Giuliano Bonfanti

Subtotal Versus Total Gastrectomy for Gastric Cancer: Five-Year Survival Rates in a Multicenter Randomized Italian Trial

OBJECTIVE To evaluate the impact of subtotal (SG) versus total (TG) gastrectomy on the oncologic outcome of patients with cancer of the distal stomach from 28 Italian institutions. SUMMARY BACKGROUND DATA There is controversy over whether SG and TG have a different impact on the 5-year survival probability of patients with cancer of the distal half of the stomach. METHODS The present analysis involved 618 patients randomized during surgery to SG (315) or TG (303), provided there was at least 6 cm from the proximal edge of the tumor to the cardia, there was no intrapertoneal or distant spread, and it was possible to remove the tumor entirely. Both surgical treatments included regional lymphadenectomy. RESULTS Four patients died after SG and seven after TG. Median follow-up was 72 months after SG (range 2 to 125) and 75 months after TG (range 7 to 113). Five-year survival probability as computed by the Kaplan-Meier method was 65.3% for SG and 62.4% for TG. The test of equivalence led to the conclusion that the two procedures may be considered equivalent in terms of 5-year survival probability. The analysis of survival using a multivariate Cox regression model showed a statistically significant impact on survival of tumor site, tumor spread within the gastric wall, extent of resection to the spleen plus or minus neighboring organs or structures, and relative frequency of metastasis in resected lymph nodes. CONCLUSIONS Both procedures have a similar survival probability. The authors believe that SG, which has been reported to be associated with a better nutritional status and quality of life, should be the procedure of choice, provided that the proximal margin of the resection falls in healthy tissue.

Perioperative Total Parenteral Nutrition in Malnourished, Gastrointestinal Cancer Patients: A Randomized, Clinical Trial

BACKGROUND Clinical trials investigating the potential benefits of perioperative total parenteral nutrition (TPN) for reducing the risk of surgery in malnourished cancer patients have yielded controversial results. METHODS Ninety elective surgical patients with gastric or colorectal tumors and weight loss of 10% or more of usual body weight were randomly assigned to 10 days of preoperative and 9 days of postoperative nutrition vs a simple control group. The daily per kilogram body weight TPN regimen included 34.6 +/- 6.3 kcal nonprotein and 0.25 +/- 0.04 g nitrogen per kilogram in a volume of 42.6 +/- 7.3 mL of fluid. The glucose-to-fat calorie ratio was 70:30. Control patients did not receive preoperative nutrition but received 940 kcal nonprotein plus 85 g amino acids postoperatively. RESULTS Complications occurred in 37% of the patients receiving TPN vs 57% of the control patients (p = .03). Noninfectious complications mainly accounted for this difference, which was 12% vs 34%, respectively (p = .02). Mortality occurred in only 5 of the control group patients (p = .05). The total length of hospitalization for TPN patients was longer than for control (p = .00), whereas the length of postoperative stay in the two groups did not differ significantly. CONCLUSIONS This study shows that 10 days of preoperative TPN that is continued postoperatively is able to reduce the complication rate by approximately one third and to prevent mortality in severely malnourished patients with gastrointestinal cancer.

Total Versus Subtotal Gastrectomy: Surgical Morbidity and Mortality Rates in a Multicenter Italian Randomized Trial

OBJECTIVE The purpose of this study was to analyze postoperative morbidity and mortality of patients included in a randomized trial comparing total versus subtotal gastrectomy for gastric cancer. SUMMARY BACKGROUND DATA There is controversy as to whether the optimal surgery for gastric cancer in the distal half of the stomach is subtotal or total gastrectomy. Although only a randomized trial can resolve this oncologic dilemma, the first step is to demonstrate whether the two procedures are penalized by different postoperative morbidity and mortality rates. METHODS A total of 624 patients with cancer in the distal half of the stomach were randomized to subtotal gastrectomy (320) or total gastrectomy (304), both associated with a second-level lymphadenectomy, in a multicenter trial aimed at assessing the oncologic outcome after the two procedures. The end points considered were the occurrence of a postoperative event, complication, or death and length of postoperative stay. RESULTS Nonfatal complications and death occurred in 9% and 1% of subtotal gastrectomy patients and in 13% and 2% of total gastrectomy patients, respectively. Multivariate analysis of postoperative events showed that splenectomy or resection of adjacent organs was associated with a twofold risk of postoperative complications. Random surgery and extension of surgery influenced the length of stay. The mean length of stay, adjusted for extension of surgery, was 13.8 days for subtotal gastrectomy and 15.4 days for total gastrectomy. CONCLUSIONS Our data show that subtotal and total gastrectomies, with second-level lymphadenectomy, performed as an elective procedure have a similar postoperative complication rate and surgical outcome. A conclusive long-term evaluation of the two operations and an accurate estimate of the oncologic impact of surgery on long-term survival, not penalized by excess surgical risk of one of the two operations, are consequently feasible.

Adequacy of margins of resection in gastrectomy for cancer.

This study determines the infiltration rate of proximal and distal margins of resection in patients operated on for gastric cancer at the Istituto Nazionale Tumori of Milan. Two hundred and eighty-five proximal margins and 286 distal margins were reviewed, and the incidence of infiltration was related to the length of grossly tumor-free edge, the location, site, size, and gross appearance of the tumor, degree of invasion of the gastric wall, histologic type, and status of perigastric lymph nodes. Infiltration occurred in 7.3% of oral margins of transection and in 2.6% of aboral margins. Except for the degree of invasion of the gastric wall, no correlation was found among the infiltration rate and the above parameters. In fact, the incidence of infiltration of the proximal edge was significantly higher (6.4% vs. 0.8%, p < 0.01) when the tumor penetrated the serosa or spread beyond it than when the lesion was confined to the mucosa, submucosa, or muscular layer. With reference to the length of margin of resection, it is noteworthy that no involvement was found when cranial distance between the lesion and line of transection was equal to or greater than 6 cm. Proximal or distal infiltration for a distance greater than 3 cm did not occur in patients with lesions confined to the mucosa, submucosa, and muscularis. This data should provide the surgeon with a rational basis for assessing the extent of resection when performing gastrectomy for cancer.

Intrahepatic chemotherapy for unresectable hepatocellular carcinoma

From 1976 to 1983, 28 patients (24 male and four female) with unresectable hepatocellular carcinoma (HCC) were treated by intraarterial chemotherapy at the Istituto Nazionale Tumori of Milan, Milan, Italy. Tumors were retrospectively classified by a previously proposed staging system. Two patients were classified as Stage I and 26 as Stage II. Liver cirrhosis was present only in the males (in 50% of them). Nineteen patients were treated with doxorubicin (Adriamycin [Adria Laboratories, Columbus, OH]) and nine with 5‐fluorouraciI. Systemic toxicity was mild, but the treatment induced hepatic toxicity (ascites, clinical jaundice, or biochemical impairment) in 18% of noncirrhotic and 66% of cirrhotic patients. Clinical reduction of hepatomegaly was observed in 50% of noncirrhotic versus 16% of cirrhotic patients. Doxorubicin was effective in 66% of noncirrhotic patients and 20% of cirrhotic patients, with an overall response rate of 42%. 5‐fluorouracil was effective only in patients without cirrhosis, with an overall response rate of 22%. Overall median actuarial survival was 3.5 months, with a significant difference between noncirrhotic and cirrhotic patients (6 versus 2 months, respectively). Overall median survival of patients who responded to the treatment was 13 versus 2 months for nonresponders (P < 0.001). Liver cirrhosis was the most important prognostic factor in terms of liver toxicity, response rate, and survival. This study emphasized the negative impact of the treatment on cirrhotic patients. Also, the real value of intraarterial administration of doxorubicin was investigated.

Nutritional support in patients with cancer of the esophagus: Impact on nutritional status, patient compliance to therapy, and survival

Aims and background The multimodal approach to patients with esophageal squamous cell carcinoma often includes poly-chemotherapy combined with radiation therapy. Cancer dysphagia and drug-related anorexia, mucositis and vomiting can all lead to malnutrition. The aim of this study was to analyze the impact of the administration of enteral nutrition (EN) on the patients nutritional status, tolerance of chemotherapy and radiotherapy, and final oncological outcome. Methods Fifty esophageal cancer patients who were to be submitted to chemotherapy (days 1-4 5-fluorouracil (FU) 1 g/m2/day and cisplatin (CDDP) 100 mg/m2/day 1) for two cycles plus radiotherapy (31 Gy) were referred to the Nutrition Support Unit prior to any therapy due to their malnourished status. Twenty-nine dysphagic patients received nutrition via tube (37 kcal/kg/day + 2.0 g proteins/kg/day for 34 days), while 21 others who were not dysphagic were given a standard oral diet (SD). The patients who received EN had a more severe weight loss than the SD patients (16.8% vs 12.8%, P <0.02). Results The dose of administered EN represented 86% of the planned support, and 70% of the nutritional therapy was administered in the home setting. Administration of EN support resulted in stable body weight and unchanged levels of visceral proteins, while SD patients had a decrease in body weight, total proteins and serum albumin (P <0.01). There was no difference between the two groups in terms of tolerance and response to cancer therapy, suitability for radical resection and median survival (9.5 months). Conclusions EN in patients with cancer of the esophagus undergoing chemotherapy and radiotherapy is well tolerated, feasible even in the home setting, prevents further nutritional deterioration and achieves the same oncological results in dysphagic patients as those achieved in non-dysphagic patients.

Adenocarcinoma of the Lower Third of the Rectum Surgically Treated With a <10-MM Distal Clearance: Preliminary Results in 35 N0 Patients

Background: Recent reports suggest that a distal clearance (DC) of 10 mm at the lower surgical margin may be considered adequate in the surgical treatment of rectal cancer, but there are no data on the possible adequacy of a <10-mm DC in N0 patients in whom a good prognosis can otherwise be expected, that is, those with negative surgical margins and negative lymph nodes.Methods: Between November 1991 and December 1998, 154 consecutive patients with adenocarcinoma of the lower third of the rectum had a total rectal resection with total mesorectal excision and coloendoanal anastomosis. Among 76 N0 patients, there were 35 with <10-mm DC and 41 with ≥10-mm DC. Each group was divided into two subgroups depending on whether the surgical margins were involved or not, and the rate of local recurrence in the various categories was compared. All B2 Astler-Coller stage patients in the series received postsurgical chemoradiotherapy.Results: The local recurrence rate in the 35 patients with DC <10 mm was 11.4% and that of the 41 patients with DC ≥10 mm was 7.3%. When only patients with negative surgical margins were considered, the local recurrence rate was 3.4% for those with <10-mm DC and 5.1% for those with ≥10-mm DC.Conclusions: Our results suggest that a radical surgery with <10-mm DC followed by chemoradiotherapy may be adequate in N0 patients, provided that a careful pathologic examination of the surgical specimen excludes the presence of lymph node metastases and that the distal rectal and mesorectal resection margins fall in healthy tissue.

A phase II study of mitoxantrone combined with beta-interferon in unresectable hepatocellular carcinoma

Background. Chemoimmunotherapy is being evaluated in the most common gastrointestinal tumors, but little data are available on hepatocellular carcinoma (HCC). Considering the encouraging objective response rates and the absence of important side effects obtained with mitoxantrone in HCC, we tested the activity and feasibility of a schedule combining beta‐interferon (β‐IFN) and mitoxantrone.

Total rectal resection and complete mesorectum excision followed by coloendoanal anastomosis as the optimal treatment for low rectal cancer: the experience of the National Cancer Institute of Milano.

Background: At present, abdominoperineal resection remains the most diffuse method of treatment of very low rectal cancer. Today, we can avoid this method in some patients by using a sphincter-saving procedure.Methods: From March 1990 to January 1999, 273 consecutive total rectal resections and coloendoanal anastomoses were performed at our Institute; this study concerns 141 consecutive patients treated for a primary adenocarcinoma of the distal rectum, from 3.5 to 8 cm from the anal verge. Patient stratification, based on definitive pathological report, was 31 Dukes’ stage A (T2N0), 44 stage B (T3N0), and 66 stage C (T2N+−T3N+).Results: Overall recurrence rate was 9.2%; postoperative morbidity attributable to the procedure was low. A perfect continence was documented in 61% of cases. The only pathological factor related to local recurrence rate is peritumoral lymphocytic reaction inside and around the tumor (P = .0005 and .031) independently from the number of metastatic lymph nodes, depth of fatty tissue infiltration, and lymphatic and venous neoplastic emboli. The minimum follow-up time is 12 months.Conclusions: Our data, in accordance with other authors, seem to highlight the relevant role that a well-practiced surgery, together with accurate information on the spreading of this disease, has in achieving an optimal local control of cancer.

Blood Culture as a Guide for the Diagnosis of Central Venous Catheter Sepsis

The purpose of this study was to evaluate the predictability of peripheral (PBC) and central blood cultures (CBC) in the diagnosis of central venous catheter (CVC) sepsis (growth of the same microorganism in the peripheral blood and on the catheter tip). The contamination and sepsis rate of 256 CVCs and the relationship with PBC and CBC was evaluated in a series of cancer patients included in a prospective protocol on CVC infections at the Istituto Nazionale Tumori of Milan. Overall CVC contamination was 10.5% and sepsis rate was 3.1%. The positive predictive value for CVC sepsis was 46.7% for positive PBC + CBC, 38.1% for positive PBC and 16.6% for positive CBC. The small gain in the predictive positive value obtained with the use of PBC and CBC and the slight increase in the specificity does not justify, in our opinion, the use of both these parameters for the diagnosis of CVC sepsis.