Francesca Costa

The Learning Curve in Robotic Pancreaticoduodenectomy

Background/Purpose: Few data are available on the learning curve (LC) in robot-assisted pancreaticoduodenectomy (RAPD) and no study specifically addresses the LC of a single surgeon. Methods: The LC of a single surgeon in RAPD was determined using the cumulative sum method, based on operative time (OT). Data were extracted from a prospectively maintained database and analyzed retrospectively considering all events occurring within 90 days of index operation. Results: Seventy RAPD were analyzed. One operation was converted to open surgery (1.4%). One patient died within 30 days (1.4%) and one within 90 days (2.8%). Postoperative complications occurred in 53 patients (75.7%) and exceeded Clavien-Dindo grade IIIb in 7 patients (10%). OT dropped after 33 operations from a mean of 564 ± 101.7 min to a mean of 484.1 ± 77.9 min (p = 0.0005) and was associated to reduced incidence of delayed gastric emptying (72.7 vs. 48.7%; p = 0.039). The rate of hospital readmission improved after 40 operations from 20.0 (8 of 40) to 3.3% (1 of 30) (p = 0.04). Conclusions: RAPD was safely feasible in selected patients. OT dropped after the first 33 operations and was associated with reduced rate of delayed gastric emptying. Readmission rate improved after 40 operations.

Adjuvant chemotherapy seems beneficial for invasive intraductal papillary mucinous neoplasms

AIMS The incidence of intraductal papillary mucinous neoplasm (IPMN) is rising and these neoplasms now represent up to 25% of resected pancreatic neoplasms. The optimal postoperative management of resected invasive IPMN is still debated in the absence of large prospective clinical trials and of validated prognostic factors in this setting. The objective of our study was to identify potential prognostic factors and to investigate the role of adjuvant therapies for patients radically resected for invasive IPMN. METHODS We retrospectively reviewed clinical and pathological data regarding a large series of patients with invasive IPMN who underwent surgical resection in the last six years at University Hospital of Pisa. RESULTS Sixty-four patients were considered for the analysis, thirty-three of whom received adjuvant chemotherapy with gemcitabine. In our series node involvement and high tumoral grade emerged as the major pathologic prognostic factors. Patients treated with adjuvant chemotherapy with gemcitabine experienced a longer disease-free survival than those who received surgery alone. CONCLUSIONS Gemcitabine-based chemotherapy seems beneficial as adjuvant treatment for patients with resected invasive IPMN.

Analysis of Instrument Traffic During Laparoscopic Robot-Assisted Pancreaticoduodenectomy

Context Robotic surgery entails specific issues that are not present, or are not equally relevant, in open surgery or conventional laparoscopy. Instrument traffic (IT) is one of such issues. IT is the time during which surgery is paused because the surgeon at the console is waiting for the action of the surgeon the table (e.g., instrument change, camera cleaning, introduction/withdrawal of needles). Objective We provide the first objective evaluation of IT during robotic pancreaticoduodenectomy (PD). Methods The operative videos of 12 robot-assisted PDs were reviewed to define IT. The analysis included: crude IT time (CITT), relative IT time (RITT) (defined as the percentage of operative time spent for IT), number of robotic instruments changes (RIC), time spent for RIC (TRIC), number of pure laparoscopic actions (PLA), and time spent for PLA (TPLA). Figures were estimated for the entire operation as well as for dissection and reconstruction phases. Details on pancreaticojejunostomy (PJ) or hepaticojejunostomy (HJ) were related to IT to define their relative impact on operative time. Results Mean operative time was 517 min (range 420-600 min). Mean CITT was 3,681.6 sec (RITT 11.89%). Mean RIC or PLA was 315.7. Each RIC or PLA paused surgery for 11.8 sec. Mean RIC was 184.4 (TRIC 2,633.8 sec). Mean PLA was 131.4 (TPLA 1,039.5 sec). Mean dissection time was 326.9 min. Mean CITT was 2,095.1 sec (RITT 10.68%). Mean RIC was 105.8 (TRIC 1,645.2 sec). Mean PLA was 35.7 (TPLA 382.5 sec). Each RIC or PLA paused surgery for 14.4 sec. PJ was made by invaginating technique or duct-to-mucosa. The last one required fewer stitches, but did not reduced CITT or RIC. HJ was performed using either 4 half running sutures or interrupted external stitches plus inner half running sutures. Despite similar CITT the former technique was associated with fewer RIC. Conclusions Some 12% of operative time of laparoscopic robot-assisted PD is wasted because of IT. Since in this series operative time of robotic PD averaged 517 minutes, IT prolonged surgery of more than one hour. Technology improvements and/or refinements in surgical technique are expected to reduce IT during robotic PD.

Pancreatic Metastasis from Colorectal Cancer

Context Pancreatic metastases are rare (2% of all pancreatic carcinomas). Very few cases about surgical treatment of colorectal cancer metastases to the pancreas are reported. Case report We report a case of single colorectal cancer metastasis to the pancreas managed by distal splenopancreatectomy in a patient undergone to left hemicolectomy for the primary tumor eight years before and to middle lung lobectomy for metastasis one year before. A 61-year-old asymptomatic woman with a history of colorectal cancer was admitted to our department after that during the oncological imaging follow-up a thoracic-abdominal contrast-enhanced computed tomography (CT) demonstrated a single 25 mm hypodense lesion in the pancreatic tail. She also presented high levels of CEA (61.7 ng/mL) and CA 19-9 (82.9 U/mL) before the admission. Eight years before the patient underwent to left hemicolectomy for a B2-Dukes classification colorectal cancer. The resected margins were free of tumor and no regional lymph nodes were positive. One year before the patient underwent to a lung lobectomy for a single 30 mm pulmonary metastases. Considering history and imaging findings, the pancreatic lesion was suspected a colorectal cancer metastasis. A distal splenopancreatectomy was performed. The patient was discharged in healthy conditions. Final pathology disclosed the pancreatic lesion was a colorectal cancer metastasis (CD20+, CK7-) with infiltration of the peri-pancreatic adipose tissue. The resected margins were free of tumor and no lymph nodes were metastasized. The patient is still alive. Conclusion Metastases to the pancreas are commonly considered rare, especially those from colorectal cancer. The improvement of imaging techniques has led to an increase of diagnoses and surgical procedures for metastases to the pancreas. Secondary tumors may be considered in the differential diagnosis of primitive pancreatic lesions. The diagnosis may be facilitated by clinical history and serum markers assessment. Metastatic colorectal cancer to the pancreas is an indication for pancreatic resection to increase the overall survival and, as palliative procedure, to treat symptoms like jaundice and pain.

Robotic Pancreatectomy for Pancreatic and Periampullary Cancer

Context Minimally invasive surgery, when feasible, should accept no oncologic compromise in the setting of pancreatic and periampullary cancer since local radicality is key for all these tumor types. Objective We herein report on 50 patients undergoing robotic pancreatic resection because of pancreatic or periampullary cancer. Methods Fifty patients diagnosed with malignant tumors were selected for laparoscopic robot-assisted pancreatectomy between October 2008 to June 2012. There were 28 males (56%) and 22 females (44%), with a mean age of 60 years (range 24-78 years). Twenty-five patients underwent pancreaticoduodenectomy (PD) (50%), 16 distal pancreatectomy (DP) (32%), 7 total pancreatectomy (TP) (14%), and 2 to central pancreatectomy (CP) (4%). Results Final pathology disclosed neuroendocrine carcinoma (NEC) in 7 patients (14%), cancer arising on IPMN in 9 cases (18%), ductal adenocarcinoma (DA) in 19 cases (38%), cholangiocarcinoma (CHC) in 5 patients (10%), carcinoma of the papilla of Vater in 5 cases (10%) (4 PD), solid pseudopapillary tumor in 2 (4%) and adenosquamous carcinoma in 1 case (2%). Resection margins were all negative. A mean number of 30 lymph nodes (range 5-74) was retrieved en-bloc with the specimen. 22 patients had lymph node metastasis (44%) including 11 diagnosed with DA (60%), 4 with CHC (80%) and 4 with NEC (5.7%). After a mean follow-up period of 14.1 months (range 1-42 months) all but 2 patients are disease-free (96%). Conclusions After a learning curve, best completed on patients with benign pancreatic diseases, laparoscopic robot-assisted pancreatic resection seems to offer the potential for radical tumor clearance in selected patients without locally advanced pancreatic and periampullary cancer. Further experience and longer follow-up are both needed before any final conclusion can be drawn.

Resection of an Isolated Arterial Segment During Pancreatectomy

Context Isolated involvement of an arterial segment in pancreatic tumors occurs infrequently and does not necessarily mean tumor unresctability being possibly caused by tumor location rather than by excessive growth. Objective We report on the outcome of a highly selected group of patients undergoing pancreatectomy plus resection of an isolated arterial segment at a single Institution. Methods From January 1993 to May 2011 resection of an isolated arterial segment was performed during 26 pancreatectomies. There were 12 males (46.2%) and 14 females (53.8%) with a mean age of 63.6 years. One patient was operated by robotic surgery. Two patients underwent total pancreatectomy (7.7%), 5 pancreaticoduodenectomy (19.2%) and 19 distal splenopancreatectomy (73.1%). Resected arterial segments were celiac trunk (CT) (n=14), hepatic artery (HA) (n=8), CT and HA (n=4). In 6 patients the hepatic arterial flow was re-established by end-to-end anastomosis (n=1), transposition of the left gastric artery (n=1) and interposition of a saphenous vein jump-graft (n=4). Multivisceral resection was required in 9 patients. Results Final pathology disclosed ductal adenocarcinoma (DA) in 18 patients (69.2%), other pancreatic tumor types or periampullary carcinoma in 5 (19.2%) patients and metastatic tumor in 3 patients (11.5%). Fifteen DA patients were node positive (83.3%). Post-operative morbidity and mortality were 55.5% and 3.8%, respectively. After a mean follow up period of 111 months (range 5-225 months), actual survival rate was 64% at 1 year and 20% at 3 years. Equivalent figures for DA were 30% and 15%, respectively. These data favorably compare with an historical cohort of patients with locally advanced DA undergoing palliation without resection. No patient developed local recurrence, despite none received pre- or post-operative radiation. Conclusions In patients affected by DA the resection remains key for cure and possibly provides the best palliative treatment. Highly selected patients with isolated involvement of CT and/or HA may undergo pancreatectomy with results similar to patients without vascular involvement and superior to those offered by palliation or medical therapy alone. The lack of local recurrence seems to be a relevant treatment endpoint.

Ninety-Percent Distal Pancreatectomy

Context Brittle diabetes typically plagues the quality of life of patients after total pancreatectomy. Sparing even a small amount of endocrine tissue avoids extreme glycemic fluctuations, by maintaining a source of servo-regulated endogenous production of all pancreatic hormones (insulin, glucagon, somatostatin and pancreatic polypeptide). Objective We report on the outcome of a selected group of patients undergoing ninety-percent distal pancreatectomy (90% DP). Methods From April 2000 to May 2012, 90% DP was performed in 26 patients: 7 males (27%) and 19 females (73%), with a mean age of 68 years (range 40-79 years). Twenty-three patients underwent conventional open resection while 3 had a laparoscopic operation (robot-assisted in 2 of them). Splenectomy was associated in 24 patients (92%), while 2 had a multivisceral resection. Segmental resection of peripancreatic vessels was associated in 4 patients (1 celiac trunk-hepatic artery, and 3 superior mesenteric/portal vein). Results Seventeen patients were diagnosed with ductal adenocarcinoma (65%), 3 with well-differentiated endocrine tumor (12%), 3 with a serous cystadenoma, 1 with a mucinous cystadenocarcinoma (4%), 1 with carcinoma on IPMN, and 1 patient with chronic pancreatitis. Mean operative-time was 330 minutes (range 180-535 minutes). There was no post-operative mortality with a morbidity of 40%. Pancreatic fistula was recorded in 8 patients (32%) and was always managed conservatively. Thirteen patients developed insulin dependent diabetes mellitus (50%) and 16 developed exocrine insufficiency (61%) requiring enzyme supplementation. Conclusions 90% DP may be considered in patients with centrally located pancreatic lesions to avoid the complications due to pancreatic exocrine and endocrine insufficiency. In selected patients 90% DP may be performed laparoscopically, especially if robotic assistance is available. Careful patient selection and extended experience in pancreatic surgery are crucial to achieve the best results.

The Titanium Surface Modulates the Expression of Beta-Catenin and DLX5 Genes in Pancreatic Ductal Carcinoma in Vitro. Can the Metallic Stent Increase PDAC Aggressiveness?

Context Adenoductal pancreas (PDAC) is a fatal cancer. Its aggressiveness is associated in part with the EMT process of metastasis. Two genes specifically involved in these phenomena are b-catenin and DLX5. While the first gene has been widely studied also in pancreatic cancer, few data are associated with DLX5. However, its over-expression has been recently associated with the formation of metastases in breast cancer in vivo . An exogenous factor involved in the modulation of the expression of these genes seems to be titanium. This compound is usually employed for the pallia action of patients with PDAC, to reduce choledochal stenosis due to compression. Objective The purpose of this study was to assess whether titanium is able to modulate the expression of these two genes in vitro . Methods We used a primary cell culture of PADC (PP78). The cells were seeded and cultivated in contact with two different titanium surfaces for 10 days. After this period the total mRNA was extracted and the quantification of β-catenin and DLX5 genes was performed by RT-PCR according to the ΔΔCt analysis. Then cells were stained using the immunofluorescence technique (IF) to quantify the b-catenin protein expression .using a computerized high-resolution acquisition system (D-Sight, Menarini, Florence, Italy) The cells were scored evaluating the cytoplasmic positivity as follows (0 absent, 1 low, 2 middle, 3 strong). The experiment was carried out in triplicate and untreated cells (without titanium contact) were used as control. Results Quantitative analyses showed that both titanium surfaces positively affected beta-catenin (mean 2.8 fold) and DLX5 (2.0 fold) mRNA expressions with respect to the controls (P<0.0007). Both titanium surfaces also increased the protein score 3 values of β-catenin in treated cells with respect to their controls (P=0.0158). Conclusion Our data showed that several titanium surfaces positively modulated the expression of two genes associated with the increase of the aggressiveness of PDAC in vitro. Clinical studies are needed to find out which type of stent can be used in the surgical operation with palliative intent.