Should a History of Extraperitoneal Disease Be a Contraindication to Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy for Colorectal Cancer Peritoneal Metastases?

BACKGROUND: Survival improvements have been reported in selected patients affected by colorectal peritoneal metastases who were undergoing cytoreductive surgery with intraperitoneal hyperthermic chemotherapy. Treatment of peritoneal metastases associated with extraperitoneal disease is still controversial. OBJECTIVE: We assessed the prognostic impact of a history of extraperitoneal disease that was curatively treated either at the same time as or before the onset of peritoneal metastases. DESIGN: We reviewed 2 prospective databases. Peritoneal involvement was scored by Peritoneal Cancer Index. SETTINGS: Our study was conducted in 2 high-volume peritoneal malignancy management institutions. PATIENTS: A total of 148 patients with peritoneal metastases were included. In 27 patients, extraperitoneal disease involving the liver (n = 23), lung (n = 1), both lung and liver (n = 2), or inguinal lymph nodes and liver (n = 1) was curatively treated either simultaneously with peritoneal metastases (n = 22) or before their onset (n = 5). INTERVENTIONS: All of the macroscopic tumors were removed by means of peritonectomy procedures and visceral resections. Microscopic residual disease was treated by mitomycin C/cisplatin-based hyperthermic intraperitoneal chemotherapy. MAIN OUTCOME MEASURES: Overall survival was the primary outcome measure. RESULTS: After a median follow-up of 34.6 months (95% CI, 22.6-65.7 mo), 5-year survival of patients treated for both peritoneal and extraperitoneal disease versus peritoneal metastases alone was 16.5% versus 52.0% (p = 0.019). After multivariate analysis, reduced survival correlated with extraperitoneal disease (p = 0.001), Peritoneal Cancer Index >19 (p = 0.004), and peritoneal residual disease >2.5 mm (p = 0.018). Three prognostic groups were defined, and median survival was not reached for group 1 (Peritoneal Cancer Index ≤19 and no extraperitoneal disease), reached in 27.0 months for group 2 (Peritoneal Cancer Index ≤9 and extraperitoneal disease), and reached in 11.6 months for group 3 (Peritoneal Cancer Index >19 and no extraperitoneal disease or Peritoneal Cancer Index >9 and extraperitoneal disease). LIMITATIONS: The main study limitation is its observational nature. CONCLUSIONS: A history of extraperitoneal disease is associated with poorer prognosis. However, survival benefit may be obtained in selected patients with limited peritoneal involvement. See Video Abstract at http://links.lww.com/DCR/A655.

Hyperthermic Intraperitoneal Chemotherapy (HIPEC) at the Time of Primary Curative Surgery in Patients with Colorectal Cancer at High Risk for Metachronous Peritoneal Metastases.

BACKGROUND: Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) are maximally effective in early-stage colorectal cancer peritoneal metastases (CRC-PM); however, the use of HIPEC to treat subclinical-stage PM remains controversial. This prospective two-center study assessed adjuvant HIPEC in CRC patients at high risk for metachronous PM ( www.clinicaltrials.gov NCT02575859). METHODS: During 2006-2012, a total of 22 patients without systemic metastases were prospectively enrolled to receive HIPEC simultaneously with curative surgery, plus adjuvant systemic chemotherapy (oxaliplatin/irinotecan-containing ± biologics), based on primary tumor-associated criteria: resected synchronous ovarian (n = 2) or minimal peritoneal (n = 6) metastases, primaries directly invading other organs (n = 4) or penetrating the visceral peritoneum (n = 10). A control group retrospectively included 44 matched (1:2) patients undergoing standard treatments and no HIPEC during the same period. The cumulative PM incidence was calculated in a competing-risks framework. RESULTS: Patient characteristics were comparable for all groups. Median follow-up was 65.2 months [95 % confidence interval (CI) 50.9-79.5] in the HIPEC group and 34.5 months (95 % CI 21.1-47.9) in the control group. The 5-year cumulative PM incidence was 9.3 % in the HIPEC group and 42.5 % in the control group (p = 0.004). Kaplan-Meier estimated 5-year overall survival (OS) was 81.3 % in the HIPEC group versus 70.0 % in the control group (p = 0.047). No operative death occurred. Grade 3-4 [National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) version 4] morbidity rates were 18.2 % in the HIPEC group and 25 % in controls (p = 0.75). At multivariate analysis, HIPEC correlated to lower PM cumulative incidence [hazard ratio (HR) 0.04, 95 % CI 0.01-0.31; p = 0.002], and better OS (HR 0.25, 95 % CI 0.07-0.89; p = 0.039) and progression-free survival (HR 0.31, 95 % CI 0.11-0.85; p = 0.028). CONCLUSION: Adjuvant HIPEC may benefit CRC patients at high-risk for peritoneal failure. These results warrant confirmation in phase III trials.

Pilot study of adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at high risk for the development of peritoneal metastases.

AIMS AND BACKGROUND: The prognosis of peritoneal metastases from colorectal cancer has recently improved with cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. Although outcomes are further improved when early stage peritoneal metastases are treated, adjuvant hyperthermic intraperitoneal chemotherapy has never been thoroughly addressed. This prospective pilot study assessed feasibility, safety and efficacy of hyperthermic intraperitoneal chemotherapy combined with primary curative surgery in colorectal cancer at high risk for peritoneal metastases. METHODS: Twelve patients were prospectively selected according to predetermined risk factors for the development of peritoneal metastases. Patients underwent conventional colon surgery, closed-abdomen mitomycin-C plus cisplatin-based hyperthermic intraperitoneal chemotherapy, and cytoreductive surgical procedures, as needed. RESULTS: Preoperative tumor-related risk factors were confirmed by intraoperative findings and pathological examination in all patients: minimal synchronous peritoneal metastases (n = 2), synchronous ovarian metastases (n = 1), positive peritoneal washing cytology (n = 2), primary tumor directly invading other organs (n = 6), or penetrating visceral peritoneum (n = 1). Major morbidity occurred in 2 patients and operative death in none. Median follow-up was 49 months (range, 22-72). Peritoneal metastases occurred in 1 patient and distant metastases in 2. Five-year overall survival was 83.3%. CONCLUSIONS: Preoperative/early intraoperative assessment can reliably identify colorectal cancer patients at high risk for peritoneal metastases. Adjuvant hyperthermic intraperitoneal chemotherapy is well tolerated and safe. These preliminary results would support the design of future phase-III trials of adjuvant hyperthermic intraperitoneal chemotherapy.

Peritoneal carcinomatosis.

Several gastrointestinal and gynecological malignancies have the potential to disseminate and grow in the peritoneal cavity. The occurrence of peritoneal carcinomatosis (PC) has been shown to significantly decrease overall survival in patients with liver and/or extraperitoneal metastases from gastrointestinal cancer. During the last three decades, the understanding of the biology and pathways of dissemination of tumors with intraperitoneal spread, and the understanding of the protective function of the peritoneal barrier against tumoral seeding, has prompted the concept that PC is a loco-regional disease: in absence of other systemic metastases, multimodal approaches combining aggressive cytoreductive surgery, intraperitoneal hyperthermic chemotherapy and systemic chemotherapy have been proposed and are actually considered promising methods to improve loco-regional control of the disease, and ultimately to increase survival. The aim of this review article is to present the evidence on treatment of PC in different tumors, in order to provide patients with a proper surgical and multidisciplinary treatment focused on optimal control of their locoregional disease.

Solitary liver metastasis of chromophobe renal cell carcinoma 17 years after nephrectomy. A case report and review of the literature.

The prognosis for renal metastatic carcinoma is poor: in fact only a small portion of patients have metastases surgically treatable for their number and sizes with often a multiorgan involvement. We present a case in whit a solitary liver metastasis was incidentaly detected 17 years after nephrectomy for renal clear cell carcinoma. during a staging computed tomography performed for colonic cancer. We discuss the main feature of this rare condition.

Learning curve for cytoreductive surgery and hyperthermic intraperitoneal chemotherapy in peritoneal surface malignancies: analysis of two centres.

BACKGROUND: We assessed the learning curve (LC) of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treating peritoneal surface malignancies (PSM) in two centers and evaluated in which extent surgical tutoring could abbreviate the learning process. METHODS: Six hundred and forty-one cases submitted to CRS using peritonectomy procedures and HIPEC were considered. After having overcome its own LC, the NCI of Milan has provided technical assistance to Bentivoglio's centre for the development of a new PSM program since 2003. The risk-adjusted sequential probability ratio test (RA-SPRT) was employed to assess the LC of the two centers. Outcomes were incomplete cytoreduction, G3-5 morbidity (NCI-CTCAE.v3) and procedure-related mortality (PRM). RESULTS: Rates of incomplete cytoreduction, G3-5 morbidity, and PRM were 8.4%, 30.1%, and 3.9%, respectively, in the entire series. The breaking points of the LC concerning incomplete cytoreduction, G3-5 morbidity, and PRM were achieved at 141, 158, and 144 cases, in the Milan's experience, and at 126, 134, and 60 cases in the Bentivoglio's experience. CONCLUSIONS: Surgical tutoring could substantially shorten the steep LC associated with CRS and HIPEC. Our data should be confirmed by further studies on LC focusing oncological outcomes. Other factors that could influence the length of learning process should be identified.

Synchronous right nephrectomy, left kindey tumorectomy, right lateral hepatic sectorectomy and inferior vena cava thrombectomy for metastastic clear cell renal carcinoma. Report of a case and review of the literature.

The prognosis of stage IV renal cell carcinoma is very poor, since non-operative modalities for advanced renal carcinoma have failed to yield effective results. In fact, there is no indication for radiotherapy and systemic chemotherapy is not effective. Surgery, when indicated, seems to be the only therapeutic option possible.. Hepatectomy for metastatic renal cell carcinoma is very rarely reported, because multiple organ metastases ordinarily coexist. We report a case of a 61-year-old woman with a bilateral renal clear cell carcinoma, two synchronous liver metastasisi synchronous hepatic metastasis that were treated simultaneously with radical right nephrectomy, left upper pole kidney tumorectomy and right lateral liver sectorectomy. To the best of our knowledge this is the first case of a double liver metastasis and double renal carcinomas treated simultaneously. We discuss the specific features concerning the treatment of this unusual case.

Pseudomyxoma peritonei treated with cytoreductive surgery and hyperthermic chemotherapy: a 7-year single-center experience.

AIMS AND BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare clinical entity characterized by diffuse intraabdominal gelatinous collections with mucinous implants on the peritoneal surfaces and omentum. This condition should be considered a borderline malignancy with disease progression over time. Encouraging treatment results have been recently reported with the combination of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC). METHODS: . From December 2003 to December 2010, 18 patients with PMP were referred to our institution. All patients underwent peritonectomy and CRS combined with HIPEC in accordance with Sugarbaker's procedure. RESULTS: The mean Peritoneal Cancer Index score was 27.6 (range, 5-39). Twelve (67%) patients had disseminated peritoneal adenomucinosis and 6 (33%) peritoneal mucinous carcinomatosis. Optimal cytoreduction with no visible residual disease or residual disease ≤2.5 mm in diameter was achieved in all patients. The mean duration of the surgical procedure including HIPEC was 9 hours and 30 minutes (range, 5-13 hours); major morbidity occurred in 30% of patients and the mortality was 11%. The mean follow-up was 27 months (range, 1-72) and the 5-year overall survival 66%. CONCLUSIONS: In line with the existing literature, our experience suggests that patients with PMP could benefit from CRS + HIPEC in terms of survival and locoregional disease control.

Cytoreductive surgery and hyperthermic intraperitoneal chemotherapy as upfront therapy for advanced epithelial ovarian cancer: multi-institutional phase-II trial.

OBJECTIVE: The primary end-point of this multi-institutional phase-II trial was to assess results in terms of overall survival after cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) in treatment-naive epithelial ovarian cancer (EOC) with advanced peritoneal involvement. Secondary end-points were treatment morbi-mortality and outcome effects of time to subsequent adjuvant systemic chemotherapy (TTC). METHODS: Twenty-six women with stage III-IV EOC were prospectively enrolled in 4 Italian centers to undergo CRS and closed-abdomen HIPEC with cisplatin and doxorubicin. Then they received systemic chemotherapy with carboplatin (AUC 6) and paclitaxel (175 mg/m(2)) for 6 cycles. RESULTS: Macroscopically complete cytoreduction was achieved in 15 patients; only minimal residual disease (≤2.5 mm) remained in 11. Major complications occurred in four patients and postoperative death in one. After a median follow-up of 25 months, 5-year overall survival was 60.7% and 5-year progression-free survival 15.2% (median 30 months). Excluding operative death, all the patients underwent systemic chemotherapy at a median of 46 days from combined treatment (range: 29-75). The median number of cycles per patient was 6 (range: 1-8). The time to chemotherapy did not affect the OS or PFS. CONCLUSIONS: In selected patients with advanced stage EOC, upfront CRS and HIPEC provided promising results in terms of outcome. Morbidity was comparable to aggressive cytoreduction without HIPEC. Postoperative recovery delayed the initiation of adjuvant systemic chemotherapy but not sufficiently to impact negatively on survival. These data warrant further evaluation in a randomized clinical trial.

Giant ileal gastrointestinal stromal tumour presenting as an intestinal subocclusion and subsequent haemoperitoneum: a case report and a review of the literature.

We describe a case of a 76-year-old man with a giant ileal gastrointestinal stromal tumour (GIST) causing an intestinal subocclusion and a subsequent haemoperitoneum. During his hospital stay for a sudden hypovolemic shock, the patient underwent an urgent laparotomy and a 20 cm × 15 cm ruptured ileal GIST causing haemoperitoneum was found. Only 13 cases of ileal GIST causing peritoneal bleeding have been described since 2000, the one we presented is the largest. Although rare this pathological entity should be kept in mind in case of sudden abdominal pain and hypovolemic shock in patients with a large intraabdominal mass.

Hepatobiliary cystoadenoma: a wolf in sheep's clothing.

Hepatobiliary cystoadenoma is a rare cystic tumor of the liver that can undergo malignant change and become lethal. Accurate diagnosis of such lesions, even though not always possible, is of importance as the management is totally different from that of other nonneoplastic cysts. We report a case of a 60-year-old woman with aspecific symptoms, which was diagnosed using ultrasound scan and CT scan and treated with hepatic resection, and review the main features of this tumor.

Prompt recognition of stump appendicitis is important to avoid serious complications: a case report.

INTRODUCTION: Stump appendicitis is a rare complication of appendectomy due to recurrent inflammation of the residual appendix. The diagnosis is often delayed due to low index of suspicious, which may result in serious complications. CASE PRESENTATION: We describe a case of stump appendicitis occurred 12 months after appendectomy in 25 years old man. Despite past medical history of appendectomy the diagnosis was made by means of ultrasound scan and an high degree of clinical suspicion. CONCLUSIONS: Stump appendicitis is a rare but important complication of appendectomy, often misdiagnosed. Prompt recognition is important to avoid serious complications. This pathologic entity should always be kept in mind on case of right lower quadrant pain.

Jejunal adenocarcinoma: still an elusive diagnosis. Case report and review of the literature.

Tumours arising in the small bowel are rare, accounting for less then 2% of all gastrointestinal neoplasms. Adenocarcinoma accounts for 40% of small bowel malignancies. They are rarely considered as a differential diagnosis, and their discovery is usually greeted with surprise. We present a case in which aspecific symptoms of this neoplasm, non-informative instrumental examinations and a coexisting hiatal hernia led to the misdiagnosis of reflux disease until a complication such as abdominal occlusion occurred. To the best of our knowledge this is the second case in the literature in which a jejunal adenocarcinoma mimicked a gastro-oesophageal reflux disease and delayed the correct diagnosis.

[Adjuvant hyperthermic intraperitoneal chemotherapy in patients with colorectal cancer at risk of carcinomatosis: preliminary experience of a single centre]. / Chemioipertermia intraperitoneale adiuvante in pazienti con carcinoma colorettale a rischio di carcinosi: esperienza preliminare di un singolo centro.

The treatment of patients at high risk of developing colorectal peritoneal carcinomatosis is still debated since the absence of peritoneal disease synchronous with the primitive cancer makes the application of aggressive treatments less obvious. In this subset of patients hyperthermic intraperitoneal chemotherapy (HIPEC), after the resection of the primitive cancer, may improve long-term survival. Over the period from December 2003 to June 2008 142 patients affected by different kinds of cancers underwent HIPEC in the surgical division of Bentivoglio Hospital, A.U.S.L. Bologna. In 13 patients HIPEC was combined only with the resection of the primitive cancer and no major cytoreductive surgery was performed. Nine of these 13 patients were affected by colorectal cancer and at high risk of developing carcinomatosis. The average surgical time was 420 min (range: 300-510). No intraoperative complications occurred, but 3 cases of postoperative morbidity were reported; only 1 of these was a major complication At an average follow-up of 22 months 1 patient with a liver metastasis died of complications unrelated to progression of the disease, 1 patient had a lymph node relapse and is currently on systemic chemotherapy, while the remaining 7 patients are alive and free from peritoneal disease.

Hamartochondroma arising from a tracheal bronchus.

Tracheal bronchus is a congenital abnormality rarely described in the literature. It is mostly completely asymptomatic. This condition may rarely be associated with inflammatory diseases. Exceptional are those cases in which the condition is associated with malignancy. We describe a case of a 45-year-old man in whom a 3-month history of non-productive cough and chest pain led to a diagnosis of a solitary pulmonary nodule associated with a tracheal bronchus. The histopathological examination after VATS enucleation showed the presence of a hamartochondroma. To the best of our knowledge this is the first case in which a hamartochondroma has been found to be associated with a tracheal bronchus.

Synchronous nephrectomy and right hepatectomy for metastatic chromophobe renal cell carcinoma: report of a case and review of the literature.

The prognosis of metastatic renal cell carcinoma is poor, since non-operative modalities for advanced renal carcinoma have failed to yield effective results. In fact, there is no indication for radiotherapy, except for palliative treatment of symptomatic bone metastases, and systemic chemotherapy is not effective. Despite the promising early results with immunotherapy, a complete response occurs in less than 15% of patients and is rarely lasting. Surgery, when indicated, seems to be the only therapeutic option possible. Liver metastases occur in 20% of cases and are often multiple. Experience with hepatectomy for metastatic renal tumours has rarely been reported. Not only does a small group of patients have isolated liver metastases that may be treated with radical surgery, but also extrahepatic metastases ordinarily coexist at the time of diagnosis. We report a case of a 55-year-old man with a chromophobe renal cell carcinoma with a single synchronous hepatic metastasis that were treated simultaneously with radical nephrectomy and right hepatectomy. To the best of our knowledge this is the first case of a single metastasis of a chromophobe renal cell carcinoma treated with synchronous kidney and hepatic resection.

Predicting conversion to open surgery in laparoscopic left hemicolectomy.

PURPOSE: The objective of this study was to quantify the risk of conversion to open surgery of laparoscopic left hemicolectomy at an early stage of the learning curve. METHODS: A multiple logistic regression analysis of 100 laparoscopic left hemicolectomies completed between April 2001 and May 2004 was performed. RESULTS: The overall conversion rate was 12%. At univariate analysis, 2 factors were found to be predictive of conversion to open surgery: malignancy (17.2% vs. 5%; P=0.046), and weight level (<60 kg=6.1%; 60 to 90 kg=11.3%; >90 kg=28.6%; P=0.049). At multiple logistic regression, the risk of conversion rose only for patients weighing more than 90 kg. CONCLUSIONS: On the basis of the results of this study, the surgeon will be able to quantify the risk of conversion to laparotomy with some precision in order to obtain the informed consent of the first 100 patients to whom laparoscopic left hemicolectomy is proposed.

Hypovolemic shock caused by a true aneurysm of the pancreatico-duodenal artery: case report and review of the literature.

True pancreatico-duodenal artery aneurysm (PDAA) is a rare condition that since 1973 has been described in only 54 cases. It is frequently associated with celiac axis stenosis and often present with rupture. Even if most PDAAs that are not ruptured are asymptomatic and are diagnosed during investigation for other diseases, they may have some symptoms, such as chronic abdominal discomfort and an abdominal pulsating mass, that can be helpful for diagnosis. The treatment of this condition has evolved in time from a merely surgical one to an angiographic noninvasive approach. We present a case of a PDAA that manifested with sudden hypovolemic shock requiring an emergency operation, and through a review of the literature, we discuss the different diagnostic/therapeutic protocols to use in different situations.

[Laparoscopic colorectal surgery: is the "learning curve" necessary?]. / Chirurgia colo-rettale laparoscopica: e necessaria la "curva di apprendimento"?

AIM OF THE STUDY: To present the early experience of the Authors' division in the field of colorectal laparoscopic surgery, in order to evaluate the so-called "learning curve". MATERIALS AND METHOD: From February 2003 to May 2004, we have performed 220 surgical procedures for colorectal pathology: 63 were conducted by a laparoscopic approach with 10 patients who, converted to a laparotomic procedure in theatre, were not taken under consideration. The present work is thus based on a population of 53 patients, 27 men and 26 women, at a median age of 64.4 y.o. (range 42-81). RESULTS: We performed 1 total colectomy, 24 right hemicolectomy, 1 resection of the splenic flexure, 12 left hemicolectomy (in 1 case a left hepatic lobectomy was associated), 11 anterior resection of the rectum, 1 Hartmann' sigmoid resection and 3 abdomino-perineal resection. Mean operative time was 200.34 +/- 64.17 min, while the mean hospital stay was 6.44 +/- 2.68 days. Peri-operative mortality was 0%, 30-days mortality was 1/53 patients (9%) while morbidity was 5/53 patients (9.4%): in 2 cases reintervention was necessary. DISCUSSION: From the evaluation of the results, we found some significant data: first, the conversion rate was similar to those reported by other authors, so also the mortality and morbidity rates. CONCLUSIONS: The advantages of the laparoscopic technique, indirectly documented by shorter in-hospital stay. At least for patients submitted to right or left hemicolectomy without complications (5.5 e 5.7 days, respectively), could be seen also after only a 1 year of activity. As far as the "learning curve" is concerned, dividing our activity into 3 times, we verified a progressive shortening of the operative time and, at least for the patients submitted to a right emicolecomy, also of the morbidity rates.