The road to tailored adjuvant chemotherapy for all four non-pancreatic periampullary cancers: An international multimethod cohort study.

BACKGROUND: Despite differences in tumour behaviour and characteristics between duodenal adenocarcinoma (DAC), the intestinal (AmpIT) and pancreatobiliary (AmpPB) subtype of ampullary adenocarcinoma and distal cholangiocarcinoma (dCCA), the effect of adjuvant chemotherapy (ACT) on these cancers, as well as the optimal ACT regimen, has not been comprehensively assessed. This study aims to assess the influence of tailored ACT on DAC, dCCA, AmpIT, and AmpPB. PATIENTS AND METHODS: Patients after pancreatoduodenectomy for non-pancreatic periampullary adenocarcinoma were identified and collected from 36 tertiary centres between 2010 - 2021. Per non-pancreatic periampullary tumour type, the effect of adjuvant chemotherapy and the main relevant regimens of adjuvant chemotherapy were compared. The primary outcome was overall survival (OS). RESULTS: The study included a total of 2866 patients with DAC (n = 330), AmpIT (n = 765), AmpPB (n = 819), and dCCA (n = 952). Among them, 1329 received ACT, and 1537 did not. ACT was associated with significant improvement in OS for AmpPB (P = 0.004) and dCCA (P < 0.001). Moreover, for patients with dCCA, capecitabine mono ACT provided the greatest OS benefit compared to gemcitabine (P = 0.004) and gemcitabine - cisplatin (P = 0.001). For patients with AmpPB, no superior ACT regime was found (P > 0.226). ACT was not associated with improved OS for DAC and AmpIT (P = 0.113 and P = 0.445, respectively). DISCUSSION: Patients with resected AmpPB and dCCA appear to benefit from ACT. While the optimal ACT for AmpPB remains undetermined, it appears that dCCA shows the most favourable response to capecitabine monotherapy. Tailored adjuvant treatments are essential for enhancing prognosis across all four non-pancreatic periampullary adenocarcinomas.

The Five Periampullary Cancers, not Just Different Siblings but Different Families: An International Multicenter Cohort Study.

BACKGROUND: Cancer arising in the periampullary region can be anatomically classified in pancreatic ductal adenocarcinoma (PDAC), distal cholangiocarcinoma (dCCA), duodenal adenocarcinoma (DAC), and ampullary carcinoma. Based on histopathology, ampullary carcinoma is currently subdivided in intestinal (AmpIT), pancreatobiliary (AmpPB), and mixed subtypes. Despite close anatomical resemblance, it is unclear how ampullary subtypes relate to the remaining periampullary cancers in tumor characteristics and behavior. METHODS: This international cohort study included patients after curative intent resection for periampullary cancer retrieved from 44 centers (from Europe, United States, Asia, Australia, and Canada) between 2010 and 2021. Preoperative CA19-9, pathology outcomes and 8-year overall survival were compared between DAC, AmpIT, AmpPB, dCCA, and PDAC. RESULTS: Overall, 3809 patients were analyzed, including 348 DAC, 774 AmpIT, 848 AmpPB, 1,036 dCCA, and 803 PDAC. The highest 8-year overall survival was found in patients with AmpIT and DAC (49.8% and 47.9%), followed by AmpPB (34.9%, P < 0.001), dCCA (26.4%, P = 0.020), and finally PDAC (12.9%, P < 0.001). A better survival was correlated with lower CA19-9 levels but not with tumor size, as DAC lesions showed the largest size. CONCLUSIONS: Despite close anatomic relations of the five periampullary cancers, this study revealed differences in preoperative blood markers, pathology, and long-term survival. More tumor characteristics are shared between DAC and AmpIT and between AmpPB and dCCA than between the two ampullary subtypes. Instead of using collective definitions for "periampullary cancers" or anatomical classification, this study emphasizes the importance of individual evaluation of each histopathological subtype with the ampullary subtypes as individual entities in future studies.

Long-term Outcomes After Laparoscopic, Robotic, and Open Pancreatoduodenectomy for Distal Cholangiocarcinoma: An International Propensity Score-matched Cohort Study.

OBJECTIVE: This study aimed to compare surgical and oncological outcomes after minimally invasive pancreatoduodenectomy (MIPD) versus open pancreatoduodenectomy (OPD) for distal cholangiocarcinoma (dCCA). BACKGROUND: A dCCA might be a good indication for MIPD, as it is often diagnosed as primary resectable disease. However, multicenter series on MIPD for dCCA are lacking. METHODS: This is an international multicenter propensity score-matched cohort study including patients after MIPD or OPD for dCCA in 8 centers from 5 countries (2010-2021). Primary outcomes included overall survival (OS) and disease-free interval (DFI). Secondary outcomes included perioperative and postoperative complications and predictors for OS or DFI. Subgroup analyses included robotic pancreatoduodenectomy (RPD) and laparoscopic pancreatoduodenectomy (LPD). RESULTS: Overall, 478 patients after pancreatoduodenectomy for dCCA were included of which 97 after MIPD (37 RPD, 60 LPD) and 381 after OPD. MIPD was associated with less blood loss (300 vs 420 mL, P =0.025), longer operation time (453 vs 340 min; P <0.001), and less surgical site infections (7.8% vs 19.3%; P =0.042) compared with OPD. The median OS (30 vs 25 mo) and DFI (29 vs 18) for MIPD did not differ significantly between MIPD and OPD. Tumor stage (Hazard ratio: 2.939, P <0.001) and administration of adjuvant chemotherapy (Hazard ratio: 0.640, P =0.033) were individual predictors for OS. RPD was associated with a higher lymph node yield (18.0 vs 13.5; P =0.008) and less major morbidity (Clavien-Dindo 3b-5; 8.1% vs 32.1%; P =0.005) compared with LPD. DISCUSSION: Both surgical and oncological outcomes of MIPD for dCCA are acceptable as compared with OPD. Surgical outcomes seem to favor RPD as compared with LPD but more data are needed. Randomized controlled trials should be performed to confirm these findings.

Implementation of ERAS in pancreaticoduodenectomy in an Australian tertiary centre.

BACKGROUND/OBJECTIVES: Recent studies have demonstrated that enhanced recovery after surgery (ERAS) protocols in pancreaticoduodenectomy (PD) may decrease morbidity and length of stay. This study aimed to critically assess the implementation of ERAS in patients who have undergone a PD in a tertiary centre. METHODS: A retrospective cohort study of all patients who underwent a PD prior to ERAS, compared to following implementation were assessed. Outcome measures of length of stay, morbidity, mortality and readmission rates between the two groups were evaluated. RESULTS: 169 patients were included in the study (pre-ERAS, n = 29; stage 1, n = 14; stage 2, n = 53, stage 3, n = 73) with mean age of 64 ± 11.3 years. ERAS significantly increased the proportion of patients reaching the target length of stay of nine days (P = 0.017). It did not significantly impact overall mortality, morbidity, radiological intervention, reoperation or readmission (P > 0.05). ERAS did not have a significant impact on development of pancreatic fistula, ileus, infection or haemorrhage (P > 0.05). ERAS did significantly reduce rates of delayed gastric emptying (DGE) from 82.8% pre-ERAS to 49.0% in the stage 2 of implementation phase (P < 0.001). CONCLUSIONS: The early implementation of the ERAS programme was safe although some obstacles were encountered. ERAS was beneficial in increasing the proportion of patients reaching the target length of stay without increasing readmission, reoperation, or morbidity. Our findings support the continued development of ERAS in PD in order to standardise care and improve patient recovery.

Juvenile melanomas: Western Australian Melanoma Advisory Service experience.

BACKGROUND/OBJECTIVES: Juvenile melanoma (before 20 years of age) is a rare condition with poorly defined risk factors. We describe features of juvenile melanoma in Western Australia over the last two decades. METHOD: A retrospective review of juvenile melanomas was conducted from prospectively maintained databases, reviewed for patients' characteristics, clinical information, histology, treatment, recurrence and survival data. RESULTS: Altogether 95 cases of juvenile melanoma were reported to the Western Australian Cancer Registry between 2000 and 2013. Of these, 27 patients were referred to the Western Australian Melanoma Advisory Service. Over 72% were aged between 13 and 19 years. The most common site for primary melanoma was the head and neck (31.8%). Eight patients (36.4%) had a pre-existing naevus, 13.6% reported 1-5 blistering sunburns in the past and 59.1% had a Fitzpatrick skin grade of 3 or less. Most (88%) were diagnosed with a primary invasive lesion at presentation. Superficial spreading melanomas predominated (27.3%). All but one patient had localised disease at presentation, with six patients undergoing further treatment, including chemotherapy and neck dissection for metastases. At the time of review, two patients had died, due to stroke and metastatic disease. CONCLUSIONS: Juvenile melanoma remains a rarity in Western Australia despite a very high incidence of adult melanoma. Unlike in adults, no definitive risk factors have been established. A significant proportion of this cohort had a pre-existing naevus and while most melanomas occurred in sun-exposed areas in light-skinned individuals the association between sunburn and melanoma was not strong.

Postoperative fluid therapy in enhanced recovery after surgery for pancreaticoduodenectomy.

Backgrounds/Aims: Optimal intravenous fluid management during the perioperative period for patients undergoing pancreaticoduodenectomy (PD) within the framework of enhanced recovery after surgery (ERAS) is unclear. Studies have indicated that excessive total body salt and water can contribute to the development of oedema, leading to increased morbidity and extended hospital stays. This study aimed to assess the effects of an intravenous therapy regimen during postoperative day (POD) 0 to 2 in PD patients within ERAS. Methods: A retrospective interventional cohort study was conducted, and it involved all PD patients before and after implementation of ERAS (2009-2017). In the ERAS group, a targeted maintenance fluid regimen of 20 mL/kg/day with a sodium requirement of 0.5 mmoL/kg/day was administered. Outcome measures included the mmol of sodium and chloride administered, length of stay, and morbidity (postoperative pancreatic fistula, POPF; acute kidney injury, AKI; ileus). Results: The study included 169 patients, with a mean age of 64 ± 11.3 years. Following implementation of the intravenous fluid therapy protocol, there was a significant reduction in chloride and sodium loading. However, in the multivariable analysis, chloride administered (mmoL/kg) did not independently influence the length of stay; or rates of POPF, ileus, or AKI (p > 0.05). Conclusions: The findings suggested that a postoperative intravenous fluid therapy regimen did not significantly impact morbidity. Notably, there was a trend towards reduced length of stay within an increasingly comorbid patient cohort. This targeted fluid regimen appears to be safe for PD patients within the ERAS program. Further prospective research is needed to explore this area.

Different Periampullary Types and Subtypes Leading to Different Perioperative Outcomes of Pancreatoduodenectomy: Reality and Not a Myth; An International Multicenter Cohort Study.

This international multicenter cohort study included 30 centers. Patients with duodenal adenocarcinoma (DAC), intestinal-type (AmpIT) and pancreatobiliary-type (AmpPB) ampullary adenocarcinoma, distal cholangiocarcinoma (dCCA), and pancreatic ductal adenocarcinoma (PDAC) were included. The primary outcome was 30-day or in-hospital mortality, and secondary outcomes were major morbidity (Clavien-Dindo 3b≥), clinically relevant post-operative pancreatic fistula (CR-POPF), and length of hospital stay (LOS). Results: Overall, 3622 patients were included in the study (370 DAC, 811 AmpIT, 895 AmpPB, 1083 dCCA, and 463 PDAC). Mortality rates were comparable between DAC, AmpIT, AmpPB, and dCCA (ranging from 3.7% to 5.9%), while lower for PDAC (1.5%, p = 0.013). Major morbidity rate was the lowest in PDAC (4.4%) and the highest for DAC (19.9%, p < 0.001). The highest rates of CR-POPF were observed in DAC (27.3%), AmpIT (25.5%), and dCCA (27.6%), which were significantly higher compared to AmpPB (18.5%, p = 0.001) and PDAC (8.3%, p < 0.001). The shortest LOS was found in PDAC (11 d vs. 14-15 d, p < 0.001). Discussion: In conclusion, this study shows significant variations in perioperative mortality, post-operative complications, and hospital stay among different periampullary cancers, and between the ampullary subtypes. Further research should assess the biological characteristics and tissue reactions associated with each type of periampullary cancer, including subtypes, in order to improve patient management and personalized treatment.

Drain fluid amylase and lipase as a predictive factor of postoperative pancreatic fistula.

BACKGROUND: Early detection of a postoperative pancreatic fistula (POPF) may improve outcomes after pancreaticoduodenectomy (PD). The aim was to assess the role of postoperative drain fluid amylase (DFA) and lipase (DFL) measurements as a predictive indicator in the development of POPF. METHODS: This retrospective cohort study included all PD procedures performed between 2009 and 2017 at Fremantle and Fiona Stanley Hospital in Western Australia. The DFA and DFL measurements on postoperative day (POD) three and five were correlated with the development of POPF. RESULTS: A total of 169 patients were included in this study with a mean age of 64 ± 11.3 years. Of these, 17 (10.1%) developed a clinically significant POPF. In patients who had both a DFA and DFL measured on both POD 3 and 5, DFA and DFL was significantly higher in patients who developed POPF than those who did not (P < 0.001). In a receiver operating characteristic curve analysis, the most accurate test was POD 3 DFL measurement with an AUC 0.85 (CI 0.75-0.95, P < 0.001). A negative predictive value of 97.4% was observed. DFA and DFL were concordant in 89.2% of cases on POD 3 and 90.6% of cases on POD 5. CONCLUSION: In this study, DFL measured on POD 3 as a single measurement appears to carry the most benefit in prediction of clinically significant POPF. Reduction to a measurement on this day may lead to a reduction in cost, earlier drain removal and earlier identification of high-risk patients.

The role of intraperitoneal ropivacaine in laparoscopic appendicectomy: a prospective, double-blinded randomized control Australian study.

BACKGROUND: Currently, intraoperative use of local anaesthetic is not routinely given in all laparoscopic appendicectomies. Although its use has been widely studied in laparoscopic hernia repairs, gynaecological laparoscopy and laparoscopic cholecystectomies, there are no published trials of the use of intraperitoneal local anaesthetic during laparoscopic appendicectomy in the Australasian setting. The aim of this study was to determine whether the use of intraperitoneal ropivacaine during laparoscopic appendicectomy will reduce the amount of post-operative opiate analgesia used, abdominal pain, post-operative nausea or vomiting, shoulder tip pain and length of hospital stay. METHODS: A randomized double-blinded placebo versus control trial was conducted with patients with clinically diagnosed appendicitis undergoing laparoscopic appendicectomy. Primary outcomes measured were the number of times the patient-controlled analgesia (PCA) button was pressed post-operatively and the average and total amount of fentanyl from PCA consumed during the post-operative period from 0 to 6 h and from 6 to 16 h. RESULTS: A total of 86 patients with 43 patients in the placebo normal saline group and 43 patients in the treatment ropivacaine group were included in the study. During the immediate post-operative period (0-6 h), there was a statistically significant reduction in the number of times the PCA button was pressed in the ropivacaine group compared to the normal saline group (16 versus 24 times, P = 0.02). CONCLUSION: Intraperitoneal ropivacaine has an analgesic effect for patients up to 6 h following emergency laparoscopic appendicectomy.

Gastric outlet obstruction secondary to orbera intragastric balloon.

Intragastric balloons are used as a temporary restrictive method in obesity to induce weight loss. They are typically recommended when patients have mild obesity and have failed traditional first line treatments of diet, exercise and behaviour modification. We report a case of a 45-year-old female who presented with nausea, vomiting and abdominal pain two weeks following an uncomplicated insertion of an intragastric balloon. Following investigation, she was found to have a gastric outlet obstruction which required endoscopic removal of the balloon. While a rare occurrence, gastric outlet obstruction as seen in this case, highlights the importance of early recognition in order to proceed with swift diagnosis and intervention in order to prevent significant morbidity such as ischaemia and perforation.

Cutaneous mucormycosis in an immunocompromised patient: a case report.

Mucormycosis is a rare and highly aggressive fungal infection, with a potential to reach its fulminant phase rapidly. We report a case of a 73-year-old immunocompromised vasculopath with cutaneous mucormycosis. The disease resulted in eventual death despite aggressive surgical debridement, revascularization of his limb and amphotericin-B. This case highlights the need to recognize this disease early as a differential of a necrotic ulcer, to prevent a potentially avoidable fatality.