Surgeon-performed transcutaneous laryngeal ultrasound for vocal cord assessment after total thyroidectomy: a prospective study : Original article.

PURPOSE: Assessing vocal cord mobility is crucial for patients undergoing thyroid surgery. We aimed to evaluate the feasibility and efficacy of surgeon-performed transcutaneous laryngeal ultrasound (TLUS) compared to flexible nasolaryngoscopy. METHOD: From February 2022 to December 2022, we conducted a prospective observational study on patients scheduled for total thyroidectomy at our Institution. All patients underwent TLUS followed by flexible nasolaryngoscopy by a blinded otolaryngologist. Findings were classified as normal or vocal cord movement impairment and then compared. Patients evaluable on TLUS were included in Group A, while those not evaluable were included in Group B, and their features were compared. RESULTS: Group A included 180 patients, while Group B included 21 patients. Male sex (p < 0.001), age (p = 0.034), BMI (p < 0.001), thyroid volume (p = 0.038), and neck circumference (p < 0.001) were associated with Group B. TLUS showed a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 100%, 99.4%, 94.4%, 100%, and 99.4%, respectively. Cohen's K value was 0.984. CONCLUSION: TLUS is a valid, easy-to-perform, non-invasive, and painless alternative for evaluating vocal cords in selected patients. It can be used either as a first level exam and as screening tool for selecting cases for flexible nasolaryngoscopy. TLUS should be integrated into routine thyroid ultrasound examination.

First report of benign track seeding after robot-assisted transaxillary thyroid surgery.

BACKGROUND: Robot-assisted transaxillary thyroidectomy is a well-established remote-access thyroid procedure that has been demonstrated to be as safe and effective as its time-honored conventional clamp-and-tie counterpart. However, it has been incriminated for a set of unprecedented complications that surgeons need to be aware of and deal with appropriately. PATIENT FINDINGS: The patient is a young woman who underwent robot-assisted thyroid lobectomy for a sizeable nodule that was reported as benign after fine-needle aspiration cytology. She presented 3 years later with subcutaneous nodules along the surgical track that were found to represent seeding of benign thyroid tissue. This is the first report of benign thyroid tissue seeding after a gasless transaxillary procedure. SUMMARY: Seeding along the surgical track is a potential complication of gasless remote-access thyroid surgery, even in case of benign disease, that surgeons need to be acquainted with. CONCLUSIONS: Surgeons should be aware of the potential for benign seeding after remote-access thyroid procedures. Accordingly, adequate precautions should be taken, patients should be counseled in this regard, and alternative medical strategies to control local seeding of thyroid tissue could be suggested.

Robot-Assisted Transaxillary Thyroidectomy (RATT): A Series Appraisal of More than 250 Cases from Europe.

BACKGROUND: Robot-assisted transaxillary thyroidectomy (RATT) is widely accepted in Asian countries. However, concerns regarding the balance between its real advantages and safety and cost have been raised by North American authorities. In Europe, assessments have been limited by small numbers since now. The purpose here is to report a large European experience with RATT. METHODS: A retrospective analysis was conducted of 257 patients who underwent RATT for nodular disease between February 2012 and September 2016. Data collected included patient demographics, diagnosis, ultrasound-estimated mean thyroid volume and nodule size, type of resection, operative time, postoperative pain and morbidity, and the hospital length of stay. Pain was assessed by visual analog scale score 12 h postoperatively (on the first postoperative day, before discharge). Feasibility, effectiveness, and safety were the outcomes of interest. Follow-up of thyroid carcinoma patients was carried out measuring thyroglobulin levels and ultrasound examination (median follow-up 24 months (6-48 months)). First control after 12 months and successively once a year. RESULTS: There were 253 women and 4 men, with a mean age of 37.3 years. Indications included benign disease in 116, papillary carcinoma in 56, and indeterminate nodule in 85. Mean thyroid volume was 16.8 mL, and nodule size was 25.3 mm. A hemithyroidectomy was performed in 138 patients and total thyroidectomy in 118. The mean operative time was 77.5 min for the former and 99.7 min for the latter. One conversion was required. Complications included transient hypoparathyroidism in 7/118 (total thyroidectomy) patients (5.9%), transient vocal fold palsy in 3/257 (1.1%), 1 delayed tracheal injury (0.4%), and 3 postoperative hematoma (1.1%). Mean visual analog scale score was 1.79, and the mean length of stay was 1.6 days for hemithyroidectomy and 1.9 days for total thyroidectomy. CONCLUSION: RATT is safe and effective and could serve as a viable treatment modality in selected cases.

Cosmetic result and overall satisfaction after minimally invasive video-assisted thyroidectomy (MIVAT) versus robot-assisted transaxillary thyroidectomy (RATT): a prospective randomized study.

BACKGROUND: No studies have compared robot-assisted transaxillary thyroidectomy (RATT) and minimally invasive video-assisted thyroidectomy (MIVAT) regarding cosmetic outcome and satisfaction METHODS: Patients matching the inclusion criteria (benign nodule less than 4 cm and thyroid volume less than 30 mL) were randomly allotted to undergo MIVAT (group A) or RATT (group B). Cosmetic result, overall satisfaction, operative time, and complications were evaluated. RESULTS: A total of 62 patients underwent hemithyroidectomy (30 in group A and 32 in group B). All patients were women, with the exception of one man in each group. The mean patient age was 36.9 years (group A) and 32.5 years (group B). Total operative time (intubation-extubation) was shorter in group A (71.6 min) than in group B (120.4 min). Complications included one transient laryngeal nerve injury in each group and one subcutaneous hematoma in group B. Postoperative hospital stay was longer in group B (1.85 days) than in group A (1.15 days). On the PASQ questionnaire, "scar appearance" and "satisfaction with appearance" scores were better in group A than in group B. In the Short Form (SF-36) 36-Item Health Survey Questionnaire, domains of "social activity" and "general health" were better in group B than in group A, whereas "bodily pain" scored higher in group B than in group A. CONCLUSIONS: RATT seems not to supersede MIVAT in terms of satisfaction when comparing two groups of patients undergoing thyroidectomy for benign disease.

Increased costs of perioperative risk assessment for thyroid surgery in elderly people (over 80 years) presenting with benign disease.

BACKGROUND/OBJECTIVES: Evaluate how surgical treatment of benign thyroid disease in elderly people is prone to induce an increase of costs in the next future due to the aging process of the population. METHODS: A retrospective analysis has been performed on a total of 116 patients operated between January 2007 and September 2011, divided in a group of 58 patients aged over 80 years (Group A) and 58 patients younger than 80 years (Group B). The analyzed data included age, preoperative diagnosis, severe co-morbidities, procedures other than standard needed to evaluate anaesthesiological risk, postoperative hospital stay, complications, duration of postoperative intensive care monitoring, pathologic characteristics, and costs of anaesthesiological risk assessment. RESULTS: Statistical analysis of collected data showed that the costs related to perioperative risk assessment (p value < 0.001) and the duration of hospital stay (p value < 0.001) were higher in Group A than in Group B. Instead, surgery-related complications were not statistically different. CONCLUSIONS: Despite feasibility and safety of modern surgical techniques, indications for surgery in elderly patients affected by benign thyroid disease should be reserved mainly for those patients with severe medical necessity.

The learning curve on robot-assisted transaxillary thyroidectomy performed by a single endocrine surgeon in a third-level institution in Europe: a cumulative sum (CUSUM) analysis.

Robot-assisted transaxillary thyroidectomy is widely performed in Asian countries, although it is still under discussion in the Western World. However, there have been few studies reporting on the learning curve of robot-assisted transaxillary thyroidectomy. We used the cumulative sum (CUSUM) analysis to assess the learning curve of gasless robot-assisted transaxillary thyroidectomy at a third-level institution in Europe. We included all consecutive patients operated by a single surgeon without previous experience of robotic surgery from February 2012 to January 2023. The primary endpoint of the study was the learning curve extracted from the median operative time using the CUSUM method for the quantitative assessment. Overall, 583 patients were enrolled. The median operative time for thyroid lobectomy and total thyroidectomy was 70 and 90 min, respectively. The CUSUM analysis showed that the learning curve for thyroid lobectomy and total thyroidectomy is 66 and 56 cases, respectively. Moreover, the presence of thyroiditis resulted associated with shorter operative time for total thyroidectomy (p = 0.044), whereas no factors resulted associated with surgical complications. The learning curve for performing robotic transaxillary thyroid lobectomy for a surgeon without previous robotic experience is 66 cases. After that, 56 cases must be performed to acquire proficiency in robotic transaxillary total thyroidectomy. Training programs may reduce the slope of the learning curve.

Comparison of surgical completeness in patients operated on conventional open total thyroidectomy (OT) or trans-axillary robot-assisted total thyroidectomy (RATT) by a single axillary approach.

Trans-axillary robot-assisted total thyroidectomy (RATT) is nowadays worldwide accepted but the completeness obtained by RATT is still debated. The Aim of this study was to compare the completeness and safety of RATT with conventional open thyroidectomy (OT). We enrolled patients with nontoxic multinodular goiter, cytologically indeterminate nodules and well differentiated thyroid cancer without local and/or distant metastasis. In all cases the biggest nodule should be < 6 cm. The surgical completeness was evaluated by means of serum thyroglobulin (hs-Tg) and neck ultrasound (nUS) performed three months postoperatively. 100 patients underwent either RATT or OT. The type of surgical procedure was chosen by patients. They were then divided in two subgroups based on benign or malignant histology. There were no significant differences in the postoperatively values of hs-Tg in patients operated with RATT or OT, both in benign and malignant subgroups. The post-operative thyroid remnant volume estimated by nUS was not significantly different between the two groups, both in benign and malignant subgroups. We also analyzed the difference of the volume of the thyroid remnant ipsilateral to the axillary access vs that of the remnant on the contralateral side and there was not significantly difference in both subgroups. RATT was demonstrated to determine a comparable surgical completeness as OT, both in benign and malignant thyroid diseases, with no differences in the prevalence of surgical complications. In our hands the surgical completeness of RATT by a single trans-axillary was satisfying.

Robot-assisted transaxillary surgery for thyroid cancer: Oncologic and surgical outcomes in long term follow-up.

BACKGROUND: The use of robot-assisted transaxillary thyroidectomy (RATT) has rapidly spread in the last 2 decades, although it is mostly limited to Asian countries. METHOD: We retrospectively enroled all patients with histologic diagnoses of thyroid cancer who underwent RATT at the University Hospital of Pisa from May 2012 to September 2020. RESULTS: The study included 242 patients; 128 (47%) underwent total thyroidectomy and 114 (53%) underwent thyroid lobectomy, among which 28 patients (24.6%) required completion thyroidectomy. Radioactive iodine ablation therapy was required in 90 patients (37%). The complication rate was 5.3%. After a median follow-up of 38 months, an excellent response to therapy was achieved in 107 patients (74%), whereas the response was indeterminate in 12 (8%) and incomplete in 16 (11%). No local or distant relapses or increases in thyroglobulin or antibody levels were documented. CONCLUSIONS: In experienced hands, RATT represents a valid option for the treatment of thyroid cancer in selected cases.

Robotic transaxillary thyroidectomy: time to expand indications?

In 2016, the American Thyroid Association published a statement on remote-access thyroid surgery claiming that it should be reserved to patients with thyroid nodule ≤ 3 cm, thyroid lobe < 6 cm and without thyroiditis. We retrospectively enrolled all patients who underwent robotic transaxillary thyroidectomy between February 2012 and March 2022. We compared surgical outcomes between patients who presented a thyroid gland with a nodule ≤ 3 cm, thyroid lobe < 6 cm and without thyroiditis (Group A) and patients without these features (Group B). The rate of overall complications resulted comparable (p = 0.399), as well as the operative time (p = 0.477) and the hospital stay (p = 0.305). Moreover, bleeding resulted associated to thyroid nodule > 3 cm (p = 0.015), although all bleedings but one occurred in the remote-access site from the axilla to the neck. In experienced hands, robotic transaxillary thyroidectomy is feasible and safe even in patients with large thyroid nodules or thyroiditis.

Postsurgical complications after robot-assisted transaxillary thyroidectomy: critical analysis of a large cohort of European patients.

In the last decade, robot-assisted trans-axillary thyroidectomy has spread rapidly and has been proven to be a safe and effective procedure. However, several case series have reported new complications that have led to criticism regarding this approach. This study analyzed the incidence of complications in a large cohort of European patients. We enrolled all patients who underwent robot-assisted trans-axillary thyroidectomy from 2012 to 2020 at the University Hospital of Pisa Department of Endocrine Surgery. We analyzed complications and divided them into 2 groups. Group A included conventional complications, such as transient or permanent recurrent laryngeal nerve palsy, transient or permanent hypocalcemia, hemorrhage, and tracheal injury. Group B included unconventional complications, such as brachial plexus palsy, track seeding, seroma, great vessels injury, and skin flap perforation. There were 31 postsurgical complications (5.7%). Group A included 25 complications (4.6%): transient and permanent recurrent laryngeal nerve palsy occurred in 7 patients (1.3%) and in 1 (0.2%), respectively; transient and permanent hypocalcemia occurred in 9 patients (1.7%) and in 1 (0.2%), respectively. Postoperative bleeding occurred in 6 patients (1.1%) and tracheal injury in 1 (0.2%). Group B included 6 complications (1.1%): 1 patient with brachial plexus injury (0.2%), 1 with track seeding (0.2%), and 4 with seroma (0.7%). Robotic trans-axillary thyroidectomy is a safe approach with a risk of postoperative complications comparable to the conventional technique. Almost all complications after a novel introduction are anecdotal. With an accurate patient selection, high-volume institutions with experienced surgeons can perform this technique safely.

The effect of robot-assisted transaxillary thyroidectomy (RATT) on body image is better than the conventional approach with cervicotomy: a preliminary report.

BACKGROUND: Cosmetic satisfaction is not only based on the patient's perception of the scar itself but is also related to body image self-evaluation. Cosmetic superiority of Robot-assisted transaxillary thyroidectomy (RATT) over conventional thyroidectomy (CT) has not yet been clearly demonstrated. Aim of our study was to compare body image in patients undergoing CT versus RATT. METHODS: The study included 160 (80 CT and 80 RATT) patients undergoing thyroidectomy between August 2014 and March 2018 at the Endocrine Surgery Department. The inclusion criteria were age 18 to < 60 years, female sex, thyroid volume < 30 mL, and nodule diameter < 5 cm. Scar length, operative time, and complications were analyzed. The body image questionnaire (BIQ) was used 3 months postoperatively. The Student t test was used for statistical analysis. RESULTS: Age was lower in RATT group (38.2 vs 41.4 years) (P < 0.0001). The nodule diameter was larger in RATT group (27.1 vs 23.1 mm) (P = 0.028). Operative time was longer in RATT group (93.7 vs 47.6 min) (P < 0.0001). The scar was longer in RATT group (59.9 vs 37.7 mm) (P < 0.0001). The groups had similar complication rates. BIQ showed that RATT patients answered more favorably to question 2, "Do you feel the operation has damaged your body?" (P = 0.042) and to question 3, "Do you feel less attractive as a result of your treatment?" (P = 0.024). Also self-global satisfaction was better in RATT group (P = 0.019). CONCLUSIONS: In our experience, RATT has a significantly better impact on body image than the conventional approach.

Minimally invasive video-assisted thyroidectomy (MIVAT).

BACKGROUND: Minimally invasive video-assisted thyroidectomy (MIVAT) was first described in 1999 and it has become a widespread technique performed worldwide. Although initially limited to benign thyroid nodules, MIVAT was progressively adopted for all types of thyroid diseases, while remaining within the selection criteria. It is reported that, in selected cases, MIVAT is comparable to standard open thyroidectomy (SOT) in terms of oncologic radicality, time, costs and complications rate, with the advantage of a better cosmetic result and a lower post-operative pain. METHODS: The authors conducted a retrospective analysis about patients who underwent MIVAT between 1998 and 2019 in the Endocrine Surgery Unit of the University Hospital in Pisa. Indications and contraindications are mentioned and strictly followed. RESULTS: Total thyroidectomy was performed in 1,862 cases (69%) and hemithyroidectomy was performed in 763 cases (28.3%). Conversion occurred in 43 cases (1.6%). In 188 cases (7%) a postoperative transient hypoparathyroidism was reported, whereas definitive hypoparathyroidism was reported in 12 cases (0.4%). Thirty-eight patients (1.4%) suffered from a definitive postoperative recurrent laryngeal nerve palsy. No definitive bilateral recurrent laryngeal nerve palsy occurred. CONCLUSIONS: From our multi-years' experience which spreads over 20 years, we can reaffirm the concept that MIVAT is a safe procedure which is not burdened by an increase complications rate or additional costs. Furthermore, this technique offers advantages in terms of cosmetic results and post-operative pain.

Modified lateral neck lymphadenectomy: prospective randomized study comparing harmonic scalpel with clamp-and-tie technique.

OBJECTIVE: To compare the use of harmonic scalpel (HS) with clamp-and-tie technique to evaluate their comparative merits in modified lateral lymphadenectomy (LL). STUDY DESIGN: Prospective and randomized. SUBJECTS AND METHODS: Thirty-seven patients were recruited and divided into Group A (conventional; n = 20) and Group B (HS; n = 17). Thyroid volume, neck circumference, operative time, diameter of the tumor and lymph node, drainage volume, pain, and complications were compared. Operation consisted of thyroidectomy and LL. RESULTS: Groups were homogeneous for thyroid volume, diameter of thyroid nodule and lymph node, and neck circumference. Operative time was shorter in Group B than in Group A. The fluid collection in the vacuum between 24 and 48 hours and the increase of neck circumference were lower in Group B. Pain was significantly lower in Group B after 12 hours and decrease was faster in Group B. CONCLUSION: The use of HS during LL is as safe as conventional technique and may allow shorter operative time, lower lymphatic spillage, and faster decrease of pain.

Posterior retroperitonoscopic adrenalectomy; a back door access with an unusually rapid learning curve.

Posterior retroperitonoscopic adrenalectomy (PRA) has become a standard approach to the adrenal gland. The aim of this study was to report an initial experience with the procedure following a proper preparatory phase highlighting the rapidity, safety and effectiveness by which it could be introduced into a surgeon's practice. Between May 2015 and July 2016, 14 PRAs were performed in 14 patients (9 females and 5 males). The average age was 46 years, BMI: 25.5 kg/m2, and ASA score: 2. Indications included: incidenatloma (n = 5), Conn's adenoma (n = 5), and Cushing's adenoma (n = 4). Lesions were on average 3.3 cm in size. Outcomes of interest included: operative time (OT), conversion rate, postoperative morbidity and mortality rates, and the length of hospital stay. Mean OT was 87.5 min (range 35-150 min). A significant reduction in OT occurred after the sixth procedure and was progressive thereafter. After the tenth case, the OT became less than 1 h. No conversion was required. No intra- or post-operative complications occurred, and mortality was zero. All patients commenced oral intake and ambulated following full recovery from anesthesia. The mean length of hospital stay was 3 days (range 2-6 days). PRA offers a direct access to the adrenal gland allowing for target-oriented dissection. Cognitive reorientation to the anatomy of this back door access and an adequate learning curve could be rapidly achieved by experienced and properly prepared laparoscopic surgeons.

Postoperative Pain Evaluation After Robotic Transaxillary Thyroidectomy Versus Conventional Thyroidectomy: A Prospective Study.

BACKGROUND: Robot-assisted transaxillary thyroidectomy (RATT) is an emerging technique with excellent cosmetic results but is supposedly more invasive and painful than conventional thyroidectomy (CT). This prospective study compared pain after RATT and CT. METHODS: Inclusion criteria were a nodule <5 cm and volume <30 mL. Patients received the same analgesia. Pain was evaluated by visual analog scale (VAS) in the recovery room (VASrr), on the first postoperative day at 8:00 a.m. (VAS 8 a.m.) and 8:00 p.m. (VAS 8 p.m.), at 8:00 a.m. on the second postoperative day (VAS 8*a.m.), and after 7 days (VAS 7). Operative time and complications were evaluated. RESULTS: From May 2015 to September 2015, 124 patients (all women) underwent thyroidectomy: 62 underwent RATT and 62 underwent CT. Mean age was 39.7 ± 10.2 years in the RATT group and 41.4 ± 12.5 years in the CT group. Groups were comparable for thyroid volume and nodule diameter. Operative time was longer in the RATT group than in the CT group (119.4 ± 25.5 versus 70.3 ± 11.0 minutes). Complications were three transient hypocalcemia in RATT and four in the CT group. No definitive complications occurred. VASrr was lower in the RATT group (1.79 ± 2.06 versus 2.5 ± 1.18; P < .0001). There was no difference between groups for VAS 8 a.m., VAS 8 p.m., and VAS 8*a.m., but VAS 7 was higher in the RATT group (0.85 ± 1.77 versus 0.17 ± 0.52; P < .010). DISCUSSION: RATT is as safe and effective as CT. Patients undergoing RATT, surprisingly, experienced less pain in the immediate postoperative period. However, the VAS 7 score was higher in the RATT group, probably because the intact neck is favorable in the early phase of recovery, but the large dissection takes longer for healing.

Prevention and management of bleeding in thyroid surgery.

Post-thyroidectomy neck hematoma represents a major concern for surgeons because it can result in severe and even life-threatening complications. In fact, postoperative hemorrhage may result in airway compression and respiratory distress, and therefore, effective hemostasis is an important goal in thyroid surgery. Postoperative hematoma occurs at a rate of approximately 0.1% to 1.1%. Almost all cases occur in the first 6 h after surgery and can be the result of several surgeon or patient factors. For many years the clamp-and-tie technique has been the most common way to divide the main vascular pedicles of the thyroid gland. Alternatively, bipolar electrocautery has been used for only very small vessels. Other hemostatic systems have been introduced and proved to be potentially very useful in neck surgery and, in particular, for thyroid surgery. This new class of instruments is generally known as "energy devices" because they use different forms of energy, such as advanced bipolar (LigaSureTM Small Jaw Medtronic, Covidien product, Mineapolis, MN, USA) and ultrasound (Harmonic Focus; Ethicon, Johnson and Johnson, Cincinnati, OH, USA), and hybrid devices that join these two technologies (Thunderbeat by Olympus, Japan). Although they all generate a significant elevation of temperature in the tissues, as in any form of energy, the temperatures reached by these instruments are never as high as the standard monopolar electrocautery. For small bleeding very close to critical structures, where energy devices are too dangerous to be used and clamp and tie is not possible, several studies have assessed the use of adjunctive hemostatic agents. In conclusion, all energy devices have been shown to significantly decrease operative times without increasing costs or complications. Adjunctive hemostatic agents have shown equivalent differences when added to standard methods from a clinically significant perspective.

Track Recurrence After Robotic Transaxillary Thyroidectomy: A Case Report Highlighting the Importance of Controlled Surgical Indications and Addressing Unprecedented Complications.

BACKGROUND: Robot-assisted transaxillary thyroid surgery (RATS), widely accepted and used in Asian countries, can be an appealing treatment option both for patients with major concerns regarding a cervical scar and for their surgeons. Patients benefit from scarless neck surgery, while their surgeons benefit from improved dexterity and ergonomics compared with remote-access endoscopic thyroid surgery. However, validating any novel surgical procedure for thyroid pathology should be based on evidence regarding its feasibility, radicality, and safety compared to the time-honored, safe and effective, conventional open thyroidectomy. It should also be evaluated for potential risks that are not present with conventional approaches. PATIENT FINDINGS: This study reports a patient with surgical track and cervical nodal recurrence, and distant metastasis following a two-stage robot-assisted surgery, and radioactive iodine ablation therapy for a papillary thyroid carcinoma that was initially regarded a single indeterminate nodule. SUMMARY: This case emphasizes the importance of thoroughly evaluating the oncological safety of RATS, and points out the possibility of "malignant seeding along the surgical access" being an untraditional potential complication associated with the procedure. CONCLUSIONS: While tailoring the surgical strategy to the patients' concerns and desires is important, adhering to fundamental onco-surgical principles is a priority. Furthermore, unconventional complications associated with novel surgical procedures should be properly evaluated and addressed.

Pancreatoduodenectomy for groove pancreatitis Report of two cases.

Groove pancreatitis is a rare condition with patients having clinical characteristics similar to those of chronic pancreatitis. Differentiating on clinical and radiological basis between groove pancreatitis and paraduodenal head cancer can be extremely challenging. Due to diagnostic uncertainty and to poor response to medical treatment surgery may offer these patients the best chance of cure. As the main localization of the inflammatory process is at the groove between the duodenum and the head of the pancreas, pancreato-duodenectomy is proposed as the most reliable surgical procedure. We report about two patients presenting with clinical and radiological features suggesting a groove pancreatitis in which control of symptoms was achieved by pancreatoduodenectomy. KEY WORDS: Groove pancreatitis, Paraduodenal pancreatic cancer.