Multiagent neoadjuvant chemotherapy and tumor response are associated with improved survival in pancreatic cancer.

BACKGROUND: Neoadjuvant therapy (NT) for borderline resectable pancreatic cancer (BRPC) has evolved to include multi-agent regimens and chemoradiation. We report our experience and compare outcomes of initially resectable pancreatic cancer (IRPC) vs BRPC receiving NT across two eras of chemotherapy regimens. METHODS: Data were collected retrospectively on pancreaticoduodenectomy patients between January 2008 and October 2015. Outcomes and survival were compared based on patient, laboratory and treatment factors. RESULTS: 195 patients were included and 133 had IRPC and 62 BRPC. IRPC operations were shorter (449 min vs 520 min, p = 0.003), had less blood loss (663 ml vs 954 ml, p = 0.002) and involved fewer vascular resections (29% vs 76%, p = 0.002). The rate of R0 resection was identical (82%, p = 1) and the IRPC group had higher node-positive ratio (19.3% vs 7.2% p < 0.0001). 15 patients received a single agent regimen while 47 received multi-agent regimens with 90% receiving radiation.Survival was similar between BRPC and IRPC (log-rank p = 0.7). Histopathologic response (CAP grade 0 or 1) was not associated with survival (p = 0.13), but completion of ≥4 cycles of multi-agent pre-operative chemotherapy (p = 0.001) and complete response to NT (p = 0.04) were significant predictors of survival. CONCLUSIONS: BRPC patients treated with NT have similar morbidity and survival to their IRPC counterparts. Pathologic response and modern NT are associated with improved survival.

Planned delay of oral intake after esophagectomy reduces the cervical anastomotic leak rate and hospital length of stay.

Cervical anastomotic leak rates are high after esophagectomy. We examined the effect of a purposeful delay in institution of oral diet after esophagectomy on the leak rate and hospital length of stay. A retrospective analysis of 120 patients submitted to esophagectomy with cervical esophagogastric anastomosis was conducted. Eighty-seven resumed diet within 7 days of surgery (early eaters), and 33 had delayed diet until a mean of 12 days after surgery (late eaters). Mean age was 62.3 years; 98 patients were male. One hundred one resections were for cancer, and 49 % of cancer patients received neoadjuvant therapy. The overall leak rate was 17.5 %, and hospital length of stay was 10.9 days. Anastomotic leak rate was 3 % for late eaters versus 23 % for early eaters (OR of 9.57, p = 0.010). Hospital length of stay was 6 days for late eaters versus 11.8 days for early eaters (p < 0.001). Anastomotic leak was significantly associated with increased length of stay (p < 0.001), adding an average of 7.6 days to hospital stay. Respiratory complications (p < 0.001) and delayed gastric emptying (p = 0.014) were also independent predictors of increased length of stay, but early eater status was not. Delayed resumption of oral diet after esophagectomy significantly reduces cervical anastomotic leak rate and avoids the increased length of stay associated with leak.

Type VI biliary cyst: report of a case.

An isolated cyst of the cystic duct is an extremely rare lesion. Only single case reports are documented in the literature. The most accepted classification system of biliary cysts, the Todani classification, does not include this lesion. We report a case of isolated cyst of the cystic duct. The initial referral was for evaluation of a gallbladder mass discovered during evaluation of abdominal pain. Preoperative diagnosis was challenging as multiple imaging studies were unable to differentiate this lesion from a choledochal cyst. Surgical planning thus included cyst excision and biliary reconstruction. Operative exploration revealed a type VI biliary cyst and cholecystectomy with cystic duct ligation near the common bile duct was curative.

Focal nodular hyperplasia: report of an unusual case and review of the literature.

Focal nodular hyperplasia (FNH) is the second most common benign lesion of the liver and a common differential in the workup of solid liver lesions. With increasing use of modern imaging modalities FNH is becoming clinically more relevant. We present a case of pedunculated FNH presenting as a pericholecystic mass. This was resected laparoscopically due to persistent symptoms and uncertainty in diagnosis. We summarize the current literature with regard to the diagnosis, etiology, and management of FNH lesions.

Colchicine inhibits pressure-induced tumor cell implantation within surgical wounds and enhances tumor-free survival in mice.

Iatrogenic tumor cell implantation within surgical wounds can compromise curative cancer surgery. Adhesion of cancer cells, in particular colon cancer cells, is stimulated by exposure to increased extracellular pressure through a cytoskeleton-dependent signaling mechanism requiring FAK, Src, Akt, and paxillin. Mechanical stimuli during tumor resection may therefore negatively impact patient outcome. We hypothesized that perioperative administration of colchicine, which prevents microtubule polymerization, could disrupt pressure-stimulated tumor cell adhesion to surgical wounds and enhance tumor-free survival. Ex vivo treatment of Co26 and Co51 colon cancer cells with colchicine inhibited pressure-stimulated cell adhesion to murine surgical wounds and blocked pressure-induced FAK and Akt phosphorylation. Surgical wound contamination with pressure-activated Co26 and Co51 cells significantly reduced tumor-free survival compared with contamination with tumor cells under ambient pressure. Mice treated with pressure-activated Co26 and Co51 cells from tumors preoperatively treated with colchicine in vivo displayed reduced surgical site implantation and significantly increased tumor-free survival compared with mice exposed to pressure-activated cells from tumors not pretreated with colchicine. Our data suggest that pressure activation of malignant cells promotes tumor development and impairs tumor-free survival and that perioperative colchicine administration or similar interventions may inhibit this effect.

Spontaneous gastric decompression of peripancreatic collection.

Peripancreatic collections related to acute pancreatitis can range from simple serous fluid to infected phlegmon. The latter can be associated with significant morbidity and mortality. A patient with striking abdominal computed tomography images of an infected phlegmonous peripancreatic collection was seen at our institution. The clinical picture was much different from what the images predicted. Endoscopic retrograde cholangiopancreatography revealed a fistulous connection between the collection and the stomach, also seen on retrospective abdominal computed tomography scan review, indicating spontaneous decompression, which cured the patient.

Paxillin modulates squamous cancer cell adhesion and is important in pressure-augmented adhesion.

Paxillin is an adapter protein regulating signaling and focal adhesion assembly that has been linked to malignant potential in many malignancies. Overexpression of paxillin has been noted in aggressive tumors. Integrin-mediated binding through the focal adhesion complex is important in metastatic adhesion and is upregulated by extracellular pressure in malignant colonocytes through FAK and Src activation. Neither head and neck cancers nor paxillin have been studied in this regard. We hypothesized that paxillin would play a role in modulating squamous cancer adhesion both at baseline and under conditions of increased extracellular pressure. Using SCC25 tongue squamous cancer cells stably transfected with either an empty selection vector or paxillin expression and selection vectors, we studied adhesion to collagen, paxillin, FAK, and Src expression and phosphorylation in cells maintained for 30 min under ambient or 15 mmHg increased pressure conditions. Paxillin-overexpressing cells exhibited adhesion 121 +/- 2.9% of that observed in vector-only cells (n = 6, P < 0.001) under ambient pressure. Paxillin-overexpression reduced FAK phosphorylation. Pressure stimulated adhesion to 118 +/- 2.3% (n = 6, P < 0.001) of baseline in vector-only cells, similar to its effect in the parental line, and induced paxillin, FAK, and Src phosphorylation. However, increased pressure did not stimulate adhesion or phosphorylate paxillin, FAK, or Src further in paxillin-overexpressing cells. Metastasizing squamous cancer cell adhesiveness may be increased by paxillin-overexpression or by paxillin activation by extracellular pressure during surgical manipulation or growth within a constraining compartment. Targeting paxillin in patients with malignancy and minimal tumor manipulation during surgical resection may be important therapeutic adjuncts.

Divalent cations influence colon cancer cell adhesion in a murine transplantable tumor model.

BACKGROUND: Cancer cells adhere principally by integrins, matrix receptors that may be influenced by divalent cations. Surgical wound fluid is high in Mg2+ and low in Ca2+. We hypothesized that Mg+ and Mn2+ promote perioperative adhesion of shed cancer cells to surgical sites and that washing surgical wounds with Ca2+ inhibits implantation. METHODS: We tested our hypothesis in a murine colon 26 adenocarcinoma model. We added 10 mmol/L CaCl2, 0.25 mmol/L MgCl2, or 0.5 mmol/L MnCl2 to suspended murine colon 26 cancer cells and placed these suspensions into wounds in anesthetized mice. After 30 minutes, we washed away nonadherent cells. In some studies, we 51Cr-labeled the cells and assayed tumor adhesion by wound radioactivity. In parallel studies, we closed the wounds and observed the mice for 90 days. RESULTS: Mg2+ increased adhesion to 188% +/- 15% of control (n = 10, P < .001) and Mn2+ to 130% +/- 6% (n = 7, P < .001). However, Ca2+ inhibited adhesion to 61% +/- 12% (n = 7, P = .006) of control. Seventy-two percent of survival controls developed tumors during follow-up. Mg2+ and Mn2+ stimulated tumor formation to 96% and 92%, respectively, but adding Ca2+ to the wounds reduced subsequent tumor formation to 56% without altering serum Ca2+. The survival curves each differed significantly by log-rank test (P < .01 each). All pair-wise multiple comparisons were significant (Holm-Sidak, P < .05 each). CONCLUSION: Thus, the high Mg2+ in endogenous wound fluid may potentiate tumor cell adhesion. However, 10 micromol/L Ca2+ inhibits cancer cell adhesion to murine wounds and subsequent tumor development. Irrigating with dilute CaCl2 could decrease local tumor recurrence by inhibiting the adhesion of shed tumor cells.