Necessity of therapy for post-thyroidectomy hypocalcaemia: a multi-centre experience.

PURPOSE: Hypoparathyroidism is one of the most common and most feared complications of total thyroidectomy (TT). The aim of this study is to detect possible markers that may facilitate early tracing of hypocalcaemia-prone patients in order to reduce clinical cost by optimizing patient discharge and to avoid unnecessary treatment. METHODS: Over an 18-month period, 995 patients, 23 % male and 77 % female, aged 52.9 ± 13.4 years, underwent TT in ten Lombardy hospitals. The following parameters were analyzed: calcaemia before and 12-24 and 48 h after surgery, pre- and post-operative parathyroid hormone (PTH) at 24 h and pre-operative 25OH vitamin D. RESULTS: Mortality was nil and morbidity was 22.4 %. Mean 24-h calcaemia and PTH were 2.17 ± 0.15 mmol/l and 31.81 ± 20.35 pg/ml, respectively; mean 24-h PTH decay was 36.7 ± 34.12 %. Four hundred seventy-three (47.5 %) patients were hypocalcaemic at discharge; 142 of whom had transient hypoparathyroidism that became permanent in 27. Patients developing hypocalcaemia had significantly higher values of PTH and calcium decay. At multiple logistic regression, only 24-h calcium decay, PTH drop and the presence of symptoms and parathyroid auto-grafting were significantly related to hypoparathyroidism. The association of these factors had a 99.2 % negative predictive value (NPV) for the development of hypoparathyroidism. A 70 % PTH drop had a 93.75 NPV for transient hypoparathyroidism. A 12 % calcaemia decay had a 95.7 NPV for hypoparathyroidism. CONCLUSIONS: Hypocalcaemic asymptomatic patients with less than 70 % PTH and 12 % calcaemia decay may be safely discharged without treatment. Symptomatic patients and those with parathyroid grafting should receive calcium and vitamin D.

Peritonectomy and hyperthermic intraperitoneal chemotherapy: cost analysis and sustainability.

BACKGROUND: Malignancies of the peritoneum remain a challenge in any hospital that accepts to manage them, due not only to difficulties associated with the complexity of the procedures involved but also the costs, which - in Italy and other countries that use a diagnosis-related group (DRG) system - are not adequately reimbursed. MATERIAL AND METHODS: We analyzed data relative to 24 patients operated on between September 2010 and May 2013 with special regard to operating room expenditure, ICU stay, duration of hospitalization, and DRG reimbursement. The total costs per patient included clinical, operating room, procedure, pathology, imaging, ward care, allied healthcare, pharmaceutical, and ICU costs. RESULTS: Postoperative hospital stay, drugs and materials, and operating room occupancy were the main factors affecting the expenditure for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. We had a median hospitalization of 14 days, median ICU stay of 2.4 days, and median operating room occupancy of 585 min. The median expenditure for each case was € 21,744; the median reimbursement by the national health system € 8,375. CONCLUSIONS: In a DRG reimbursement system, the economic effort in the management of patients undergoing peritonectomy procedures may not be counterbalanced by adequate reimbursement. Joint efforts between medical and administration parties are mandatory to develop appropriate treatment protocols and keep down the costs.

Sentinel lymph node biopsy in gastric cancer: possible applications and limits.

AIMS: To explore the feasibility and accuracy of sentinel lymph node (SLN) biopsy in gastric cancer. PATIENTS AND METHODS: Twenty-nine patients with clinical T1 and T2 N0 M0 gastric cancer less than 5 cm in diameter underwent SLN biopsy with the intraoperative Patent blue method. The procedure continued with radical gastrectomy and D2 lymphadenectomy. We investigated all technical aspects of the blue dye technique and determined the accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the SLN technique. RESULTS: SLNs were detected in 28 of 29 patients; the total number of excised SLNs was 45, with a median of two (range 1-3). Seventeen patients had metastatic SLN, with 21 lymph nodes retrieved. Twenty-two patients had SLNs located at the first level. Four patients had SLNs at the second level, one at the first and second levels, and one at the first and third levels. Five patients had false negative SLNs. The ability of SLN biopsy to predict the status of the other lymph nodes was summarised by an accuracy of 75%, a sensitivity of 75%, a specificity of 75%, a positive predictive value of 88%, and a negative predictive value of 55%. CONCLUSIONS: Our study demonstrates that pick-up SLN biopsy in gastric cancer is technically feasible but has very low sensitivity. Regarding the utility of SLN navigation when attempting to detect the nodal basin, the high rate of false negative SLNs and lymph node level jumping warrant further studies with a large accrual before the method can be introduced into daily practice.

Metabolic effects of intraportal nutrition in humans.

OBJECTIVE: We investigated the metabolic effects of intravenous nutrition through a portal (PN) or systemic (SN) peripheral vein. METHODS: Twenty patients were randomized to receive PN or SN nutrition after colorectal surgery. The daily regimen included 900 kcal and 100 g of amino acid (AA). Visceral proteins and hepatic enzymes were measured on days 0, 1, 3, 5, and 7, and plasma arterovenous differences and limb flux of AA were measured on days 0, 3, and 7; urinary nitrogen and 3-CH3-histidine were analyzed daily. RESULTS: Serum albumin on day 7 was still depressed (P = 0.01) in SN and fully restored in PN patients. Prealbumin levels increased significantly (P = 0.05) in the PN group only. Plasma levels of glutamine and asparagine were higher in PN than in SN patients, and this difference was statistically significant (P = 0.05). SN patients had significantly more negative limb-muscle balance of valine and tyrosine, whereas PN patients had a higher muscle release of citrulline and taurine. CONCLUSIONS: In conclusion, short-term PN is safe and has some metabolic benefits: it accelerates recovery from postoperative hypoalbuminemia and hypopnealbuminemia and is associated with a higher plasma level of glutamine and an AA plasma pattern that is closer to normal. PN blunts the catabolic response of the muscle, decreasing loss of proteins and release of some AA involved in hepatic gluconeogenesis.

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 parenteral nutrition and tumor growth in malnourished patients with gastric cancer.

AIMS AND BACKGROUND: Evidence that total parenteral nutrition (TPN) can stimulate tumor growth in humans is scanty and contradictory. The purpose of this study was to evaluate the impact of TPN on tumor cell proliferation in malnourished patients receiving preoperative TPN. METHODS: We evaluated variations in the S-phase cell fraction, defined as 3H-thymidine labeling index (TLI), before and after 10 days of TPN or non-administration of nutritional support in 19 malnourished patients (weight loss, > or = 10%) with gastric cancer. TLI was determined on endoscopic biopsies at the time of diagnosis, and subsequently on the operative specimen or through intraoperative sampling. RESULTS: At diagnosis, a higher median TLI value was observed in the control than in the TPN group. Administration of TPN enhanced tumor cell proliferation in 50% of patients; however, at surgery there was no difference in the median TLI value of the two groups. CONCLUSIONS: The TPN regimen seems to be associated with increased tumor cell proliferation, even though this stimulating effect was moderate and at surgery the TLIs of TPN patients and controls were not different. Although the potential stimulation probably has little consequence for patients receiving short-term preoperative nutrition, it may call for further investigation in cancer patients undergoing long-term home TPN.

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.

Outcome of cancer patients receiving home parenteral nutrition. Italian Society of Parenteral and Enteral Nutrition (S.I.N.P.E.).

BACKGROUND: Indication for home parenteral nutrition (HPN) in cancer patients is controversial because intestinal failure and malnutrition are often only two of the many problems found in such patients that may deserve priority of treatment. METHODS: This was a retrospective study of 75 cancer patients from nine institutions included in the Italian HPN Registry. The patients had a mean weight loss of 12.5%, serum albumin of 3.1 g/dL, lymphocyte count of 1150/mm3, and serum total iron-binding capacity of 190 micrograms/dL. The main indication for HPN was intestinal obstruction (66%); 72% of the patients had metastatic disease. A series of demographic, oncologic, and nutritional characteristics were analyzed in an attempt to predict a possible benefit of HPN. RESULTS: A total of 9897 days of HPN were delivered to 75 cancer patients, for a median of 4 months (range 1 to 15 months) per patient. Sixty-nine patients died while receiving HPN, five had a remission of their intestinal failure, and one chose to stop the treatment. Complications related to parenteral nutrition were as follows: 19 cases of sepsis, 6 catheter occlusions, 4 catheter dislocations, and 2 metabolic imbalances. HPN preserved nutritional status and slightly improved weight, lymphocyte count, serum albumin, and Karnofsky performance status in patients who survived > 3 months. Quality of life during HPN was judged by the clinicians to have improved in only 9% of those who survived < 3 months, but in 68% of the patients who survived for > 3 months. Karnofsky performance status > 50 at the start of HPN was correlated with longer survival (p = .02). CONCLUSIONS: Our study demonstrated a positive effect of HPN on nutritional status and quality of life in patients who survived > 3 months and suggests that HPN should be avoided when Karnofsky performance status is < 50.

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.

Total nutritional manipulation in humans: report of a cancer patient.

We report here on a patient requiring home total parenteral nutrition (TPN) for a huge intra-abdominal desmoid associated with chronic small bowel pseudo-obstruction who was kept on a special lipid-based calorie regimen for 5 months. The rationale was to attempt to feed the host with a minimal stimulation of tumour growth by using lipid as caloric substrate instead of glucose which is utilized by the tumour. Gluconeogenesis was tentatively inhibited at the level of phosphoenolpyruvate-carboxy-kinase through the oral intake of hydrazine sulphate. The regimen consisted of 28 non-protein lipid Kcal/kg/day plus 1.5 g amino acid per kg/day. Only a small amount of glucose (approx. 40 g/day) was allowed. Tolerance to the regimen was good and body weight maintained. Liver enzymes remained within the normal range and liver sonography was normal throughout the 5 months' therapy and there were no episodes of symptomatic hypoglycaemia. The tumour volume did not substantially change.

Guidelines on artificial nutrition versus hydration in terminal cancer patients. European Association for Palliative Care.

Whether a terminally ill cancer patient should be actively fed or simply hydrated through subcutaneous or intravenous infusion of isotonic fluids is a matter of ongoing controversy among clinicians involved in the care of these patients. Under the auspices of the European Association for Palliative Care, a committee of experts developed guidelines to help clinicians make a reasonable decision on what type of nutritional support should be provided on a case-by-case basis. It was acknowledged that part of the controversy related to the definition of the terminal cancer patient, since this is a heterogeneous group of patients with different needs, expectations, and potential for a medical intervention. A major difficulty is the prediction of life expectancy and the patient's likely response to vigorous nutritional support. In an attempt to reach a decision on the type of treatment support (artificial nutrition vs. hydration) which would best meet the needs and expectations of the patient, we propose a three-step process: Step 1: define the eight key elements necessary to reach a decision; Step II: make the decision; and Step III: reevaluate the patient and the proposed treatment at specified intervals. Step I involves assessing the patient concerning the following: 1) oncological/clinical condition; 2) symptoms; 3) expected length of survival; 4) hydration and nutritional status; 5) spontaneous or voluntary nutrient intake; 6) psychological profile; 7) gut function and potential route of administration; and 8) need for special services based on type of nutritional support prescribed. Step II involves the overall assessment of pros and cons, based on information determined in Step I, in order to reach an appropriate decision based on a well-defined end point (i.e., improvement of quality of life; maintaining patient survival; attaining rehydration). Step III involves the periodic reevaluation of the decision made in Step II based on the proposed goal and the attained result.

Restorative effect of total parenteral nutrition on natural killer cell activity in malnourished cancer patients.

Decreased natural killer cell activity (NKCA) is associated with malnutrition in both cancer and non-cancer patients. We have studied the effect of total parenteral nutrition (TPN) on NKCA in 9 malnourished cancer patients, candidates for surgery. TPN was administered for a median of 10 days (range 7-11), providing 1.5-fold the estimated resting energy expenditure, with 30% as fat. Calorie:nitrogen ratio was 150:1. Basal human recombinant interferon-alpha 2a (rIFN-alpha 2a) and human recombinant IL-2 rIL-2) activated NKCA were measured, as were the main nutritional parameters, prior to and after TPN. NKCA increased in all patients and reached the normal range in 5, 3 and 4 subjects, respectively, for basal, rIFN-alpha 2a and rIL-2 activated NKCA. As regards nutritional assessment, body weight and IgM levels significantly increased from 47.7 to 50.1 kg and from 174 to 237 mg/dl, respectively. This study demonstrates that a 10-day TPN course increases and sometimes restores normal NKCA. Such effect was constant and preceded nutritional changes.

Relationship between nutritional status and tumor growth in humans.

AIMS AND BACKGROUND: There is considerable evidence from studies on tumor-bearing animals that nutritional support aimed at maintaining a good nutritional status can indeed promote tumor growth. Experience in humans, however, is scanty and controversial, this issue never having been extensively investigated. The purpose of this study was to analyze whether there exists a relationship between nutritional status and tumor growth in patients with non-Hodgkin's lymphoma. The hypothesis behind it was that if it is true than an abundant availability of substrates promotes tumoral growth, then the better the nutritional status the higher the tumor cell proliferation. METHODS: Two hundred and forty six adult patients with non-Hodgkin's lymphoma were characterized according to nutritional status (percent of weight loss as compared to usual body weight, serum albumin, serum cholinesterase, number of lymphocytes) and rate of incorporation of 3H thymidine labelling index in the tumor tissue. The values of serum albumin, serum cholinesterase and lymphocytes were subdivided into three classes adopting as cut-off points the tertile values of their distribution, while weight loss was scored as a "no" and a "yes". The association between nutritional parameters and labelling index was evaluated by a univariate analysis (X2 test and Mantel-Haenszel X2 test and the odds ratio) and by a logistic multiple regression model. RESULTS: Results of the univariate analysis show a statistically significant association between "poor" nutritional status (depressed nutritional indexes) and "high" labelling index (increased tumoural growth), while the multiple regression analysis found that the only significant association was that between low serum cholinesterase and high labelling index. CONCLUSIONS: These data demonstrate for the first time in a large series of patients that maintenance of a good nutritional status does not have any deleterious effect on the tumor growth.

Phase II study of the etoposide, leucovorin and fluorouracil combination for patients with advanced gastric cancer unsuitable for aggressive chemotherapy.

Many patients with advanced gastric cancer cannot be treated with intensive chemotherapy. In an attempt to provide a feasible regimen for such patients, the combination of etoposide, leucovorin and fluorouracil (ELF) has been developed with promising results. The present study involved 42 patients with advanced gastric cancer who where unsuitable for cisplatin- or anthracycline-containing regimens because of their age (24 patients over 65 years), poor performance status (12) or the presence of concomitant illness (6). The treatment consisted of etoposide 120 mg/m2 i.v., 1-leucovorin 150 mg/m2 i.v. and fluorouracil 500 mg/m2 i.v. for 3 consecutive days every 3 weeks. Among the 41 evaluable patients, there was a 32% objective response rate (95% confidence interval 19-48%), with 7% of complete remissions. The median response duration was 4 months, the median time to progression in all patients was 5 months and the median overall survival was 10 months. No drug-related deaths or WHO grade 4 side effects were observed. On the basis of these results, we concluded that the ELF regimen is feasible and that its activity warrants randomized studies comparing the ELF combination with fluorouracil plus folinic acid.

Does parenteral nutrition increase tumor growth? A review.

Total parenteral nutrition (TPN) is a supportive therapy commonly used in clinical oncology, in spite of its possible interference on tumor growth. In fact, studies performed on animals have demonstrated that TPN increases tumor growth and that load and quality of amino acids are probably the main factors involved. In contrast, some authors obtained a decrease in tumor growth using a special amino acids mixture or a TPN formula rich in lipids. However, data collected on animals are not transferable to humans owing to the large difference between tumor-host weight ratio and tumor doubling time. Analysis of the studies on effect of TPN on tumor growth in humans has not demonstrated a bad effect, but the results reported in the literature are limited by the small number of patients, the lack of a sure and reproducible method to analyze tumor growth, and some methodologic defects. In conclusion, it is not evident that TPN is dangerous for cancer patients. However, it may be possible in the future to employ different formulas to improve the host nutritional status and inhibit tumor growth.

Comparing surgical resection of limited hepatic metastases from colorectal cancer to non-operative treatment.

The survival of two groups of patients, affected by liver metastases (Stage I and II by Gennari et al.) from a previously operated colorectal cancer and treated by surgical resection (Group 1, 39 patients) or chemotherapy with various cytotoxic drugs (Group 2, 31 patients) at the Istituto Nazionale Tumori, Milan, is reported. In comparison with Group 2, Group 1 included more patients with metachronous lesions, with high level of serum bilirubin and with primary tumour originating from the colon. A univariate analysis (log rank test) identified a statistically significant prognostic role of type of treatment (surgery vs chemotherapy) and of the level of serum bilirubin. However the multivariate analysis by the Cox's regression model showed that the only independent statistically significant prognostic factor was type of treatment, since the hazard ratio of surgery vs chemotherapy was 0.490 with a 95% confidence interval of 0.256-0.936. The survival probabilities at 24 and 36 months were respectively 60% and 47% in surgical patients, vs 30% and 23% in those receiving chemotherapy, the difference between the curves being statistically different (P = 0.001). The median survival of Group 1 patients was 30 months whereas the median survival of Group 2 patients was 19 months, a value quite similar to that published in literature for untreated patients with limited metastatic disease-thus indicating that this patients' population was not selected according to unfavourable criteria. These findings suggest a beneficial role of surgical resection in patients with colorectal metastases confined to the liver in Stages I and II.