Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases: analysis of short- and long-term outcomes.

BACKGROUND: Peritoneal metastases carry the worst prognosis among all sites of colorectal cancer (CRC) metastases. In recent years, the advent of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) has improved survival for selected patients with limited peritoneal involvement. We report the evolution of CRS and HIPEC for colorectal peritoneal metastases at a tertiary referral center over a 10-year period. METHODS: Patients with colorectal peritoneal metastases undergoing CRS and HIPEC were included and retrospectively analyzed at a tertiary referral center from January 2006 to December 2015. Main outcomes included evaluation of grade III/IV complications, mortality rate, overall and disease-free survival, and prognostic factors influencing survival on a Cox multivariate analysis. RESULTS: Sixty-seven CRSs were performed on 67 patients during this time for colorectal peritoneal metastases. The median patient age was 57 years with 55.2% being female. The median peritoneal carcinomatosis index (PCI) was 7, with complete cytoreduction achieved in 65 (97%) cases. Grade > 2 complications occurred in 6 cases (8.9%) with no mortality. The median overall survival for the entire cohort was 41 months, with a 3-year overall survival of 43%. In case of complete cytoreduction, median overall and disease-free survival were 57 months and 36 months respectively, with a 3-year disease-free survival of 62%. Complete cytoreduction and nonmucinous histology were key factors independently associated with improved overall survival. CONCLUSIONS: CRS and HIPEC for limited peritoneal metastases from CRC are safe and effective, with acceptable morbidity. In selected patients, it offers a highly favorable long-term outcomes.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

BACKGROUND: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined, and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, peritoneal carcinomatosis index > 1) and prophylactic (PCI = 0) intent. METHODS: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS: A total of 85 patients with AGC were analyzed. A 5-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27% and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). A 5-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

Survival advantage of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) for advanced gastric cancer: experience from a Western tertiary referral center.

BACKGROUND: Selection criteria and prognostic factors for patients with advanced gastric cancer (AGC) undergoing cytoreductive surgery (CRS) plus hyperthermic intra-operative peritoneal chemotherapy (HIPEC) have not been well defined and the literature data are not homogeneous. The aim of this study was to compare prognostic factors influencing overall (OS) and disease-free survival (DFS) in a population of patients affected by AGC with surgery alone and surgery plus HIPEC, both with curative (PCI, Peritoneal Carcinomatosis Index >1) and prophylactic (PCI=0) intent. METHODS: A retrospective analysis of a prospectively collected database was conducted in patients affected by AGC from January 2006 to December 2015. Uni- and multivariate analyses of prognostic factors were performed. RESULTS: A total of 85 patients with AGC were analyzed. Five-year OS for surgery alone, CRS plus curative HIPEC, and surgery plus prophylactic HIPEC groups was 9%, 27%, and 33%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p = 0.05), curative HIPEC vs surgery alone group (p = 0.03), and curative vs prophylactic HIPEC (p = 0.04). Five-year DFS for surgery alone, CRS + curative HIPEC, and surgery + prophylactic HIPEC groups was 9%, 20%, and 30%, respectively. Statistical significance was reached comparing both prophylactic HIPEC vs surgery alone group (p < 0.0001), curative HIPEC vs surgery alone group (p = 0.008), and curative vs prophylactic HIPEC (p = 0.05). CONCLUSIONS: Patients with AGC undergoing surgery plus HIPEC had a better OS and DFS with respect to patients treated with surgery alone.

Single-Docking Full Robotic Surgery for Rectal Cancer: A Single-Center Experience.

PURPOSE: Robotic surgery has gradually gained importance in the treatment of rectal cancer. However, recent studies have not shown any advantages when compared with laparoscopy. The objective of this study is to report a single surgeon's experience in robotic rectal surgery focusing on short-term and long-term outcomes. METHODS: Sixty consecutive robotic rectal resections for adenocarcinoma, over a 4-year period, were retrospectively reviewed. Patients' characteristics and perioperative outcomes were analyzed. Oncological outcomes and surgical resection quality as well as overall and disease-free survival were also assessed. RESULTS: Thirty patients out of 60 (50%) underwent neoadjuvant therapy. Anterior rectal resection was performed in 52 cases (86.7%), and abdominoperineal resection was done in 8 cases (13.3%). Mean operative time was 283 (±68.6) minutes. The conversion rate was 5% (3 patients). Postoperative complications occurred in 10 cases (16.7%), and reoperation was required in 1 case (1.7%). Mean hospital stay was 9 days, while 30-day mortality was 1.7% (1 patients). The histopathological analysis reported a negative circumferential radial margin and distal margins in 100% of cases with a complete or near complete total mesorectal excision in 98.3% of patients. Mean follow-up was 32.8 months with a recurrence rate of 3.4% (2 patients). Overall survival and disease-free survival were 94% and 87%, respectively. CONCLUSIONS: Robotic surgery for rectal cancer proves to be safe and feasible when performed by highly skilled surgeons. It offers acceptable perioperative outcomes with a conversion rate notably lower than with the laparoscopic approach. Adequate pathological results and long-term oncological outcomes were also obtained.

Indications and results of pancreatic stump duct occlusion after duodenopancreatectomy.

Severe post-operative complications after pancreaticoduodenectomy (PD) are largely due to pancreatic fistula onset. The occlusion of the main pancreatic duct using synthetic glue may prevent these complications. Aim of this study is to describe this technique and to report short- and long-term results as well as the post-operative endocrine and exocrine insufficiency. Two hundred and four patients who underwent PD with occlusion of the main pancreatic duct in a period of 15 years were retrospectively analyzed. Post-operative complications and their management were the main aim of the study with particular focus on pancreatic fistula incidence and its treatment. At 1-year follow-up endocrine and exocrine functions were analyzed. We observed a 54 % pancreatic fistula incidence, most of which (77/204 patients) were a grade A fistula with little change in medical management. Twenty-eight patients developed a grade B fistula while only 2 % of patients (5/204) developed a grade C fistula. Nine patients required re-operation, 5 of whom had a post-operative grade C fistula. Post-operative mortality was 3.4 %. At 1-year follow-up, 31 % of patients developed a post-operative diabetes while exocrine insufficiency was encountered in 88 % of patients. The occlusion of the main pancreatic duct after PD can be considered a relatively safe and easy-to-perform procedure. It should be reserved to selected patients, especially in case of soft pancreatic texture and small pancreatic duct and in elderly patients with comorbidities, in whom pancreatic fistula-related complications could be life threatening.

Anastomotic leakage after anterior resection for rectal cancer with mesorectal excision: incidence, risk factors, and management.

We investigated risk factors and prognostic implications of symptomatic anastomotic leakage after anterior resection for rectal cancer, and the influence of a diverting stoma. Our retrospective review of prospective collected data analyzed 475 patients who underwent anterior resection for rectal cancer. Uni- and multivariate analysis was made between anastomotic leakage and patient, tumor, and treatment variables, either for the overall group (n = 475) and in the midlow rectal cancer subgroup (n = 291). Overall rate of symptomatic leakage was 9 per cent (43 of 475) with no related postoperative mortality. At univariate analysis, significant factors for leak were a tumor less than 6 cm from the anal verge (13.7 vs 6.6%; P = 0.011) and intraoperative transfusions (16.9 vs 4.3%; P = 0.001). Similar results were observed in the midlow rectal cancer subgroup. At multivariate analysis, no parameter resulted in being an independent prognostic factor for risk of leakage. In patients with a leakage, a temporary enterostomy considerably reduced the need for reoperation (12.5 vs 77.8%; P < 0.0001) and the risk of a permanent stoma (18.7 vs 28.5%; P = 0.49). The incidence of anastomotic failure increases for lower tumors, whereas it is not influenced by radiotherapy. Defunctioning enterostomy does not influence the leak rate, but it mitigates clinical consequences.

Gastrointestinal stromal tumors: prognostic factors and therapeutic implications.

BACKGROUND: Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the digestive tract. They have recently been recognized as a separate nosological entity and the literature on these stromal tumors has rapidly expanded. MATERIALS AND METHODS: The surgical records of 50 patients with primary GISTs treated at the Digestive Surgery Department of the Catholic University of Rome from January 1993 to December 2010 were reviewed and the prognostic factors were analyzed. RESULTS: Surgery was performed in all patients with curative intent. The median age at presentation was 66.5 years (range, 28-81). Adjuvant therapy was administered in 26 (52%) cases. Median follow-up was 71 months (range, 5-208). There was an 8% recurrence rate. The actuarial 5-year overall and disease-free survival rates were 66.3% and 57.2%, respectively. High mitotic rate (P <0.001), tumor size greater than 10 cm (P = 0.007) and tumor rupture (P = 0.05) were the only prognostically significant negative factors for overall survival in multivariate analysis. CONCLUSIONS: The present study confirmed the important role of aggressive surgical management of GISTs to offer these patients the most appropriate treatment for long-term survival.

[Presentation, treatment and prognosis of intraductal papillary mucinous neoplasm]. / Aspetti clinici, trattamento e prognosi della neoplasia papillare intraduttale mucosecernente.

Intraductal papillary mucinous neoplasms (IPMNs) are rare tumours rising from the pancreatic duct epithelium. They are characterized by intraductal papillary growth and thick mucin secretion; mucin fills the Wirsung and/or branch pancreatic ducts and may cause ductal dilatation. IPMNs are classified into three types, according to the site of involvement: main duct type, branch duct type, and combined type. Most branch type IPMNs are benign, while the other two types are frequently malignant. Recent advances in diagnostic imaging have led to an increased frequency of diagnosis of IPMNs, but the clinical features of them can range broadly from benign, borderline, and malignant non-invasive to invasive lesions, and their management has not yet been clearly defined. The most of patients are asymptomatic. The possibility of malignancy is increased in cases which large mural nodules are presented. Presence of a large branch type IPMN and marked dilatation of the main duct indicate the existence of adenoma. Not infrequently, synchronous or metachronous malignancies may be developed in various organs. Endoscopic retrograde cholangiopancreatography (ERCP), endoscopic ultrasonography (EUS), intraductal ultrasonography, and magnetic resonance cholangiopancreatography (MRCP) are the most valuable imaging techniques for diagnosis of these lesions. Prognosis is excellent after complete resection of benign and non-invasive malignant IPMNs. Total pancreatectomy should be reserved for patients with resectable but extensive IPMN involving the whole pancreas; its benefits must be balanced against perioperative risks.

Risk factors associated with pancreatic fistula after distal pancreatectomy, which technique of pancreatic stump closure is more beneficial?

AIM: To identify risk factors related to pancreatic fistula in patients undergoing distal pancreatectomy (DP) and to determine the effectiveness of using a stapled and a sutured closed of pancreatic stump. METHODS: Sixty-four patients underwent DP during a 10-year period. Information regarding diagnosis, operative details, and perioperative morbidity or mortality was collected. Eight risk factors were examined. RESULTS: Indications for DP included primary pancreatic disease (n=38, 59%) and non-pancreatic malignancy (n=26, 41%). Postoperative mortality and morbidity rates were 1.5% and 37% respectively; one patient died due to sepsis and two patients required a reoperation due to postoperative bleeding. Pancreatic fistula was developed in 14 patients (22%); 4 of fistulas were classified as Grade A, 9 as Grade B and only 1 as Grade C. Incidence of pancreatic fistula rate was significantly associated with four risk factors: pathology, use of prophylactic octreotide therapy, concomitant splenectomy, and texture of pancreatic parenchyma. The role that technique (either stapler or suture) of pancreatic stump closure plays in the development of pancreatic leak remains unclear. CONCLUSION: The pancreatic fistula rate after DP is 22%. This is reduced for patients with non-pancreatic malignancy, fibrotic pancreatic tissue, postoperative prophylactic octreotide therapy and concomitant splenectomy.

[Retroperitoneal Castleman's disease. A report of two cases and analysis of the literature]. / Malattia di Castleman retroperitoneale. Due casi clinici e analisi della letteratura.

Castleman's disease is a rare disorder of the lymphoid tissue with three possible histological variants--the hyalin-vascular type, with a good prognosis, the plasma-cellular type and the mixed type; the latter two are both more aggressive than the hyalin-vascular type. Two clinical types of this disease have already been described: the localized or unifocal type and the multicentric or multifocal type. The aetiology of Castleman's disease remains unclear due to polymorphic clinical features that give rise to many diagnostic and treatment problems. Its diagnosis, therefore, can only be confirmed by histological examination. Surgical treatment is the treatment of choice in patients with Castleman's disease, but radical removal of the tumour mass, especially in the multicentric type, is not always possible. We are still in no position to draw definitive conclusions as to treatment, because there are only a few reports with different regimens regarding patients with multicentric Castleman's disease. A better understanding of the pathogenesis of this rare disorder may help in deciding the best treatment approach. In this study, we report two cases of Castleman's disease, one hyalin-vascular and the other plasma-cellular, both of which were unifocal and located in a retroperitoneal-pararenal site. We also analyse the main clinical, diagnostic and treatment problems associated with this rare condition, with an overview of the literature.

[Chronic pain after inguinal hernia mesh repair: possible role of surgical manipulation of the inguinal nerves. A prospective multicentre study of 973 cases]. / Il dolore cronico dopo ernioplas ica inguinale con protesi: il possibile ruolo della manipolazione chirurgica dei nervi del canale inguinale.

The aim of the study was to evaluate whether the surgical treatment reserved for the ilioinguinal, iliohypogastric and genital branches of the genitofemoral nerves, during open hernia mesh repair, is effective in reducing chronic post-operative pain. A multicentre prospective study involving 11 Italian Institutions led to the recruitment of 973 cases of hernioplasty. All surgeons were asked to report whether or not each nerve had been identified and preserved or divided. The main endpoint of the study was the evaluation of moderate-severe chronic pain at 6 months and 1 year. Overall, presence of groin pain at 6 months and 1 year follow-up was 9.7% and 4.1%, respectively. Pain was mild in 7.9% and moderate-to-severe in 2.1% at 6 months, and mild in 3.6% and moderate-to-severe in 0.5% at 1 year. Univariate and multivariate analysis showed that lack of identification of nerves is significantly correlated with presence of chronic pain, the risk of developing inguinal pain increasing with the number of nerves not detected. Likewise, division of nerves was clearly correlated with presence of chronic pain. The present findings indicate that identification and preservation of nerves during open inguinal hernia repair reduce chronic incapacitating groin pain.

Influence of preservation versus division of ilioinguinal, iliohypogastric, and genital nerves during open mesh herniorrhaphy: prospective multicentric study of chronic pain.

OBJECTIVE: To evaluate whether the various surgical treatment reserved for ilioinguinal, iliohypogastric, and genital branch of the genitofemoral nerves, during open hernia mesh repair, is effective in reducing chronic postoperative pain. BACKGROUND: Interest in chronic groin pain following herniorrhaphy has escalated, in recent years, due both to treatment and legal implications. However, much debate still exists concerning which treatment to reserve for the 3 inguinal sensory nerves. METHODS: A multicentric prospective study involving 11 Italian institutions led to the recruitment of 973 cases of hernioplasty. All surgeons were asked to report whether or not each nerve had been identified and preserved or divided. The main endpoint of the study was the evaluation of moderate to severe chronic pain at 6 months and 1 year. RESULTS: Overall, the presence of groin pain at the 6-month and 1-year follow-up was 9.7% and 4.1%, respectively. Pain was mild in 7.9% and moderate to severe in 2.1%, at 6 months, and mild in 3.6% and moderate to severe in 0.5%, at 1 year. Univariate and multivariate analysis showed that lack of identification of nerves is significantly correlated with presence of chronic pain, the risk of developing inguinal pain increasing with the number of nerves not detected. Likewise, division of nerves was clearly correlated with presence of chronic pain. CONCLUSIONS: The present findings indicate that identification and preservation of nerves during open inguinal hernia repair reduce chronic incapacitating groin pain and that, in the majority of patients with chronic pain at 6 months, the pain at 1 year is resolved only with conservative or medical treatment.

Pancreatoduodenectomy for tumors of Vater's ampulla: report on 94 consecutive patients.

Evaluation of prognostic factors of adenocarcinoma of Vater's ampulla is still a matter of debate. The aim of this study was to evaluate retrospectively factors that influence early and long-term outcomes in a 20-year single-institution experience on ampullary carcinoma. A total of 94 consecutive patients with ampullary carcinoma or adenoma with severe dysplasia were managed from 1981 to 2002. Among them, 64 underwent pancreatoduodenectomy, and the remaining 30 submitted to surgical (n = 5) or endoscopic (n = 25) palliative treatment. Demographic, clinical, and pathologic data were collected, and a comparison was made between patients who did or did not undergo resection. Standard statistical analyses were carried out in an attempt to establish a correlation between clinical variables, intraoperative and pathologic factors, and survival in patients with resection. A total of 85 (90.4%) patients had potentially resectable lesions due to the extent of the tumor, but only 64 (68%) underwent curative resection. The surgical morbidity rate was 34.3%. Postoperative mortality was 9.3%, with no deaths among the 38 more recently treated patients. Median survivals were 9 and 54 months for nonresected and resected patients, respectively. The overall 5-year survival was 64.4% for patients undergoing pancreatoduodenectomy. Survival was found to be significantly affected by resection, tumor size, tumor grade, and tumor infiltration. Patients with negative lymph nodes show a trend toward longer survival. In a multivariate analysis, only the depth of tumor infiltration influenced patient survival. Pancreatoduodenectomy is the treatment of choice for ampullary carcinoma and adenomas with high-grade dysplasia, with a good chance of long-term survival. Surgical resection remains the most important factor influencing outcome.

Chemoradiation with raltitrexed (Tomudex) in preoperative treatment of stage II-III resectable rectal cancer: a phase II study.

PURPOSE: To evaluate the impact of preoperative chemoradiation with raltitrexed (Tomudex(1)) on tumor response, sphincter preservation, and toxicity in patients with locally advanced rectal cancer. METHODS AND MATERIALS: Between 1998 and 2002, 54 consecutive patients with Stage T3 or T2N+ resectable rectal carcinoma were treated with preoperative chemoradiation, i.v. bolus of raltitrexed on Days 1, 19, and 38 and concurrent 50 Gy external beam radiotherapy. Surgery was performed 6-8 weeks after the end of chemoradiation. RESULTS: No patients had Grade 4 acute toxicity. Grade 3 acute toxicity occurred in 16.6% of cases and was hematologic in 6 patients and GI in 2. The overall clinical response rate was 88.8%, with a complete response in 5.5%, partial response in 83.3%, and no change in 9.2%. No patient showed disease progression. All patients underwent surgery. Sphincter saving was obtained in 83.3% of patients. No perioperative mortality occurred, and the perioperative morbidity rate was 5.5%. Of 20 resected patients (37%) who were candidates for abdominoperineal resection at diagnosis (anorectal ring distance < or =30 mm), 13 (65%) underwent a sphincter-saving procedure. At pathologic examination, 13 (24%) of 54 patients had a complete pathologic response (pT0) and 10 (18.5%) had rare isolated residual cancer cells (pT, microscopic foci). Overall, 42.5% had major downstaging. The tumor regression grade (TRG), using Mandard's score system, was also applied and was TRG1 in 13 patients, TRG2 in 11, TRG3 in 20, and TRG4 in 10 patients; no patient had TRG5. CONCLUSION: The use of raltitrexed in a neoadjuvant chemoradiation schedule promoted high pathologic tumor downstaging and use of a sphincter-saving procedure. The low toxicity profile supports the rationale to explore raltitrexed combined with other drugs with different biologic targets.

[Posterior laparostomy for retroperitoneal infections caused by periampullar endoscopic procedures: an old technique for an emerging disease]. / La laparostomia posteriore nelle infezioni retroperitoneali da lesioni endoscopiche periampollari: una vecchia tecnica per una patologia emergente.

Duodenal perforations occur in 0.4-1% of endoscopic manoeuvres. In cases of periampullary injury, the best therapeutic approach is still controversial. Generally, the first treatment will be conservative, but in some patients large retroperitoneal infections requiring surgical treatment develop. Six patients, referred to our unit for extensive retroperitoneal collections and unstable septic conditions as a consequence of periampullary duodenal perforation during ERCP, were treated by right posterior laparostomy with twelfth rib resection. The septic process was treated efficaciously by the open posterior approach that favoured the spontaneous closure of the duodenal leak after a mean period of 14.5 +/- 5.2 days. No hospital deaths or major complications were recorded. Late incisional hernia developed in one case. The technique of posterior laparostomy with twelfth rib resection permits adequate debridement and drainage of both the upper and lower parts of the retroperitoneal space involved in infection after periampullary duodenal perforations. The good control of both the retroperitoneal septic process and the duodenal secretions facilitates the spontaneous closure of the duodenal leak, thus avoiding the risk of more complex and dangerous procedures.

[A rare case of digestive tract hemorrhage of extraluminal origin after total gastrectomy]. / Un raro caso di emorragia digestiva da fonte extraluminale dopo gastrectomia totale.

The authors report on a case of digestive bleeding (melaena and enterorrhagia) in a patient undergoing total gastrectomy for gastric cancer and later splenectomy for subcapsular haematoma in a different hospital. The source of bleeding was not intraluminal; the bleeding arose from double erosion of the gastroduodenal artery in the tract above the anterior surface of the pancreas, close to the dehiscent duodenal stump. The blood flowed mainly into the enteric district through the open stump thus causing the clinical signs described. The diagnosis was made during an emergency surgical operation for haemorrhagic shock. The patient underwent haemostasis with two stitches on the gastroduodenal artery, external drainage of the duodenum with a Petzer tube, laparostomy of the infected area and ileostomy. After three months he had completely recovered.