Joe U. Levi

A retrospective study of neoadjuvant FOLFIRINOX in unresectable or borderline-resectable locally advanced pancreatic adenocarcinoma

Background5-fluorouracil, leucovorin, irinotecan and oxaliplatin (FOLFIRINOX) is superior to gemcitabine in patients with metastatic pancreatic cancer who have a good performance status. We investigated this combination as neoadjuvant therapy for locally advanced pancreatic cancer (LAPC).MethodsIn this retrospective series, we included patients with unresectable LAPC who received neoadjuvant FOLFIRINOX with growth factor support. The primary analysis endpoint was R0 resection rate.ResultsEighteen treatment-naïve patients with unresectable or borderline resectable LAPC were treated with neoadjuvant FOLFIRINOX. The median age was 57.5 years and all had ECOG PS of 0 or 1. Eleven (61 %) had tumors in the head of the pancreas and 9 (50 %) had biliary stents placed prior to chemotherapy. A total of 146 cycles were administered with a median of 8 cycles (range 3-17) per patient. At maximum response or tolerability, 7 (39 %) were converted to resectability by radiological criteria; 5 had R0 resections, 1 had an R1 resection, and 1 had unresectable disease. Among the 11 patients who remained unresectable after FOLFIRINOX, 3 went on to have R0 resections after combined chemoradiotherapy, giving an overall R0 resection rate of 44 % (95 % CI 22–69 %). After a median follow-up of 13.4 months, the 1-year progression-free survival was 83 % (95 % CI 59-96 %) and the 1-year overall survival was 100 % (95 % CI 85-100 %). Grade 3/4 chemotherapy-related toxicities were neutropenia (22 %), neutropenic fever (17 %), thrombocytopenia (11 %), fatigue (11 %), and diarrhea (11 %). Common grade 1/2 toxicities were neutropenia (33 %), anemia (72 %), thrombocytopenia (44 %), fatigue (78 %), nausea (50 %), diarrhea (33 %) and neuropathy (33 %).ConclusionsFOLFIRINOX followed by chemoradiotherapy is feasible as neoadjuvant therapy in patients with unresectable LAPC. The R0 resection rate of 44 % in this population is promising. Further studies are warranted.

Extent of resection in the management of duodenal adenocarcinoma.

BACKGROUND It has been postulated that segmental duodenal resection (SR) is not an adequate operation for patients with adenocarcinoma of the duodenum and that pancreaticoduodenectomy (PD) is the procedure of choice, regardless of the tumor site. However, data from previous studies do not clearly support this position. METHODS We reviewed the records of 63 patients treated for duodenal adenocarcinoma from 1979 through 1998. Perioperative outcome, patient survival, and extent of lymphadenectomy were compared in patients who underwent PD and SR. RESULTS The overall morbidity for PD and SR was 27% and 18%, respectively (not significant [NS]). Patients who underwent SR had a 5-year survival of 60% versus 30% for patients who underwent PD (NS). Lymph node status was a prognostic factor for survival (P = 0.014). The mean number of lymph nodes in the specimens was 9.9 +/- 2.1 for PD and 8.3 +/- 4.4 for SR (NS). CONCLUSIONS Segmental duodenal resection for patients with duodenal adenocarcinoma is associated with acceptable postoperative morbidity and long-term survival. The procedure is especially well suited for distal duodenal tumors. Clearance of lymph nodes and outcome are comparable to PD.

Large cystic lesions of the liver in adults: a 15-year experience in a tertiary center

BACKGROUND Cystic lesions of the liver consist of a heterogeneous group of disorders and may present a diagnostic and therapeutic challenge. Large hepatic cysts tend to be symptomatic and can cause complications more often than smaller ones. STUDY DESIGN We performed a retrospective review of adults diagnosed with large (> or = 4 cm) hepatic cystic lesions at our center, over a period of 15 years. Polycystic disease and abscesses were not included. RESULTS Seventy-eight patients were identified. In 57 the lesions were simple cysts, in 8 echinococcal cysts, in 8 hepatobiliary cystadenomas, and in 1 hepatobiliary cystadenocarcinoma. In four patients, the precise diagnosis could not be ascertained. Mean size was 12.1 cm (range, 4 to 30 cm). Most simple cysts were found in women (F:M, 49:8). Bleeding into a cyst (two patients) and infection (one patient) were rare manifestations. Percutaneous aspiration of 28 simple cysts resulted in recurrence in 100% of the cases within 3 weeks to 9 months (mean 4(1/2) months). Forty-eight patients were treated surgically by wide unroofing or resection (laparoscopically in 18), which resulted in low recurrence rates (11% for laparoscopy and 13% for open unroofing). Four of the eight patients with echinococcal cysts were symptomatic. All were treated by open resection after irrigation of the cavity with hypertonic saline. There was no recurrence during a followup period of 2 to 14 years. Hepatobiliary cystadenomas occurred more commonly in women (F:M, 7:1) and in the left hepatic lobe (left:right, 8:0). Seven were multiloculated. All were treated by open resection, with no recurrence, and none had malignant changes. Cystadenocarcinoma was diagnosed in a 77-year-old man, and was treated by left hepatic lobectomy. CONCLUSIONS Large symptomatic simple cysts invariably recur after percutaneous aspiration. Laparoscopic unroofing can be successfully undertaken, with a low recurrence rate. Open resection after irrigation with hypertonic saline is a safe and effective treatment for echinococcal cysts. Hepatobiliary cystadenomas have predilection for women and for the left hepatic lobe. Malignant transformation is an uncommon but real risk. Open resection is a safe and effective treatment for hepatobiliary cystadenoma, and is associated with a low recurrence rate.

Laparoscopic cholecystectomy in cirrhotic patients

BACKGROUND Reported mortality for open cholecystectomy in patients with cirrhosis ranges from 10% to 80%. Laparoscopic cholecystectomy has gained acceptance in the general population and has become the procedure of choice for symptomatic cholelithiasis. We reviewed our experience with the use of laparoscopic cholecystectomy in this group. STUDY DESIGN We did a retrospective review of the records of 25 consecutive laparoscopic choleoystectomy procedures performed on cirrhotic patients from May 1992 to July 1996. RESULTS There were no mortalities in our group. All procedures were completed laparoscopically. Mean length of stay was 1.7 days (range, 1 to 8 days). Morbidity consisted of wound hematomas, pneumonia, and ascites for a rate of 32%. Only patients with Childs Class A and Class B cirrhosis were operated on. CONCLUSIONS Laparoscopic cholecystectomy can be performed safely in cirrhotic patients with well compensated liver function.

Radical resection of periampullary tumors in the elderly: evaluation of long-term results.

Increasingly, patients of advanced age are coming for evaluation of periampullary tumors. Although several studies have demonstrated the safety of resecting periampullary tumors in older patients, few long-term survival data have been reported. Between 1983 and 1992 various periampullary masses were resected in 70 patients over age 65 (range 65–87 years). Total pancreatectomy was performed in 11 patients, and 59 patients underwent pancreaticoduodenectomy. The mean duration of hospitalization was 17 ± 15 days. Major complications occurred in 27 patients (39%), and operative mortality rate was 8.5%. Overall median survival was 24 months; and 5-year survival was 25%. Perioperative outcome was compared in patients aged 65 to 74 years and in patients ≥75 years old. The older age group required longer periods in the surgical intensive care unit postoperatively, but the long-term survival was similar in the two age groups. Radical resection with the intent to cure periampullary tumors is safe in selected patients of advanced age, and long-term survival is in the range of expected survival for younger patients with the same tumors.

The comparative survivals of alcoholics versus nonalcoholics after distal splenorenal shunt.

Survival after distal splenorenal shunt is appreciably better in nonalcoholic patients than in alcoholics. This increase in survival does not appear to be dependent upon the state of biochemical liver function or the severity of changes in liver histology since these latter were similar for both groups. We suggest that the poorer survival of alcoholics may be related to continuing alcohol toxicity, and that a possible reason for the failure to demonstrate this difference in survival after portacaval shunts may be due to the harmful effects of total portal diversion on the liver.

Experience with staging laparoscopy in pancreatic malignancy

BACKGROUND The role of diagnostic laparoscopy in the staging of abdominal malignancies is not well defined. METHODS We retrospectively reviewed the usefulness of diagnostic laparoscopy as a staging procedure in pancreatic malignancy. This experience between February 1988 and May 1997 involves 109 cases of suspected or proven pancreatic malignancy. All laparoscopies were performed with the patient under conscious sedation and local anesthesia in an endoscopy suite. RESULTS Of the 109 patients with pancreatic cancer, 45 (42%) had metastatic disease. The use of computed tomography (CT) alone revealed the existence of liver metastases in 10 of 109 (9%) patients, which were confirmed laparoscopically. The further use of laparoscopy identified metastases in 29 more cases: hepatic, 23; hepatic and peritoneal, 3; peritoneal and mesenteric, 1; and mesenteric, 2. CT in conjunction with laparoscopy therefore revealed metastatic liver, peritoneal, or mesenteric lesions in 39 of 109 (36%) patients with pancreatic cancer. After staging laparoscopy, 67 of 69 patients underwent laparotomy. Metastatic disease was identified at laparotomy in 6 more patients; however, only 4 of these patients had metastases to the liver whereas 2 had metastases to the peripancreatic lymph nodes. Therefore, in patients with pancreatic malignancy, the negative predictive value for the diagnosis of metastases to the liver, peritoneum or mesentery was 94% (61 of 65 patients). The positive predictive value of laparoscopy alone for the detection of metastatic disease to the liver, peritoneum, or mesentery was 88% (29 of 33 patients). Laparoscopy was successfully performed without complications in all patients with pancreatic cancer; however, one had a technically unsatisfactory examination. The overall rate of resectability after staging by imaging studies and laparoscopy was 57% (35 of 61 patients). CONCLUSIONS In patients with a negative CT for metastases, laparoscopic identification of metastases avoided unnecessary laparotomy in 29 of 99 (29%) patients with pancreatic cancer. Staging laparoscopy is indicated in all cases of pancreatic malignancy before an attempt at a surgical cure.

EUS visualization and direct celiac ganglia neurolysis predicts better pain relief in patients with pancreatic malignancy (with video)

BACKGROUND EUS-guided celiac plexus neurolysis (EUS-CPN) improves pain control in patients with pancreatic cancer. EUS allows visualization of the celiac ganglion. OBJECTIVE To determine predictors of response to EUS-CPN in a cohort of 64 patients with pancreatic malignancy. DESIGN Retrospective analysis of prospective database. SETTING Academic medical center. PATIENTS Sixty-four patients with pancreatic cancer referred for EUS between March 2008 and January 2010. INTERVENTIONS EUS-CPN injected directly into celiac ganglia when visible by linear EUS or bilateral injection at the celiac vascular trunk. MAIN OUTCOME MEASUREMENTS Predictors of pain improvement at week 1 by univariate and multivariate analysis. RESULTS At week 1, 32 patients (50%) had a symptomatic response. In a multivariate model with 8 potential predictors, visualization of the ganglia was the best predictor of response; patients with visible ganglia were >15 times more likely to respond (odds ratio 15.7; P<.001). Tumors located outside the head of the pancreas and patients with a higher baseline pain level were weakly associated with a good response. LIMITATIONS Retrospective design and lack of blinding. CONCLUSIONS Visualization of celiac ganglia with direct injection is the best predictor of response to EUS-CPN in patients with pancreatic malignancy.

Pancreatic carcinoma is associated with delayed gastric emptying

Fifteen patients with histologically confirmed pancreatic carcinoma, without evidence of gastroduodenal invasion or obstruction, were prospectively studied to determine the frequency of gastric emptying disorders as determined by a solid-phase gastric emptying study. Nine of these (60%) had gastric emptying curves more than two standard deviations below normal mean values. The majority of patients did not have symptoms of gastric stasis. Nausea and/or vomiting was present in 33% of patients with abnormal gastric emptying and in none of those with normal emptying. Abdominal and/or back pain was present in 8/9 with delayed gastric emptying and in 3/6 with normal emptying. Disordered gastric emptying did not correlate with tumor stage, histology, location, or hyperbilirubinemia. Delayed solid-food gastric emptying may be responsible for the nonspecific abdominal complaints that occur during the course of pancreatic carcinoma, although more frequently, gastroparesis exists on a subclinical level.

Therapeutic percutaneous aspiration of pancreatic pseudocysts

The therapeutic efficacy and safety of percutaneous aspiration of chronic pancreatic pseudocysts was evaluated. Eight patients underwent aspiration a total of ten times. Permanent resolution was obtained in two patients and a third nonsurgical candidate was offered an alternative therapeutic modality. This procedure is simple, rapid, and safe and could become the initial approach to selected patients with a chronic pancreatic pseudocyst.