Cancer of the anal region.

Anal canal accounts for 2% of all cancer and its incidence increases with age with a predominance in woman. About 80% of all primary anal canal cancers are squamous; adenocarcinoma arising from the glands or glandular ducts shows a behaviour that is similar to that of the adenocarcinoma of the rectum. Risk factors includes sexually transmitted infection with Human Papillomavirus, cigarette smoking, immunosuppression, and sexual practices. The standard treatment for anal canal is chemo - radiation with a combination of fluoropyrimidines and mitomycin or cisplatin. Salvage surgery may be necessary for residual disease after radiotherapy or chemoradiation, for locoregional relapse and/or for sequelae. In the metastatic setting a multidisciplinary approach is preferred and includes medical treatment, surgery, and RT, if appropriate. Discussing these possible options in the initial stage is of most importance to ensure the best quality of life (QoL) for patients.

Percutaneous transhepatic biliary drainage and occlusion balloon in the management of duodenal stump fistula.

BACKGROUND: Duodenal stump fistula (DSF) after gastrectomy is a complication with a high mortality rate. We report a series of patients with postoperative DSF treated with percutaneous transhepatic biliary drainage and occlusion balloon (PTBD-OB). The aim of this study is to explore the feasibility and efficacy of PTBD-OB in the treatment of DSF. PATIENTS AND METHODS: Six patients developing DSF underwent PTBD-OB because of high DSF output and because medical and surgical management was unsuccessful. In these patients, an occlusion balloon was percutaneously inserted into the common bile duct and a biliary drain was positioned above the balloon to obtain external drainage of bile. RESULTS: In all cases, percutaneous access to the biliary tree was achieved. Patients maintained the PTBD-OB for a median of 43 days. In all patients, DSF output decreased after PTBD-OB placement from a median of 500 to 100 ml/day (p = 0.02). The DSF resolved in three patients and three patients died of sepsis, but in two of them, death was related to other digestive fistulas that developed before PTBD-OB placement. CONCLUSIONS: This paper presents the first published series on DSF management with PTBD-OB and shows that it is a feasible and safe procedure which reduces DSF output.

Hepatic metastases from breast cancer.

The prognosis of patients with hepatic metastasis from breast cancer treated with systemic or regional chemotherapy is disappointing. When technically feasible, liver resection offers the best results. Eighteen patients out of 22 submitted to laparotomy underwent radical liver resection. Median follow-up from liver resection was 36 months. The median time interval between breast cancer diagnosis and disease recurrence was 35 months. Median disease-free survival and overall survival from liver resection were 66 and 74 months, respectively. Median survival time from breast cancer surgery was 88.5 months. Surgical treatment of liver metastases should be carried out on young and older patients alike when site of metastases is the liver alone. Neoadjuvant treatment and preoperative diagnostic laparoscopy should be planned in future experience.

Rectal squamous cell carcinoma treated with chemoradiotherapy: report of six cases.

PURPOSE: Squamous cell carcinoma (SCC) of the colon and rectum is a rare pathologic entity. From May 2006 to August 2008 six consecutive patients with SCC of the rectum were treated at our institution. A retrospective analysis of these cases was performed in order to evaluate the role of chemoradiotherapy as an alternative to surgery. METHODS: All tumors were locally advanced and the clinical stage was T3N0M0 in three cases, T3N1M0, T4N1M0 and T3N2M1 in the other three cases. All patients received primary chemoradiation reserving surgery for unresponsive or recurrent tumors except in one of complete responders. Radiation treatment was given to standard pelvic volume up to 50.4 Gy in 28 fractions, with a boost to the primary tumor up to 59.4 Gy in two patients. RESULTS: A complete clinical response with a negative endoscopic biopsy was achieved in four patients and a partial response in two. Surgery as a part of the primary treatment was performed in the non-metastatic patient with partial response and in the first patient with complete response. At a median follow-up of 39 months (range, 24-41) from the end of chemoradiotherapy, five out of six patients remain alive and free of recurrence, three of them without having undergone surgery. CONCLUSION: Our data, though from a small series, give support to the hypothesis that concomitant chemoradiation may be considered a safe and effective therapeutic approach for patients with rectal SCC.

Duodenal fistula after elective gastrectomy for malignant disease : an italian retrospective multicenter study.

BACKGROUND: Duodenal fistula (DF) after gastrectomy continues to be a life-threatening problem. We performed a retrospective multicenter study analyzing the characteristics of DF after elective gastrectomy for malignant disease. METHODS: Three thousand seven hundred eighty-five patients who had undergone gastrectomy with duodenal stump in 11 Italian surgical units were analyzed. RESULTS: Sixty-eight DFs occurred, with a median frequency of 1.6% and a mortality rate of 16%. Complications were mainly septic but fistulas or bleeding of surrounding organs accounted for about 30%. Reoperation was performed in 40% of patients. We observed a correlation between mortality and age (hazard ratio 1.09; 95% CI 1.00-1.20) and serum albumin (hazard ratio 0.90; 95% CI 0.83-0.99). The appearance of further complications was associated with reoperation (P < 0.001) and death (P = 0.054), while the preservation of oral feeding was related to DF healing (P < 0.001). CONCLUSIONS: This paper represents the largest series ever published on DF and shows that its features have changed in the last 20 years. DF alone no longer leads to death and some complications observed in the past have disappeared, while new ones are emerging. Nowadays, medical therapy is preferred and surgery is indicated only in cases of abdominal sepsis or bleeding.

Current role of surgery in the treatment of digestive fistulas.

UNLABELLED: Surgery is the main treatment of digestive fistulas (DF) but its role has changed over the last 40 years. The aim of this review is to analyze the surgical management of DF paying attention to timing and type of surgery. METHODS: We performed a review considering the following electronic databases: Medline, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, EMBASE and the reference lists of the key papers. Literature searches were carried out using the following medical subject headings: "digestive fistula"; "gastrointestinal fistula"; "enterocutaneous fistula"; 'AND surgery"; "AND surgical treatment". Because the absence of randomized studies, we have considered the larger series or original techniques. RESULTS: Surgical treatment of DF has two indications: to treat complications due to DF juice action such as peritonitis, abscesses, gangrene, bleeding; and when a fistula fails to heal. In this case the surgical indication is often difficult to establish, because of the risk of making an inconclusive act. CONCLUSIONS: Indications to surgery, timing and choice of operation cannot often be standardized because they depend on a mixture of DF and patient characteristics. In specific cases, involvement of nutritionist and plastic surgeon is required.

Horner's syndrome as a complication of thyroidectomy: report of a case.

We report a case of Horner's syndrome (HS) occurring as a complication after total thyroidectomy. Horner's syndrome is characterized by myosis, eyelid ptosis, enophthalmos, and lack of sweating, with vascular dilatation of the lateral part of the face, caused by damage of the cervical sympathetic chain. We found only 28 other reports of HS developing after thyroidectomy, and only seven of these patients recovered completely. Of the 495 thyroidectomies performed at our hospital between 1997 and 2007, only one (0.2%) was complicated by the development of HS. The patient was a 35-year-old woman who underwent total thyroidectomy for Basedow-Graves' disease. Horner's syndrome manifested on postoperative day 2, but without anhydrosis or vascular dilatation of the face, and the symptoms resolved spontaneously 3 days later. The possible causes of HS after thyroidectomy include postoperative hematoma, ischemia-induced neural damage, and stretching of the cervical sympathetic chain by the retractor. The prompt and complete recovery of this patient suggests that the cervical sympathetic chain was damaged by retractor stretching.

Utility of 18F-FDG PET and contrast-enhanced CT scan in the assessment of residual liver metastasis from colorectal cancer following adjuvant chemotherapy.

BACKGROUND: Neoadjuvant chemotherapy has been successfully used in the treatment of patients with colorectal liver metastases. The selection of patients for surgical resection after chemotherapy still poses a significant clinical challenge. (18)F-FDG PET is a useful tool in the assessment of liver metastases but the data regarding its sensitivity after chemotherapy is scarce. Our aim was to assess the value of this imaging modality in the selection of patients with colorectal liver metastasis for surgery following adjuvant chemotherapy. MATERIAL AND METHODS: We reviewed the diagnostic performances of (18)F-FDG PET and contrast-enhanced CT scan data from patients with colorectal liver metastases following treatment with chemotherapy. Nineteen patients (12 males, 7 females; median age 61 years; range 41-79) were evaluated. Chemotherapy regimens were: FOLFOX (14 patients), FOLFIRI (3 patients), 5-FU/FA (1 patient) and UFT-irinotecan-oxaliplatin (1 patient). Median time between end of chemotherapy and CT scan was 3.4 weeks, between end of chemotherapy and PET was 5.9 weeks and between end of chemotherapy and surgery was 9.9 weeks. All patients underwent surgery and had histopathological confirmation of liver lesions. Nine patients had segmentectomy, 2 patients had wedge resection, 5 patients had right hepatectomy and 3 patients had explorative laparotomy with liver biopsies. RESULTS: Data from all 19 patients, comprising 65 liver lesions, were confirmed by histo-pathology. Results on a per-lesion basis showed a sensitivity of 62% for (18)F-FDG PET and 70% for CT scan. A complete agreement between (18)F-FDG PET or CT scan and histology was documented in 5 and 3 patients, respectively. The sensitivity of (18)F-FDG PET was shown to increase for lesions larger than 1 cm (74% vs. 18%). CONCLUSIONS: These results suggest that (18)F-FDG PET and CT scan have sub-optimal sensitivity in the evaluation of colorectal liver lesions after neo-adjuvant chemotherapy, especially for lesions < 1 cm. The combined use of the two imaging techniques does not significantly increase the sensitivity of lesion detection.

Reduced likelihood of metastases in patients with microsatellite-unstable colorectal cancer.

PURPOSE: The outcome of patients with colorectal cancer is more favorable when the tumor exhibits high-frequency microsatellite instability (MSI). Although associated with earlier-stage tumors, MSI has been proposed as an independent predictor of survival. We tested the prognostic value of MSI in a large series of patients diagnosed with colorectal cancer in the last decade. EXPERIMENTAL DESIGN: The survival of 893 consecutive patients with colorectal cancer characterized by microsatellite status was analyzed. The 89 (10%) patients with MSI cancer were classified according to tumor mismatch repair (MMR) defect, MMR germ-line mutation, hMLH1 and p16 promoter methylation, BRAF and K-ras mutations, and frameshifts of target genes. RESULTS: The colorectal cancer-specific survival was significantly (P = 0.02) better in patients with MSI cancer than in those with stable tumor (MSS). MSI did not predict a significantly lower risk of cancer-related death if tumor stage was included in the multivariate analysis [hazard ratio, 0.72; 95% confidence interval (95% CI), 0.40-1.29; P = 0.27]. Instead, MSI was strongly associated with a decreased likelihood of lymph node (odds ratio, 0.31; 95% CI, 0.17-0.56; P < 0.001) and distant organ (odds ratio, 0.13; 95% CI, 0.05-0.33; P < 0.001) metastases at diagnosis, independently of tumor pathologic features. Molecular predictors of reduced metastatic risk, and then of more favorable prognosis, included TGFbetaRII mutation for all MSI tumors, hMSH2 deficiency for hereditary non-polyposis colorectal cancer, and absence of p16 methylation for sporadic hMLH1-deficient cancers. CONCLUSIONS: Tumor MSI is a stage-dependent predictor of survival in patients with colorectal cancer. The decreased likelihood of metastases in patients with MSI cancer is associated with specific genetic and epigenetic changes of the primary tumor.

The efficacy of hybrid chemotherapy with intravenous oxaliplatin and folinic acid and intra-hepatic infusion of 5-fluorouracil in patients with colorectal liver metastases: a phase II study.

Intra-arterial chemotherapy in patients with liver metastases from colorectal cancer has some limitations such as hepatic toxicity and extra-hepatic progression. With the aim of overcoming these limitations, a phase II trial was designed to assess the efficacy and tolerability of a hybrid chemotherapy regimen with systemic infusion of oxaliplatin and folinic acid associated with intra-arterial 5-fluorouracil. Thirty-nine patients with colorectal liver metastases were recruited. The median age was 59 years, 30 patients (77%) had synchronous metastases, and half of the patients were chemo-naive. A total of 313 chemotherapy cycles were administered (median number 8). Treatment was well tolerated and hepatic toxicity negligible. Out of 34 evaluable patients an ORR of 41%. was observed. Eight patients (21%) underwent radical liver surgery. The median time to progression (TTP) was 10 months (range 2-63) and the median overall survival (OS) 21 months (range 6-63). Extra-hepatic progression was observed in six patients. Our results suggest that this regimen is active even if technical complications are frequent. Our aim to reduce hepatic toxicity and extra-hepatic progression was reached.

Neutropenic enterocolitis: is there a right timing for surgery? Assessment of a clinical case.

Neutropenic enterocolitis is a severe and potentially life-threatening complication that may affect patients undergoing chemotherapy for acute leukemia or lymphoma. These patients may develop systemic sepsis through bacterial or fungal translocation across the intestinal wall. In many cases neutropenic enterocolitis is confined to the cecum, but the entire colon is sometimes involved. Most patients are treated conservatively because an improvement occurs when the absolute neutrophil count rises. However, a surgical approach consisting of resection of the colon may sometimes be necessary, even in patients with complete aplasia and a high risk of complications. The right time to perform surgery is hard to define. Intestinal wall thickness, evaluated by ultrasound, is an important prognostic factor which could act as a guide to surgical indication. We analyze a case of neutropenic enterocolitis which occurred in a patient with acute myeloid leukemia during chemotherapy and we suggest that, as well as intestinal wall thickness, hemodynamic worsening should be considered an indication for surgery.

[The lymph node dissection in thyroid carcinoma]. / La linfadenectomia nei carcinomi della tiroide.

Rule and indications of lymph node dissection (LD) in thyroid carcinoma is still under debate because of the biological variety of different histological types and the difficulty to have an accurate preoperative diagnosis of metastatic lymph nodes; moreover prognostic factors of metastatic lymph nodes are still unclear. The AA. have separately analyzed different thyroid carcinomas and different clinical situations requiring thyroid LD. Metastatic lymph nodes from differentiated carcinomas, including papillary and follicular type, range from 12 to 90% and apparently do not worsen the prognosis. Level II-VI LD is indicated in presence of metastatic lymph nodes or macroscopic nodal recurrence after a previous LD. No prognostic advantages have been demonstrated when LD is performed without clinical or instrumental evidence of metastatic disease, including suspected recurrence characterised only by plasma Thyreoglobulin increased values. Lymph node metastases from medullary carcinoma range from 25 to 63%. Level II-VI LD is indicated if node metastases are present, whereas prophylactic LD, confined to level VI, is always recommended. Controversies still remain about: 1) LD extension whether it is prophylactic (level VI vs. II- VI) or in case of nodal involvement (levels II- VI monolateral or bilateral), 2) LD indications in case of an increased plasma Calcitonin levels during the follow-up after total thyroidectomy, without clinical or instrumental evidence of nodes involvement. Anaplastic carcinoma represents 5% of all thyroid carcinomas; it is the most aggressive type with an early tendency to invade surrounding organs and to give metastases; prognosis is very poor. LD is indicated only for a palliation in cases with compression syndromes.

[Does the Roux-en-Y-stasis syndrome still exist?]. / Esiste ancora la sindrome dell'ansa alla Roux?

Roux-en-Y-stasis syndrome (RYS) is a complication of subtotal gastrectomy characterized by delayed gastric emptying and vomiting. The aim of the study was to analyze RYS frequency with particular attention to diagnosis and therapy. From November 1996 to June 2004, we performed 147 distal gastrectomies with 5 cases of RYS: mean age 78 years, 3 male, 2 female, 4 adenocarcinoma and 1 GIST. Among the 5 cases, RYS was due to different causes: it was functional in 2 cases (with difficult gastric emptying due to a long gastric remnant in one patient, while the other was associated with duodenal fistula) and healed through medical therapy in both; a third patient had an edematous stenosis of the gastrojejunal anastomosis treated with medical therapy and the remaining 2 patients had jejunal obstruction due to adherences and required reoperations. RYS is a rare complication of subtotal gastrectomy determined by different causes. Recognizing the cause is very important for choice of appropriate therapy.

Gastric cancer: extent of lymph node dissection and requirements for a correct staging.

AIMS AND BACKGROUND: Lymphatic spread is an important prognostic factor in gastric cancer. The TNM classification requires at least 15 lymph nodes to stage and identify three prognostic groups according to the number of metastatic lymph nodes: N1 (1-6), N2 (7-15), N3 (> 15). The aim of this study was to investigate which type of lymph node dissection allows an accurate staging. METHODS: From 1996 to 2001, we treated 140 gastric cancer patients, 27 with D1 and 113 with D2 dissection. We evaluated lymph node count, status and ratio between metastatic and total number of excised lymph nodes, keeping 20% as the cutoff value. RESULTS: The mean number of lymph nodes was 18 and 33 respectively for D1 and D2 (P < 0.001), 41% of patients in D1 and 5% in D2 had less than 15 lymph nodes (P < 0.001). 59% in D1 and 73% in D2 (P = 0.145) had lymph node metastases, but this incidence decreased to 36% (P = 0.045) and 16% (P < 0.001) respectively for D1 and D2 when less than 15 lymph nodes were available. Considering the ratio between metastatic and total number of lymph nodes, 45% of D1 versus 3% of D2 (P < 0.001) in the N1 group exceeded 20%. CONCLUSIONS: D2 lymph node dissection is better than D1 in providing at least 15 lymph nodes required for a correct staging. We confirm the risk of a downstage when less than 15 lymph nodes are available.

Cancer of the anal region.

Cancer of the anal region represents 3-3.5% of all anorectal tumours. The peak incidence is between 58 and 64 years. Since 1960 an increased incidence among men younger than 45 years, and among women has been observed. The number of women diagnosed with anal canal cancer (7 per 1,000,000 person per years) is twice as much as that of men, while anal margins cancers are more frequent in men (4 per 1,000,000 person per years). Tumour extension determines the different treatment strategies, aiming at definite cure, with a conservative approach. Small tumours can be resected without mutilating surgery, while for larger tumours combination of chemotherapy and radiotherapy is the standard treatment, even though a combination of chemotherapy and radiotherapy has been recently introduced. Long-term quality of life (QOL) scores are acceptable, with the exception of patients who experience severe anal dysfunction.

[Integrated treatments of rectal carcinoma (review)]. / I trattamenti integrati del carcinoma rettale (review).

We have reviewed the international literature regarding the treatment of rectal carcinoma. Over the last decades the evolution of treatment methods has led to a drastic fall in the incidence of local recurrences which has gone from a wide range (15-40%) to a much lower figure (10%). This favourable result has been reached also due to improvement in surgical techniques (total mesorectal excision) and to the use of an association of preoperative radio and chemotherapy. However, the drugs and dosage of these as well as of the RT still have to be defined. In our experience the integrated treatment has brought a downstaging of the T in 60% of cases and of the N in 15%.

Prognostico dos tumores desmoides associados a polipose adenomatosa familiar: experiencia do I.N.T. - Milao / Prognosis of desmoid tumor associated with familial adenomatous polyposis: milano experience

Relatamos estudo retrospectivo sobre a rara associaçao polipose adenomatosa familiar e desmoides, comparando, nestes casos, o comportamento do desmoide com a sua forma classica. Durante o periodo de janeiro de 1979 a dezembro de 1987 o I.N.T. - Milao atendeu seis casos com esta condiçao. O tratamento do desmoide foi cirurgico em todos os casos. Todos os pacientes evoluiram para o tumor desmoide mesenterico irressecavel, exceto um caso, cujo seguimento foi inferior a mediana. Dois pacientes faleceram em decorrencia do desmoide mesenterico. O percentual de multicentricidade do desmoide foi de 83%, assim como o de recidiva. Comparando estes achados e os de outras series da associaçao com a forma classica de tumor desmoide, concluimos que nestes casos ha um pior prognostico, face a multicentricidade e a frequencia de ocorrencia de desmoide intra-abdominal, principalmente mesenterico