[Systematic lymphadenectomy in cancer of the stomach: rationale and technique].
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Biomedical subjects
Publications and source records attributed to A Garofalo.
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The peritoneal surface malignancy is an high risk condition which implies high postoperative mortality also for simple explorative laparotomy. A technique of staging laparoscopy was assessed and is here described: the technique reveals to be safe, feasible and reliable. The accuracy of the procedure depends our the surgeons experience and familiarity with the concepts of PCI and cytoreduction.
Malignant peripheral nerve sheath tumors (MPNST) are spindle-cell sarcomas that appear in a setting of neurofibroma or schwannoma or are associated with peripheral nerves or demonstrate nerve sheath differentiation. Malignant triton tumor (MTT) is a subtype of MPNST that also contain tissue with skeletal muscle differentiation (embryonal, plemorphic and botryoid rhabdomyosarcoma). The estimated incidence of MPNSTs in patients with NF1 is 2-5% compared with 0.0001% in the general population and approximately 69% of the reported cases of MTT are associated with von Recklinghausen disease. In July 2002 a 37-year old man was readmitted to the Department of Oncologic Surgery of the S. Camillo-Forlanini Hospital in Rome for both a right-sided retroperitoneal paravertebral not palpable mass, incidentally detected at a follow-up MRI, and a left-sided popliteal mass, discovered at clinical evaluation. Seventeen months before, when the patient underwent surgery at the same Department for both a left-sided paravertebral inferior mediastinal neurofibroma and a right-sided axillary neurofibroma, diagnosis of von Recklinghausen disease (NF1) was made, according to the criteria established by the NIH Consensus Development. Conference on Neurofibromatosis of 1987. A xifopubic laparotomy was performed: the tumor appeared to be localized, well-capsulated and strictly associated to the lumbar and sacral nervous radicles (L4, L5, S1) without evidence of invasion. The tumor was completely resected with sparing of the psoas muscle and the lumbar plexus through a subperineural dissection technique. No intra-operative pathologic examination was performed. Postoperative pathologic findings showed evidence for a trition tumor. The popliteal mass was resected too and resulted to be a neurofibroma just like the tumors resected 17 months before when diagnosis of von Recklinghausen disease was made. The patient was disease free 6 months after initial surgery. Sarcoma arising in anatomic site other than extremity and superficial trunk are often more difficult to control because of anatomic constraints, delayed disease presentation, proximity to neurovascular and osseous structures and toxicity for normal adjacent tissues that limits the use of adequate radiation doses. Indeed, the anatomic site is an important prognostic factor in STS and the prognosis for retroperitoneal tumors is considerably worse than for extremity tumors. Reported local recurrence rates for retroperitoneal sarcomas range from 40% to 80% and, in marked contrast to extremity STS, most of patients can and do die from local recurrence in the absence of metastasis. In contrast to the benefit most patients with high grade soft tissue sarcomas of the extremities receive from adjuvant radiation and chemotherapy, these modalities have been of little value for retroperitoneal tumors. To overcome the problem of dose limitation, intraoperative electron beam radiotherapy (IORT) in combination with ERBT has been proposed. IORT plus ERBT was found to improve local control of disease in recent clinical trials. Current chemotherapy for retroperitoneal sarcomas is ineffective. Local adjuvant therapy such as intraperitoneal chemotherapy or experimental immunotherapy seems to be attractive in theory, but needs further investigations through prospective randomized multicentric trials. In conclusion, to date aggressive surgical management remains the most effective modality for selected primary and recurrent retroperitoneal soft tissue sarcomas including MPNSTs and the subtype MTT. Patients with incomplete resection and other risk factors such as younger age and high grade tumors may be suitable candidates for investigational adjuvant therapy.
The surgical treatment of gastric adenocarcinoma foresees, toghether with the gastric resection, the lymph nodes resection as indicated by the Japanese Research Society for Gastric Cancer. Obstructive jaundice, as a consequence of lymph nodes metastases, is one of the most debilitating pattern of recurrence. In the present paper three cases of jaundice, observed during the follow-up, after D2-D3 gastric adenocarcinoma resection, with no evidence of lymph nodes recurrence either at the restaging or at the intraoperative esploration are reported. We believe that the jaundice etiology, in the present series, could be due to neoplastic lymphangites of the biliar wall.
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A prospective study has been carried on 37 patients, 35 of them affected by peritoneal carcinomatosis from ovarian (16), appendiceal (7), colorectal (5), mesothelial (4), gastric (3) primary and 2 affected by sarcomatosis. Mean PCI was 22 (median, 22). Eighty-five percent of the patients presented debilitating ascites associated in 23% to initial symptoms of intestinal obstruction. All the patients have been treated with peritonectomy and intraoperative hyperthermic chemoperfusion and CC 0-1 cytoreduction was achieved in 81%. Major morbidity and mortality was respectively 37.8% and 16.2%, where 5 out 6 deaths recorded in the first 19 months of our experience, representing our learning curve. At a median follow-up of 8 months (range, 1-54), 18 patients are alive and disease-free and 4 patients are alive with disease. Two-yr overall survival was 49.1% for all series. Difference in survival evaluating CC 0-1 vs CC 2 patients was statistically significant.
A prospective study has been carried on 37 patients affected by peritoneal carcinomatosis from various primary. Patients have been treated by cytoreductive surgery and intraoperative hyperthermic chemoperfusion. CC 0-1 has been achieved in 81%. The temperature distribution study showed a "barrier effect" with no statistically significant correlation to the survival. Major morbidity and mortality was respectively 37.8% and 16.2%. Two-yr overall survival was 49.1% for all series. Morbidity was significantly directly correlated to the duration of the surgical treatment. A learning curve of 19 months have been observed, after that only one death out 21 procedures has been recorded. Peritoneal carcinomatosis patients, that are submitted to integrated treatment, need a peculiar management that is not comparable to any other in the oncological setting and that requires specific competence.
A method of laparoscopic continuous hyperthermic peritoneal perfusion (CHPP) is proposed for the treatment of debilitating malignant ascites. The authors report 14 cases of peritoneal malignancy, not amenable to peritonectomy due to massive infiltration of the small bowel. The ascites disappeared in all treated cases.
Intraoperative morbidity in the laparoscopic approach for colorectal surgery is 5.6%. We tried our experience in 4 out of 70 laparoscopic procedures. In 3 cases it was dealt with one missed estate of the suture of the rectal stump. Two of them were treated with new resection of the rectal stump using in one case the opening of the anastomosis. In 1 case of bleeding of a sacral vessel we practiced a service 6 cm Pfannestiel incision of 6 cm to handle the hemorrhage. Intraoperative morbidity has not modified the course of the postoperative one.
The authors report a new approach to pancreatic laparoscopic body end tail that allows resection for neoplastic disease. This procedure permits en bloc resection using endogia 45 without preventive dissection of splenic vessels.
Recent reports from US and Japan have established that mutations in the tyrosine kinase (TK) domain of the epidermal growth factor receptor (Egfr) occur in a subset of patients with lung cancer that respond to therapy with gefitinib, a TK inhibitor. To gain further insights into the role of Egfr in carcinogenesis of lung and tumors of diverse histology, that are currently under investigation with drugs of the same class, we have taken in examination a panel of tumors consisting in 110 pulmonary adenocarcinomas, 40 pulmonary squamous carcinomas, 40 gastric adenocarcinomas and 40 colorectal adenocarcinomas. The sequence analysis of exon 19 and 21 of the Egfr has allowed the identification of 10 cases exhibiting specific deletions in exon 19 and 1 case with point mutation in a conserved residue in exon 21. All Egfr mutations occur specifically in lung adenocarcinomas while tumors of different histology result unaffected. The rate of mutation affecting these other tumors is either very rare, involves different domains of the receptor or other tyrosine kinases. The molecular analysis of the Egfr gene can help identify patients that will benefit from gefitinib therapy.
Molecular characterization of gastrointestinal cancer has greatly helped the definition of the key steps of the malignant transformation process and made it the best understood among the malignant cancers. Genetic influences on prognosis may have important implications for the management of the disease and help to design patient-tailored therapy. In order to acquire additional knowledge on this issue we have commenced an institutional study with the aim to identify the most frequent molecular alterations and make a correlation with the conventional histopathological parameters.
Treatment of gastrointestinal stromal tumors (GIST) has been revolutioned by the recently discovered molecular mechanism responsible for the oncogenesis of this disease. In addition, due to the rapid progress at molecular and clinical level observed in the last few years, there is a need to review the current state of the art in order to delineate appropriate guidelines for the optimal management of these tumors. A panel of experts from several specialities, including medical oncology, surgery, pathology, molecular biology and imaging, were invited to participate in a meeting to present and discuss a number of pre-selected questions, and to achieve a consensus according to the categories of the National Comprehensive Cancer Network (NCCN) and the Standard Options Recommandations (SOR) of the French Federation of Cancer Centers. Generally, consensus points were from categories 2A of the NCCN and B2 of the SOR. Conventional histologic examination with immunohistochemistry for CD117, CD34, SMA, S-100 and desmin is considered standard. Molecular analysis for the identification of KIT and PDGFRA mutation may be indicated in CD117-negative GIST. Complete tumor resection with negative margins is the optimal surgical treatment. Adjuvant imatinib should be considered an experimental approach. Neoadjuvant imatinib is also experimental, although its use may be justified in unresectable or marginally resectable GIST. Imatinib should be started in metastatic or recurrent disease, and should be continued until progressive disease or drug intolerance. In these cases, sunitinib can be used. The optimal criteria for the assessment and monitoring of GIST undergoing imatinib therapy are not well known, but they should include reduction in tumor size and disease stabilization, as well as reduction of tumor density on CT scan and metabolic activity on PET scan.
A multicentric study has been carried out on 120 patients affected by peritoneal carcinomatosis from colorectal cancer. Patients have been treated by cytoreductive surgery and intra-operative hyperthermic chemoperfusion (HIPEC) with cisplatin (CDDP) and mitomycin-c (MMC). A small group of patients were treated with oxaliplatin (LOHP) following the Elias et al. scheme [intravenous 5-fluorouracil (400 mg/m2) and leucovorin (20 mg/m2) followed by intraperitoneal perfusion with LOHP (460 mg/m2) in 2 l/m2, during 30 min at 43 degrees C]. CC-0 cytoreduction was achieved in 85.2% of the patients. Major morbidity and mortality was 22.5% and 3.3%, respectively. No G4 toxicity was registered. The three-year survival was 25.8%. The difference in survival evaluating complete cytoreduction (CC-0) vs. incomplete (CC1-2; residual tumor nodules greater than 2.5 mm) was statistically significant (p < 0.0001). Evaluating only the patients that could be cytoreduced to CC-0, the 3-year survival was raised to 33.5%. In our experience the peritoneal cancer index (PCI) has been demonstrated to be a weak prognostic factor reaching a statistical significance only after the exclusion of patients with resected hepatic metastases. The patients treated with oxaliplatin were alive and free-of-disease after a 16-month median follow-up.
The pharmacokinetics of flavone acetic acid (FAA) were comparatively studied in Balb-c mice and in immunocompetent nude mice treated with i.v. doses of 100 and 300 mg/kg. In both strains of mice, FAA kinetics appear to be dose-dependent, since the AUC values increased disproportionally to the dose. FAA protein binding and the pattern of distribution were similar in Balb-c and nude mice, the highest drug concentrations being found in liver and small intestine and the lowest in brain. Renal excretion appears to be the major route of FAA elimination in both strains, accounting for about 75% of the total drug administered after a dose of 100 mg/kg and 50-60% after a dose of 300 mg/kg. We conclude that FAA pharmacokinetics are comparable in Balb-c and nude mice so that the previously investigated FAA dosage schedules in inbred mice can also be employed in nude mice bearing human tumors.
In the present study we have shown that erythrocyte-catalyzed 1,8-dinitropyrene reduction occurs via formation of reactive intermediate species, which bind covalently to haemoglobin and other erythrocyte proteins. In fact after mild-acid hydrolysis of lysate proteins exposed to DNP, the reduced metabolites, 1-amino-8-nitropyrene and 1,8-diaminopyrene, were released, thus indicating the formation of sulphinamide adducts to proteins. These results suggest that haemoglobin adduct biomonitoring would be a useful method of controlling exposure to nitroarene in persons at risk.
The DNA content of 59 adenocarcinomas of the stomach in patients who had undergone subtotal or total gastrectomy more than 5 years before was measured. The DNA measurements were done by flow cytometry performed on Propidium Iodide--stained cells disaggregated from paraffin-embedded tissues. Fifty-nine evaluable good quality histograms of DNA ploidy patterns were obtained. The Proliferative Index (PI) was determined in 35 cases. The remaining 24 cases didn't show a reliable reading histograms. Of the 59 tumors, 33 (56%) were diploid and 26 (44%) were aneuploid; 19 showed a high PI (> or = 3.8%) and 16 a lower one. A statistically significant difference was found between the two groups (diploid/aneuploid and low/high PI) compared to the prognostic values known as T, N and Stage. 65% of the T3-T4 cancers, 54% of the N1-N2 lesions and 58% of the stage III and IV were found to be aneuploid. 73.7% of the 19 tumors presenting high PI, showed an aneuploid pattern. A high PI was found in 71.4% of the T3-T4 tumors. 77.4% of patients of the diploid group (any stage) survived at 5 years against 36% of those presenting aneuploid patterns. Patients with PI > or = 3.8% showed a 42.1% 5-year survival rate. A 94.4% 5-year survival rate of diploid and early stage cancers was documented against a 33.5% of aneuploid and advanced stage cancers.
CA 72-4 serum marker has been shown to be one of the most specific and sensitive markers for monitoring gastric cancer. In the present study we evaluated the correlation between CA 72-4, CA 19-9 and CEA serum levels, and tumor size and lymph node involvement in gastric carcinoma patients. One-hundred sixty-one patients with primary or recurrent gastric carcinoma were studied. Elevated CA 72-4, CA 19-9, and CEA serum levels were found in 42.2%, 32.3% and 24.2%, respectively. As previously shown, the combination of CA 72-4 and CA 19-9 increased positive samples to 56.5%, while the addition of CEA did not further improve this percentage. Unlike what has been previously published, none of the markers showed a significant correlation with serosal involvement. In fact, elevated serum levels were observed for the three markers in a very low percentage of cases either in T1-T2N0 or T3-T4N0 patients. In contrast, CA 72-4 showed a highly significant correlation with lymph node involvement: T1-T4N0 patients had positive CA 72-4 levels in 5 out of 37 (13.5%), while T1-T4N1 in 12 out of 32 (37.5%), and T1-T4N2 in 20 out of 40 (50%) (p < 0.003). CA 19-9 and CEA serum levels were not significantly correlated. Since the presence of lymph node metastases is considered a negative prognostic factor, these results suggest that the measurement of CA 72-4 serum levels may be an important parameter in the diagnosis and clinical follow-up of patients with gastric carcinoma.