Nutritional management of the patient with pancreatic cancer: from the diagnostic and therapeutic pathway to an integrated hospital-territory approach.

Abstract: Pancreatic cancer is associated to a high risk of malnutrition and neoplastic cachexia even at first diagnosis. Malnutrition is a negative prognostic factor for the outcome of surgery or medical oncology treatments. Despite the good awareness of the problem and the knowledge of the guidelines, the early recognition of malnutrition and its management are still uneven, mainly due to the lack of implementation of standardized and shared protocols and the shortage of dedicated clinical nutritionists and dieticians. An early and appropriate nutritional intervention is mandatory to improve the outcome of patients with pancreatic cancer at any stage of disease. The Mini Nutritional Assessment is useful tool to screen patients malnourished or at risk of malnutrition. The need for the establishment and implementation of an integrated hospital - territorial assistance as well as a home-delivered nutrition service is discussed.

Management of Patients with Gastric or Gastroesophageal Junction Cancer: From Theory to Integrated Clinical Path- ways Implementation in the Real World.

Introduction: Best care of esophagogastric junction and gastric cancer (EGC) requires a complex, timely interaction between members of a multi-disciplinary team (MDT). An integrated clinical pathway (ICP) is necessary to achieve this goal as well as the implementation of its use in daily practice. The objective of this study was to elaborate on an integrated clinical pathway for the multi-disciplinary management of ECG. Authors also put in act an implementation program to improve adherence to guidelines thought an ICP. Method: This prospective work carried out by a multi-institutional MDT in Italy identified expert panel extracted relevant recommendations and/or statements from published papers and guidelines obtaining a set of crucial interventions employed the Estimate-Talk-Estimate method. A flow-chart diagram was elaborated to elicit the process at a glance. The primary outcome measure was the elaboration of an ICP with a high consensus rate also reported as a snapshot diagram and its implementation in daily clinical practice. An accredited certification body agency validated results, and an implementation process was started in several hospitals known to treat ECG. Results: A methodologist aggregated a multi-disciplinary panel of experts from different institutions. The panel elaborated a flow-chart diagram with crucial intervention highlight and connecting lines, as well as outcome measures. An accredited certification body agency validated the entire process, representing the basis for empowerment and implementation among patients and oncological professionals in various hospitals. Conclusion: The multi-disciplinary and multi-institutional expert panel successfully elaborated on a validated ICP for all stages ECG. An in-hospital implementation program has been programmed.

Proctocolectomy for ulcerative colitis after liver transplantation for primary sclerosing cholangitis.

BACKGROUND: Sclerosing cholangitis is a chronic cholestatic liver disease of unknown etiology. Immunologic and genetic factors may be involved in the pathogenesis of the disease, characterized by fibrosis involving bile ducts, which can progress to biliary cirrhosis and cholangiocarcinoma (8%-30%). Sclerosing cholangitis is frequently associated with inflammatory bowel diseases, especially ulcerative colitis (60%-80%), which may require a proctocolectomy with ileal pouch anal anastomosis if there is no response to therapy or the appearance of colonic carcinoma. PATIENTS AND METHODS: Among 1629 liver recipients from 1990 to 2008, 47 (2.9%) had sclerosing cholangitis as the cause of cirrhosis. Forty two percent of these also had associated inflammatory bowel disease with 34% displaying ulcerative colitis. Eight patients died after liver transplantation (OLT) in the absence of recurrence of sclerosing cholangitis. Among the remaining 39 patients, 17 (43.6%) developed recurrent of sclerosing cholangitis; three required re-OLT, and among these three patients, one developed another recurrence. After OLT, ulcerative colitis persisted in an active state in eight patients, requiring proctocolectomy with ileal pouch-anal anastomosis for three patients (median time after OLT was 78.6 months). RESULTS: One of the three patients who had proctocolectomy had an immediate complication, a pelvic hematoma, which required a surgical approach. One patient developed acute pouchitis 15 months after OLT, medically treated with antibiotics and corticoids. Histology of the colectomy specimen demonstrated colorectal cancer in two patients (pT3N0 and pT2N0) and high-grade dysplasia in the remaining subjects. All patients displayed a cure of their colonic disease (median follow-up 14 months) despite two patients developing recurrence of the liver disease. CONCLUSION: Proctocolectomy with ileal pouch anal anastomosis is safe in patients who underwent OLT for sclerosing cholangitis in association with ulcerative colitis. If not surgically treated, patients may receive immunosuppression to prevent rejection and disease recurrence, avoiding at the same time the occurrence of "de novo" neoplasms. Mammalian target or rapamycin inhibitors may have an important role but this must be established with randomized controlled trials.

Covered metal stents for management of inoperable malignant colorectal strictures.

BACKGROUND: Metal stents have been reported as an effective alternative to surgery for the palliation of patients with colorectal neoplastic obstruction. Because most of the published series describe the use of uncovered stents, the purpose of our study was to prospectively evaluate the effectiveness, feasibility, safety, and outcome of covered stents for the palliative treatment of malignant colorectal strictures. METHODS: Sixteen patients with advanced distal colorectal cancer underwent placement of 10 and 12 cm long, 23 mm diameter covered stents under fluoroscopic and endoscopic control. Clinical and endoscopic follow-up was scheduled at 3- to 6-week intervals. RESULTS: Stent insertion was successful in 15 of 16 patients (93%). Perforation occurred in one patient during stent placement requiring colostomy. Relief of bowel obstruction was documented in all successfully treated patients. The median follow-up was 21 weeks (range 1 to 46). No recurrence of obstruction was observed during the follow-up period. Stent migration occurred in 2 patients, 7 and 21 days after stent placement. CONCLUSIONS: Covered stents may provide safe and effective palliation of patients with malignant rectosigmoid strictures. Prolonged luminal patency and sealing of fistulous tracts are potential advantages of covered versus uncovered stents in the palliative treatment of colorectal malignancies. ¿

Liver transplantation for erythropoietic protoporphyria: report of a case with medium-term follow-up.

A case of liver transplantation is described in a 35-year-old male with hepatic failure due to erythropoietic protoporphyria. Data regarding protoporphyrin levels in erythrocytes and faeces, before and after transplantation, seem to indicate that, in this case, protoporphyrin overproduction was, in part, due to liver synthesis. Four years after surgery, the patient is completely free of skin photosensitivity. Liver function tests are normal and there are no significant protoporphyrin deposits in the new liver. However, recurrence of the disease in the long-term cannot be excluded, since erythrocyte protoporphyrin levels have remained elevated after liver transplantation.

Thyroid cancer in patients with familial adenomatous polyposis.

The association between thyroid cancer and familial adenomatous polyposis (FAP), albeit rare, is well known. It has been suggested that the thyroid tumors have unique histologic characteristics and may be follicular in origin. Because of their rarity, treatment and long-term prognosis are uncertain. Twelve such patients (prevalence 399/100,000) seen during 1949-1995 were retrospectively reviewed. Histology was independently re-reviewed by two pathologists. There were 11 female patients (two sisters) and 1 male patient, with a mean age of 28 years (range 15-61 years). Eight patients (66%) had multicentric tumors and five (42%) bilateral disease. Average tumor diameter was 1.8 cm (range 0.2-5.0 cm). Regional nodal metastases were present in two patients. All 12 thyroid cancers in this series were papillary. The one male patient demonstrated "typical" histology with variable papillary and follicular architecture, whereas the 11 female patients had tumors with unusual histology as described by Harach. Five patients (41%) were treated by total thyroidectomy, five with near-total thyroidectomy, and two with lobectomy alone. Mean follow-up was 142 months (range 7 months to 30 years). Regional recurrent disease occurred in two patients, one of whom died of the disease. The 5- and 20-year survivals were 90% and 77%, respectively. The results indicated that all tumors in this study were papillary, although atypical histology was encountered in 91%. The mean age (28 years) is younger than that of patients with sporadic disease. Multicentricity and bilateral disease are common. In view of this finding, total thyroidectomy should be strongly considered. Long-term prognosis is excellent. The finding of unusual histology in a young patient with papillary thyroid carcinoma should arouse the suspicion of FAP.

Advancement sleeve flaps for treatment of severe perianal Crohn's disease.

BACKGROUND: Traditionally proctectomy has been the treatment for severe, complex fistula in ano from Crohn's disease. However, based on the success of rectal advancement flaps in Crohn's disease, circumferential transanal sleeve advancement flaps (TSAFs) were proposed for this subgroup of patients with severe fistula. METHODS: From 1991 to 1995, 13 patients (12 women) with severe perianal Crohn's disease and multiple fistula tracts underwent a TSAF procedure. Data were collected retrospectively using a standard data sheet. RESULTS: There were no postoperative deaths or major morbidity. One year after surgery, the fistula had healed in eight of 13 patients (with three requiring additional surgery before healing). Of patients in whom the procedure failed, three underwent proctectomy for progression of disease and the other two had recurrence of a rectovaginal fistula 6 and 8 months after surgery. Of six variables evaluated (previous procedure, steroid use, steroid dosage, associated Crohn's disease, associated procedures and diverting stoma), only associated procedures were significantly related to a successful outcome (P=0.008). CONCLUSION: Some patients with severe perianal Crohn's fistula and a relatively normal rectum can be offered TSAFs. Even with successful outcome in eight of 13 patients, this may still be a viable option if the only alternative would be total proctocolectomy and a permanent stoma.

Perianal Bowen's disease: a clinicopathologic study of 47 patients.

PURPOSE: Perianal Bowen's disease is an uncommon squamous-cell carcinoma in situ usually treated by surgical excision. There are controversies concerning surgical margin extent, because the disease is likely to recur in nonexcised skin areas of the anal and perianal skin. The aims of this study were 1) to determine the recurrence rate after different surgical treatments and 2) to determine if molecular markers might have a prognostic role in perianal Bowen's disease. METHOD: Retrospective chart review from 1972 to 1993 of 47 patients with perianal Bowen's disease was undertaken. Follow-up was obtained by office visits and/or phone questionnaire. Immunohistochemical analysis for p53 protein and Ki-67 nuclear antigen was conducted on fixed tissue specimens. RESULTS: Twenty-six patients were treated by wide local excision with microscopic clearance of resection margins, 15 by local excision with only macroscopic clearance of resection margins, 5 by CO2 laser vaporization, and 1 by abdominoperineal resection because of fecal incontinence. Median follow-up for the entire population was 104 (range, 16-273) months. The incidence of local recurrence was 23.1 percent (6/26) after wide local excision, 53.3 percent (8/15) after local excision, and 80 percent (4/5) after CO2-laser vaporization. Recurrence rate estimated by Kaplan-Meier analysis is statistically different (P = 0.002) between radically treated patients (wide local excision/abdominoperineal resection; n = 27) and patients undergoing conservative treatment (local excision/laser vaporization; n = 20). Among patients with recurrence, the median time until recurrence was 38.5 (range, 3-89) months and 41.5 (range, 4-111) months after conservative and radical treatment, respectively. Nine of 20 (45 percent) patients in the conservative group and none of the 27 patients in the radical group had multiple episodes of recurrence (P < 0.001). In addition, 3 of 20 and 0 of 27 patients in the respective groups developed an invasive cancer (P = 0.034). Positive staining for p53 protein was observed in 12 (33.3 percent) of the 36 tissue specimens available for immunohistochemical analysis. Recurrence occurred in 9 of 24 (37.5 percent) patients negative for p53 and in 6 of 12 (50 percent) patients with positive p53 expression (P = not significant). Ki-67 antigen-graded expression from 1+ to 4+ did not reveal any correlation with incidence of recurrence. Recurrence rate did not differ by p53 and Ki-67 results, either in the overall group of 36 patients or stratified by surgical treatment groups. CONCLUSION: Wide local excision for perianal Bowen's disease leads to a significantly lower recurrence rate than local excision or laser therapy. Follow-up longer than five years is recommended because of the risk of late recurrence. p53 protein and Ki-67 antigen immunohistologic expression may not have a prognostic role in perianal Bowen's disease.

Long-term outcome of patients with perianal Paget's disease.

BACKGROUND: Perianal Paget's disease (PPD) is a rare intraepithelial adenocarcinoma with a significant rate of recurrence after treatment and high risk of progression to an invasive cancer. PATIENTS AND METHODS: Fourteen patients with a mean follow-up longer than 5 years were studied to determine the outcome after surgical treatment. The immunohistochemical accumulation of p53 protein also was assessed in tissue specimens to evaluate its prognostic role in patients with PPD. RESULTS: Four patients were excluded because of progression to invasive malignancy at the time of diagnosis. Two patients underwent local excision (LE) with macroscopic clearance of the surgical margins; the remaining eight patients underwent wide local excision (WLE), i.e., > 1 cm microscopic clearance of the surgical margins. The actuarial 8-year recurrence rate for patients treated with LE and WLE was 100% and 50% (SE = 17.7), respectively. Progression to invasive carcinoma occurred after a median time of 56 months (range 23-72) in two patients treated with LE and in one of eight patients treated with WLE. All four patients with recurrence after WLE were successfully treated (no further recurrence) with a second WLE. Actuarial 8-year survival was 0% in the LE group and 40% (SE = 21.9) in the WLE group. There was no p53 protein accumulation in any of the ten patients with PPD. CONCLUSIONS: Survival of patients with PPD treated by WLE was higher than that for those treated with LE. Thus, wide local excision is recommended over limited local excision as a preferred treatment for PPD. Follow-up longer than 5 years seems to be indicated because of the risk of late progression to invasive cancer. When PPD does recur, a second WLE may be curative. The absence of accumulated p53 protein suggests that this marker may not have a prognostic role in PPD.

Adrenal masses in patients with familial adenomatous polyposis.

PURPOSE: The aims of this study were 1) to report the characteristics and the clinical outcome of familial adenomatous polyposis (FAP) patients with adrenal masses in the FAP registry at the Cleveland Clinic Foundation and 2) to estimate the prevalence of adrenal masses detected by computed tomography in FAP patients compared with that expected in a normal population. METHODS: A retrospective review was undertaken of the FAP registry database at our institution. Only 738 patients treated at the Cleveland Clinic Foundation were included in the study. A meta-analysis was conducted to determine the relative risk of adrenal incidentaloma in this series of FAP patients and in a general population as reported in the four largest pertinent studies published in the past 15 years. RESULTS: Fifteen patients (11 females) were identified. Two patients had symptoms related to cortisol hypersecretion (arterial hypertension) and underwent surgery. The final pathology was adrenocortical carcinoma and bilateral nodular hyperplasia. Adrenal masses were found incidentally (incidentalomas) in 13 patients: 12 were detected by computed tomography and one during laparotomy for total abdominal colectomy. Only one patient underwent left adrenalectomy for a 5-cm mass. Pathologic report revealed adrenocortical adenoma. Among the 738 patients considered in this study, only 162 underwent abdominal computed tomographic scan, mainly for assessing intra-abdominal desmoid. The prevalence of incidentaloma in our series compared with that reported in the literature is significantly different (7.4 vs. 0.6-3.4 percent; P < 0.001 (chi-squared test)). DISCUSSION: Although the presence of other extracolonic manifestations represents a selection bias for computed tomographic study in our series, the incidence of incidentalomas in FAP patients seems to be higher than in a general population. However, incidental detection of an adrenal mass in FAP patients has probably a limited clinical relevance, and the management should be the same as that for the normal population.

The risk of cancer and dysplasia among ulcerative colitis patients with primary sclerosing cholangitis.

BACKGROUND: Ulcerative colitis (UC) patients with primary sclerosing cholangitis (PSC) may have an increased risk for colonic dysplasia or cancer. They also may have higher levels of carcinogenic secondary bile acids and, thus, be more likely to develop cancer in the right side of the colon, where secondary bile acid concentrations are highest. METHODS: Since 1983, 1212 UC patients have undergone total proctocolectomy with ileal pouch-anal anastomosis at the Cleveland Clinic. All 27 patients with PSC were compared with the remaining 1185 patients in a historical cohort study. RESULTS: Dysplasia detected during cancer surveillance was the indication for surgery in 16 (59.5%) PSC patients and 136 (11.5%) controls [adjusted relative risk (RR), 6.9; 95% confidence interval (CI), 3.0-16.0]. Dysplasia or cancer was found in the resected specimen in 18 (66.7%) PSC patients and 145 (12.2%) controls (RR 10.4, CI 4.1-26.1). Right-sided cancers (proximal to the splenic flexure) were found in all four PSC patients with cancer and in 20 of 49 controls with cancer (RR 2.5, CI 1.3-5.4). CONCLUSIONS: UC patients with PSC are at a significantly increased risk for dysplasia or cancer. The high proportion of right-sided cancers supports the contention that secondary bile acids are carcinogenic and increase the likelihood of cancer in the proximal colon.

A combined hepatocellular/cholangiocellular carcinoma with sarcomatoid features.

A case of primary liver cancer showing combined hepatocellular and cholangiocellular features and an associated pseudosarcomatous (schwannomatous) component is presented. Histologically, compact microtrabecular and glandular patterns in a dense fibrous stroma were recognized. The latter showed transition towards spindle cell sarcomatous growth in several areas of both the primary and the lymph-node metastasis. Glandular areas expressed acidic mucins and AE1-reactive keratins; albumin mRNA was detected by in situ hybridization in both trabecular and glandular areas. Vimentin and S-100 protein were mostly expressed in the pseudosarcomatous areas. Both the morphological patterns and the phenotypic features indicate that divergent differentiation along both epithelial and mesenchymal lineages took place in this rare primary liver tumor.

Intraoperative laparoscopic liver ultrasonography for staging of colorectal cancer. Initial experience.

PURPOSE: This study was undertaken to evaluate the feasibility of intraoperative laparoscopic ultrasonography (ILUS) to completely scan all anatomic segments of the liver through a single port site during laparoscopic resection for colorectal cancer. METHODS: ILUS was performed in patients who were undergoing laparoscopic colorectal cancer surgery using the following approach: 1) presence of a radiologist in the operating room; 2) introduction of the probe through a single cannula site; 3) standardized sequence of four probe positions on liver surface; 4) identification of all major vascular/biliary hepatic structures as a guideline to scan all parenchymal segments of the liver. RESULTS: Twenty-two patients who were undergoing laparoscopic colorectal cancer surgery were prospectively enrolled. Computed tomography (CT) scan films were available for an immediate comparative analysis in the first 12 cases. Mean duration of the procedure was 10 (range, 5-15) minutes. All major vascular and biliary structures were identified in all patients. Sixteen focal abnormalities were identified by ILUS, and ten focal abnormalities were identified by CT scan in the same seven patients. In one patient, detection of a suspected metastasis not seen by preoperative CT scan led to conversion of the surgical procedure to a laparotomy. CONCLUSIONS: ILUS is a safe and expeditious technique that permits scanning of all anatomic liver parenchyma segments through a single cannula site. Because intraoperative palpation of the liver is not possible during laparoscopic colorectal cancer surgery, ILUS should probably be a standard component of the curative laparoscopic colorectal cancer operation.

Right colonic arterial anatomy. Implications for laparoscopic surgery.

PURPOSE: Hemorrhagic complications can be a major cause of conversion and/or morbidity during laparoscopic intestinal surgery. The limited exposure currently provided in laparoscopic intestinal resection demands a precise knowledge of mesenteric vascular anatomy to avoid such complications and to expedite the procedure. Most surgical texts depict a "normal pattern" of arterial supply to the right colon consisting of three arterial branches (ileocolic artery, right colic artery, and middle colic artery) arising independently from the superior mesenteric artery (SMA). Based on previous reports and clinical observations, we hypothesized that the right colic artery arises infrequently from the SMA, and most commonly, there are only two colonic arteries arising independently from the SMA. METHODS: We performed detailed dissections of the SMA in 56 human cadavers. RESULTS: We found the ileocolic artery in all of our cases and the middle colic artery in 55 of 56 cadavers but only six cases of a right colic artery emanating directly from SMA. CONCLUSIONS: Our data, combined with review of published anatomic studies, lead us to conclude that in the vast majority of cases there are only two independent branches arising from SMA that supply the large intestine, the ileocolic and the middle colic arteries. The right colic artery directly arising from SMA is unusual (10.7 percent). This knowledge may help lower the risk of vascular complications during laparoscopic intestinal surgery.

Laparoscopic Techniques for Inflammatory Bowel Disease.

Very little has been written concerning the use of laparoscopic techniques in inflammatory bowel disease. Its most useful indications appear to be in Crohn's disease, especially for intestinal diversions when severe perineal/perianal sepsis occurs. In this instance, avoidance of a laparotomy is a major advantage, and the simplicity of a laparoscopic stoma formation makes this a procedure that most surgeons may perform, even with minimal laparoscopic experience. Laparoscopic techniques may also be used for the limited resections required in Crohn's ileal or ileocolonic disease and for diagnostic purposes when indicated. The laparoscopic approach to the surgical treatment of ulcerative colitis (total abdominal colectomy, possibly with proctectomy and ileoanal pouch formation) remains to be evaluated before it can be contemplated as an alternative to conventional procedures.

[Antibiotic prophylaxis with ++vancomycin in corrective surgery with alloplastic material]. / Antibioticoprofilassi con vancomicina nella chirurgia riparativa con materiale alloplastico.

The authors report a controlled series of 40 patients treated for recidivating inguinal hernia and laparocele with the implant of alloplastic material. Short-term prophylaxis with vancomycin was performed in all cases. The antibiotic was found to be well tolerated at the doses used and this was associated with a good clinical success rate. The use of vancomycin in prophylaxis for this type of surgery is considered a rational choice and the use of short-term prophylaxis reduces the risks linked to possible collateral effects.

[Critical evaluation of preoperative instrumental staging of rectal tumors. Research on the adequate use of US, CT and MR]. / Valutazione critica della stadiazione strumentale preoperatoria dei tumori del retto. Ricerca di un impiego adeguato di US, TC e RM.

Both traditional exams (rectal exploration, rectoscopy, barium enema, CEA) and advanced imaging (31 US, 40 CT and 11 MR) were performed for preoperative evaluation of rectal carcinoma in order to assess the accuracy of radiological imaging in the T and N staging. The results obtained have not been considered satisfactory and it is felt that US, CT and MR should not be employed routinely for rectal staging. Indeed accuracy of US, CT and MR is respectively 64%, 75% and 81% in the T evaluation and 64%, 70% and 64% in the N staging. In order to evaluate the effective usefulness of these three latter imaging techniques a double therapeutical choice was proposed. The first treatment option was suggested on the basis of traditional staging while a second choice was given considering US, TC and MR data also. Operatory findings subsequently allowed a definitive judgement on the influence of the different techniques on treatment selection. US has furnished useful data that could have allowed us to modify treatment in one case while in 5 other cases diagnostic error would have influenced treatment negatively. CT was useful in 5 cases while in 7 cases it would have influenced treatment choice negatively. MR would have been useful in one case and harmful in another. It is concluded that only patients with large neoplasms (stages T3 and T4) benefit from CT and MR staging with the exception of those cases that have tumors above the peritoneal fold or in strict relation with the sphincter structures. US was useful only in evaluating relations of neoplasms of the anterior rectal wall with nearby pelvic structures.