Preliminary results of a program for the implementation of laparoscopic colorectal surgery in an Italian comprehensive cancer center during the COVID-19 pandemic.

Despite operative benefit and oncological non-inferiority, videolaparoscopic (VLS) colorectal surgery is still relatively underutilized. This study analyzes the results of a program for the implementation of VLS colorectal surgery started in an Italian comprehensive cancer center shortly before COVID-19 outbreak. A prospective database was reviewed. The study period was divided in four phases: Phase-1 (Open surgery), Phase-2 (Discretional phase), Phase-3 (VLS implementation phase), and Phase-4 (VLS consolidation phase). Formal surgical and perioperative protocols were adopted from Phase-3. Postoperative complications were scored by the Clavien-Dindo classification. 414 surgical procedures were performed during Phase-1, 348 during Phase-2, 360 during Phase-3, and 325 during Phase-4. In the four phases, VLS primary colorectal resections increased from 11/214 (5.1%), to 55/163 (33.7%), 85/151 (57.0%), and 109/147 (74.1%), respectively. The difference was statistically significant (P < 0.001). All-type VLS procedures were 16 (3.5%), 61 (16.2%), 103 (27.0%), and 126 (38.6%) (P < 0.001). Conversions to open surgery of attempted laparoscopic colorectal resections were 17/278 in the overall series (6.1%), and 12/207 during Phase-3 and Phase-4 (4.3%). Severe (grades IIIb-to-V) postoperative complications of VLS colorectal resections were 9.1% in Phase-1, 12.7% in Phase-2, 12.8% in Phase-3, and 5.3% in Phase-4 (P = 0.677), with no significant differences with open resections in each of the four phases: 9.4% (P = 0.976), 11.1% (P = 0.799), 13.8% (P = 1.000), and 8.3% (P = 0.729). Despite the difficulties deriving from the COVID-19 outbreak, our experience suggests that volume of laparoscopic colorectal surgery can be significantly and safely increased in a specialized surgical unit by means of strict operative protocols.

Rutin restores adenosine deaminase activity in serum and the liver and improves biochemical parameters in streptozotocin-induced diabetic rats / Rutina restaura a atividade da Adenosina desaminase no soro e no fígado e melhora os parâmetros bioquímicos em ratos diabéticos induzidos por estreptozotocina

ABSTRACT denosine deaminase (ADA) is a critical control point in the regulation of adenosine levels. This study aimed to investigate the effects of a polyphenolic flavonoid, rutin, on the activity of ADA in serum, the cerebral cortex, liver, kidney, and biochemical parameters in diabetic rats. The animals were divided into four groups (n=6) for the following treatments: control; diabetic (streptozotocin 55 mg/kg); diabetic with rutin (100 mg/kg/day); diabetic with glibenclamide (10 mg/kg/day). After 30 days, ADA activity and biochemical parameters were analyzed. The ADA activity in the serum was significantly elevated in the diabetic group compared to the control group (p<0.01). The treatment with rutin prevented the increase in ADA activity in the STZ-induced rats when compared to control group. Our data showed that rutin reduced glucose, LDL levels, and hepatic enzymes in comparison with the control group. These results demonstrate that the increase of ADA activity observed in diabetic rats may be an important indicator of the immunopathogenesis of hyperglycemic disorders and suggest that rutin is important for regulating the enzymatic activities associated with immune, hyperglycemic, and inflammatory response in diabetes mellitus.

RESUMO A Adenosina desaminase (ADA) representa um ponto de controle crítico na regulação dos níveis de adenosina. A rutina, um flavonóide polifenólico presente em muitas plantas, foi testado para verificar a sua influência na atividade da ADA no soro, córtex cerebral, fígado rim e parâmetros bioquímicos em ratos diabéticos. Os animais foram divididos em quatro grupos cada grupo com 6 animais), tal como: controle; diabética (estreptozotocina 55 mg/kg); diabética + rutina (100 mg/kg/dia); diabético + glibenclamida (10 mg/kg/dia). Após 30 dias foram analisadas a atividade da ADA sérica e tecidual e parâmetros bioquímicos. A atividade de ADA no soro foi significativamente elevada no grupo diabético quando comparado ao grupo controle (p<0,01). O tratamento com Rutina preveniu o aumento na atividade da ADA nos ratos diabéticos, quando comparado com o grupo controle. Os resultados mostraram que a rutina reduziu a glicose, os níveis de LDL e as enzimas hepáticas, em comparação com o grupo controle. Estes resultados mostram que o aumento da atividade da ADA observado em ratos diabéticos pode ser um indicador importante da imuno-patogênese de perturbações hiperglicêmicas e sugerem que a Rutina é importante na regulação das atividades enzimáticas associadas com a resposta imunitária, hiperglicêmica e inflamatória no Diabetes mellitus.

Differential effects of organic and inorganic selenium compounds on adenosine deaminase activity and scavenger capacity in cerebral cortex slices of young rats.

Selenium (Se) has anti-inflammatory and antioxidant properties and is necessary for the development and normal function of the central nervous system. This study was aimed to compare the in vitro effects of 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one (C21H2HOSe; organoselenium) and sodium selenate (inorganic Se) on adenosine deaminase (ADA) activity, cell viability, lipid peroxidation, scavenger of nitric oxide (NO) and nonprotein thiols (NP-SH) content in the cerebral cortex slices of the young rats. A decrease in ADA activity was observed when the slices were exposed to organoselenium at the concentrations of 1, 10 and 30 µM. The same compound showed higher scavenger capacity of NO than the inorganic compound. Inorganic Se was able to protect against sodium nitroprusside-induced oxidative damage and increased the NP-SH content. Both the compounds displayed distinctive antioxidant capacities and were not cytotoxic for the cerebral cortex slices in the conditions tested. These findings are likely to be related to immunomodulatory and antioxidant properties of this compound.

Transhepatic contemporary palliation of biliary and duodenal stenoses by means of metallic stents.

We describe the treatment of a stenosing lesion of the horizontal duodenum by means of a large-bore metallic stent inserted percutaneously in a patient with transhepatic biliary drainage. In the same session, we used an expandable metallic stent in the biliary tree to relieve jaundice. We recommend the transhepatic approach for duodenal metallic stent insertion in patients with percutaneous biliary drainage.

Surgical treatment of gastric metastases from cutaneous melanoma: experience of the National Cancer Institute of Milan.

AIM: To evaluate the role of a surgical approach in patients affected with gastric metastases from cutaneous melanoma. METHODS: A retrospective review of our local melanoma database of 2100 patients identified 31 cases with gastric metastatic deposits. Nine of them were considered candidates for surgical resection. RESULTS: Median overall survival of the 9 patients who underwent surgery was 14.2 months. Six (67%) underwent a local radical resection of disease, and 3 (33%) had a simple exploratory laparotomy. The median survival was 21.6 months (range, 4-32 months) for the subset receiving radical surgery and 3.6 months (range, 2-6 months) for the patients who had no resection. Median follow-up was 14.2 months. No specific correlation of serologic LDH levels and final outcome, as documented elsewhere, was observed. A marked decreased or substantial remission of symptoms with an improvement in quality of life was observed in all radically resected patients. CONCLUSIONS: Patients with gastric metastases from melanoma may benefit from surgery if all macroscopic disease can be removed. In addition, gastric resection in patients with symptomatic melanoma spread to the stomach provides important symptomatic palliation.

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 > or =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 > or =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 > or =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.

Double-contrast barium enema and computerised tomography in the pre-operative evaluation of rectal carcinoma: are they still useful diagnostic procedures?

PURPOSE: In modern management of rectal carcinoma, the preoperative evaluation of disease parameters is important for selection of therapeutic options. Such parameters are currently defined through endorectal ultrasonography or endoscopic ultrasonography. A retrospective analysis of the parameters obtained with double-contrast barium enema (DCBE) and endorectal balloon computed tomography (CT) was conducted to verify the diagnostic reliability of the radiological techniques and to establish whether there is still an indication for their use. METHODS: 53 consecutive patients with adenocarcinoma of the distal half of the rectal ampulla underwent double contrast barium enema examination and CT of the pelvis with endorectal balloon. On the basis of the DCBE and CT assessment we evaluated: 1) the distance between the cranial extremity of the anal canal and the distal margin of the neoplasm; 2) the radial diffusion of the tumor; 3) the metastatic involvement of the perirectal and inferior mesenteric lymph nodes. RESULTS: 1) CT and DBCE measurements of the distal margin tended to coincide, but both tended to overestimate the measurement when compared to the pathologic examination; 2) in the identification of neoplastic infiltration of perirectal fat (T3) CT had 100% sensitivity, 78.7% specificity and 86.8% accuracy; 3) the CT sensitivity for detecting lymph node metastasis was 52.6%, specificity 85.3% and accuracy 73.6%. CONCLUSIONS: The diagnostic information provided by the radiological examinations is comparable to that of clinical and instrumental methods currently employed for staging of rectal carcinoma, although the latter are preferred because they are more readily accessible and less costly. DCBE and CT can therefore be usefully employed for staging of cancer of the rectum in those cases in which there are limitations of the current standard methods.

Diagnostic and interventional radiology in the post-operative period and follow-up of patients after rectal resection with coloanal anastomosis.

Surgical treatment of carcinoma of the distal third of the rectum with anal sphincter preservation is increasingly used in accredited cancer centers. This study aimed to evaluate the diagnostic usefulness of radiological investigations in the management of patients who had undergone resection with coloanal anastomosis for carcinoma of the rectum, in the immediate post-operative period, during closure of the protective colostomy and in the follow-up of symptomatic recanalized patients. A total of 175 patients who had undergone total rectal resection with end-to-side anastomosis for carcinoma of the distal third of the rectal ampulla, most of whom had received postoperative radiotherapy, were evaluated radiologically. In the postoperative period radiological investigation was ordered only for symptomatic patients to detect pathology of the anastomosis and the pouch sutures and was used direct film abdominal radiography and contrast-enhanced radiography of the rectal stump with a water-soluble radio-opaque agent. Before closure of the colostomy, 2 months after rectal excision or approximately 4 months after if postoperative radiotherapy was given, the anastomosis and pouch of all patients, even asymptomatic ones, were studied with water-soluble contrast enema to check for normal canalization. In the follow-up after recanalization radiological examinations were done to complete the study of the large intestine if the endoscopist was not able to examine it up to the cecum. Of the 175 patients examined radiologically during the postoperative period and/or subsequent follow-up, 95 showed no pathological findings. Seventy-nine patients had fistulas of the coloanal anastomosis or the pouch, 23 of which supplied a presacral collection. In the absence of severe sepsis, the only therapeutic measures were systemic antibiotics and washing of the surgical catheters to maintain efficient operation. In 2 patients in whom transanal drainage was performed radiologically the fistula was cured in 1 week. In 36 cases of cicatricial stenosis, 17 at the coloanal anastomosis and 19 at the pouch, radiological examination always detected the lesion, correctly defining its anatomical characterisitics, nature and extension. Of the 19 cases of stenosis treated radiologically, 15 recovered an adequate intestinal calibre for tients operated on, 21 cases of reccurrence were detected. Radiological examination was requested as the first investigation in only one of these cases, for a patient with subocclusion. Radiological investigations in patients who have undergone colonanal anastomosis are of read diagnostic value in the immediate post-operative period, during closure of the protective colostomy and in the follow-up of symptomatic recanalized patients.

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.

Early gastric cancer: unrecognized indicator of multiple malignancies.

The aim of this study was to evaluate the postoperative outcome and occurrence of second primary malignancies in patients who underwent radical resection for early gastric cancer. Altogether 105 patients with early gastric cancer underwent radical resection and were followed up for a median period of 71 months. Overall lethality was analyzed with regard to mortality due to gastric cancer or other causes. Standardized mortality and morbidity ratios were calculated using data from the Tumor Registry of Lombardy. The 5-year survival rate was 82.8% (operative mortality excluded), which was not different from that expected from an age- and sex-matched Italian population. Ten second primary malignancies were identified, giving a standardized mortality ratio of 1.12 and a standardized morbidity ratio of 1.50. Patients undergoing surgery for early gastric cancer (especially the intestinal type) may have a circa 50% higher risk of a second tumor and should be periodically checked for other tumors, mainly in the supramesocolic area.

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.

Subtotal versus total gastrectomy for gastric cancer: five-year survival rates in a multicenter randomized Italian trial. Italian Gastrointestinal Tumor Study Group.

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.

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 polychemotherapy 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 patient's 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.

Total versus subtotal gastrectomy: surgical morbidity and mortality rates in a multicenter Italian randomized trial. The Italian Gastrointestinal Tumor Study Group.

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.

Comparing reconstruction with Roux-en-Y to a pouch following total gastrectomy.

BACKGROUND: Although more than 50 methods of gastric replacement after total gastrectomy have been used, none of them has demonstrated a substantial nutritional advantage. The Roux-en-Y esophagojejunostomy is still the preferred type of reconstruction, more because of its simplicity than the lack of postprandial disturbances. STUDY DESIGN: A randomized controlled trial was conducted to compare two reconstructive procedures, Roux-en-Y esophagojejunostomy (n = 24) and Hunt-Rodino-Lawrence pouch (HRL, n = 24), by evaluating nutritional status (body weight, arm circumference, and serum nutritional parameters), nutritional habits (number of meals, energy intake, and postprandial disturbances), and emptying time of the jejunal loop. RESULTS: Twenty-seven patients were studied two years after operation (12 had undergone Roux-en-Y and 15 had undergone HRL). No difference was found in either postoperative morbidity or mortality, emptying time, frequency of meals, or variation of body weight. Postprandial disturbances were more frequent in patients having Roux-en-Y. In a subset of patients, there was a correlation between nutrient intake and change of body weight, but not between nutrient intake and type of reconstruction. CONCLUSIONS: The simple use of a reservoir such as the HRL pouch after total gastrectomy is of no benefit to the patient as compared with the Roux-en-Y reconstruction.