Distal intramural spread in adenocarcinoma of the lower third of the rectum treated with total rectal resection and coloanal anastomosis.

PURPOSE: This study was designed to evaluate the frequency of microscopic distal intramural spread in rectal adenocarcinoma and its correlation to other histopathologic prognostic factors. METHODS: We examined 55 patients with adenocarcinomas of the lower one-third of the rectum and measured the extent of distal intramural spread in the submucosa and/or muscular layer in comparison with Dukes Stage, diameter of tumor, distance of distal margin of resection from tumor, depth of infiltration into perirectal adipose tissue, nodal status, neoplastic infiltration of lymphatic vessels, blood vessels, and nervous branches. RESULTS: Distal intramural spread was found in 40 percent of patients, 77 percent of whom had advanced tumors with nodal metastases. Distal intramural spread appeared to be strictly related to tumor size (superior to 40 mm), infiltration of the perirectal adipose tissue, multiple positive lymph nodes, presence of neoplastic emboli in the intramural lymphatic vessels, and neoplastic invasion of the nervous branches. Local recurrence occurred in one Dukes Stage B patient with a positive distal margin of resection and in four patients with a negative distal margin of resection: three Dukes Stage C and one Dukes Stage B patients with neoplastic involvement of the circumferential margin of resection of the mesorectum. CONCLUSION: These preliminary data suggest that distal intramural spread may carry little importance in determining local recurrence of rectal adenocarcinoma.

Total rectal resection, mesorectum excision, and coloendoanal anastomosis: a therapeutic option for the treatment of low rectal cancer.

BACKGROUND: There is recent and sporadic evidence indicating that patients with very low rectal cancer may be treated via a sphincter-saving procedure, obviating the need for abdominoperineal resection and definitive colostomy. This study confirms these findings. METHODS: From March 1990 to October 1994, 79 patients affected with primary low rectal cancers were submitted for total rectal resection, mesorectum excision, and coloendoanal anastomosis. All lesions were located within 8 cm of the anal verge (within 6 cm in 64 cases). RESULTS: Eight patients relapsed at the pelvic level, and one patient only at the paraanastomotic site. Postoperative morbidity attributable to the procedure was low. A perfect continence was documented in 66% of cases after colostomy closure, and many patients (63%) had one or two bowel movements a day. Sixty-two patients of this series are alive, 49 without actual evidence of disease. Follow-up ranged from 2 to 56 months (median 23). CONCLUSIONS: The clinical and pathological data derived from this study suggest that radical mesorectum excision more than a large clearance margin of resection remains the most important factor in reducing the incidence of local relapse after low rectal cancer surgery and that total rectal resection and coloendoanal anastomosis is a suitable and safe option to traditional, demolitive surgical techniques.

Biological activity and clinical efficacy of intravenous high-dose thymopentin in metastatic melanoma patients.

Eight patients with cutaneous metastatic melanoma were submitted to high-dose intravenous thymopentin (TP5) treatment for 5 weeks: three patients received 1 g three times a week, three received 1 g daily and two received 2 g daily. Four out of eight patients presented a partial response of cutaneous lesions lasting for 1-7 months, and six remain alive with evidence of disease after a follow-up of 2-7 months. A remarkable histologic observation is the presence of tumour necrosis, which was seen as both single cells and large confluent areas. The majority of lymphoid cells present in the tumour are CD45RO+ and CD4+. The CD4+ cells might play an important role in the anti-tumour immune local response by secreting cytokines and inducing apoptotic and necrotic cell death. This hypothesis seems to be confirmed by the presence of a high number of CD4+ cells around intratumoral vessels, while the presence of endovascular micro-thrombosis provides indirect evidence of cytokine activity. Cellular lysis may be produced by the activity of both CD8+ and CD4+ lymphoid cells. The role of TP5 may be an activation of CD4+ and CD8+ lymphoid cells. Clinical and pathological data indicate that TP5 is able to produce consistent clinical and immunological effects in melanoma patients with cutaneous metastases.

Manual dissection of adenocarcinoma of the lower third of the rectum specimens for detection of lymph node metastases smaller than 5 mm.

BACKGROUND: The question of whether manual dissection when searching for metastatic lymph nodes from rectal cancer (less than 5 mm) is a reliable method remains controversial. METHODS: We examined 50 consecutive cases of primary adenocarcinoma of the rectum treated with a sphincter-sparing total rectum resection, total mesorectum excision, and coloanal anastomosis. We used a manual method for the detection of lymph nodes. RESULTS: One thousand seven hundred ninety-three lymph nodes were found (mean, 36 per patient). One hundred seventy-four contained metastases. Seventy-nine (45.4%) of the affected lymph nodes were less than 5 mm in greatest dimension. The percentage of metastases to small lymph nodes was similar to the percentage reported by Kotanagi (50%), but lower than the report of Herrera (78%), who used a clearing technique to search for regional lymph nodes. CONCLUSIONS: A median 17 months follow-up in these patients demonstrated that metastases in small lymph nodes are important in the accurate staging of rectal tumors and that a manual method of searching for small lymph nodes is reliable.

Scintigraphic detection of melanoma metastases with a radiolabeled benzamide ([iodine-123]-(S)-IBZM).

UNLABELLED: Iodine-123-(S)-2-hydroxy-3-iodo-6-methoxy-N-[(1-ethyl-2-pyrrolidinyl) methyl] benzamide ([123I]-(S)-IBZM) is a radiolabeled benzamide usually employed to study neuropsychiatric disorders, such as schizophrenia and Parkinson's disease. The ectodermic origin of melanocytes and the presence of melanin in the substantia nigra are the theoretic basis of the experimental use of this class of tracers for melanoma imaging. METHODS: Eleven patients with proven metastatic melanoma entered the study. Whole-body and planar scintigrams were performed 2, 4 and 24 hr after intravenous injection of a mean tracer activity of 205 MBq. The dosimetric evaluation was performed by the Medical Internal Radiation Dose Committee method. RESULTS: The [123I]-(S)-IBZM scans allowed the detection of all six cutaneous lesions, five of six superficial pathologic lymph nodes, four of five pulmonary and one of two hepatic metastases. The maximum tumor-to-background ratio was 2.6 in planar images. The hepatobiliary excretion of the tracer may limit detection of intra-abdominal lesions. Dosimetry is similar to data for nononcologic patients. CONCLUSION: Although it is unclear if the mechanism of radiopharmaceutical uptake in melanoma is due to binding to membrane receptors or due to interactions with intracellular structures, radiolabeled benzamide is a promising tracer to detect melanoma.

Mucinous carcinoma of the breast. A clinicopathologic, histochemical, and immunocytochemical study with special reference to neuroendocrine differentiation.

We studied the clinical, histologic, histochemical, and immunocytochemical characteristics of 61 mucinous tumors (38 pure, 23 mixed) retrieved from a consecutive series of 1,689 infiltrating carcinomas of the female breast. The only statistically significant predictors of favorable survival were histologic (pure) type coupled with the absence of axillary lymph node metastases. Other factors, including classification into A and B types according to Capella et al., and neuroendocrine status, as assessed by the presence of argyrophilia, granins, neuron-specific enolase (NSE), and synaptophysin (SYN),-all had no influence on survival. Argyrophilic cells were found in 16 pure mucinous tumors (42%) and in the mucinous component of four mixed tumors (17%). Granin (chromogranin A or B), NSE, and SYN immunoreactivities were demonstrated in all the argyrophilic tumors. We also found NSE- and SYN-immunoreactive cells in 31 of 41 and 16 of 41 nonargyrophilic (granin-unreactive) mucinous tumors, which supports the view that mucinous carcinomas of the breast as a whole are neuroendocrine-programmed tumors.

Total rectal resection and colo-anal anastomosis with colonic reservoir for low rectal cancer.

From March 1990 to December 1992, 47 patients with primary or recurrent low rectal cancer underwent total rectal resection and a coloendoanal anastomosis. Rectal resection was extended downward to the ano-rectal junction. The restorative technique included a colo-endoanal anastomosis between the dentate line and a J-shaped colic reservoir. All lesions were located within 7 cm of the anal verge (within 6 cm in 33 primary cases). Macroscopic and histological radicality was documented in all cases. Pelvic recurrence occurred in six patients and was para-anastomotic in one case. Post-operative morbidity was low. Perfect continence was documented in 36 patients and 72 of the cases had one or two bowel movements a day. All but four patients are alive at a follow-up ranging from 6 to 40 months (median 20 months). This approach is a safe option to conventional total rectal excision with permanent colostomy for lower third rectal carcinoma.

Prevalence of sexual dysfunction in male cancer patients treated with rectal excision and coloanal anastomosis.

Impotency due to parasympathetic nerve injury is one of the most feared consequences of rectal cancer surgery. Sexual relationships make a significant contribution to the quality of life for almost everybody. Rectal excision and coloanal anastomosis (CAA) is a new surgical procedure for low rectal tumor with little data regarding the prevalence of sexual impairment as yet. We have examined the sexual life of 21 male patients who have undergone CAA by means a self-administered questionnaire. Only two patients reported reactive impotency. On the other hand 17 out of 21 patients had no ejaculation after undergoing surgery. According to our data it appears that CAA results in surgery a low degree of sexual impairment (impotency). Both sexual dysfunction and quality of life investigations should be integrated with oncological results when reporting data about colorectal surgery.

New perspective in the treatment of low rectal cancer: total rectal resection and coloendoanal anastomosis.

PURPOSE: Presently abdominoperineal resection still remains the most diffuse modality of treatment of low rectal cancer. However, a new surgical approach is now available to avoid such a demolitive surgery and a definitive colostomy. METHODS: From March 1990 to March 1993, 58 total rectal resections were performed in 55 patients affected with primary or recurring cancers of the low rectum. As a restorative procedure, a colic J-shaped pouch and a handsewn pouch-endoanal anastomosis was adopted. All of the primary lesions were within 7 cm of the anal verge; in 74 percent the distal tumor margin was located less than 6 cm from the cutaneous edge. RESULTS: Histologic clearance of the rectum cut edge was documented in all cases. Seven patients relapsed locally from 7 to 14 months after surgery and in 3 more cases distant metastases were documented. Postoperative morbidity is low. After colostomy closure in 78 percent of patients, perfect continence was achieved and in 74 percent less than two bowel movements a day were recorded. Fifty patients are presently alive, 46 without evidence of disease. The follow-up ranged from 2 to 37 (median, 13) months. CONCLUSION: This experience, along with data obtained from last year's literature, indicates that a conservative surgical procedure, such as total rectal resection and coloendoanal anastomosis, can be considered a feasible and radical option for treatment of low rectal cancer.

Total rectal resection and colo-anal anastomosis for low rectal tumours: comparative results in a group of young and old patients.

Rectal cancer incidence is increasing among the elderly who are more often considered for palliation rather than for surgical cure. Moreover, sphincter-sparing surgery is often avoided when treating the elderly. We report our experience on a consecutive series of 38 subjects, suffering from a lower third rectal tumour with a median distance of 5.6 cm from the anal verge (7 Dukes' A, 6 Dukes' B, 17 Dukes' C, 3 Dukes' D, 3 anastomotic recurrences and 2 large villous adenomas). All subjects were prospectively collected in a 2-year period and treated with total resection and colo-anal hand-sewn anastomosis on a J colic reservoir. 20 patients younger than 65 years and 18 over 65 years were matched for surgical complications, late morbidity, oncological and functional results but no statistical difference was found. Our hope is that a conservative approach in treating the low rectal tumours will progressively be accepted for elderly patients.

Total rectal resection, colo-endoanal anastomosis and colic reservoir for cancer of the lower third of the rectum.

The treatment of low rectal cancer is still a widely debated topic in surgical oncology. From March 1990 to August 1991, 18 patients with tumors sited in the lower third of the rectum underwent a total rectal resection extended to the ano-rectal junction. As restorative procedure, a colic J-shaped pouch and a handsewn pouch-endoanal anastomosis was adopted. All the lesions were less than 8 cm from the anal verge; in 94.5% the distal tumor margin was located within 6.5 cm of the cutaneous edge. Histological clearance of the rectum cut edge was documented in all cases. Only one patient (Dukes C) relapsed four months later at the para-anastomotic level. No mortality or major complications related to surgical procedure were found. In 13 patients perfect continence was achieved and in 12 cases less than two bowel movements a day were recorded. No one complained of severe sexual dysfunction. All patients are still alive. The follow up ranged from 6 to 22 months (median: 12). This experience together with data obtained from last years' literature indicate that a conservative surgical procedure, as total rectal resection and colo-anal anastomosis, can be considered a feasible and radical option for treatment of low rectal cancer.

Argyrophilia and granin (chromogranin/secretogranin) expression in female breast carcinomas. Their relationship to survival and other disease parameters.

Ninety-one tumors (5.6%) containing argyrophilic cells were identified in a series of 1,628 consecutive primary breast carcinomas diagnosed between 1968 and 1972 at the Istituto Nazionale Tumori, Milan, Italy. Histological evaluation of these argyrophilic tumors showed the presence, either throughout the whole tumor mass (pure form) or in some areas (mixed form), of distinctive though not pathognomonic cellular features. Immunocytochemistry revealed the presence of chromogranin A or chromogranin B (secretogranin I) immunoreactivity in 86% of these argyrophilic carcinomas and of neuron-specific enolase (NSE) immunoreactivity in all of them. The three neuroendocrine markers were also immunolocalized at the ultrastructural level in the dense-core granules (granins) and the cytoplasmic matrix (NSE). Immunoblotting studies confirmed the chromogranin A and B and NSE immunoreactivities and documented the presence of secretogranin II. We also studied the relation of the histologic, histochemical, and immunocytochemical features to prognosis. There was no significant correlation between argyrophilia and such clinical parameters as age, menopausal status, tumor size, and overall survival; however, the pure form of argyrophilic tumors had a significant association with less frequent lymph node involvement and a low histologic grade.

Prognostic significance of HER-2/neu expression in breast cancer and its relationship to other prognostic factors.

Archival surgical specimens from 1,210 female breast cancer patients treated between 1968 and 1971 and with a 19-year follow-up were reanalyzed with special reference to several parameters, such as size of the primary tumor, axillary nodal involvement, histologic grade, degree of inflammatory infiltrate (LPI) of the tumor and expression of the neu oncoprotein (p185) as detected by immunohistochemistry. In a multifactorial analysis the 4 former factors were found to be independent prognostic parameters. Over-expression of p185 was found to be related to tumor size and grade and to LPI but not to pathologic nodal status. Over-expression of p185 showed a negative impact upon survival in node-positive but not in node-negative patients. However, in the subset of node-negative patients without LPI, p185 over-expression showed the same correlation with a poor prognosis as in node-positive patients. In contrast, in node-negative and LPI-positive patients, p185 over-expression correlated with a good prognosis. Also, the prognosis of patients with positive nodes, presence of LPI and no p185 over-expression was similar to that of patients with negative nodes, absence of LPI and p185 over-expression.

Comparison of long-term survival of 1986 consecutive patients with breast cancer treated at the National Cancer Institute of Milano, Italy (1971 to 1972 and 1977 to 1978).

Long-term survival of 1986 consecutive patients with infiltrating duct carcinoma of the breast treated at the National Cancer Institute of Milano (Italy) in two periods of time (1971 to 1972 and 1977 to 1978) was comparatively evaluated to verify if the evolving concepts in the management of breast cancer had an impact on survival. The authors found that 10-year survival of our patients increased from 59.4% of the first period of time to 65% of the second (P = 0.005). Both node-negative (N-) and node-positive (N+) patients had an improvement of survival rates at 10 years of the same magnitude: 6.8% and 5.9% respectively. Taking into consideration both the maximum diameter of the primary tumor and the status of axillary nodes it was found that in (1) both N- and N+ patients with a primary tumor of no more than 2 cm in greatest diameter, the improvement of survival was not statistically significant; and (2) both N- and N+ patients with a primary greater than 2 cm in maximum diameter had a better chance of survival in the second time period.

[Administration of cytostatic drugs by intra-arterial route. Theoretical basis]. / Somministrazione di farmaci citostatici per via endoarteriosa. Basi teoriche.

The Authors discuss the theoretical principles of the intra-arterial administration route of antineoplastic drug in the treatment of primaries or metastatic diseases.

[Indications for regional lymphadenectomy in skin melanomas: a problem still in debate. Personal experience and review of the literature]. / Indicazioni alla linfoadenectomia regionale nei melanomi cutanei: un problema ancora dibattuto. Esperienza personale e revisione della letteratura.

The Authors discuss indications to the regional dissection on the basis of personal experience and data reported in the literature concluding for the lack of specific advantages for elective operations.