of all 21 patients. In addition, immunohistochemical assay for TAG72 and CEA expression was performed. RESULTS: In group A patients, RIGS identified primary tumor in seven of 11 patients (63.3%) and unpalpable multicentric tumor lesions were located in two of four (50%). Positive axillary lymph nodes were histologically documented in eight of 11 patients (72.7%) and RIGS identified three of eight (37.5%). In group B, RIGS located the primary tumor lesion in four of 10 patients (40%); in two cases, the tumor was not clinically evident. Multicentricity was observed in one of two patients and lymph node involvement in three of nine (33.3%). No false-positive results were observed in either group A or B. CONCLUSION: RIGS appears to be a safe and reliable technique. However, the MAbs used in this study are not sufficiently specific. RIGS represents a technique for which the full potential for intraoperative assessment of breast cancer lesions can be reached when more specific antibodies become readily available.

Role of B72.3 iodine 125-labeled monoclonal antibody in colorectal cancer detection by radioimmunoguided surgery.

BACKGROUND: Radioimmunoguided surgery (RIGS) by means of radiolabeled monoclonal antibodies and a probe has been reported to be useful in recognizing subclinical tumor deposits during operation. Aim of this study was to understand the limits of this technique and to assess the potential diagnostic use of RIGS in colorectal cancer surgery. METHODS: Monoclonal antibody B72.3 reacting with TAG 72 antigen, labeled with iodine 125, was injected in 32 patients with primary tumors and in 22 patients with recurrent colorectal cancer. One hundred thirty-three suspected tumor sites were evaluated during operation by means of probe and resected with immunohistochemistry as control. RESULTS: Primary tumor sites were localized by RIGS in 60% of cases, and recurrent sites were localized in 82% of cases. There was a significant correlation both for primary (p < 0.001) and recurrent (p < 0.001) tumor sites between intraoperative RIGS findings and TAG 72 tumor antigen expression. Results obtained with the probe were instrumental in modifying the surgical approach in six (27%) of 22 patients with recurrences, allowing the removal of tumor masses that would otherwise have been overlooked. CONCLUSIONS: The results of RIGS seems to be encouraging in terms of clinical use. The potential high diagnostic resolution appears to improve surgical ablation of colorectal cancer, especially in patients with recurrent cancer or suspected recurrent tumors who have negative results for intraabdominal disease by all other roentgenographic criteria with rising carcinoembryonic antigen or TAG 72 antigen levels.

Long-term femoral vein central venous access in cancer patients.

Subclavian percutaneous access with reservoir placement has been shown to be difficult or contraindicated in some patients. Of 465 cancer patients who required a port placement between January 1992 to January 1995, 41 (8.8%) had alternative percutaneous femoral access with a totally implantable port reservoir located in the abdomen because of the inaccessibility to subclavian or jugular veins and/or the presence of massive cutaneous metastases or severe radiodermitis in the upper part of the torso. Overall implant days was 9880, with an average of 241 days (range: 65-445). Ports were alternatively used for chemotherapy and nutritional purposes in 11 of 41 patients. Late morbidity causing the removal of the implanted ports was observed in two of 41 (4.9%) and 25 of 424 (5.9%) patients in the femoral and subclavian series, respectively (P = 0.86). The femoral percutaneous access for totally implantable port devices appears to be a safe alternative for cancer patients when subclavian and/or jugular vein catheterization and reservoir in the upper part of the torso is contraindicated.

Long-term postoperative results in 54 cases of early gastric cancer: the choice of surgical procedure.

Surgical experience on the management of early gastric carcinoma (EGC) related to a series of 54 subjects was observed from 1974 to 1984. Thirty-four patients were male, 20 were female; median age was 61.84 (range 22-79) years. Malignancy always occurred in the middle or distal third of the stomach. A partial subtotal gastrectomy (two-thirds of the stomach) with Roux en Y or Billroth II reconstruction was performed. Omentectomy and lymph node dissection of the primary and secondary groups of nodes, according to General Rules, was always performed. Age-corrected 5- and 10-year survival rates were 95.7% and 84.3%, respectively. Based on their experience, the authors discuss the surgical approach to EGC stressing the need for an accurate lymph node dissection and pointing out that results of subtotal gastrectomy are similar to that reported in the literature for total gastrectomy. The only absolute need for a total gastrectomy may be the presence of an EGC in the proximal third of the stomach. To this end the authors compare their results with 5- and 10-year series from Japanese and western countries reported in the literature.

Pseudomixoma peritonei: a case report.

Pseudomixoma peritonei is a rare neoplasm characterized by mucinous ascites and the mucinous involvement of peritoneal surfaces, omentum and bowel loops. Usually pseudomixoma peritonei is associated with benign or malignant mucinous tumor of the appendix or ovary. The diagnosis of pseudomixoma peritonei is difficult because laboratory and radiology results are frequently nondiagnostic. We report a case that was initially mistaken for carcinomatosis of unknown origin and that underwent cytoreductive procedure and omentectomy as the treatment of choice.

Phase II study of weekly oxaliplatin and high-dose infusional 5-fluorouracil plus leucovorin in pretreated patients with metastatic colorectal cancer.

BACKGROUND: Chemotherapy with oxaliplatin, fluorouracil (5-FU) and leucovorin (LV) has proven efficacy in patients with advanced colorectal carcinoma (CRC), although the optimal dosage and administration schedule are still unclear. This phase II trial investigated the tolerability and activity of weekly oxaliplatin, high-dose infusional 5-FU and LV in pretreated patients with metastatic CRC. MATERIALS AND METHODS: Patients received weekly courses of i.v. oxaliplatin 50 mg/m2 (1-h infusion), LV 100 mg/m2 (1-h infusion) and 5-FU 2100 mg/m2 (24-h infusion) until disease progression or unacceptable toxicity. NCI-CTC criteria were used for assessment of side-effects (at each cycle) and WHO criteria for assessment of tumour response (every 8 cycles). For descriptive purposes, time to progression, overall survival and duration of objective response were also calculated. RESULTS: Forty-four patients were enrolled and received a total of 606 cycles (median 13/patient, range 4-33), and 70% of courses (421/606) were delivered at 100% of the planned dose. The most frequent side-effects were gastrointestinal and neurological and incidence rates were: diarrhoea 66% (grade III: 29%), nausea/vomiting 54%, neurotoxicity 34% (grade III: 2%), fatigue 27%, mucositis 22%, leucopenia 14%. No grade IV toxicity was observed. Objective response rates were: partial response 23% (10 patients), stable disease 59% (26) and progressive disease 11% (5). Median time to progression was 7 months, overall survival 13 months and the duration of partial response and stable disease were 9 and 6 months, respectively. CONCLUSION: The study demonstrated that this regimen has a favourable tolerability profile and is an active combination in the pretreated metastatic CRC patient, deserving further evaluation in phase III trials.

Intrahepatic epidoxorubicin in metastatic and primary liver tumours: a phase II study.

Primary and metastatic gastrointestinal tumours in the liver have been treated by intrahepatic artery infusion of chemotherapeutic drugs in an attempt to increase the efficacy of the administered agents. Among the several active agents, 4' epidoxorubicin, an anthracycline analogue, was selected for this study because of the therapeutic level reached in the liver by this drug. Seven patients with primary hepatic carcinoma and twenty with metastatic adenocarcinoma of the colon to the liver received intraarterial hepatic infusion of epidoxorubicin at the dosage of 30 mg weekly. No haematological or gastrointestinal grade 3-4 toxicity was recorded, only one patient experienced transient cardiac toxicity. No objective response was observed in primary hepatic carcinoma and six objective responses, 1 complete and 5 partial (30%), were achieved in metastatic colorectal cancer patients. This results is not far from those reported with FUDR, but does not justify epidoxorubicin in colorectal cancer patients as first line intraarterial treatment.

Selective lymph node dissection in patients with intermediate thickness melanoma: our experience.

The role of elective lymph node dissection (ELND) for the treatment of cutaneous melanoma has been debated for many years. Actually, the value of ELND is seriously questioned because an increasing of overall survival rates has not been demonstrated. The lymphatic mapping technique, initially performed by an intradermic injection of vital blue dye, subsequently improved by the use of radioguided surgery (RGS), proved effective for the detection of clinical occult lymph node metastasis. We performed a sentinel node biopsy on 71 patients with stage pT2/T3N0M0 melanoma. Vital blue dye mapping alone was performed on 39 patients; the remaining 32 patients had a combined lymphatic mapping with both blue dye and RGS. The sentinel node (SN) was complexively identified in 69/71 (97.2%) patients. Sixteen patients (23.2%) were found to have metastatic melanoma cells in their SN(s); all these patients underwent lymph node dissection of the affected basin. Our experience confirmed that the intraoperative detection of sentinel nodes using both blue dye and radio-guided surgery is an effective and reliable technique for selecting patients to be submitted to lymph node dissection.

Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.

BACKGROUND: Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken. PATIENTS AND METHODS: Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines. RESULTS: The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively. CONCLUSIONS: L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.

A phase I study of recombinant interleukin-2 intraperitoneal infusion in patients with neoplastic ascites: toxic effects and immunologic results.

A phase I study to evaluate the use of i.p. infusion of recombinant interleukin-2 (rIL-2) was planned. The following dose levels were calculated: 0.1, 0.3, 1.0, 3.0 and 10 mg/m2/day for 14 days, but only the second levels were reached. In this trial the acute toxic effects at this dosage included cardiac ischemia, transient liver impairment and septic peritonitis. The maximum tolerated dose (MTD) was 0.3 mg/m2/day for 14 days. In addition, two patients developed peritoneal fibrosis. No objective responses were observed. Therefore, in order to explore the biological activity of low (nontoxic) doses, three patients (one untreated and two previously treated with rIL-2) were infused with 0.01 and 0.03 mg/m2/day for 7 days. Potentiation of cytolytic activities in peritoneal lymphocytes and activation of a lymphokine cascade in the ascitic fluid were observed at doses ranging from 0.03 mg/m2/day to 0.3 mg/m2/day. These findings in association with the toxic effects observed at the MTD suggest the use of the minimum effective dose for future locoregional immunotherapeutic protocols.

Colorectal cancer: relationship of histologic grading to disease prognosis.

Ninety patients underwent curative surgery for colorectal adenocarcinoma and they were followed for a period of 3 years. The aim of this retrospective study was to relate the cell differentiation (grading) and TNM classification of the UICC (1978) with the disease evaluation and patient survival. The results showed a consistent relation between grading and lymph node metastasis in patients with moderately and poorly differentiated adenocarcinoma, whereas no relationship was found between grading and local invasion of the tumor. Therefore, histocytologic grading of colorectal cancer appears to significantly influence survival grading parameters, and it may be a good method for monitoring the disease and follow-up of the patients.

Sentinel lymph node mapping and biopsy for breast cancer: a review of the literature relative to 4791 procedures.

The status of axillary nodes is the most important prognostic factor in breast cancer to select patient subgroups for adjuvant chemotherapy; the current standard of care for surgical management of invasive breast cancer is complete removal of the tumor by either mastectomy or lumpectomy followed by axillary lymph node dissection (ALND). The recent introduction of intraoperative lymphatic mapping and sentinel lymph node biopsy (SLND) represents a major new opportunity for appropriate and less invasive surgical management of many tumors. There is an almost uniformly enthusiasm concerning the potential of this technique in breast carcinoma management, shown by published data. A peculiar attention to the so-called "sentinel node debate" in breast cancer surgery is a constant in the last years issues of the major medical journals. Even patients have become more aware about medical enthusiasm and their request of concise information on the topic and the possibilities of this approach is an increasing reality in medical practice. The aim of this paper is to review recent literature to offer an overview about the main controversial methodological aspects and a wide analysis of reported results. The most significative international literature papers from Medline were retrieved from 1993 to September 1999, and 4782 procedures were analysed. This extensive review of the literature has confirmed accuracy, feasibility and reliability of the SN detecting technique in axillary mapping. Provided a good proficiency in SN localisation and pathological evaluation, human resources and efforts should be mainly focused on its clinical validation as an alternative to ALND instead of on further phase I-lI clinical studies.

[Current status of the classification and clinical staging of primary and secondary tumors of the liver]. / Considerazioni sullo stato attuale della classificazione e stadiazione clinica dei tumori primitivi e secondari del fegato.

Over the past few decades there has been outstanding expansion in the surgical exeresis of primary and metastatic liver tumours and particularly hepatic metastases of colorectal carcinomas. With the advance in surgical technique it becomes increasingly necessary to codify the system for the classification and clinical staging of these conditions for the purposes of correct programming of treatment and assessment of the clinical results obtained. The most commonly used systems of classification and clinical staging are analysed, in particular the classifications proposed by the American Joint Committee on Cancer and D. Manfredi for primary liver tumours and those proposed by Gennari et al and Sugerbaker et al for hepatic metastases of colorectal carcinomas. The selection criteria adopted in each system are analysed as the basis for a more thorough discussion of the problem that is felt to be fundamental for the standardisation of classification and clinical staging systems in the future. Such standardisation is essential for the assessment of the value and limitations of liver surgery in cancer.

[Role of surgery in the prognosis of AIDS and related syndromes. Case reports ]. / Ruolo della chirurgia nella prognosi dell'AIDS e sindromi correlate. Contributo casistico.

The authors review the epidemiologic and etiopathogenetic aspects of AIDS, in agreement with data published in december by the Center for Disease Control and by the WHO for the States, Europe and Italy. In their experience twenty-one patients, with clinical clues of AIDS, undergoing lymph node biopsy, have been analysed (18 LAS-ARC and 3 AIDS) and the role of prophylaxis for the surgical approach to the patient with aids or related syndrome has been underlined.

[Comparison of the performance of a totally implantable pump and conventional access systems in regional arterial chemotherapy of liver tumors]. / Paragone di affidabilità tra pompa totalmente impiantabile e sistemi tradizionali di accesso per la chemioterapia arteriosa regionale dei tumori epatici.

Forty-nine patients with liver tumors have been submitted to regional arterial chemotherapy by means of either totally implantable Infusaid 400 pumps (29 casse) or implantable ports (20 cases). The latter were subsequently perfused with external pumps. There was one single major operative complication and no operative deaths. Most patients underwent continuous FUDR infusion. Access related complications in the Pump and Port groups respectively included 1 and 0 malfunctions, 7 and 2 seromas, 2 and 0 pocket necroses, 8 and 10 thromboses, 2 and 4 catheter dislocations, 0 and 2 portal breakages. Treatment was stopped for access related complications in 5 and 5 patients respectively. In most of those cases, however, more than 6 cycles of chemotherapy have been performed. The Infusaid 400 pumps showed a 12-month duration of 58.4% with a 13 month median versus 17% and 9 month median of the Ports. The difference was not significant. The new implantable systems give better results in comparison with traditional regional methods; the performance of the Port systems appear very similar to the totally implantable pumps, with an obvious advantage, however, for the pumps as far as quality of life is concerned.

Gastric cancer: a review of 400 consecutive cases.

Four hundred out of 422 patients with primary gastric cancer seen from 1965 to 1979 underwent surgical treatment and were studied retrospectively. Fifty-eight percent underwent curative procedures. The five year survival rate was 19.14%. Subtotal and total gastrectomy gave survival rates of 35.8% and 9% respectively (p less than 0.05). Postoperative mortality (24.2%) was influenced by both the type of procedure performed (p less than 0.001) and the stage of the neoplasis (p less than 0.001). This study confirms the influence of staging on short, intermediate and long term survival and demonstrates the importance of the early diagnosis of gastric cancer in carrying out effective surgical treatment.

[Extended and palliative surgery in the treatment of gastric cancer in advanced stage]. / Chirurgia allargata e palliativa nel trattamento del cancro gastrico in fase avanzata.

Five hundred and fifty patients operated between 1965 and 1983 for stomach carcinoma were included in the study. Of these, 244 (44.4%) underwent extended (54 patients) or palliative surgery (190 patients) due to the extragastric diffusion of the neoplasia. Global postoperative mortality for patients undergoing extended surgery was 16.7% and the five-year survival rate was 18.5%; in the case of those undergoing palliative surgery the postoperative mortality rate was 30.5% and the two-year survival rate was 14% for resection and 4% for derivatives. Patients who underwent a derivative operation showed an easing of symptoms and an improved quality of life. On the basis of these results the Authors consider that the possibility of extended surgery should still be carefully evaluated in patients in whom a stomach tumour has exceeded the gastric boundary, irrespective of its extent, since the limit of radical surgery is not related to the extension of surgical demolition but to the entity of the extragastric diffusion of the neoplasia. In addition, surgical abstention is not always justified even in patients in whom surgery cannot be curative since a 10% five-year survival rate was observed in patients undergoing palliative resection.

[Long-term central venous access in oncology. Review of a caseload of 750 cases]. / Accessi venosi centrali a lungo termine in oncologia. Revisione di una casistica relativa a 750 casi.

Totally implantable central venous accesses systems are presently widely used in cancer patients. Perioperative and long-term morbidity of 750 consecutive implants performed from 1985 to 1994 were retrospectively reviewed. Our Series consisted in 616 (82.1%). Ports and 134 (17.9%) external tunnelled catheters with subcutaneous Dacron cuff (Hickmann or similar catheters) implanted by percutaneous access route in local anesthesia. Subclavian vein was the elective access route in 700 (93.3%) patients while in the remaining 50 (6.7%) the access was performed in the femoral vein, due to peculiar clinical conditions. One-day surgery was only required for 19 (2.6%) patients while outpatient surgery was the routine in 731 (97.4%) patients. Perioperative morbidity was at all similar both for Port and external catheters Series (p > 0.07). Late morbidity requiring the removal of the device occurred in 27/134 patients (18.7%) and in 40/616 (6.5%) for external catheters and Port Series, respectively (p < 0.002). The rate of infection, 2.3% for ports (p < 0.002). Patient's compliance was higher for Ports compared to external catheters. Apart from peculiar clinical conditions such as hematologic cancers, bone marrow transplantation or short life expectancy, Ports seem to guarantee for a lower morbidity coupled with better long-term results.

[Surgery of biliary lithiasis. I. Physiopathology and diagnosis]. / La chirurgia della litiasi biliare. Nota I. Fisiopatologia e diagnostica.

Experimental studies and clinical observations are referred to in stressing the frequent correlation between duodenal, biliary and pancreatic disturbances, and the importance of the role of spontaneous or iatrogenic impairment of Oddi's sphincter in the origin of this pathology. These physiopathological concepts are regarded as fundamental in the correct surgical management of cholelithiasis. A pre- and postoperative diagnostic protocol designed to investigate the anatomofunctional aspects of the duodenum and pancreas as well as bile duct morphology and Oddi sphincter function is described. Its employment enabled 633 cases to be divided six well-defined groups for diversified treatment.

[The diagnosis and therapy of recurrent tumor of the rectum]. / Considerazioni sulla diagnosi e terapia del tumore recidivo del retto.

The authors review the pathogenesis of locoregional recurrences of rectal cancer, pointing out clues for the diagnosis and staging of the disease which are valuable for the definition of a treatment strategy. Surgery is the mainstay of any attempt to cure those recurrences that are amenable to radical resection; over and above the diagnostic role of second-look laparotomy in suspected cases, surgery must include those measures able to reduce actinic damage whenever postoperative radiotherapy is required. On the other hand, palliative surgery is necessary to resolve the presence of intestinal obstruction, fistulous tract, or the removal of abscess and necrotic tissue. In these cases, the quality of life seems to be the prime factor in the choice of therapy (radiotherapy, loco-regional or systemic chemotherapy, hyperthermia).