Prophylactic abdominal drainage or no drainage after distal pancreatectomy (PANDORINA): a binational multicenter randomized controlled trial.

BACKGROUND: Prophylactic abdominal drainage is current standard practice after distal pancreatectomy (DP), with the aim to divert pancreatic fluid in case of a postoperative pancreatic fistula (POPF) aimed to prevent further complications as bleeding. Whereas POPF after pancreatoduodenectomy, by definition, involves infection due to anastomotic dehiscence, a POPF after DP is essentially sterile since the bowel is not opened and no anastomoses are created. Routine drainage after DP could potentially be omitted and this could even be beneficial because of the hypothetical prevention of drain-induced infections (Fisher, Surgery 52:205-22, 2018). Abdominal drainage, moreover, should only be performed if it provides additional safety or comfort to the patient. In clinical practice, drains cause clear discomfort. One multicenter randomized controlled trial confirmed the safety of omitting abdominal drainage but did not stratify patients according to their risk of POPF and did not describe a standardized strategy for pancreatic transection. Therefore, a large pragmatic multicenter randomized controlled trial is required, with prespecified POPF risk groups and a homogeneous method of stump closure. The objective of the PANDORINA trial is to evaluate the non-inferiority of omitting routine intra-abdominal drainage after DP on postoperative morbidity (Clavien-Dindo score ≥ 3), and, secondarily, POPF grade B/C. METHODS/DESIGN: Binational multicenter randomized controlled non-inferiority trial, stratifying patients to high and low risk for POPF grade B/C and incorporating a standardized strategy for pancreatic transection. Two groups of 141 patients (282 in total) undergoing elective DP (either open or minimally invasive, with or without splenectomy). Primary outcome is postoperative rate of morbidity (Clavien-Dindo score ≥ 3), and the most relevant secondary outcome is grade B/C POPF. Other secondary outcomes include surgical reintervention, percutaneous catheter drainage, endoscopic catheter drainage, abdominal collections (not requiring drainage), wound infection, delayed gastric emptying, postpancreatectomy hemorrhage as defined by the international study group for pancreatic surgery (ISGPS) (Wente et al., Surgery 142:20-5, 2007), length of stay (LOS), readmission within 90 days, in-hospital mortality, and 90-day mortality. DISCUSSION: PANDORINA is the first binational, multicenter, randomized controlled non-inferiority trial with the primary objective to evaluate the hypothesis that omitting prophylactic abdominal drainage after DP does not worsen the risk of postoperative severe complications (Wente etal., Surgery 142:20-5, 2007; Bassi et al., Surgery 161:584-91, 2017). Most of the published studies on drain placement after pancreatectomy focus on both pancreatoduodenectomy and DP, but these two entities present are associated with different complications and therefore deserve separate evaluation (McMillan et al., Surgery 159:1013-22, 2016; Pratt et al., J Gastrointest Surg 10:1264-78, 2006). The PANDORINA trial is innovative since it takes the preoperative risk on POPF into account based on the D-FRS and it warrants homogenous stump closing by using the same graded compression technique and same stapling device (de Pastena et al., Ann Surg 2022; Asbun and Stauffer, Surg Endosc 25:2643-9, 2011).

Risk factors and outcomes of conversion in minimally invasive distal pancreatectomy: a systematic review.

PURPOSE: The reported conversion rates for minimally invasive distal pancreatectomy (MIDP) range widely from 2 to 38%. The identification of risk factors for conversion may help surgeons during preoperative planning and patient counseling. Moreover, the impact of conversion on outcomes of MIDP is unknown. METHODS: A systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on Minimally Invasive Pancreas Resection (IG-MIPR). The PubMed, Cochrane, and Embase databases were searched for studies concerning conversion to open surgery in MIDP. RESULTS: Of the 828 studies screened, eight met the eligibility criteria, resulting in a combined dataset including 2592 patients after MIDP. The overall conversion rate was 17.1% (range 13.0-32.7%) with heterogeneity between studies associated with the definition of conversion adopted. Only one study divided conversion into elective and emergency conversion. The main indications for conversion were vascular involvement (23.7%), concern for oncological radicality (21.9%), and bleeding (18.9%). The reported risk factors for conversion included a malignancy as an indication for surgery, the proximity of the tumor to vascular structures in preoperative imaging, higher BMI or visceral fat, and multi-organ resection or extended resection. Contrasting results were seen in terms of blood loss and length of stay in comparing converted MIDP and completed MIDP patients. CONCLUSION: The identified risk factors for conversion from this study can be used for patient selection and counseling. Surgeon experience should be considered when contemplating MIDP for a complex patient. Future studies should divide conversion into elective and emergency conversion.

The role of older age and obesity in minimally invasive and open pancreatic surgery: A systematic review and meta-analysis.

BACKGROUND/OBJECTIVES: The aim of this study was to assess the impact of older age (≥70 years) and obesity (BMI ≥30) on surgical outcomes of minimally invasive pancreatic resections (MIPR). Subsequently, open pancreatic resections or MIPR were compared for elderly and/or obese patients. METHODS: A systematic review was conducted as part of the 2019 Miami International Evidence-Based Guidelines on MIPR (IG-MIPR). Study quality assessment was according to The Scottish Intercollegiate Guidelines Network (SIGN). A meta-analysis was performed to assess the impact of MIPR or open pancreatic resections in elderly patients. RESULTS: After screening 682 studies, 13 observational studies with 4629 patients were included. Elderly patients undergoing laparoscopic distal pancreatectomy (LDP) had less blood loss (117 mL, p < 0.001) and a shorter hospital stay (3.5 days p < 0.001) than elderly patients undergoing open distal pancreatectomy (ODP). Postoperative pancreatic fistula (POPF) B/C, major complication and reoperation rate were not significantly different in elderly patients undergoing either laparoscopic or open pancreatoduodenectomy (OPD). One study compared robot PD with OPD in obese patients, indicating that patients with robotic surgery had less blood loss (mean 250 ml vs 500 ml, p = 0.001), shorter operative time (mean 381 min vs 428 min, p = 0.003), and lower rate of POPF B/C (13% vs 28%, p = 0.039). CONCLUSION: The current available limited evidence does not suggest that MIPR is contraindicated in elderly or obese patients. Additionally, outcomes in MIPR are equal or more beneficial compared to the open approach when applied in these patient groups.

ZIP4 is a novel diagnostic and prognostic marker in human pancreatic cancer: a systemic comparison between EUS-FNA and surgical specimens.

Aberrant expression of a zinc transporter ZIP4 in pancreatic ductal adenocarcinoma (PDAC) has been shown to contribute to tumor progression and is a potential target for individualized therapy. The overall objective of this study was to determine whether ZIP4 could serve as a novel diagnostic and prognostic marker in human PDAC, and if it can be assessed by minimally invasive sampling using endoscopic ultrasound guided fine needle aspiration (EUS-FNA). Immunohistochemistry was performed to compare ZIP4 expression in the PDAC samples obtained from EUS-FNA and matched surgical tumors (parallel control). Samples were reported by sensitivity, specificity, and predictive values, all with 95% confidence intervals (CI). A total of 23 cases with both FNA and surgical specimens were evaluated. We found that ZIP4 was significantly overexpressed in tumor cells from both sets of samples. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of ZIP4 for the diagnosis of PDAC were 72.9%, 72.5%, 76.1%, and 69.0% in EUS-FNA samples, and were 97.9%, 65.4%, 83.9%, and 94.4% in surgical specimens, respectively. The association between the positive rate of ZIP4 expression in FNA and surgical samples is statistically significant (P=0.0216). Both the intensity and percentage of ZIP4 positive cells from the surgical samples correlated significantly with tumor stage (P=0.0025 and P=0.0002). ZIP4 intensity level in FNA samples was significantly associated with tumor differentiation and patient survival. These results indicate that EUS-FNA is capable of non-operative detection of ZIP4, thus offering the potential to direct pre-operative detection and targeted therapy of PDAC.

Risk of gastric or peritoneal recurrence, and long-term outcomes, following pancreatic cancer resection with preoperative endosonographically guided fine needle aspiration.

BACKGROUND AND STUDY AIMS: There have been concerns regarding tumor cell seeding along the needle track or within the peritoneum caused by preoperative endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). The aim of this study was to evaluate whether preoperative EUS-FNA is associated with increased risk of stomach/peritoneal recurrence and whether the procedure affects long term survival. METHODS: The records of patients diagnosed with malignant solid and cystic pancreatic neoplasms who underwent surgery with curative intent between 1996 and 2012 were reviewed. RESULTS: A total of 256 patients with similar baseline characteristics were included: 48 patients in the non-EUS-FNA group and 208 in the EUS-FNA group. Recurrence data were available for 207 patients. Median length of follow-up was 23 months (range 0 - 111 months). A total of 19 patients had gastric or peritoneal recurrence; 6 (15.4 %) in the non-EUS-FNA group vs. 13 (7.7 %) in the EUS-FNA group (P = 0.21). Three patients had recurrence in the stomach wall: one (2.6 %) patient in the non-EUS-FNA group vs. two patients (1.2 %) in EUS-FNA group (P = 0.46). A total of 16 patients had peritoneal recurrence: 5 patients (12.8 %) in the non-EUS-FNA group and 11 patients (6.5 %) in the EUS-FNA group (P = 0.19). In a multivariate analysis, undergoing EUS-FNA was not associated with increased cancer recurrence or decreased overall survival. CONCLUSION: Pre-operative EUS-FNA was not associated with an increased rate of gastric or peritoneal cancer recurrence in patients with resected pancreatic cancer. Two patients had gastric wall recurrence following the procedure, but this may be explained by direct tumor extension. This suggests that EUS-FNA is not associated with an increased risk of needle track seeding.

Current status of laparoscopic distal pancreatectomy.

Distal pancreatectomy is the therapeutic option of choice for patients with a benign or malignant lesion located in the body and/or tail of the pancreas when surgical intervention is indicated. With recent advances in and wide spread use of imaging studies, lesions of the pancreas are being diagnosed more commonly and it is likely that this will translate into an increased number of patients undergoing surgical resection. The laparoscopic approach to pancreatic resections has not been adopted as rapidly as it has for most other general surgical procedures. This is despite the fact that the current literature appears to validate laparoscopy as an acceptable and safe approach for distal pancreatectomy in patients with benign lesions, and has demonstrated the known benefits inherent to the laparoscopic technique. These benefits include lower intraoperative blood loss, less pain and analgesic requirements, earlier return of bowel function, and shorter recovery and hospital stay. Yet controversy still exists for the role of laparoscopy in the resection of malignant lesions. Recent reports however, have shown that laparoscopic distal pancreatectomy can safely be performed in known malignancies and, most importantly, after a laparoscopic oncological resection, the oncological benchmarks that have been related to survival, (such as negative surgical margins and number of peripancreatic lymph nodes resected), can also be accomplished. We sought to review the current literature on distal pancreatectomy, specifically the indications, laparoscopic approaches, splenectomy and spleen-preserving techniques, intraoperative and short-term outcomes, morbidity, mortality and oncological outcomes.

Hypertrichosis terminalis, gingival hyperplasia, and a characteristic face: a new distinct entity.

Congenital generalized hypertrichosis terminalis has been described in association with other features as gingival hyperplasia, osteochondrodysplasia, and a dysmorphic face. Bondeson and Miles [1993: Am J Med Genet 47:198-212] described a woman with universal congenital hypertrichosis terminalis associated with gingival hyperplasia; the face of this patient was coarse and different from other forms of hypertrichosis described before. We present an 11-year, 6-month-old girl with universal congenital hypertrichosis terminalis, gingival hyperplasia, and a characteristic coarse face resembling the patient described by Bondeson and Miles [1993: Am J Med Genet 47:198-212]. We propose that this type of congenital generalized hypertrichosis terminalis, associated with gingival hyperplasia and a coarse face, is a distinctive new entity.

The effects of pneumoperitoneum on gastric blood flow and traditional hemodynamic measurements.

BACKGROUND: The purpose of this study was to investigate the effects of increasing intraabdominal pressure (IP) on gastric blood flow, as measured by gastric tonometry and traditional hemodynamic measurements. METHODS: Nine swine were anesthetized, intubated, and ventilated. Arterial and pulmonary artery catheters were placed by cutdown, a trocar was placed in the abdomen, and a gastric tonometer was placed in the stomach. Serial measurements of arterial and mixed venous blood gases, cardiac output, wedge pressure, lactic acid, and gastric intramucosal pH (pHi) were collected at intraperitoneal pressures of 0, 8, 10, 12, 14, 16, and 18 mm Hg after 30 min equilibration. Statistical analysis included Pearson correlation and Student's t test. RESULTS: Increasing levels of IP were correlated with decreased arterial pH (p < 0.00003), increased mixed venous CO2 (p < 0.003), decreased intramucosal pH (p < 0.014), and increased arterial CO2 (p < 0.015). Gastric pHi differed significantly from baseline at IP levels of 16 mm Hg (p < 0.004) and 18 mm Hg (p < 0.01). No significant effects were observed on cardiac output or arterial lactate. No significant effects were observed in a control group that had been insufflated to 8 mm Hg and held constant over 3 h. CONCLUSIONS: In this model, gastric blood flow is adversely affected by increasing i.p. with pronounced effects in excess of 15 mm Hg. These results suggest that gastric tonometry may be used to monitor the adverse effects of pneumoperitoneum. Gastric pHi may be an earlier indicator of altered hemodynamic function during laparoscopy than traditional measures.

An experimental model of cellular aerosolization during laparoscopic surgery.

Laparoscopic surgery for cancer has led to the unwelcome occurrence of malignant seeding of port sites. It is hypothesized that this seeding may be a result of aerosolization and forced egress of cells from the peritoneum as a result of pneumoperitoneum. The purpose of this study was to develop a model that would allow for future investigations of cellular aerosolization. Six swine were anesthetized, intubated, and ventilated. A port was placed in the midline and the abdomen insufflated. After insufflation a 14-gauge angiocath was placed in the abdomen through a separate site and attached to a closed system that allowed escaping air to bubble through 3 ml of saline. Intraabdominal pressure was serially increased at 30-min intervals to 8, 10, 12, 14, 16, and 18 mm Hg, and separate saline samples were collected at each interval. Saline samples were centrifuged, and epithelial cells were counted by direct vision and Giemsa staining. Epithelial cells were recovered at all levels of pneumoperitoneum. There was a moderate correlation between the level of pneumoperitoneum and the number of cells collected (r = 0.61, p < 0.19). Results of this study suggest that during pneumoperitoneum there is an ongoing egress of aerosolized cells from the abdomen. Application of this model may aid in future study of aerosolization of cancer cells during laparoscopic surgery.

Successfully establishing laparoscopic surgery programs in developing countries. Clinical results and lessons learned.

BACKGROUND: Laparoscopic surgery has not been widely established in developing countries due to the lack of access to training and lack of money. We describe our experience using on-site training programs to efficiently teach and propagate laparoscopic surgery in Leon, Nicaragua; La Paz, Bolivia; and Santa Cruz, Bolivia. METHODS: A group of well-trained and motivated local surgeons was identified in each country as the initial target for teaching. Participants were taught basic and advanced laparoscopic surgery during on-site didactics, animal laboratories, and proctoring sessions. Follow-up courses were held until the target group of surgeons was capable of independently teaching and supervising laparoscopic surgery among other surgeons in each country. RESULTS: Multiple technical and logistic difficulties were encountered. In Leon, Nicaragua, and La Paz, Bolivia, a total of eight surgeons were fully trained and proctored in laparoscopic cholecystectomy. In La Paz and Santa Cruz, Bolivia, a total of seven surgeons were instructed in advanced laparoscopic procedures. To date, over 180 patients have undergone laparoscopic cholecystectomy or advanced procedures with a morbidity similar to that reported in literature series in the United States. CONCLUSIONS: Our experience demonstrates that in spite of numerous limitations, basic and laparoscopic surgery can be efficiently and safely taught in developing countries. Many lessons were learned in how to safely and efficiently use laparoscopic equipment and instruments within strict financial constraints.

Gastroduodenal polyps in familial adenomatous polyposis.

BACKGROUND: Malignant degeneration of gastroduodenal polyps has been noted in patients with familial adenomatous polyposis. To evaluate this problem further, patients with familial adenomatous polyposis were contacted and offered upper gastrointestinal tract endoscopy. METHODS: A prospective endoscopic examination was performed in 42 patients. RESULTS: The median age of patients at endoscopy was 35 years. The duration of known familial adenomatous polyposis at the time of endoscopy was 8 years. Polyps were visualized in 21 patients (50%). Gastric polyps were seen in 14 patients (33%), duodenal polyps were seen in 11 patients (26%), and ampullary polyps were seen in 7 patients (17%). Nine patients (43%) had polyps in more than one site. Adenomatous change was noted in 73% of duodenal lesions and in only 14% of gastric polyps. Surgical intervention was required in four patients; one patient had an early ampullary carcinoma, and three patients had severe dysplasia involving the duodenum or ampulla. All four patients had undergone a previous screening examination, results of which were normal in three patients. Compared with other patients, these four patients were older (median age, 58 years; p = 0.02) and had a longer duration of disease (median duration, 25 years; p = 0.002). CONCLUSIONS: All patients with familial adenomatous polyposis require lifelong endoscopic surveillance to detect malignant degeneration, which may appear later in life.

Operative enteroscopy. A useful tool in the evaluation and intervention of bilioenteric anastomoses.

Roux-en-Y hepaticojejunostomy is the procedure of choice in the management of patients with major bile duct injuries. In instances of anastomotic stricture, this anastomosis is inaccessible to conventional endoscopy. A technique is described for assessment and intervention of bilioenteric anastomoses that escape the reach of conventional endoscopy. Three cases are presented illustrating the feasibility of open and laparoscopic-assisted small-bowel endoscopy. All patients presented with recurrent cholangitis and had multiple interventions in their biliary tree prior to referral. At operation, the limb of jejunum going to the bilioenteric anastomosis was identified, an enterotomy was made, and a flexible endoscope was passed to evaluate the anastomosis. In two cases the anastomosis was revised by endoscopically excising scar tissue. In the third case the anastomosis was patent and unnecessary intervention was avoided. There was no morbidity or mortality and the patients had complete resolution of their symptoms. Operative endoscopy appears to be useful in the evaluation and intervention of bilioenteric anastomoses that cannot be evaluated by conventional endoscopy.

Techniques of laparoscopic cholecystectomy. The difficult operation.

Laparoscopic cholecystectomy has settled as the treatment of choice for patients with gallstone disease. Injury to the bile ducts, still the main drawback of the technique, is decreasing progressively with better understanding of the mechanisms of injury and adequate training. With the expansion of indications for laparoscopic cholecystectomy, more difficult operations are being performed. Adequate understanding of the obstacles that may arise during the laparoscopic procedure as well as knowledge of specific maneuvers to deal with the difficult operation are important for the success and safety of the procedure.

Hepatoma registry of the Western world. Repeat Hepatic Resection Registry.

The western HCC registry comprised data from 322 patients who underwent hepatic resection for HCC over a 50-year period. The majority of patients had lesions > 4 cm and were symptomatic at presentation. Lesions were mostly unicentric. Cirrhosis was not a prevalent problem, unlike the East. In the most recent decade, 1980-1989, we noted a significant decrease in operative mortality from 19% to 10% overall, and 15% to 4% in the noncirrhotic group. We identified four variables that resulted in poorer postresectional outcome: cirrhosis, regional nodal disease, multicentric disease, and tumor-free resectional margin < 1 cm. Although these factors are associated with a poorer outcome after resection, whether they should serve as contraindications to surgery should be determined by individual surgeons, taking into account the patient's overall status, concomitant risk factors, and treatment objectives.

Resection of hepatic metastases from colorectal carcinoma. The registry data.

When liver metastases from colorectal carcinoma are detected, the surgeon must decide whether or not the patient is a candidate for resection. Even though long-term survival after resection is far from optimal, the relegation of patients to nonresective treatment means denying them the only chance for cure currently available. Better understanding of liver anatomy and improvement in resection techniques have decreased the morbidity and mortality. The RHM and the GITSG reports have better defined the prognostic factors for resections of colorectal liver metastases and allowed for a better understanding of the indications for resection. During the last decades, liver resection has been extended to older patients, patients with multiple liver lesions, and patients with larger solitary metastases. At the same time, anatomic rather than wedge resections are more common, and it is preferable to perform the colon and liver resection at different stages. The end result has been a marked increase in the number of hepatic resections performed for colorectal liver metastases during the last two decades.

Bile duct injury during laparoscopic cholecystectomy: mechanism of injury, prevention, and management.

Although several studies have shown a low incidence of bile duct injuries during laparoscopic cholecystectomy, concerns remain because of the sustained increase in the number of referrals for biliary reconstruction after the procedure. Twenty-one patients have been referred to our institution because of major bile duct injuries after laparoscopic cholecystectomy. The injury was recognized during the laparoscopic procedure in only 6 of the 21 (29%). Nineteen patients underwent hepaticojejunostomy at least once, one patient required hepaticojejunostomy and repair of a choledochoduodenal fistula, and one patient needed repair of a biliary colonic fistula. Hepaticojejunostomy above the bifurcation was required in 10 patients (50%), at the bifurcation in 3, and below the bifurcation in 7. Nine of the eleven patients in whom the initial repair was performed at the local hospital presented with early stricture (median 7 months). The common denominator of the development of bile duct injuries during laparoscopic cholecystectomy is the failure to identify the structures of the triangle of Calot. Specific steps during laparoscopic cholecystectomy to avoid bile duct injuries are described. Expertise in hepatobiliary surgery appears to optimize results of biliary reconstruction.

Acute relapsing pancreatitis as a complication of papillary stenosis after endoscopic sphincterotomy.

Endoscopic sphincterotomy has proven to be a safe alternative to surgery for selected types of biliary disease. Despite a relatively low morbidity, postprocedure complications are well described. This report presents an experience with three patients in whom acute relapsing pancreatitis developed as a possible complication of papillary stenosis after endoscopic sphincterotomy. None of the patients had a previous history of elevations in serum amylase levels before endoscopic sphincterotomy. After procedure, pancreatitis and subsequently acute relapsing pancreatitis with documented stricture of the pancreatic duct orifice developed in all three patients. After surgical transduodenal sphincteroplasty, no new episodes of acute relapsing pancreatitis occurred.

Local resection for ampullary tumors. Is there a place for it?

Two of 14 patients with adenomas were without disease 25 and 43 months after ampullary resection. Two patients with an initial diagnosis of malignant neoplasm had no recurrence at 75 and 40 months; one underwent pancreatoduodenectomy at 8 months because of recurrence. Six of nine patients with initial diagnoses of villous adenoma were without disease at 1, 2, 16, 23, 46, and 51 months; three underwent conversion to pancreatoduodenectomy because of invasive carcinoma. Frozen-section studies revealed adenocarcinoma in two patients with villous adenoma but failed to show invasion in one patient. One patient with villous adenoma was mistakenly thought to have carcinoma based on results of frozen-section studies. Local ampullary resection is valuable in treating benign and selected premalignant and malignant ampullary lesions. The threshold for conversion to pancreatoduodenectomy should be low unless ampullectomy is performed with palliative intent.